Mechanism of non-appearance of hiatus in Tibetan Plateau.

PubMed

Ma, Jieru; Guan, Xiaodan; Guo, Ruixia; Gan, Zewen; Xie, Yongkun

2017-06-30

In the recent decade, hiatus is the hottest issue in the community of climate change. As the area of great importance, the Tibetan Plateau (TP), however, did not appear to have any warming stoppage in the hiatus period. In fact, the TP showed a continuous warming in the recent decade. To explore why the TP did not show hiatus, we divide the surface air temperature into dynamically-induced temperature (DIT) and radiatively-forced temperature (RFT) by applying the dynamical adjustment method. Our results show that DIT displayed a relatively uniform warming background in the TP, with no obvious correlations with dynamic factors. Meanwhile, as the major contribution to warming, the RFT effect over the TP played the dominant role. The warming role is illustrated using the temperature change between perturbed and control simulation responses to CO 2 or black carbon (BC) forcing via Community Earth System Model (CESM). It shows that an obvious warming in the TP is induced by the CO 2 warming effect, and BC exhibits an amplifying effect on the warming. Therefore, the continuous warming in the TP was a result of uniform DIT warming over a large scale and enhanced RFT warming at a regional scale.

Petrologic evidence that most ocean islands derive from thermally driven mantle plumes

NASA Astrophysics Data System (ADS)

Putirka, K. D.

2006-12-01

Perhaps the most crucial test of the mantle plume hypothesis concerns whether hot spots are indeed hot. To conduct this test, olivine-liquid equilibria are used to estimate mantle potential temperatures (Tp) for 15 putative plume localities (using the GEOROC database). Ocean islands (OIB) were selected on the availability of rocks that attain olivine control (where olivine addition/removal alone controls rock composition) so that primitive FeO contents could be estimated. Several other variables in addition to FeO must also be known: Except at Iceland and Hawaii, where large numbers of olivine analyses allow individual estimates for the maximum forsterite contents (Fomax) of olivines, a single Fomax value, 91.5, is adopted for all OIB (and MORB; determined from a global database of olivine compositions); as a null hypothesis, MORB-like values for oxygen fugacity (QFM-1; Bezos and Humler, 2005) and the Fe-Mg exchange coefficient between olivine and liquid (0.31; calculated from Toplis, 2005, Herzberg and O'Hara, 1998) are adopted. Generalized differences in water contents between OIB and MORB (Dixon et al., 2002) are also accounted for. All temperatures are calculated at 1 GPa, using averages of existing (Beattie, 1993) and new (Putirka et al., 2006) olivine geothermometers. Except for Galapagos, primitive OIBs have nearly uniform FeO contents that are higher compared to MORB (at MgO>10 wt. %, mean OIB FeOt = 11.6 wt. %). These high FeO contents require higher mean temperatures of olivine-liquid equilibration for OIB, by an average of 150±20°C compared to MORB. Olivine equilibration temperatures do not depend on mantle source composition, so are independent of whether eclogite-type components occur in the mantle. If a peridotite bulk composition is assumed (to estimate melt fraction from partial melting experiments) olivine equilibration temperatures can be converted to Tp; OIB (Galapagos excepted) yield a mean Tp of 1583°C, compared to 1397°C for MORB. When inter- island compositional variation is accounted for, all OIB except Galapagos yield excess temperatures (Tp^{OIB} - Tp^{MORB}) of 133-280°C, with a mean of 186± 36°C. Galapagos lavas yield an excess temperature of 16°C; perhaps mixing has diluted its thermal signal, but in any event, its Tp is essentially identical to MORB. Nevertheless, most OIB (93% in this sample) exhibit large excess temperatures. Thermally driven mantle plumes, as proposed by Morgan (1971), thus appear to be common, not rare. A second implication, less certain than the first, involves the narrow standard deviation of ±36°C for Tp at OIB, which almost certainly reflects a lower limit to actual thermal variability. This narrow range indicates that all hot spots derive from a single thermal boundary layer.

Climate variability rather than overstocking causes recent large scale cover changes of Tibetan pastures.

PubMed

Lehnert, L W; Wesche, K; Trachte, K; Reudenbach, C; Bendix, J

2016-04-13

The Tibetan Plateau (TP) is a globally important "water tower" that provides water for nearly 40% of the world's population. This supply function is claimed to be threatened by pasture degradation on the TP and the associated loss of water regulation functions. However, neither potential large scale degradation changes nor their drivers are known. Here, we analyse trends in a high-resolution dataset of grassland cover to determine the interactions among vegetation dynamics, climate change and human impacts on the TP. The results reveal that vegetation changes have regionally different triggers: While the vegetation cover has increased since the year 2000 in the north-eastern part of the TP due to an increase in precipitation, it has declined in the central and western parts of the TP due to rising air temperature and declining precipitation. Increasing livestock numbers as a result of land use changes exacerbated the negative trends but were not their exclusive driver. Thus, we conclude that climate variability instead of overgrazing has been the primary cause for large scale vegetation cover changes on the TP since the new millennium. Since areas of positive and negative changes are almost equal in extent, pasture degradation is not generally proceeding.

Profile measurements of the electron temperature on the ASDEX Upgrade, COMPASS, and ISTTOK tokamak using Thomson scattering, triple, and ball-pen probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamek, J., E-mail: adamek@ipp.cas.cz; Horacek, J.; Bilkova, P.

The ball-pen probe (BPP) technique is used successfully to make profile measurements of the electron temperature on the ASDEX Upgrade (Axially Symmetric Divertor Experiment), COMPASS (COMPact ASSembly), and ISTTOK (Instituto Superior Tecnico TOKamak) tokamak. The electron temperature is provided by a combination of the BPP potential (Φ{sub BPP}) and the floating potential (V{sub fl}) of the Langmuir probe (LP), which is compared with the Thomson scattering diagnostic on ASDEX Upgrade and COMPASS. Excellent agreement between the two diagnostics is obtained for circular and diverted plasmas and different heating mechanisms (Ohmic, NBI, ECRH) in deuterium discharges with the same formula T{submore » e} = (Φ{sub BPP} − V{sub fl})/2.2. The comparative measurements of the electron temperature using BPP/LP and triple probe (TP) techniques on the ISTTOK tokamak show good agreement of averaged values only inside the separatrix. It was also found that the TP provides the electron temperature with significantly higher standard deviation than BPP/LP. However, the resulting values of both techniques are well in the phase with the maximum of cross-correlation function being 0.8.« less

Pyroelectric effect and lattice thermal conductivity of InN/GaN heterostructures

NASA Astrophysics Data System (ADS)

Hansdah, Gopal; Sahoo, Bijay Kumar

2018-06-01

The built-in-polarization (BIP) of InN/GaN heterostructures enhances Debye temperature, phonon mean free path and thermal conductivity of the heterostructure at room temperature. The variation of thermal conductivities (kp: including polarization mechanism and k: without polarization mechanism) with temperature predicts the existence of a transition temperature (Tp) between primary and secondary pyroelectric effect. Below Tp, kp is lower than k; while above Tp, kp is significantly contributed from BIP mechanism due to thermal expansion. A thermodynamic theory has been proposed to explain the result. The room temperature thermal conductivity of InN/GaN heterostructure with and without polarization is respectively 32 and 48 W m-1 K-1. The temperature Tp and room temperature pyroelectric coefficient of InN has been predicted as 120 K and -8.425 μC m-2 K-1, respectively which are in line with prior literature studies. This study suggests that thermal conductivity measurement in InN/GaN heterostructures can help to understand the role of phonons in pyroelectricity.

A comprehensive data set of lake surface water temperature over the Tibetan Plateau derived from MODIS LST products 2001–2015

PubMed Central

Wan, Wei; Li, Huan; Xie, Hongjie; Hong, Yang; Long, Di; Zhao, Limin; Han, Zhongying; Cui, Yaokui; Liu, Baojian; Wang, Cunguang; Yang, Wenting

2017-01-01

Lake surface water temperature (LSWT) is sensitive to long-term changes in thermal structure of lakes and regional air temperature. In the context of global climate change, recent studies showed a significant warming trend of LSWT based on investigating 291 lakes (71% are large lakes, ≥50 km2 each) globally. However, further efforts are needed to examine variation in LSWT at finer regional spatial and temporal scales. The Tibetan Plateau (TP), known as ‘the Roof of the World’ and ‘Asia’s water towers’, exerts large influences on and is sensitive to regional and even global climates. Aiming to examine detailed changing patterns and potential driven mechanisms for temperature variations of lakes across the TP region, this paper presents the first comprehensive data set of 15-year (2001–2015) nighttime and daytime LSWT for 374 lakes (≥10 km2 each), using MODIS (Moderate Resolution Imaging Spectroradiometer) Land Surface Temperature (LST) products as well as four lake boundary shapefiles (i.e., 2002, 2005, 2009, and 2014) derived from Landsat/CBERS/GaoFen-1 satellite images. The data set itself reveals significant information on LSWT and its changes over the TP and is an indispensable variable for numerous applications related to climate change, water budget analysis (particularly lake evaporation), water storage changes, glacier melting and permafrost degradation, etc. PMID:28742066

A comprehensive data set of lake surface water temperature over the Tibetan Plateau derived from MODIS LST products 2001-2015.

PubMed

Wan, Wei; Li, Huan; Xie, Hongjie; Hong, Yang; Long, Di; Zhao, Limin; Han, Zhongying; Cui, Yaokui; Liu, Baojian; Wang, Cunguang; Yang, Wenting

2017-07-25

Lake surface water temperature (LSWT) is sensitive to long-term changes in thermal structure of lakes and regional air temperature. In the context of global climate change, recent studies showed a significant warming trend of LSWT based on investigating 291 lakes (71% are large lakes, ≥50 km 2 each) globally. However, further efforts are needed to examine variation in LSWT at finer regional spatial and temporal scales. The Tibetan Plateau (TP), known as 'the Roof of the World' and 'Asia's water towers', exerts large influences on and is sensitive to regional and even global climates. Aiming to examine detailed changing patterns and potential driven mechanisms for temperature variations of lakes across the TP region, this paper presents the first comprehensive data set of 15-year (2001-2015) nighttime and daytime LSWT for 374 lakes (≥10 km 2 each), using MODIS (Moderate Resolution Imaging Spectroradiometer) Land Surface Temperature (LST) products as well as four lake boundary shapefiles (i.e., 2002, 2005, 2009, and 2014) derived from Landsat/CBERS/GaoFen-1 satellite images. The data set itself reveals significant information on LSWT and its changes over the TP and is an indispensable variable for numerous applications related to climate change, water budget analysis (particularly lake evaporation), water storage changes, glacier melting and permafrost degradation, etc.

Climate variability rather than overstocking causes recent large scale cover changes of Tibetan pastures

PubMed Central

Lehnert, L. W.; Wesche, K.; Trachte, K.; Reudenbach, C.; Bendix, J.

2016-01-01

The Tibetan Plateau (TP) is a globally important “water tower” that provides water for nearly 40% of the world’s population. This supply function is claimed to be threatened by pasture degradation on the TP and the associated loss of water regulation functions. However, neither potential large scale degradation changes nor their drivers are known. Here, we analyse trends in a high-resolution dataset of grassland cover to determine the interactions among vegetation dynamics, climate change and human impacts on the TP. The results reveal that vegetation changes have regionally different triggers: While the vegetation cover has increased since the year 2000 in the north-eastern part of the TP due to an increase in precipitation, it has declined in the central and western parts of the TP due to rising air temperature and declining precipitation. Increasing livestock numbers as a result of land use changes exacerbated the negative trends but were not their exclusive driver. Thus, we conclude that climate variability instead of overgrazing has been the primary cause for large scale vegetation cover changes on the TP since the new millennium. Since areas of positive and negative changes are almost equal in extent, pasture degradation is not generally proceeding. PMID:27073126

Climate variability rather than overstocking causes recent large scale cover changes of Tibetan pastures

NASA Astrophysics Data System (ADS)

Lehnert, L. W.; Wesche, K.; Trachte, K.; Reudenbach, C.; Bendix, J.

2016-04-01

The Tibetan Plateau (TP) is a globally important “water tower” that provides water for nearly 40% of the world’s population. This supply function is claimed to be threatened by pasture degradation on the TP and the associated loss of water regulation functions. However, neither potential large scale degradation changes nor their drivers are known. Here, we analyse trends in a high-resolution dataset of grassland cover to determine the interactions among vegetation dynamics, climate change and human impacts on the TP. The results reveal that vegetation changes have regionally different triggers: While the vegetation cover has increased since the year 2000 in the north-eastern part of the TP due to an increase in precipitation, it has declined in the central and western parts of the TP due to rising air temperature and declining precipitation. Increasing livestock numbers as a result of land use changes exacerbated the negative trends but were not their exclusive driver. Thus, we conclude that climate variability instead of overgrazing has been the primary cause for large scale vegetation cover changes on the TP since the new millennium. Since areas of positive and negative changes are almost equal in extent, pasture degradation is not generally proceeding.

Aridity changes in the Tibetan Plateau in a warming climate

DOE PAGES

Gao, Yanhong; Li, Xia; Leung, Lai-Yung R.; ...

2015-03-10

Desertification in the Tibetan Plateau (TP) has drawn increasing attention in the recent decades. It has been postulated as a consequence of climate aridity due to the observed warming. This study quantifies the aridity changes in the TP and attributes the changes to different climatic factors. Using the ratio of P/PET (precipitation to potential evapotranspiration) as an aridity index to indicate changes in dryness and wetness in a given area, P/PET was calculated using observed records at 83 stations in the TP, with PET calculated using the Penman–Monteith (PM) algorithm. Spatial and temporal changes of P/PET in 1979-2011 are analyzed.more » Results show that stations located in the arid and semi-arid northwestern TP are becoming significantly wetter and stations in the semi-humid southeastern TP are becoming drier, though not significantly, in the recent three decades. The aridity change patterns are significantly correlated with precipitation, sunshine duration and diurnal temperature range changes at confidence level of 99.9% from two-tail t-test. Temporal correlations also confirm the significant correlation between aridity changes with the three variables, with precipitation being the most dominant driver of P/PET changes at interannual time scale. PET changes are insignificant but negatively correlated with P/PET in the cold season. In the warm season, however, correlation between PET changes and P/PET changes are significant at confidence level of 99.9% when the cryosphere melts near the surface. Significant correlation between wind speed changes and aridity changes occurs in limited locations and months. Consistency in the climatology pattern and linear trends in surface air temperature and precipitation calculated using station data, gridded data, and nearest grid-to-stations for the TP average and across sub-basins indicate the robustness of the trends despite the large spatial heterogeneity in the TP that challenge climate monitoring.« less

Temperature-precipitation relationship of the Common Era in northern Europe

NASA Astrophysics Data System (ADS)

Luoto, Tomi P.; Nevalainen, Liisa

2018-05-01

Due to the lack of knowledge on dynamics of the North Atlantic Oscillation (NAO) prior to the last millennium, synchronized records of air temperature and precipitation variability are needed to understand large-scale drivers of the hydroclimate. Here, we use completely synchronized paleolimnological proxy-based records of air temperature and effective precipitation from two Scandinavian lakes with ˜2000-year sediment profiles. We show that the relationship between air temperature and precipitation (T/P ratio) is synchronous in both study sites throughout the records suggesting warm and dry conditions at ˜300-1100 CE and cold and wet conditions at ˜1200-1900 CE. Owing to the significantly increased air temperatures, the most recent T/P ratio has again turned positive. During the first millennium of the Common Era, the T/P mimics patterns in Southern Oscillation index, whereas the second millennium shows response to the NAO index but is also concurrent with solar irradiance shifts. Since our T/P reconstruction is mostly linked with the NAO, we propose the T/P ratio as an indicator of the NAO. Our results from the coherent records provide first-time knowledge on the long-term temperature-precipitation relationship in Northern Europe that increase understanding of the comprehensive hydroclimate system in the region and the NAO dynamics also further back in time.

Leaching behavior of total organic carbon, nitrogen, and phosphorus from banana peel.

PubMed

Jiang, Ruixue; Sun, Shujuan; Xu, Yan; Qiu, Xiudong; Yang, Jili; Li, Xiaochen

2015-01-01

The leaching behavior of organic carbon and nutrient compounds from banana peel (BP) was investigated in batch assays with respect to particle size, contact time, pH value, and temperature. The granularity, contact time, pH, and temperature caused no significant effects on the leaching of total phosphorus (TP) from the BP. The maximum leached total nitrogen (TN) content was found at pH 5.0 and 90 minutes, while no significant effects were caused by the granularity and temperature. The maximum leached total organic carbon (TOC) content was found by using a powder of 40 mesh, 150 minutes and at pH 6.0, while the temperature had no effect on the TOC leaching. The proportions of the TN, TP, and TOC contents leached from the dried BP ranged from 33.6% to 40.9%, 60.4% to 72.7%, and 8.2% to 9.9%, respectively, indicating that BP could be a potential pollution source for surface and ground water if discharged as domestic waste or reutilized without pretreatment.

Delayed warming hiatus over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

An, Wenling; Hou, Shugui; Hu, Yongyun; Wu, Shuangye

2017-03-01

A reduction in the warming rate for the global surface temperature since the late 1990s has attracted much attention and caused a great deal of controversy. During the same time period, however, most previous studies have reported enhanced warming over the Tibetan Plateau (TP). In this study we further examined the temperature trend of the TP and surrounding areas based on the homogenized temperature records for the period 1980-2014, we found that for the TP regions lower than 4000 m the warming rate has started to slow down since the late 1990s, a similar pattern consistent with the whole China and the global temperature trend. However, for the TP regions higher than 4000 m, this reduction in warming rate did not occur until the mid-2000s. This delayed warming hiatus could be related to changes in regional radiative, energy, and land surface processes in recent years.

Petrology of some oceanic island basalts: PRIMELT2.XLS software for primary magma calculation

NASA Astrophysics Data System (ADS)

Herzberg, C.; Asimow, P. D.

2008-09-01

PRIMELT2.XLS software is introduced for calculating primary magma composition and mantle potential temperature (TP) from an observed lava composition. It is an upgrade over a previous version in that it includes garnet peridotite melting and it detects complexities that can lead to overestimates in TP by >100°C. These are variations in source lithology, source volatile content, source oxidation state, and clinopyroxene fractionation. Nevertheless, application of PRIMELT2.XLS to lavas from a wide range of oceanic islands reveals no evidence that volatile-enrichment and source fertility are sufficient to produce them. All are associated with thermal anomalies, and this appears to be a prerequisite for their formation. For the ocean islands considered in this work, TP maxima are typically ˜1450-1500°C in the Atlantic and 1500-1600°C in the Pacific, substantially greater than ˜1350°C for ambient mantle. Lavas from the Galápagos Islands and Hawaii record in their geochemistry high TP maxima and large ranges in both TP and melt fraction over short horizontal distances, a result that is predicted by the mantle plume model.

Spatio-temporal characteristics of global warming in the Tibetan Plateau during the last 50 years based on a generalised temperature zone-elevation model.

PubMed

Wei, Yanqiang; Fang, Yiping

2013-01-01

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions.

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

PubMed Central

Wei, Yanqiang; Fang, Yiping

2013-01-01

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961–2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of −6°C and −4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961–2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991–2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions. PMID:23565182

Purification and Characterization of a Highly Efficient Calcium-Independent α-Amylase from Talaromyces pinophilus 1-95

PubMed Central

Xian, Liang; Wang, Fei; Luo, Xiang; Feng, Yu-Liang; Feng, Jia-Xun

2015-01-01

Alpha-amylase is a very important enzyme in the starch conversion process. Most of the α-amylases are calcium-dependent and exhibit poor performance in the simultaneous saccharification and fermentation process of industrial bioethanol production that uses starch as feedstock. In this study, an extracellular amylolytic enzyme was purified from the culture broth of newly isolated Talaromyces pinophilus strain 1-95. The purified amylolytic enzyme, with an apparent molecular weight of 58 kDa on SDS-PAGE, hydrolyzed maltopentaose, maltohexaose, and maltoheptaose into mainly maltose and maltotriose and minor amount of glucose, confirming the endo-acting mode of the enzyme, and hence, was named Talaromyces pinophilus α-amylase (TpAA). TpAA was most active at pH 4.0–5.0 (with the temperature held at 37°C) and 55°C (at pH 5.0), and stable within the pH range of 5.0–9.5 (at 4°C) and below 45°C (at pH 5.0). Interestingly, the Ca2+ did not improve its enzymatic activity, optimal temperature, or thermostability of the enzyme, indicating that the TpAA was Ca2+-independent. TpAA displayed higher enzyme activity toward malto-oligosaccharides and dextrin than other previously reported α-amylases. This highly active Ca2+-independent α-amylase may have potential applications in starch-to-ethanol conversion process. PMID:25811759

Influence of carbon nanotubes on the properties of epoxy based composites reinforced with a semicrystalline thermoplastic

NASA Astrophysics Data System (ADS)

Díez-Pascual, A.; Shuttleworth, P.; Gónzalez-Castillo, E.; Marco, C.; Gómez-Fatou, M.; Ellis, G.

2014-08-01

Novel ternary nanocomposites based on a thermoset (TS) system composed of triglycidyl p-aminophenol (TGAP) epoxy resin and 4,4'-diaminodiphenylsulfone (DDS) curing agent incorporating 5 wt% of a semicrystalline thermoplastic (TP), an ethylene/1-octene copolymer, and 0.5 or 1.0 wt% multi-walled carbon nanotubes (MWCNTs) have been prepared via physical blending and curing. The influence of the TP and the MWCNTs on the curing process, morphology, thermal and mechanical properties of the hybrid nanocomposites has been analyzed. Different morphologies evolved depending on the CNT content: the material with 0.5 wt% MWCNTs showed a matrix-dispersed droplet-like morphology with well-dispersed nanofiller that selectively located at the TS/TP interphase, while that with 1.0 wt% MWCNTs exhibited coarse dendritic TP areas containing agglomerated MWCNTs. Although the cure reaction was accelerated in its early stage by the nanofillers, curing occurred at a lower rate since these obstructed chain crosslinking. The nanocomposite with lower nanotube content displayed two crystallization peaks at lower temperature than that of pure TP, while a single peak appearing at similar temperature to that of TP was observed for the blend with higher nanotube loading. The highest thermal stability was found for TS/TP (5.0 wt%)/MWCNTs (0.5 wt%), due to a synergistic barrier effect of both TP and the nanofiller. Moreover, this nanocomposite displayed the best mechanical properties, with an optimal combination of stiffness, strength and toughness. However, poorer performance was found for TS/TP (5.0 wt%)/MWCNTs (1.0 wt%) due to the less effective reinforcement of the agglomerated nanotubes and the coalescence of the TP particles into large areas. Therefore, finely tuned morphologies and properties can be obtained by adjusting the nanotube content in the TS/TP blends, leading to high-performance hybrid nanocomposites suitable for structural and high-temperature applications.

Electron Attachment to C2 Fluorocarbon Radicals at High Temperature (Postprint)

DTIC Science & Technology

2016-01-28

Vehicles Directorate 3550 Aberdeen Avenue SE Kirtland AFB, NM 87117-5776 8. PERFORMING ORGANIZATION REPORT NUMBER AFRL -RV-PS-TP-2015-0014 9...cy AFRL /RVIL Kirtland AFB, NM 87117-5776 2 cys Official Record Copy AFRL /RVBXT/Dr. Raymond Bemish 1 cy Approved for public release; distribution... AFRL -RV-PS- TP-2015-0014 AFRL -RV-PS- TP-2015-0014 ELECTRON ATTACHMENT TO C2 FLUOROCARBON RADICALS AT HIGH TEMPERATURE (POSTPRINT) Nicholas S

Genetic ablation of phosphatidylcholine transfer protein/StarD2 in ob/ob mice improves glucose tolerance without increasing energy expenditure.

PubMed

Krisko, Tibor I; LeClair, Katherine B; Cohen, David E

2017-03-01

Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is highly expressed in liver and oxidative tissues. PC-TP promotes hepatic glucose production during fasting and aggravates glucose intolerance in high fat fed mice. However, because PC-TP also suppresses thermogenesis in brown adipose tissue (BAT), its direct contribution to obesity-associated diabetes in mice remains unclear. Here we examined the effects of genetic PC-TP ablation on glucose homeostasis in leptin-deficient ob/ob mice, which exhibit both diabetes and altered thermoregulation. Mice lacking both PC-TP and leptin (Pctp -/- ;ob/ob) were prepared by crossing Pctp -/- with ob/+ mice. Glucose homeostasis was assessed by standard assays, and energy expenditure was determined by indirect calorimetry using a comprehensive laboratory animal monitoring system, which also recorded physical activity and food intake. Body composition was determined by NMR and hepatic lipids by enzymatic assays. Core body temperature was measured using a rectal thermocouple probe. Pctp -/- ;ob/ob mice demonstrated improved glucose homeostasis, as evidenced by markedly improved glucose and pyruvate tolerance tests, without changes in insulin tolerance. However, there were no differences in EE at any ambient temperature. There were also no effects of PC-TP expression on physical activity, food intake or core body temperature. Improved glucose tolerance in Pctp -/- ;ob/ob mice in the absence of increases in energy expenditure or core body temperature indicates a direct pathogenic role for PC-TP in diabetes in leptin deficient mice. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishaq, M., E-mail: ishaqmusarat@gmail.com; Comonwealth Scientific and Industrial Research Organization, Sydney, New South Wales; Bazaka, K.

Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied,more » focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.« less

Direct numerical simulations of two-phase laminar jet flows with different cross-section injection geometries

NASA Astrophysics Data System (ADS)

Abdel-Hameed, H.; Bellan, J.

2002-10-01

Direct numerical simulations are performed of spatial, three-dimensional, laminar jets of different inlet geometric configurations for the purpose of quantifying the characteristics of the flows; both single-phase (SP) and two-phase (TP) free jets are considered. The TP jets consist of gas laden with liquid drops randomly injected at the inlet. Drop evaporation ensues both due to the gaseous flow being initially unvitiated by the vapor species corresponding to the liquid drops, and to drop heating as the initial drop temperature is lower than that of the carrier gas. The conservation equations for the TP flow include complete couplings of mass, momentum, and energy based on thermodynamically self-consistent specification of the vapor enthalpy, internal energy, and latent heat of vaporization. Inlet geometries investigated are circular, elliptic, rectangular, square, and triangular. The results focus both on the different spreading achieved according to the inlet geometry, as well as on the considerable change in the flow field due to the presence of the drops. The most important consequence of the drop interaction with the flow is the production of streamwise vorticity that alters entrainment and species mixing according to the inlet geometry. Similar to their SP equivalent, TP jets are shown to reach steady-state entrainment; examination of the flows at this time station shows that the potential cores of TP jets are shorter by an order of magnitude than their SP counterpart. Moreover, whereas the TP circular jet exhibits a symmetric entrainment pattern well past the streamwise location of the potential core, noncircular jets display at the same location strong departures from symmetry. Furthermore, the SP-jet phenomenon of axis switching is no longer present in TP jets. The distributions of drop-number density, liquid mass, and evaporated species are compared for different inlet cross sections and recommendations are made regarding the optimal choice for different applications.

Moisture increase in response to high-altitude warming evidenced by tree-rings on the southeastern Tibetan Plateau

NASA Astrophysics Data System (ADS)

Li, Jinbao; Shi, Jiangfeng; Zhang, David D.; Yang, Bao; Fang, Keyan; Yue, Pak Hong

2017-01-01

Rapid warming has been observed in the high-altitude areas around the globe, but the implications on moisture change are not fully understood. Here we use tree-rings to reveal common moisture change on the southeastern Tibetan Plateau (TP) during the past five centuries, and show that regional moisture change in late spring to early summer (April-June) is closely related to large-scale temperature anomaly over the TP, with increased moisture coincident with periods of high temperature. The most recent pluvial during the 1990s-2000s is likely the wettest for the past five centuries, which coincides with the warmest period on the TP during the past millennium. Dynamic analysis reveals that vertical air convection is enhanced in response to anomalous TP surface warming, leading to an increase in lower-tropospheric humidity and effective precipitation over the southeastern TP. The coherent warm-wet relationship identified in both tree-rings and dynamic analysis implies a generally wetter condition on the southeastern TP under future warming.

Interplay between behavioural thermoregulation and immune response in mealworms.

PubMed

Catalán, Tamara P; Niemeyer, Hermann M; Kalergis, Alexis M; Bozinovic, Francisco

2012-11-01

Since the preferential body temperature should positively correlate with physiological performance, behavioural fever should enhance an organism's immune response under an immune challenge. Here we have studied the preferential body temperature (T(p)) and its consequences on immune response performance after an immune challenge in larvae of Tenebrio molitor. We evaluated T(p) and immune responses of larvae following a challenge with various concentrations of lipopolysaccharide (LPS), and we studied the correlation between T(p) and two immune traits, namely antibacterial and phenoloxidase (PO) activities. Larvae that were immune challenged with higher LPS concentrations (C(50) and C(100)) preferred in average, warmer temperatures than did larvae challenged with lower concentrations (C(0) and C(25)). T(p) of C(25)-C(100) (challenged)-mealworms was 2.3°C higher than of C(0) (control) larvae. At lower LPS concentration immune challenge (C(0) and C(25)) antibacterial activity correlated positively with T(p), but at C(50) and C(100) correlation was lose. PO activity was higher at higher LPS concentration, but its magnitude of response did not correlate with T(p) Our data suggest that behavioural fever may have a positive effect on host performance by enhancing antibacterial response under a low pathogen load situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Origin of low proton-to-electron temperature ratio in the Earth's plasma sheet

NASA Astrophysics Data System (ADS)

Grigorenko, E. E.; Kronberg, E. A.; Daly, P. W.; Ganushkina, N. Yu.; Lavraud, B.; Sauvaud, J.-A.; Zelenyi, L. M.

2016-10-01

We study the proton-to-electron temperature ratio (Tp/Te) in the plasma sheet (PS) of the Earth's magnetotail using 5 years of Cluster observations (2001-2005). The PS intervals are searched within a region defined with -19 < X ≤ -7 RE and |Y| < 15 RE (GSM) under the condition |BX| ≤ 10 nT. One hundred sixty PS crossings are identified. We find an average value of 6.0. However, in many PS intervals Tp/Te varies over a wide range from a few units to several tens of units. In 86 PS intervals the Tp/Te decreases below 3.5. Generally, the decreases of Tp/Te are due to some increase of Te while Tp either decreases or remains unchanged. In the majority of these intervals the Tp/Te drops are observed during magnetotail dipolarizations. A superposed epoch analysis applied to these events shows that the minimum value of Tp/Te is observed after the dipolarization onset during the "turbulent phase" of dipolarization, when a number of transient BZ pulses are reduced, but the value of BZ is still large and an intensification of wave activity is observed. The Tp/Te drops, and associated increases of Te often coincide either with bursts of broadband electrostatic emissions, which may include electron cyclotron harmonics, or with broadband electromagnetic emission in a frequency range from proton plasma frequency (fpp) up to the electron gyrofrequency (fce). These findings show that the wave activity developing in the current sheet after dipolarization onset may play a role in the additional electron heating and the associated Tp/Te decrease.

Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid emulsion and accumulation effect on pancreas.

PubMed

Li, Xue; Mao, Yuling; Li, Kai; Shi, Tianyu; Yao, Huimin; Yao, Jianhua; Wang, Shujun

2016-05-01

Triptolide (TP) shows strong anti-tumor activities on various cancer cells, especially on pancreatic cancer. TP inhibits HSP70 expression leading to cell death in pancreatic cancer cells and induces cell death by apoptotic and autophagic pathways. In order to increase the therapeutic index of TP, a novel intravenous TP-loaded delivery system, TP-loaded lipid emulsion (TP-LE), has been developed to treat solid tumor. In the present study, the preparation and characterization of TP-LE were described. The pharmacokinetics and tissue distribution study of TP-LE in mice were also evaluated. Results demonstrated that TP-LE had an average particle size of 154.6 nm, entrapment efficiency (EE%) of 87%, zeta potential of -0.903 mV and autoclaved stability. The pharmacokinetic study showed that blood concentrations of both TP-LE and TP reached a maximum at the end of intravenous administration (1.25 mg/kg) and declined rapidly within the first 10 min with a mean residence time (MRT) of about 10 min. In the tissue distribution study, a preferential accumulation and longer residence time of drug in pancreas were found in TP-LE. The AUC0-60min of TP-LE in pancreas was 2.19 times in comparison to free TP, suggesting that the use of TP-LE conferred improvements in biodistribution, accumulation and therapeutic efficacy in pancreas. Moreover, the concentrations of TP-LE in heart, lung and kidney were lower than that of the TP group, indicating the potential for reduced toxicity of TP-LE. Together, all the results show that TP-LE appears to be a promising formulation for using TP in treating cancer, and more specifically pancreatic cancer.

Novel Trichoderma polysporum Strain for the Biocontrol of Pseudogymnoascus destructans, the Fungal Etiologic Agent of Bat White Nose Syndrome.

PubMed

Zhang, Tao; Chaturvedi, Vishnu; Chaturvedi, Sudha

2015-01-01

White-nose syndrome (WNS), an emerging disease of hibernating bats, has rapidly spread across eastern North America killing millions of bats. Pseudogymnoascus destructans (Pd), the sole etiologic agent of WNS, is widespread and persistent in bat hibernacula. Control of Pd in the affected sites is urgently needed to break the transmission cycle while minimizing any adverse impact on the native organisms. We isolated a novel strain of Trichoderma polysporum (Tp) from one of the caves at the epicenter of WNS zoonotic. Detailed experimental studies revealed: (1) Tp WPM 39143 was highly adapted to grow at temperatures simulating the cave environment (6°C-15°C), (2) Tp WPM 39143 restricted Pd colony growth in dual culture challenges, (3) Tp WPM 39143 caused four logs reduction of Pd colony forming units and genome copies in autoclaved soil samples from one of the WNS affected caves, (4) Tp WPM 39143 extract showed specific fungicidal activity against Pd in disk diffusion assay, but not against closely related fungus P. pannorum (Pp), (5) Tp WPM 39143 extract retained inhibitory activity after exposure to high temperatures, light and proteinase K, and (6) Inhibitory metabolites in Tp WPM 39143 extract comprised of water-soluble, high polarity compounds. These results suggest that Tp WPM 39143 is a promising candidate for further evaluation as a biocontrol agent of Pd in WNS affected sites.

Novel Trichoderma polysporum Strain for the Biocontrol of Pseudogymnoascus destructans, the Fungal Etiologic Agent of Bat White Nose Syndrome

PubMed Central

Zhang, Tao; Chaturvedi, Vishnu; Chaturvedi, Sudha

2015-01-01

White-nose syndrome (WNS), an emerging disease of hibernating bats, has rapidly spread across eastern North America killing millions of bats. Pseudogymnoascus destructans (Pd), the sole etiologic agent of WNS, is widespread and persistent in bat hibernacula. Control of Pd in the affected sites is urgently needed to break the transmission cycle while minimizing any adverse impact on the native organisms. We isolated a novel strain of Trichoderma polysporum (Tp) from one of the caves at the epicenter of WNS zoonotic. Detailed experimental studies revealed: (1) Tp WPM 39143 was highly adapted to grow at temperatures simulating the cave environment (6°C-15°C), (2) Tp WPM 39143 restricted Pd colony growth in dual culture challenges, (3) Tp WPM 39143 caused four logs reduction of Pd colony forming units and genome copies in autoclaved soil samples from one of the WNS affected caves, (4) Tp WPM 39143 extract showed specific fungicidal activity against Pd in disk diffusion assay, but not against closely related fungus P. pannorum (Pp), (5) Tp WPM 39143 extract retained inhibitory activity after exposure to high temperatures, light and proteinase K, and (6) Inhibitory metabolites in Tp WPM 39143 extract comprised of water-soluble, high polarity compounds. These results suggest that Tp WPM 39143 is a promising candidate for further evaluation as a biocontrol agent of Pd in WNS affected sites. PMID:26509269

Lab-on-a-chip based total-phosphorus analysis device utilizing a photocatalytic reaction

NASA Astrophysics Data System (ADS)

Jung, Dong Geon; Jung, Daewoong; Kong, Seong Ho

2018-02-01

A lab-on-a-chip (LOC) device for total phosphorus (TP) analysis was fabricated for water quality monitoring. Many commercially available TP analysis systems used to estimate water quality have good sensitivity and accuracy. However, these systems also have many disadvantages such as bulky size, complex pretreatment processes, and high cost, which limit their application. In particular, conventional TP analysis systems require an indispensable pretreatment step, in which the fluidic analyte is heated to 120 °C for 30 min to release the dissolved phosphate, because many phosphates are soluble in water at a standard temperature and pressure. In addition, this pretreatment process requires elevated pressures of up to 1.1 kg cm-2 in order to prevent the evaporation of the heated analyte. Because of these limiting conditions required by the pretreatment processes used in conventional systems, it is difficult to miniaturize TP analysis systems. In this study, we employed a photocatalytic reaction in the pretreatment process. The reaction was carried out by illuminating a photocatalytic titanium dioxide (TiO2) surface formed in a microfluidic channel with ultraviolet (UV) light. This pretreatment process does not require elevated temperatures and pressures. By applying this simplified, photocatalytic-reaction-based pretreatment process to a TP analysis system, greater degrees of freedom are conferred to the design and fabrication of LOC devices for TP monitoring. The fabricated LOC device presented in this paper was characterized by measuring the TP concentration of an unknown sample, and comparing the results with those measured by a conventional TP analysis system. The TP concentrations of the unknown sample measured by the proposed LOC device and the conventional TP analysis system were 0.018 mgP/25 mL and 0.019 mgP/25 mL, respectively. The experimental results revealed that the proposed LOC device had a performance comparable to the conventional bulky TP analysis system. Therefore, our device could be directly employed in water quality monitoring as an alternative to conventional TP analysis systems.

Will the warmer temperature bring the more intensity precipitation?

NASA Astrophysics Data System (ADS)

Yutong, Z., II; Wang, T.

2017-12-01

Will the warmer temperature bring the more intensity precipitation?Over the past several decades, changes in climate are amplified over the Tibetan Plateau(TP), with warming trend almost being twice as large as the global average. In sharp contrast, there is a large spatial discrepancy of the variations in precipitation extremes, with increasing trends found in the southern and decreasing trends in central TP. These features motivate are urgent need for an observation-based understanding of how precipitation extremes respond to climate change. Here we examine the relation between precipitation intensity with atmospheric temperature, dew point temperature (Td) and convective available potential energy (CAPE) in Tibet Plateau. Owing to the influences of the westerlies and Indian monsoon on Tibetan climate, the stations can be divided into three sub-regions in TP: the westerlies region (north of 35°N, N = 28), the monsoon region (south of 30°N in TP, N = 31), and the transition region (located between 30°N and 35°N, N = 48). We found that the intensity precipitation does not follow the C-C relation and there is a mix of positive and negative slope. To better understand why different scaling occurs with temperature in district region, using the dew point temperature replace the temperature, although there is significant variability in relative humidity values, at most stations, there appears to be a general increase in relative humidity associated. It is likely that the observed rise in relative humidity can assist in explaining the negative scaling of extreme precipitation at westerlies domain and monsoon domain, with the primary reason why precipitation extremes expected to increase follows from the fact that a warmer atmosphere can "hold" more moisture. This suggests that not only on how much the moisture the atmosphere can hold, but on how much moisture exits in atmosphere. To understand the role of dynamic on extreme precipitation, we repeat the precipitation intense analysis using ln(CAPE) as regression. The CAPE is the vertical integral of parcel buoyancy between the level of free convection and level of neutral buoyancy. We find almost all pixels are positive and pass through the 0.05 confidence limit. We can conclude that the intensity of moist convection is an important for the extreme precipitation.

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

Adhesion strength between thermoplastics and its polyurethane coating made by using the technology combination of injection molding and reaction injection molding

NASA Astrophysics Data System (ADS)

Bloß, P.; Böhme, A.; Müller, J.; Krajewsky, P.; Michaelis, J.

2014-05-01

A complete equipment for injection molding (IM) of a thermoplastic (TP) carrier and reaction injection molding (RIM) of polyurethane (PUR) coatings including IM and RIM machines, a color module for PUR, and a robot was built up. A modularly composed sliding split mold was constructed and manufactured allowing different parts including thicker (2 mm thickness) soft touch and thin (0.4 mm) lacquer PUR coatings. As TP PC/ABS and PA6 GF15 compounds were used, and aromatic and aliphatic PUR systems as well. From the parts made by IM+RIM, test specimens for peel force measurements were cut. These investigations were performed prior and after ageing under climatic conditions @ 50 % RH and temperature changes between -30 °C and 90 °C. By varying IM processing parameters, we have found that mold and TP temperatures are particularly important for the adhesion strength between TP and PUR. The waiting time between the end of TP cooling and PUR injection has a minor influence on its mean value. However, to short waiting times may result in inhomogeneous adhesion. It was surprising that surface defects of the TP carrier leads also to inhomogeneous adhesion. We have observed that ageing may cause an increase and decrease of adhesions strength depending on the TP+PUR system used. We have found that the results are valid only for the actual TP and PUR combination. A generalization seems to be inappropriate, hence, the actual combination should be investigated to prevent unwanted surprises when the coated TP part is in its application.

Warming slowdown over the Tibetan plateau in recent decades

NASA Astrophysics Data System (ADS)

Liu, Yaojie; Zhang, Yangjian; Zhu, Juntao; Huang, Ke; Zu, Jiaxing; Chen, Ning; Cong, Nan; Stegehuis, Annemiek Irene

2018-03-01

As the recent global warming hiatus and the warming on high elevations are attracting worldwide attention, this study examined the robustness of the warming slowdown over the Tibetan plateau (TP) and its related driving forces. By integrating multiple-source data from 1982 to 2015 and using trend analysis, we found that the mean temperature (T mean), maximum temperature (T max) and minimum temperature (T min) showed a slowdown of the warming trend around 1998, during the period of the global warming hiatus. This was found over both the growing season (GS) and non-growing season (NGS) and suggested a robust warming hiatus over the TP. Due to the differences in trends of T max and T min, the trend of diurnal temperature range (DTR) also shifted after 1998, especially during the GS temperature. The warming rate was spatially heterogeneous. The northern TP (NTP) experienced more warming than the southern TP (STP) in all seasons from 1982 to 1998, while the pattern was reversed in the period from 1998 to 2015. Water vapour was found to be the main driving force for the trend in T mean and T min by influencing downward long wave radiation. Sunshine duration was the main driving force behind the trend in T max and DTR through a change in downward shortwave radiation that altered the energy source of daytime temperature. Water vapour was the major driving force for temperature change over the NTP, while over the STP, sunshine duration dominated the temperature trend.

Characterization of a Thermophilic Bacteriophage for Bacillus stearothermophilus1

PubMed Central

Saunders, Grady F.; Campbell, L. Leon

1966-01-01

Saunders, Grady F. (University of Illinois, Urbana), and L. Leon Campbell. Characterization of a thermophilic bacteriophage for Bacillus stearothermophilus. J. Bacteriol. 91:340–348. 1965.—The biological and physical-chemical properties of the thermophilic bacteriophage TP-84 were investigated. TP-84 was shown to be lytic for 3 of 24 strains of Bacillus stearothermophilus tested over the temperature range of 43 to 76 C. The latent period of TP-84 on B. stearothermophilus strain 10 was 22 to 24 min. TP-84 has a hexagonal head, 53 mμ in diameter and 30 mμ on a side; its tail is 130 mμ long and 3 to 5 mμ wide. The phage has an S5020,w of 436, and bands at a density of 1.508 g/cc in CsCl (pH 8.5). The diffusion coefficient of TP-84 was calculated to be 6.19 × 10−8 cm2/sec. From the sedimentation and diffusion data, a particle molecular weight of 50 million daltons was calculated for TP-84. The phage DNA has a base composition of 42% guanine + cytosine, deduced from buoyant density and melting temperature measurements. Images PMID:5903101

RITA displays anti-tumor activity in medulloblastomas independent of TP53 status.

PubMed

Gottlieb, Aline; Althoff, Kristina; Grunewald, Laura; Thor, Theresa; Odersky, Andrea; Schulte, Marc; Deubzer, Hedwig E; Heukamp, Lukas; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H; Künkele, Annette

2017-04-25

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma.

RITA displays anti-tumor activity in medulloblastomas independent of TP53 status

PubMed Central

Gottlieb, Aline; Althoff, Kristina; Grunewald, Laura; Thor, Theresa; Odersky, Andrea; Schulte, Marc; Deubzer, Hedwig E.; Heukamp, Lukas; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H.; Künkele, Annette

2017-01-01

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40–70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma. PMID:28427187

Simulated cold bias being improved by using MODIS time-varying albedo in the Tibetan Plateau in WRF model

NASA Astrophysics Data System (ADS)

Meng, X.; Lyu, S.; Zhang, T.; Zhao, L.; Li, Z.; Han, B.; Li, S.; Ma, D.; Chen, H.; Ao, Y.; Luo, S.; Shen, Y.; Guo, J.; Wen, L.

2018-04-01

Systematic cold biases exist in the simulation for 2 m air temperature in the Tibetan Plateau (TP) when using regional climate models and global atmospheric general circulation models. We updated the albedo in the Weather Research and Forecasting (WRF) Model lower boundary condition using the Global LAnd Surface Satellite Moderate-Resolution Imaging Spectroradiometer albedo products and demonstrated evident improvement for cold temperature biases in the TP. It is the large overestimation of albedo in winter and spring in the WRF model that resulted in the large cold temperature biases. The overestimated albedo was caused by the simulated precipitation biases and over-parameterization of snow albedo. Furthermore, light-absorbing aerosols can result in a large reduction of albedo in snow and ice cover. The results suggest the necessity of developing snow albedo parameterization using observations in the TP, where snow cover and melting are very different from other low-elevation regions, and the influence of aerosols should be considered as well. In addition to defining snow albedo, our results show an urgent call for improving precipitation simulation in the TP.

The Minimum Potential Temperature of the Hawaiian Mantle is About 1420°C

NASA Astrophysics Data System (ADS)

Gudfinnsson, G. H.; Presnall, D. C.

2002-12-01

Picritic glasses found in turbidite sands near the submarine part of Kilauea's East Rift Zone contain up to 15 wt.% MgO and are the most magnesian Hawaiian volcanic glasses reported to date (Clague et al., 1991, 1995). They have olivine phenocrysts as magnesian as Fo90.7, and when their compositions are plotted together on normative diagrams, they form a distinct olivine fractionation trend. Melt geothermometers indicate that the eruption temperatures of the picrite magmas were as high as about 1320°C. On the assumption that these glasses represent primary melt compositions that coexisted with a lherzolite phase assemblage, the CMASNF geothermometer (Gudfinnsson and Presnall, 2001) yields a maximum temperature of generation of about 1480°C, which corresponds roughly to a pressure of 2.5 GPa. This assumes that the melts were essentially free of H2O and CO2. However, both of these volatile components have the potential to lower significantly the solidus temperatures of mantle peridotite and alter the chemistry of primary melts. The approximately 0.4 wt.% H2O measured in the Hawaiian picrite glasses is probably below the saturation limit for H2O, and can be assumed to be close to the original H2O content of the picrite melts. The measured amount of CO2 in the glasses is low as most CO2 was probably lost by degassing at the time of eruption. The CO2 content of primary magmas at Kilauea has been determined as 0.7 wt.% (Gerlach and Graeber, 1985; Gerlach et al., 2001). Whereas the addition of CO2 tends to shift melts derived from peridotite toward greater alkalinity, the addition of H2O tends to move liquids toward the quartz normative side of the basalt tetrahedron. Results of CO2- and H2O-bearing melting experiments indicate that with the low amounts of H2O and CO2 expected in the primary melts of Kilauea their effect on the position of phase boundaries will be small. From phase relations involving melt in equilibrium with a garnet lherzolite phase assemblage in the system CaO-MgO-Al2O3-SiO2-CO2, we estimate that the solidus temperature of mantle lherzolite is lowered by about 10°C for each 1 wt.% increase in the amount of CO2 in the melt. The effect of H2O is to lower the solidus temperature about 40°C for each 1 wt.% increase in this component. This yields a minimum potential temperature (Tp) for Hawaii of about 1420°C, which is consistent with data indicating at most only a very slight increase of heat flow at Hawaii relative to Pacific crust of the same age (Stein and Stein, 1993). This Tp is 140-160°C higher than petrological estimates of the average Tp of the MORB source (McKenzie and Bickle, 1988; Presnall et al., 2002). Our data do not constrain the upper limit of Tp at Hawaii.

Late Holocene vegetation and climate change on the southeastern Tibetan Plateau: Implications for the Indian Summer Monsoon and links to the Indian Ocean Dipole

NASA Astrophysics Data System (ADS)

Li, Kai; Liu, Xingqi; Wang, Yongbo; Herzschuh, Ulrike; Ni, Jian; Liao, Mengna; Xiao, Xiayun

2017-12-01

The Indian Summer Monsoon (ISM) is one of the most important climate systems, whose variability and driving mechanisms are of broad interest for academic and societal communities. Here, we present a well-dated high-resolution pollen analysis from a 4.82-m long sediment core taken from Basomtso, in the southeastern Tibetan Plateau (TP), which depicts the regional climate changes of the past millennium. Our results show that subalpine coniferous forest was dominant around Basomtso from ca. 867 to ca. 750 cal. yr BP, indicating a warm and semi-humid climate. The timberline in the study area significantly decreased from ca. 750 to ca. 100 cal. yr BP, and a cold climate, corresponding to the Little Ice Age (LIA) prevailed. Since ca. 100 cal. yr BP, the vegetation type changed to forest-meadow with rising temperatures and moisture. Ordination analysis reveals that the migration of vegetation was dominated by regional temperatures and then by moisture. Further comparisons between the Basomtso pollen record and the regional temperature reconstructions underscore the relevance of the Basomtso record from the southeastern TP for regional and global climatologies. Our pollen based moisture reconstruction demonstrates the strong multicentennial-scale link to ISM variability, providing solid evidence for the increase of monsoonal strengths over the past four centuries. Spectral analysis indicates the potential influence of solar forcing. However, a closer relationship has been observed between multicentennial ISM variations and Indian Ocean sea surface temperature anomalies (SSTs), suggesting that the variations in monsoonal precipitation over the southeastern TP are probably driven by the Indian Ocean Dipole on the multicentennial scale.

Water quality parameters response to temperature change in small shallow lakes

NASA Astrophysics Data System (ADS)

Xu, Lei; Li, Hua; Liang, Xinqiang; Yao, Yuxin; Zhou, Li; Cui, Xinyi

Effects of temperature (T) on water quality of three small shallow lakes in Taihu Lake region of China were investigated. The annual temperature was classified into three levels: low temperature (LT, 4 °C < T ⩽ 10 °C), middle temperature (MT, 10 °C < T ⩽ 20 °C), and high temperature (HT, 20 °C < T ⩽ 30 °C). Results showed that total nitrogen (TN) and total phosphorus (TP) concentrations might go to a fixed value (or range) in small shallow lakes receiving domestic sewage and farm drainage water. Nitrogen concentrations in the lakes were mainly in the form of nitrate (NO3-) at above concerned three temperature levels, and nitrogen concentrations in the forms of TN, TIN, and NO3- were increased with the increase of nutrient input. At the LT and MT levels, there was a series of good cubic curve relationships between temperatures and three N forms (TN, NO3- and NH4+). The temperatural inflexion change points in the curves were nearly at 7 °C and 14 °C, respectively. However, no significant relationship between temperature and any water quality parameter was observed at the HT level. The significant relationship of TIN to TN, NO3- to TN and NH4+ to dissolve oxygen (DO) was exist in three temperature portions, and TP to Chemical oxygen demand (COD, determined by potassium permanganate oxidation methods) in LT and MT, TP to pH or DO in HT also exist. COD were less than 6 mg L-1 at each temperature level, and pH values were the largest in HT than it in LT or MT. Thus, changes between temperature and water quality parameters (TN, NO3-, NH4+ and TP) obviously nearly in 7 °C or 14 °C in lakes show that water self-purification of natural small shallow lakes were obviously with temperature changed.

UPLC/ESI-QTOF-MS-based metabolomics survey on the toxicity of triptolide and detoxication of licorice.

PubMed

Wang, Zhuo; Liu, Jian-Qun; Xu, Jin-Di; Zhu, He; Kong, Ming; Zhang, Guo-Hua; Duan, Su-Min; Li, Xiu-Yang; Li, Guang-Fu; Liu, Li-Fang; Li, Song-Lin

2017-06-01

Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Systemic administration of thrombin peptide TP508 enhances VEGF-stimulated angiogenesis and attenuates effects of chronic hypoxia

PubMed Central

Olszewska-Pazdrak, Barbara; Carney, Darrell H.

2015-01-01

Revascularization of chronic wounds and ischemic tissue is attenuated by endothelial dysfunction and the inability of angiogenic factors to stimulate angiogenesis. We recently showed that TP508, a nonproteolytic thrombin peptide, increases perfusion and NO-dependent vasodilation in hearts with chronic ischemia and stimulates NO production by endothelial cells. In this study, we investigated systemic in vivo effects of TP508 on VEGF-stimulated angiogenesis in vitro using aortic explants in normoxic and hypoxic conditions. Mice were injected with saline or TP508 and 24h later aortas were removed and cultured to quantify endothelial sprouting. TP508 injection increased endothelial sprouting and potentiated the in vitro response to VEGF. Exposure of control explants to hypoxia inhibited basal and VEGF-stimulated endothelial cell sprouting. This effect of hypoxia was significantly prevented by TP508 injection. Thus, TP508 systemic administration increases responsiveness of aortic endothelial cells to VEGF and diminishes the effect of chronic hypoxia on endothelial cell sprouting. Studies using human endothelial cells in culture suggest that protective effects of TP508 during hypoxia may involve stimulation of endothelial cell NO production. These data suggest potential clinical benefit of using a combination of systemic TP508 and local VEGF as a therapy for revascularization of ischemic tissue. PMID:23594718

High-resolution Mapping of Permafrost and Soil Freeze/thaw Dynamics in the Tibetan Plateau Based on Multi-sensor Satellite Observations

NASA Astrophysics Data System (ADS)

Zhang, W.; Yi, Y.; Yang, K.; Kimball, J. S.

2016-12-01

The Tibetan Plateau (TP) is underlain by the world's largest extent of alpine permafrost ( 2.5×106 km2), dominated by sporadic and discontinuous permafrost with strong sensitivity to climate warming. Detailed permafrost distributions and patterns in most of the TP region are still unknown due to extremely sparse in-situ observations in this region characterized by heterogeneous land cover and large temporal dynamics in surface soil moisture conditions. Therefore, satellite-based temperature and moisture observations are essential for high-resolution mapping of permafrost distribution and soil active layer changes in the TP region. In this study, we quantify the TP regional permafrost distribution at 1-km resolution using a detailed satellite data-driven soil thermal process model (GIPL2). The soil thermal model is calibrated and validated using in-situ soil temperature/moisture observations from the CAMP/Tibet field campaign (9 sites: 0-300 cm soil depth sampling from 1997-2007), a multi-scale soil moisture and temperature monitoring network in the central TP (CTP-SMTMN, 57 sites: 5-40 cm, 2010-2014) and across the whole plateau (China Meteorology Administration, 98 sites: 0-320 cm, 2000-2015). Our preliminary results using the CAMP/Tibet and CTP-SMTMN network observations indicate strong controls of surface thermal and soil moisture conditions on soil freeze/thaw dynamics, which vary greatly with underlying topography, soil texture and vegetation cover. For regional mapping of soil freeze/thaw and permafrost dynamics, we use the most recent soil moisture retrievals from the NASA SMAP (Soil Moisture Active Passive) sensor to account for the effects of temporal soil moisture dynamics on soil thermal heat transfer, with surface thermal conditions defined by MODIS (Moderate Resolution Imaging Spectroradiometer) land surface temperature records. Our study provides the first 1-km map of spatial patterns and recent changes of permafrost conditions in the TP.

No evidence of widespread decline of snow cover on the Tibetan Plateau over 2000-2015.

PubMed

Wang, Xiaoyue; Wu, Chaoyang; Wang, Huanjiong; Gonsamo, Alemu; Liu, Zhengjia

2017-11-07

Understanding the changes in snow cover is essential for biological and hydrological processes in the Tibetan Plateau (TP) and its surrounding areas. However, the changes in snow cover phenology over the TP have not been well documented. Using Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow products and the Interactive Multi-sensor Snow and Ice Mapping System (IMS) data, we reported daily cloud-free snow cover product over the Tibetan Plateau (TP) for 2000-2015. Snow cover start (SCS), melt (SCM) and duration (SCD) dates were calculated for each hydrological year, and their spatial and temporal variations were analyzed with elevation variations. Our results show no widespread decline in snow cover over the past fifteen years and the trends of snow cover phenology over the TP has high spatial heterogeneity. Later SCS, earlier SCM, and thus decreased SCD mainly occurred in the areas with elevation below 3500 m a.s.l., while regions in central and southwestern edges of the TP showed advanced SCS, delayed SCM and consequently longer SCD. The roles of temperature and precipitation on snow cover penology varied in different elevation zones, and the impact of both temperature and precipitation strengthened as elevation increases.

Characterizing response of total suspended solids and total phosphorus loading to weather and watershed characteristics for rainfall and snowmelt events in agricultural watersheds

USGS Publications Warehouse

Danz, Mari E.; Corsi, Steven; Brooks, Wesley R.; Bannerman, Roger T.

2013-01-01

Understanding the response of total suspended solids (TSS) and total phosphorus (TP) to influential weather and watershed variables is critical in the development of sediment and nutrient reduction plans. In this study, rainfall and snowmelt event loadings of TSS and TP were analyzed for eight agricultural watersheds in Wisconsin, with areas ranging from 14 to 110 km2 and having four to twelve years of data available. The data showed that a small number of rainfall and snowmelt runoff events accounted for the majority of total event loading. The largest 10% of the loading events for each watershed accounted for 73–97% of the total TSS load and 64–88% of the total TP load. More than half of the total annual TSS load was transported during a single event for each watershed at least one of the monitored years. Rainfall and snowmelt events were both influential contributors of TSS and TP loading. TSS loading contributions were greater from rainfall events at five watersheds, from snowmelt events at two watersheds, and nearly equal at one watershed. The TP loading contributions were greater from rainfall events at three watersheds, from snowmelt events at two watersheds and nearly equal at three watersheds. Stepwise multivariate regression models for TSS and TP event loadings were developed separately for rainfall and snowmelt runoff events for each individual watershed and for all watersheds combined by using a suite of precipitation, melt, temperature, seasonality, and watershed characteristics as predictors. All individual models and the combined model for rainfall events resulted in two common predictors as most influential for TSS and TP. These included rainfall depth and the antecedent baseflow. Using these two predictors alone resulted in an R2 greater than 0.7 in all but three individual models and 0.61 or greater for all individual models. The combined model yielded an R2 of 0.66 for TSS and 0.59 for TP. Neither the individual nor the combined models were substantially improved by using additional predictors. Snowmelt event models were statistically significant for individual and combined watershed models, but the model fits were not all as good as those for rainfall events (R2 between 0.19 and 0.87). Predictor selection varied from watershed to watershed, and the common variables that were selected were not always selected in the same order. Influential variables were commonly direct measures of moisture in the watershed such as snowmelt, rainfall + snowmelt, and antecedent baseflow, or measures of potential snowmelt volume in the watershed such as air temperature.

TP53 mutation-correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers.

PubMed

Győrffy, Balázs; Bottai, Giulia; Lehmann-Che, Jacqueline; Kéri, György; Orfi, László; Iwamoto, Takayuki; Desmedt, Christine; Bianchini, Giampaolo; Turner, Nicholas C; de Thè, Hugues; André, Fabrice; Sotiriou, Christos; Hortobagyi, Gabriel N; Di Leo, Angelo; Pusztai, Lajos; Santarpia, Libero

2014-05-01

Breast cancers (BC) carry a complex set of gene mutations that can influence their gene expression and clinical behavior. We aimed to identify genes driven by the TP53 mutation status and assess their clinical relevance in estrogen receptor (ER)-positive and ER-negative BC, and their potential as targets for patients with TP53 mutated tumors. Separate ROC analyses of each gene expression according to TP53 mutation status were performed. The prognostic value of genes with the highest AUC were assessed in a large dataset of untreated, and neoadjuvant chemotherapy treated patients. The mitotic checkpoint gene MPS1 was the most significant gene correlated with TP53 status, and the most significant prognostic marker in all ER-positive BC datasets. MPS1 retained its prognostic value independently from the type of treatment administered. The biological functions of MPS1 were investigated in different BC cell lines. We also assessed the effects of a potent small molecule inhibitor of MPS1, SP600125, alone and in combination with chemotherapy. Consistent with the gene expression profiling and siRNA assays, the inhibition of MPS1 by SP600125 led to a reduction in cell viability and a significant increase in cell death, selectively in TP53-mutated BC cells. Furthermore, the chemical inhibition of MPS1 sensitized BC cells to conventional chemotherapy, particularly taxanes. Our results collectively demonstrate that TP53-correlated kinase MPS1, is a potential therapeutic target in BC patients with TP53 mutated tumors, and that SP600125 warrant further development in future clinical trials. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Ice core records of climate variability on the Third Pole with emphasis on the Guliya ice cap, western Kunlun Mountains

NASA Astrophysics Data System (ADS)

Thompson, Lonnie G.; Yao, Tandong; Davis, Mary E.; Mosley-Thompson, Ellen; Wu, Guangjian; Porter, Stacy E.; Xu, Baiqing; Lin, Ping-Nan; Wang, Ninglian; Beaudon, Emilie; Duan, Keqin; Sierra-Hernández, M. Roxana; Kenny, Donald V.

2018-05-01

Records of recent climate from ice cores drilled in 2015 on the Guliya ice cap in the western Kunlun Mountains of the Tibetan Plateau, which with the Himalaya comprises the Third Pole (TP), demonstrate that this region has become warmer and moister since at least the middle of the 19th century. Decadal-scale linkages are suggested between ice core temperature and snowfall proxies, North Atlantic oceanic and atmospheric processes, Arctic temperatures, and Indian summer monsoon intensity. Correlations between annual-scale oxygen isotopic ratios (δ18O) and tropical western Pacific and Indian Ocean sea surface temperatures are also demonstrated. Comparisons of climate records during the last millennium from ice cores acquired throughout the TP illustrate centennial-scale differences between monsoon and westerlies dominated regions. Among these records, Guliya shows the highest rate of warming since the end of the Little Ice Age, but δ18O data over the last millennium from TP ice cores support findings that elevation-dependent warming is most pronounced in the Himalaya. This, along with the decreasing precipitation rates in the Himalaya region, is having detrimental effects on the cryosphere. Although satellite monitoring of glaciers on the TP indicates changes in surface area, only a few have been directly monitored for mass balance and ablation from the surface. This type of ground-based study is essential to obtain a better understanding of the rate of ice shrinkage on the TP.

An integrated photocatalytic microfluidic platform enabling total phosphorus digestion

NASA Astrophysics Data System (ADS)

Tong, Jianhua; Dong, Tian; Bian, Chao; Wang, Minrui; Wang, Fangfang; Bai, Yin; Xia, Shanhong

2015-02-01

This paper presents an integrated thermally assisted photocatalytic microfluidic chip and its application to the digestion of total phosphorus (TP) in freshwater. A micro heater, a micro temperature sensor, thermal-isolation channels and a polymethylsiloxane (PDMS) reaction chamber were fabricated on the microfluidic chip. Nano-TiO2 film sputtered on the surface of silicon in the reaction area was used as the photocatalyst, and a micro ultraviolet A-ray-light-emitting diode (UVA-LED) array fabricated by MEMS technology were attached to the top of reaction chamber for TP degradation. In this study, sodium tripolyphosphate (Na5P3O10) and sodium glycerophosphate (C3H7Na2O6P) were chosen as the typical components of TP, and these water samples were digested under UVA light irradiation and heating at the same time. Compared with the conventional high-temperature TP digestion which works at 120 °C for 30 min, the thermally assisted UVA digestion method could work at relatively low temperature, and the power consumption is decreased to less than 2 W. Since this digestion method could work without an oxidizing reagent, it is compatible with the electrochemical detection process, which makes it possible to achieve a fully functional detection chip by integrating the digestion unit and electrochemical microelectrode, to realize the on-chip detection of TP, and other water quality parameters such as total nitrogen and chemical oxygen demand.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, J.; Bugaris, D. E.; Xiao, Z. L.

We report the occurrence of reentrantmetallic behavior in theWeyl semimetal NbP. When the appliedmagnetic field H is above a critical value H-c, a reentrance appears as a peak in the temperature-dependent resistivity rho(xx) (T) at T = T-p, similar to that observed in graphite where it was attributed to local superconductivity. The Tp(H) relationship follows a power-law dependence T-p similar to (H-H-c)(1/nu) where. can be derived from the temperature dependence of the zero-field resistivity rho(0)(T) similar to T-nu. From concurrent measurements of the transverse rho(xx) (T) and Hall rho(xy)(T) magnetoresistivities, we reveal a clear correlation between the rapidly increasing rho(xy)more » (T) and the occurrence of a peak in the rho(xx) (T) curve. Quantitative analysis indicates that the reentrantmetallic behavior arises from the competition of the magnetoconductivity sigma(xx) (T) with an additional component Delta sigma(xx) (T) = kappa(H)sigma(xx)(T) where kappa(H) = [rho(xy)(T)/rho(xx)(T)](2) is the Hall factor. We find that the Hall factor (kappa(H) approximate to 0.4) at peak temperature T-p is nearly field independent, leading to the observed T-p (H) relationship. Furthermore, the reentrant metallic behavior in rho(xx) (T) also is reflected in the behavior of rho(xx) (H) that ranges from nonsaturating at T > 70K to saturation at liquid-helium temperatures. The latter can be explained with the magnetic field dependence of the Hall factor kappa(H) (H). Our paper demonstrates that a semiclassical theory can account for the "anomalies" in the magnetotransport phenomena of NbP without invoking an exotic mechanism.« less

Drivers of microbial community composition in mesophilic and thermophilic temperature-phased anaerobic digestion pre-treatment reactors.

PubMed

Pervin, Hasina M; Dennis, Paul G; Lim, Hui J; Tyson, Gene W; Batstone, Damien J; Bond, Philip L

2013-12-01

Temperature-phased anaerobic digestion (TPAD) is an emerging technology that facilitates improved performance and pathogen destruction in anaerobic sewage sludge digestion by optimising conditions for 1) hydrolytic and acidogenic organisms in a first-stage/pre-treatment reactor and then 2) methogenic populations in a second stage reactor. Pre-treatment reactors are typically operated at 55-65 °C and as such select for thermophilic bacterial communities. However, details of key microbial populations in hydrolytic communities and links to functionality are very limited. In this study, experimental thermophilic pre-treatment (TP) and control mesophilic pre-treatment (MP) reactors were operated as first-stages of TPAD systems treating activated sludge for 340 days. The TP system was operated sequentially at 50, 60 and 65 °C, while the MP rector was held at 35 °C for the entire period. The composition of microbial communities associated with the MP and TP pre-treatment reactors was characterised weekly using terminal-restriction fragment length polymorphism (T-RFLP) supported by clone library sequencing of 16S rRNA gene amplicons. The outcomes of this approach were confirmed using 454 pyrosequencing of gene amplicons and fluorescence in-situ hybridisation (FISH). TP associated bacterial communities were dominated by populations affiliated to the Firmicutes, Thermotogae, Proteobacteria and Chloroflexi. In particular there was a progression from Thermotogae to Lutispora and Coprothermobacter and diversity decreased as temperature and hydrolysis performance increased. While change in the composition of TP associated bacterial communities was attributable to temperature, that of MP associated bacterial communities was related to the composition of the incoming feed. This study determined processes driving the dynamics of key microbial populations that are correlated with an enhanced hydrolytic functionality of the TPAD system. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Heated Debate: Evidence for Two Thermal Upwellings in East Africa

NASA Astrophysics Data System (ADS)

Rooney, T.; Herzberg, C.; Bastow, I.

2008-12-01

East African Cenozoic magmatism records the thermal influence of one or more long-lived mantle plumes. We present primary magma compositions, mantle potential temperatures (Tp), and mantle melt fractions using PRIMELT2 in order to examine the geographic and historical distribution of upper mantle thermal anomalies in East Africa. Regional magmatism can be divided into an early flood basalt phase in Ethiopia/Yemen (~30 Ma), a longer-lived episode of basaltic magmatism in Kenya and Southern Ethiopia (~45 to 23 Ma), and a more recent phase (~23 Ma to Present) that is coincidental with the development of the East African Rift (EAR). We have carefully selected a total of 54 samples from these time periods, excluding erroneous results derived from lavas with evidence of clinopyroxene fractionation or volatile rich and pyroxenitic sources. Our results show that elevated Tp in the Ethiopian/Yemen flood basalt province (Tp max =1520°C) and in the early Kenya/S. Ethiopia magmatism (Tp max = 1510°C) are virtually identical. Our results indicate that the existing geochemical division between high and low Ti Ethiopia/Yemen flood basalts has a thermal basis: low-Ti lavas are hotter than the high-Ti lavas. Magmatism in the region subsequent to 23 Ma exhibits only minor cooling (Tp max = 1490°C), though more substantial cooling is observed in Turkana, Kenya (60°C) and Yemen (80°C). Rift lavas from Ethiopia exhibit a clear decrease in Tp away from Afar southwestward along the EAR before progressively rising again in Southern Ethiopia towards Turkana. South of Turkana, elevated Tp is observed in the western and eastern branches of the EAR surrounding the Tanzania Craton. The modern spatial distribution of Tp in EAR magmatism indicate two distinct heat sources, one in Afar and another under the Tanzania craton. We suggest that hot mantle plume material from Afar and Turkana (which may or may not merge at depth) is channeled beneath the thinned rift lithosphere and provides a significant thermal input to EAR magmatism resulting in elevated Tp, even in magmas clearly derived from the lithosphere. Our results add to the debate generated by numerous global-scale tomographic inversions that presently do not show consensus as to the number and location of low-velocity upwellings beneath East Africa.

A quantitative assessment of the contributions of climatic indicators to changes in nutrients and oxygen levels in a shallow reservoir in China

NASA Astrophysics Data System (ADS)

Zhang, Chen; Zhang, Wenna; Liu, Hanan; Gao, Xueping; Huang, Yixuan

2017-06-01

Climate change has an indirect effect on water quality in freshwater ecosystems, but it is difficult to assess the contribution of climate change to the complex system. This study explored to what extent climatic indicators (air temperature, wind speed, and rainfall) influence nutrients and oxygen levels in a shallow reservoir, Yuqiao Reservoir, China. The study comprises three parts—describing the temporal trends of climatic indicators and water quality parameters during the period 1992-2011, analyzing the potential impacts of climate on water quality, and finally developing a quantitative assessment to evaluate how climatic factors govern nutrient levels in the reservoir. Our analyses showed that the reservoir experienced substantial cold periods (1992-2001) followed by a warm period (2002-2011). The results showed that increasing air temperature in spring, autumn, and winter and increasing annual wind speed decrease total phosphorus (TP) concentration in the reservoir in spring, summer, and winter. According to the quantitative assessment, the increase in air temperature in spring and winter had a larger contribution to the decrease in TP concentration (47.2 and 64.1%), compared with the influence from decreased wind speed and rainfall. The field data suggest that nutrients decline due to enhanced uptake by macrophytes in years when spring was warmer and the macrophytes started to grow earlier in the season. The increasing wind speed and air temperature in spring also significantly contribute to the increase in dissolved oxygen concentration. This study helps managers to foresee how potential future climate change might influence water quality in similar lake ecosystems.

Conformational Changes in a Hyperthermostable Glycoside Hydrolase: Enzymatic Activity Is a Consequence of the Loop Dynamics and Protonation Balance

PubMed Central

de Oliveira, Leandro C.; da Silva, Viviam M.; Colussi, Francieli; Cabral, Aline D.; de Oliveira Neto, Mario; Squina, Fabio M.; Garcia, Wanius

2015-01-01

Endo-β-1, 4-mannanase from Thermotoga petrophila (TpMan) is a modular hyperthermostable enzyme involved in the degradation of mannan-containing polysaccharides. The degradation of these polysaccharides represents a key step for several industrial applications. Here, as part of a continuing investigation of TpMan, the region corresponding to the GH5 domain (TpManGH5) was characterized as a function of pH and temperature. The results indicated that the enzymatic activity of the TpManGH5 is pH-dependent, with its optimum activity occurring at pH 6. At pH 8, the studies demonstrated that TpManGH5 is a molecule with a nearly spherical tightly packed core displaying negligible flexibility in solution, and with size and shape very similar to crystal structure. However, TpManGH5 experiences an increase in radius of gyration in acidic conditions suggesting expansion of the molecule. Furthermore, at acidic pH values, TpManGH5 showed a less globular shape, probably due to a loop region slightly more expanded and flexible in solution (residues Y88 to A105). In addition, molecular dynamics simulations indicated that conformational changes caused by pH variation did not change the core of the TpManGH5, which means that only the above mentioned loop region presents high degree of fluctuations. The results also suggested that conformational changes of the loop region may facilitate polysaccharide and enzyme interaction. Finally, at pH 6 the results indicated that TpManGH5 is slightly more flexible at 65°C when compared to the same enzyme at 20°C. The biophysical characterization presented here is well correlated with the enzymatic activity and provide new insight into the structural basis for the temperature and pH-dependent activity of the TpManGH5. Also, the data suggest a loop region that provides a starting point for a rational design of biotechnological desired features. PMID:25723179

Theileria parva antigens recognized by CD8+ T cells show varying degrees of diversity in buffalo-derived infected cell lines.

PubMed

Sitt, Tatjana; Pelle, Roger; Chepkwony, Maurine; Morrison, W Ivan; Toye, Philip

2018-05-06

The extent of sequence diversity among the genes encoding 10 antigens (Tp1-10) known to be recognized by CD8+ T lymphocytes from cattle immune to Theileria parva was analysed. The sequences were derived from parasites in 23 buffalo-derived cell lines, three cattle-derived isolates and one cloned cell line obtained from a buffalo-derived stabilate. The results revealed substantial variation among the antigens through sequence diversity. The greatest nucleotide and amino acid diversity were observed in Tp1, Tp2 and Tp9. Tp5 and Tp7 showed the least amount of allelic diversity, and Tp5, Tp6 and Tp7 had the lowest levels of protein diversity. Tp6 was the most conserved protein; only a single non-synonymous substitution was found in all obtained sequences. The ratio of non-synonymous: synonymous substitutions varied from 0.84 (Tp1) to 0.04 (Tp6). Apart from Tp2 and Tp9, we observed no variation in the other defined CD8+ T cell epitopes (Tp4, 5, 7 and 8), indicating that epitope variation is not a universal feature of T. parva antigens. In addition to providing markers that can be used to examine the diversity in T. parva populations, the results highlight the potential for using conserved antigens to develop vaccines that provide broad protection against T. parva.

Statistics of optical and geometrical properties of cirrus cloud over tibetan plateau measured by lidar and radiosonde

NASA Astrophysics Data System (ADS)

Dai, Guangyao; Wu, Songhua; Song, Xiaoquan; Zhai, Xiaochun

2018-04-01

Cirrus clouds affect the energy budget and hydrological cycle of the earth's atmosphere. The Tibetan Plateau (TP) plays a significant role in the global and regional climate. Optical and geometrical properties of cirrus clouds in the TP were measured in July-August 2014 by lidar and radiosonde. The statistics and temperature dependences of the corresponding properties are analyzed. The cirrus cloud formations are discussed with respect to temperature deviation and dynamic processes.

On the role of horizontal resolution over the Tibetan Plateau in the REMO regional climate model

NASA Astrophysics Data System (ADS)

Xu, Jingwei; Koldunov, Nikolay; Remedio, Armelle Reca C.; Sein, Dmitry V.; Zhi, Xiefei; Jiang, Xi; Xu, Min; Zhu, Xiuhua; Fraedrich, Klaus; Jacob, Daniela

2018-02-01

A number of studies have shown that added value is obtained by increasing the horizontal resolution of a regional climate model to capture additional fine-scale weather processes. However, the mechanisms leading to this added value are different over areas with complicated orographic features, such as the Tibetan Plateau (TP). To determine the role that horizontal resolution plays over the TP, a detailed comparison was made between the results from the REMO regional climate model at resolutions of 25 and 50 km for the period 1980-2007. The model was driven at the lateral boundaries by the European Centre for Medium-Range Weather Forecasts Interim Reanalysis data. The experiments differ only in representation of topography, all other land parameters (e.g., vegetation characteristics, soil texture) are the same. The results show that the high-resolution topography affects the regional air circulation near the ground surface around the edge of the TP, which leads to a redistribution of the transport of atmospheric water vapor, especially over the Brahmaputra and Irrawaddy valleys—the main water vapor paths for the southern TP—increasing the amount of atmospheric water vapor transported onto the TP by about 5%. This, in turn, significantly decreases the temperature at 2 m by > 1.5 °C in winter in the high-resolution simulation of the southern TP. The impact of topography on the 2 m temperature over the TP is therefore by influencing the transport of atmospheric water vapor in the main water vapor paths.

Impacts of Climate Change on Agricultural Technology Management in the Transylvanian Plain, Romania

NASA Astrophysics Data System (ADS)

Rusu, Teodor; Ioana Moraru, Paula; Bogdan, Ileana; Ioan Pop, Adrian; Cacovean, Horea

2013-04-01

The impact of climate changes varies considerably in Europe, with different degrees of vulnerability. Romania is situated in an area with the lowest capacity to adapt to existing climate change and those that will occur, and the Transylvanian Plain (TP) is one of the most affected areas. In these conditions, the climate monitoring and implementation of measures to adapt to these changes are essential for sustainable development of agricultural technologies. The TP name comes from the Latin "silva" which means forest, namely an area covered with forests approximately 55-60% in the early nineteenth century, but today reached an average of 6.8% in the TP area. In time, the rugged terrain, deforestation, erosive slopes, and irrational agro technical practices for crop production altogether brought about the degradation of large areas of agricultural land, reducing its productivity. The degree of soil degradation in TP and climate change in recent years, have radically modified climatic conditions for cultural crops. Monitoring of temperature and water supply in TP aims to evaluate these two resources for agricultural production. The TP is a geographical region located in north-central Romania and it is bordered by large rivers to the north and south: the Somes and the Mures rivers. The altitude of the TP ranges from 231 to 662 m. TP, with an area of approx. 395,616 ha, includes areas of three counties (Cluj - CJ, Mures -MS, Bistrita-Nasaud - BN), has a predominantly agricultural character, and is characterized by hilly climate with oceanic influences, 9-100C average annual temperatures and 500-700 mm/year average annual precipitations. Monitoring the thermal and water supplies from TP was performed with twenty HOBO micro stations which determine the temperature (to a height of 1 m) and rainfalls same as temperature (at 10, 30, 50 cm depth in soil) and soil moisture (at 10 cm depth). Average precipitation recorded during 2009-2011, is 498.97 mm, which is beneath the multiannual average of the area. The year 2009 indicated an average of 503.84 mm in TP, considered in the lower limit of the area, followed by the year 2010 with an annual average of 607.84 mm, the year with the closest values to normal area precipitation values. The year 2011 is extremely dry, with an average of 376.56 mm. This situation is reflected in rainfall humidity values, recorded at a depth of 10 cm in the soil, where the area average is about 0.249%. The inner hydrological network contains rivers with low flow inside a semi-permanent or intermittent flow supply. River flow is not related to the surface water supply, being tributary to rainfalls which have an uneven character. Since the supply is pluviometrical, floods are recorded from March to April due to snow melting and in May to July after torrential rains. Quantity and quality of groundwater in Transylvanian Plain represent problems that have conditioned economic and social development of rural habitats and determined the anthropic development and maintenance of the natural lakes. Groundwaters have a particular importance within the region revealing the possibility of development of settlements and location of others settlements and supporting an efficient agriculture. Reduced volume of groundwater induces a temporary or intermittent character to the majority of surface waters during summer and early autumn. The amount of real evapotranspiration adds up to these, which from April to October, is 550 - 600 mm, half of these being registered in the summer months. Hydrographical local organization exclusively, lack of alternative water sources and unproductive correlation between S-SV exhibition of the flanks with increased slopes, all these are images of a region tributary to the critical term. Average air temperature during 2009-2011 is 10.750C, in the soil at 10 cm depth being 11.150C, respectively 11.280C at depth of 50 cm. Low amounts of precipitation, especially their poor distribution during crop vegetation, are aggravated by the deficit of hydrological resources for TP. The average air temperature is above multiannual average of the area, which significantly influenced the optimum time of sowing and amount of biologically active degrees of temperature during the vegetation period.

Subresolution Activity in Solar and Stellar Coronae from Magnetic Field Line Tangling

NASA Astrophysics Data System (ADS)

Rappazzo, A. F.; Dahlburg, R. B.; Einaudi, G.; Velli, M.

2018-05-01

The heating of coronal loops is investigated to understand the observational consequences in terms of the thermodynamics and radiative losses from the Sun as well as the magnetized coronae of stars with an outer convective envelope. The dynamics of the Parker coronal heating model are studied for different ratios of the photospheric forcing velocity timescale tp to the Alfvén crossing time along a loop tA. It is shown that for tp/tA ≳ 10-24 the heating rate and maximum temperature are largest and approximately independent of tp/tA, leading to a strong emission in X-rays and EUV. On the opposite decreasing tp/tA to smaller values leads to lower heating rates and plasma temperatures, and consequently fading high-energy radiative emission once tp/tA ≲ 1-3. The average volumetric loop heating rate is shown to scale as ℓ _p u_p B_0^2/4π L^2, where ℓp and up are respectively the convective granule length-scale and velocity, B0 is the intensity of the strong magnetic field threading the loop, and L the loop length. These findings support a recent hypothesis explaining ultracool dwarf observations of stars with similar magnetic field strength but radically different topologies displaying different radiative emission.

Contrasting responses of grassland water and carbon exchanges to climate change between Tibetan Plateau and Inner Mongolia

NASA Astrophysics Data System (ADS)

Liu, D.; Li, Y.; Wang, T.; Peylin, P. P.; MacBean, N.; Ciais, P.; Jia, G.; Ma, M.; Ma, Y.; Shen, M.; Zhang, X.; Piao, S.

2017-12-01

he grassland in Tibetan Plateau (TP) and Inner Mongolia (IM) of China play important roles in climate change mitigation. These two regions have increasingly experienced warming and changing precipitation regimes over the past three decades. However, it remains uncertain to what extent temperature and water availability regulate the water and carbon fluxes across alpine (TP) and temperate (IM) grasslands. Here, we optimize a process-based model of carbon and water fluxes using eddy covariance (EC) data and analyze the simulated results based upon the optimized model exposed to a range of annual temperature and precipitation anomalies. We found that the changes of NEE of TP grassland are relatively small because of compatible increasing rate of ecosystem respiration (Re) and the gross primary productivity (GPP) under warming. The NEE of IM grassland increases with warming due to faster reduction of GPP than Re under warm-induced drought. We also found suppression of plant transpiration as the primary cause for the muted response of evapotranspiration to warming in IM, which is in contrast to enhanced transpiration in TP. We therefore highlight that the underlying processes regulating the responses of water and carbon cycles to warming are fundamentally different between TP and IM grasslands.

TP53 mutations, expression and interaction networks in human cancers

PubMed Central

Wang, Xiaosheng; Sun, Qingrong

2017-01-01

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers. PMID:27880943

TP53 mutations, expression and interaction networks in human cancers.

PubMed

Wang, Xiaosheng; Sun, Qingrong

2017-01-03

Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers.

A six hundred-year annual minimum temperature history for the central Tibetan Plateau derived from tree-ring width series

NASA Astrophysics Data System (ADS)

He, Minhui; Yang, Bao; Datsenko, Nina M.

2014-08-01

The recent unprecedented warming found in different regions has aroused much attention in the past years. How temperature has really changed on the Tibetan Plateau (TP) remains unknown since very limited high-resolution temperature series can be found over this region, where large areas of snow and ice exist. Herein, we develop two Juniperus tibetica Kom. tree-ring width chronologies from different elevations. We found that the two tree-ring series only share high-frequency variability. Correlation, response function and partial correlation analysis indicate that prior year annual (January-December) minimum temperature is most responsible for the higher belt juniper radial growth, while more or less precipitation signal is contained by the tree-ring width chronology at the lower belt and is thus excluded from further analysis. The tree growth-climate model accounted for 40 % of the total variance in actual temperature during the common period 1957-2010. The detected temperature signal is further robustly verified by other results. Consequently, a six century long annual minimum temperature history was firstly recovered for the Yushu region, central TP. Interestingly, the rapid warming trend during the past five decades is identified as a significant cold phase in the context of the past 600 years. The recovered temperature series reflects low-frequency variability consistent with other temperature reconstructions over the whole TP region. Furthermore, the present recovered temperature series is associated with the Asian monsoon strength on decadal to multidecadal scales over the past 600 years.

Cold Fusion at Hotspots

NASA Astrophysics Data System (ADS)

Natland, J. H.

2009-12-01

Olivine-liquid FeO-MgO (OLFM) equilibria is often assumed and used to estimate eruptive (To) and melting (potential) temperatures (TP) of primitive magmas and their MgO contents at spreading ridges and linear volcanic chains. The technique involves incremental addition of melt calculated to be in equilibrium with successively more magnesian olivine until an olivine of “mantle” composition is reached. Incremental olivine addition depends on the assumption that that this olivine and the host liquid lie along a single liquid line of descent determined by crystallization of olivine and no other mineral; i.e., the parental liquid was formally picritic in composition. This assumption can be questioned on three grounds, which may vary in importance from place to place, but at least one of which always appears to be operative: 1) most picrites are hybrids between primitive and differentiated magmas, the latter expressing cotectic crystallization of olivine, plagioclase and/or clinopyroxene (e.g., Baffin-West Greenland, Hawaii, Samoa), and have higher Fe/Mg than primitive magma, making estimates of To and TP too high; 2) the rocks themselves contain phenocrysts of plagioclase (e.g., Iceland) and/or clinopyroxene (e.g., Samoa) as well as olivine; 3) not even the most primitive magmas, evidenced by mineral associations in accumulative magmatic xenoliths (dunite, wehrlite, olivine clinopyroxene; many examples) indicate stages of crystallization involving olivine by itself. An alternative approach that uses liquid compositions to estimate compositions of Cr-spinel (Poustovetov and Roeder, 2000) predicts no natural Cr-spinel that crystallized at temperature >1400C or pressure 1.5 GPa either in picrites or xenoliths at any of these localities; no parental liquid had MgO > 16%. Spinel predicted from high-MgO (>20%) parental liquids postulated by OLFM matches nothing in nature. Natural glass in Samoan harzburgite xenoliths is mainly differentiated basalt, hawaiite and mugearite with average melt temperature of ~1100C, the same temperature as given by Ca-in-orthopyroxene of the harzburgites. Cold ambient mantle draws heat from ascending magma, forcing differentiation at depth. Magma with TP greater by 200C than primitive basalt at spreading ridges does not exist at any of these places. TP does not constrain temperature of the mantle below the depth of melt extraction. High and variable 3He/4He at all these places may result from volatile incorporation from old harzburgite through which magmas must ascend. Poustovetov, A., and Roeder, P.L., 2000. Canad. Min. 39: 309-317.

Improving GEOS-5 seven day forecast skill by assimilation of quality controlled AIRS temperature profiles

NASA Astrophysics Data System (ADS)

Susskind, J.; Rosenberg, R. I.

2016-12-01

The GEOS-5 Data Assimilation System (DAS) generates a global analysis every six hours by combining the previous six hour forecast for that time period with contemporaneous observations. These observations include in-situ observations as well as those taken by satellite borne instruments, such as AIRS/AMSU on EOS Aqua and CrIS/ATMS on S-NPP. Operational data assimilation methodology assimilates observed channel radiances Ri for IR sounding instruments such as AIRS and CrIS, but only for those channels i in a given scene whose radiances are thought to be unaffected by clouds. A limitation of this approach is that radiances in most tropospheric sounding channels are affected by clouds under partial cloud cover conditions, which occurs most of the time. The AIRS Science Team Version-6 retrieval algorithm generates cloud cleared radiances (CCR's) for each channel in a given scene, which represent the radiances AIRS would have observed if the scene were cloud free, and then uses them to determine quality controlled (QC'd) temperature profiles T(p) under all cloud conditions. There are potential advantages to assimilate either AIRS QC'd CCR's or QC'd T(p) instead of Ri in that the spatial coverage of observations is greater under partial cloud cover. We tested these two alternate data assimilation approaches by running three parallel data assimilation experiments over different time periods using GEOS-5. Experiment 1 assimilated all observations as done operationally, Experiment 2 assimilated QC'd values of AIRS CCRs in place of AIRS radiances, and Experiment 3 assimilated QC'd values of T(p) in place of observed radiances. Assimilation of QC'd AIRS T(p) resulted in significant improvement in seven day forecast skill compared to assimilation of CCR's or assimilation of observed radiances, especially in the Southern Hemisphere Extra-tropics.

Superconductivity-related insulating behavior.

PubMed

Sambandamurthy, G; Engel, L W; Johansson, A; Shahar, D

2004-03-12

We present the results of an experimental study of superconducting, disordered, thin films of amorphous indium oxide. These films can be driven from the superconducting phase to a reentrant insulating state by the application of a perpendicular magnetic field (B). We find that the high-B insulator exhibits activated transport with a characteristic temperature, TI. TI has a maximum value (TpI) that is close to the superconducting transition temperature (Tc) at B=0, suggesting a possible relation between the conduction mechanisms in the superconducting and insulating phases. Tp(I) and Tc display opposite dependences on the disorder strength.

Impact of Vegetation Cover Fraction Parameterization schemes on Land Surface Temperature Simulation in the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Lv, M.; Li, C.; Lu, H.; Yang, K.; Chen, Y.

2017-12-01

The parameterization of vegetation cover fraction (VCF) is an important component of land surface models. This paper investigates the impacts of three VCF parameterization schemes on land surface temperature (LST) simulation by the Common Land Model (CoLM) in the Tibetan Plateau (TP). The first scheme is a simple land cover (LC) based method; the second one is based on remote sensing observation (hereafter named as RNVCF) , in which multi-year climatology VCFs is derived from Moderate-resolution Imaging Spectroradiometer (MODIS) NDVI (Normalized Difference Vegetation Index); the third VCF parameterization scheme derives VCF from the LAI simulated by LSM and clump index at every model time step (hereafter named as SMVCF). Simulated land surface temperature(LST) and soil temperature by CoLM with three VCF parameterization schemes were evaluated by using satellite LST observation and in situ soil temperature observation, respectively, during the period of 2010 to 2013. The comparison against MODIS Aqua LST indicates that (1) CTL produces large biases for both four seasons in early afternoon (about 13:30, local solar time), while the mean bias in spring reach to 12.14K; (2) RNVCF and SMVCF reduce the mean bias significantly, especially in spring as such reduce is about 6.5K. Surface soil temperature observed at 5 cm depth from three soil moisture and temperature monitoring networks is also employed to assess the skill of three VCF schemes. The three networks, crossing TP from West to East, have different climate and vegetation conditions. In the Ngari network, located in the Western TP with an arid climate, there are not obvious differences among three schemes. In Naqu network, located in central TP with a semi-arid climate condition, CTL shows a severe overestimates (12.1 K), but such overestimations can be reduced by 79% by RNVCF and 87% by SMVCF. In the third humid network (Maqu in eastern TP), CoLM performs similar to Naqu. However, at both Naqu and Maqu networks, RNVCF shows significant overestimation in summer, perhaps due to RNVCF ignores the growing characteristics of vegetation (mainly grass) in these two regions. Our results demonstrate that VCF schemes have significant influence on LSM performance, and indicate that it is important to consider vegetation growing characteristics in VCF schemes for different LCs.

Preparation and Identification of HER2 Radioactive Ligands and Imaging Study of Breast Cancer-Bearing Nude Mice.

PubMed

Zhang, Meng-Zhi; Guan, Yan-Xing; Zhong, Jin-Xiu; Chen, Xue-Zhong

2017-08-01

A micro-molecule peptide TP1623 of 99m Tc-human epithelial growth factor receptor 2 (HER2) was prepared and the feasibility of using it as a HER2-positive molecular imaging agent for breast cancer was evaluated. TP1623 was chemically synthesized and labeled with 99m Tc. The labeling ratio and stability were detected. HER2 expression levels of breast cancer cells (SKBR3 and MDA-MB-231) and cell binding activity were measured. Biodistribution of 99m TC-TP1623 in normal mice was detected. SKBR3/MDA-MB-231-bearing nude mice models with high/low expressions of HER2 were established. Tumor tissues were stained with hematoxylin-eosin (HE) and measured by immunohistochemistry to confirm the formation of tumors and HER2 expression. SPECT imaging was conducted for HER2-overexpressing SKBR3-bearing nude mice. The T/NT ratio was calculated and compared with that of MDA-MB-231-bearing nude mice with low HER2 expression. The competitive inhibition image was used to discuss the specific binding of 99m Tc- TP1623 and the tumor. The labeling ratio of 99m Tc-TP1623, specific activity, and radiochemical purity (RCP) after 6 h at room temperature were (97.39 ± 0.23)%, (24.61 ± 0.06) TBq/mmol, and (93.25 ± 0.06)%, respectively. HER2 of SKBR3 and MDA-MB-231 cells showed high and low expression levels by immunohistochemistry, respectively. The in vitro receptor assays indicated that specific binding of TP1623 and HER2 was retained. Radioactivity in the brain was always at the lowest level, while the clearance rate of blood and the excretion rate of the kidneys were fast. HE staining showed that tumor cells were observed in SKBR3- and MDA-MB-231-bearing nude mice, with significant heteromorphism and increased mitotic count. The imaging of mice showed that targeted images could be made of 99m Tc-TP1623 in high HER2-expressing tumors, while no obvious development was shown in tumors in low HER2-expressing nude mice. No development was visible in tumors in competitive inhibition of imaging, which indicates the combination of 99m Tc-TP1623 and tumor was mediated by HER2. High labeling ratio and specific activity of 99m Tc-TP1623 is successfully prepared; it is a molecular imaging agent for HER2-positive tumors that has potential applicative value. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Strong impacts of daily minimum temperature on the green-up date and summer greenness of the Tibetan Plateau.

PubMed

Shen, Miaogen; Piao, Shilong; Chen, Xiaoqiu; An, Shuai; Fu, Yongshuo H; Wang, Shiping; Cong, Nan; Janssens, Ivan A

2016-09-01

Understanding vegetation responses to climate change on the Tibetan Plateau (TP) helps in elucidating the land-atmosphere energy exchange, which affects air mass movement over and around the TP. Although the TP is one of the world's most sensitive regions in terms of climatic warming, little is known about how the vegetation responds. Here, we focus on how spring phenology and summertime greenness respond to the asymmetric warming, that is, stronger warming during nighttime than during daytime. Using both in situ and satellite observations, we found that vegetation green-up date showed a stronger negative partial correlation with daily minimum temperature (Tmin ) than with maximum temperature (Tmax ) before the growing season ('preseason' henceforth). Summer vegetation greenness was strongly positively correlated with summer Tmin , but negatively with Tmax . A 1-K increase in preseason Tmin advanced green-up date by 4 days (P < 0.05) and in summer enhanced greenness by 3.6% relative to the mean greenness during 2000-2004 (P < 0.01). In contrast, increases in preseason Tmax did not advance green-up date (P > 0.10) and higher summer Tmax even reduced greenness by 2.6% K(-1) (P < 0.05). The stimulating effects of increasing Tmin were likely caused by reduced low temperature constraints, and the apparent negative effects of higher Tmax on greenness were probably due to the accompanying decline in water availability. The dominant enhancing effect of nighttime warming indicates that climatic warming will probably have stronger impact on TP ecosystems than on apparently similar Arctic ecosystems where vegetation is controlled mainly by Tmax . Our results are crucial for future improvements of dynamic vegetation models embedded in the Earth System Models which are being used to describe the behavior of the Asian monsoon. The results are significant because the state of the vegetation on the TP plays an important role in steering the monsoon. © 2016 John Wiley & Sons Ltd.

Some experiments with the tunnel probe in a low temperature magnetized plasma

NASA Astrophysics Data System (ADS)

Kovačič, J.; Gyergyek, T.; Kavaš, B.; Vodnik, M.; Kavčič, J.; Gunn, J. P.

2018-02-01

Experiments were performed using a Tunnel Probe (TP) inside the weakly-ionised plasma of the Linear Magnetized Plasma Device (LMPD). The TP is designed as a concave probe, which should annihilate the problem of sheath expansion in the ion branch of the I-V characteristic. As the ion saturation current is consequently well defined, the ion parallel current and plasma density can be more accurately calculated. Furthermore the ratio between the ion saturation currents on the two collectors (tunnel ring and the back-plate) can be used to derive the electron temperature. The TP has been repeatedly used with success on the former Castor and Tore-Supra tokamaks and will be used on the upgraded version of Tore-supra, namely the WEST tokamak, as well [1, 2]. It was however never used successfully in a low-temperature plasma. We studied the feasibility of the TP use in a low-temperature plasma for direct measurements of plasma temperature and density. The various probe characteristic dimensions, such as the distance between the two collectors, the aperture size and the probe radius were varied to see influence of the individual probe feature. We also varied the level of magnetization of the charged particle species, the background gas pressure (which influences the electron energy distribution function), the plasma density (important for the ratio between the λ D and the ion Larmor radius). The sensitivity of the probe alignment to the magnetic field lines was also studied. We found, that the ion saturation current does not necessarily saturate and that the probe works according to expectations only in a limited amount of regimes.

Crystal structure of thermostable p-nitrophenylphosphatase from Bacillus Stearothermophilus (Bs-TpNPPase).

PubMed

Guo, Zheng; Wang, Fengbin; Shen, Tiantian; Huang, Jing; Wang, Yuandong; Ji, Chaoneng

2014-05-01

Thermostable p-nitrophenylphosphatase from Bacillus Stearothermophilus (Bs-TpNPPase) is involved in the Mg(2+)-dependent hydrolysis of the phosphoenzyme at an optimum reaction temperature of 55°C. Bs-TpNPPase has been cloned and overexpressed in the E.coli M15 strain. Based on the conserved active sites, the protein was suggested to be a member of the haloalkanoate dehalogenase (HAD) superfamily. Two site-specific point mutants of Bs-TpNPPase were prepared by changing the catalytic Asp10 and Thr43 to Ala10 and Ala43, respectively. The activity of the two mutants further confirms Bs-TpNPPase as a member of the HAD superfamily. HAD superfamily can be divided into the four subfamilies and play several biochemical roles such as DNA repair, signal transduction and secondary metabolism. To understand the relationship between structure and thermostability in HAD superfamily, Bs-TpNPPase from Bacillus Stearothermophilus was selected. The X-ray crystal structure of Bs-TpNPPase was determined at 1.5A resolution using the molecular replacement phasing method. The structure of Bs-TpNPPase has been deposited and the PDB code is 4KN8. Compared with Bsp, a mesophilic prokaryotic putative p-nitrophenyl phosphatase from Bacillus Subtilis, Bs- TpNPPase showed highly homology but variations in the level of leucine content, aromatic clusters, cation-Pi and hydrophobic interaction. These differences may affect the thermal stability of the protein. The crystal structure of Bs-TpNPPase described herein may serve as a guide to better understand the mechanism of thermostability and provide insights for further mutation work.

A dipole pattern of summertime rainfall across the Indian subcontinent and the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Jiang, X.; Ting, M.

2017-12-01

The Tibetan Plateau (TP) has long been regarded as a key driver for the formation and variations of the Indian summer monsoon (ISM). Recent studies, however, indicated that the ISM also exerts a considerable impact on rainfall variations in the TP, suggesting that the ISM and the TP should be considered as an interactive system. From this perspective, we investigate the co-variability of the July-August mean rainfall across the Indian subcontinent (IS) and the TP. We found that the interannual variation of IS and TP rainfall exhibits a dipole pattern in which rainfall in the central and northern IS tends to be out of phase with that in the southeastern TP. This dipole pattern is associated with significant anomalies in rainfall, atmospheric circulation, and water vapor transport over the Asian continent and nearby oceans. Rainfall anomalies and the associated latent heating in the central and northern IS tend to induce changes in regional circulation -that suppress rainfall in the southeastern TP and vice versa. Furthermore, the sea surface temperature anomalies in the tropical southeastern Indian Ocean can trigger the dipole rainfall pattern by suppressing convection over the central IS and the northern Bay of Bengal, which further induces anomalous anticyclonic circulation to the south of TP that favors more rainfall in the southeastern TP by transporting more water vapor to the region. The dipole pattern is also linked to the Silk-Road wave train due to its link to rainfall over the northwestern IS.

Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients.

PubMed

Zarate, Ana Maria; Don, Julieta; Secchi, Dante; Carrica, Andres; Galindez Costa, Fernanda; Panico, Rene; Brusa, Martin; Barra, José Luis; Brunotto, Mabel

2017-05-01

The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p < 0.05. We found: (a) a low frequency of Pro72 variant in control group and a high frequency in OC and OPMD, as well in OC and oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.

A spatially distributed model for assessment of the effects of changing land use and climate on urban stream quality: Development of a Spatially Distributed Urban Water Quality Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Ning; Yearsley, John; Baptiste, Marisa

While the effects of land use change in urban areas have been widely examined, the combined effects of climate and land use change on the quality of urban and urbanizing streams have received much less attention. We describe a modeling framework that is applicable to the evaluation of potential changes in urban water quality and associated hydrologic changes in response to ongoing climate and landscape alteration. The grid-based spatially distributed model, DHSVM-WQ, is an outgrowth of the Distributed Hydrology-Soil-Vegetation Model (DHSVM) that incorporates modules for assessing hydrology and water quality in urbanized watersheds at a high spatial and temporal resolution.more » DHSVM-WQ simulates surface runoff quality and in-stream processes that control the transport of nonpoint-source (NPS) pollutants into urban streams. We configure DHSVM-WQ for three partially urbanized catchments in the Puget Sound region to evaluate the water quality responses to current conditions and projected changes in climate and/or land use over the next century. Here we focus on total suspended solids (TSS) and total phosphorus (TP) from nonpoint sources (runoff), as well as stream temperature. The projection of future land use is characterized by a combination of densification in existing urban or partially urban areas, and expansion of the urban footprint. The climate change scenarios consist of individual and concurrent changes in temperature and precipitation. Future precipitation is projected to increase in winter and decrease in summer, while future temperature is projected to increase throughout the year. Our results show that urbanization has a much greater effect than climate change on both the magnitude and seasonal variability of streamflow, TSS and TP loads largely due to substantially increased streamflow, and particularly winter flow peaks. Water temperature is more sensitive to climate warming scenarios than to urbanization and precipitation changes. Future urbanization and climate change together are predicted to significantly increase annual mean streamflow (up to 55%), water temperature (up to 1.9 ºC), TSS load (up to 182%), and TP load (up to 74%).« less

VPAC1 Targeted 64Cu-TP3805 kit preparation and its evaluation.

PubMed

Tripathi, Sushil K; Kumar, Pardeep; Trabulsi, Edouard J; Kim, Sung; McCue, Peter A; Intenzo, Charles; Berger, Adam; Gomella, Leonard; Thakur, Mathew L

2017-08-01

Previously, our laboratory has shown that 64 Cu-TP3805 can specifically target VPAC1 receptors and be used for positron emission tomography (PET) imaging of breast (BC) and prostate cancer (PC) in humans. Present work is aimed at the formulation of a freeze-dried diaminedithiol-peptide (N 2 S 2 -TP3805) kit and it's evaluation for the preparation of 64 Cu labeled TP3805. Parameters such as pH, temperature and incubation time were examined that influenced the radiolabeling efficiency and stability of the product. Kits were prepared under different conditions and radiolabeling efficiency of TP3805 kit was evaluated for a range of pH3.5-8.5, after addition of 64 Cu in 30μl, 0.1M HCl. Incubation temperature (37-90°C) and time (30-120min.) were also investigated. Kits were stored at -10°C and their long term stability was determined as a function of their radiolabeling efficiency. Further, stability of 64 Cu-TP3805 complex was evaluated in presence of fetal bovine serum and bovine serum albumin by using SDS polyacrylamide gel electrophoresis. Kits were then used for PET imaging of BC and PC following eIND (101550) and institutional approvals. Specificity of 64 Cu-TP3805 for VPAC1 was examined with digital autoradiography (DAR) of prostate tissues obtained after prostatectomy, benign prostatic hyperplasia (BPH) tissue, and benign and malignant lymph nodes. Results were compared with corresponding tissue histology. Radiolabeling efficiency was ≥95% at final pH ~7.2 when incubated at 50°C for 90min. Kits were stable up to 18months when stored at -10°C, and 64 Cu-TP3805 complex exhibited excellent stability for up to 4h at room temperature. 64 Cu-TP3805 complex did not show any transchelation even after 2h incubation at 37°C in 10% FBS as well as in BSA as determined by SDS PAGE analysis. DAR identified ≥95% of malignant lesions 11 new PC lesions, 20 high grade prostatic intraepithelial neoplasia, 2/2 ejaculatory ducts and 5/5 urethra verumontanum not previously identified The malignant lymph nodes were correctly identified by DAR and for 3/3 BPH patients, and 5/5 cysts, DAR was negative. In human BC (n=19) and PC (n=26) were imaged with 100% sensitivity. Availability of ready to use N 2 S 2 -peptide kits for 64 Cu labeling is convenient and eliminates possible day to day variation during its routine preparation for clinical use. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaporative cooling over the Tibetan Plateau induced by vegetation growth.

PubMed

Shen, Miaogen; Piao, Shilong; Jeong, Su-Jong; Zhou, Liming; Zeng, Zhenzhong; Ciais, Philippe; Chen, Deliang; Huang, Mengtian; Jin, Chun-Sil; Li, Laurent Z X; Li, Yue; Myneni, Ranga B; Yang, Kun; Zhang, Gengxin; Zhang, Yangjian; Yao, Tandong

2015-07-28

In the Arctic, climate warming enhances vegetation activity by extending the length of the growing season and intensifying maximum rates of productivity. In turn, increased vegetation productivity reduces albedo, which causes a positive feedback on temperature. Over the Tibetan Plateau (TP), regional vegetation greening has also been observed in response to recent warming. Here, we show that in contrast to arctic regions, increased growing season vegetation activity over the TP may have attenuated surface warming. This negative feedback on growing season vegetation temperature is attributed to enhanced evapotranspiration (ET). The extra energy available at the surface, which results from lower albedo, is efficiently dissipated by evaporative cooling. The net effect is a decrease in daily maximum temperature and the diurnal temperature range, which is supported by statistical analyses of in situ observations and by decomposition of the surface energy budget. A daytime cooling effect from increased vegetation activity is also modeled from a set of regional weather research and forecasting (WRF) mesoscale model simulations, but with a magnitude smaller than observed, likely because the WRF model simulates a weaker ET enhancement. Our results suggest that actions to restore native grasslands in degraded areas, roughly one-third of the plateau, will both facilitate a sustainable ecological development in this region and have local climate cobenefits. More accurate simulations of the biophysical coupling between the land surface and the atmosphere are needed to help understand regional climate change over the TP, and possible larger scale feedbacks between climate in the TP and the Asian monsoon system.

Evaporative cooling over the Tibetan Plateau induced by vegetation growth

PubMed Central

Shen, Miaogen; Piao, Shilong; Jeong, Su-Jong; Zhou, Liming; Zeng, Zhenzhong; Ciais, Philippe; Chen, Deliang; Huang, Mengtian; Jin, Chun-Sil; Li, Laurent Z. X.; Li, Yue; Myneni, Ranga B.; Yang, Kun; Zhang, Gengxin; Zhang, Yangjian; Yao, Tandong

2015-01-01

In the Arctic, climate warming enhances vegetation activity by extending the length of the growing season and intensifying maximum rates of productivity. In turn, increased vegetation productivity reduces albedo, which causes a positive feedback on temperature. Over the Tibetan Plateau (TP), regional vegetation greening has also been observed in response to recent warming. Here, we show that in contrast to arctic regions, increased growing season vegetation activity over the TP may have attenuated surface warming. This negative feedback on growing season vegetation temperature is attributed to enhanced evapotranspiration (ET). The extra energy available at the surface, which results from lower albedo, is efficiently dissipated by evaporative cooling. The net effect is a decrease in daily maximum temperature and the diurnal temperature range, which is supported by statistical analyses of in situ observations and by decomposition of the surface energy budget. A daytime cooling effect from increased vegetation activity is also modeled from a set of regional weather research and forecasting (WRF) mesoscale model simulations, but with a magnitude smaller than observed, likely because the WRF model simulates a weaker ET enhancement. Our results suggest that actions to restore native grasslands in degraded areas, roughly one-third of the plateau, will both facilitate a sustainable ecological development in this region and have local climate cobenefits. More accurate simulations of the biophysical coupling between the land surface and the atmosphere are needed to help understand regional climate change over the TP, and possible larger scale feedbacks between climate in the TP and the Asian monsoon system. PMID:26170316

Stabilization of Reduced Molybdenum-Iron-Sulfur Single and Double Cubane Clusters by Cyanide Ligation

PubMed Central

Pesavento, Russell P.; Berlinguette, Curtis P.; Holm, R. H.

2008-01-01

Recent work has shown that cyanide ligation increases the redox potentials of Fe4S4 clusters, enabling the isolation of [Fe4S4(CN)4]4−, the first synthetic Fe4S4 cluster obtained in the all-ferrous oxidation state (Scott, T. A.; Berlinguette, C. P.; Holm, R. H.; Zhou, H.-C., Proc. Natl. Acad. Sci. USA 2005, 102, 9741). The generality of reduced cluster stabilization has been examined with MoFe3S4 clusters. Reaction of single cubane [(Tp)MoFe3S4(PEt3)3]1+ and edge-bridged double cubane [(Tp)2Mo2Fe6S8(PEt3)4] with cyanide in acetonitrile affords [(Tp)MoFe3S4(CN)3]2− (2) and [(Tp)2Mo2Fe6S8(CN)4]4− (5), respectively. Reduction of 2 with KC14H10 yields [(Tp)MoFe3S4(CN)3]3− (3). Clusters were isolated in ca. 70–90% yields as Et4N+ or Bu4N+ salts; Clusters 3 and 5 contain all-ferrous cores; 3 is the first [MoFe3S4]1+ cluster isolated in substance. The structures of 2 and 3 are very similar; the volume of the reduced cluster core is slightly larger (2.5%), a usual effect upon reduction of cubane-type Fe4S4 and MFe3S4 clusters. Redox potentials and 57Fe isomer shifts of [(Tp)MoFe3S4L3]2−,3 and [(Tp)2Mo2Fe6S8L4]4−,3− clusters with L = CN, PhS, halide, and PEt3 are compared. Clusters with π-donor ligands (L = halide, PhS) exhibit larger isomer shifts and lower (more negative) redox potentials while π-acceptor ligands (L = CN, PEt3) induce smaller isomer shifts and higher (less negative) redox potentials. When potentials of 3/2 and [(Tp)MoFe3S4(SPh)3]3−/2− are compared, cyanide stabilizes 3 by 270 mV vs. the reduced thiolate cluster, commensurate with the 310 mV stabilization of [Fe4S4(CN)4]4− vs. [Fe4S4(SPh)4]4− where four ligands differ. These results demonstrate the efficacy of cyanide stabilization of lower cluster oxidation states. (Tp = hydrotris(pyrazolyl)borate(1−)). PMID:17279830

Stabilization of reduced molybdenum-iron-sulfur single- and double-cubane clusters by cyanide ligation.

PubMed

Pesavento, Russell P; Berlinguette, Curtis P; Holm, R H

2007-01-22

Recent work has shown that cyanide ligation increases the redox potentials of Fe(4)S(4) clusters, enabling the isolation of [Fe(4)S(4)(CN)4]4-, the first synthetic Fe(4)S(4) cluster obtained in the all-ferrous oxidation state (Scott, T. A.; Berlinguette, C. P.; Holm, R. H.; Zhou, H.-C. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 9741). The generality of reduced cluster stabilization has been examined with MoFe(3)S(4) clusters. Reaction of single-cubane [(Tp)MoFe(3)S(4)(PEt(3))3]1+ and edge-bridged double-cubane [(Tp)2Mo(2)Fe(6)S(8)(PEt(3))4] with cyanide in acetonitrile affords [(Tp)MoFe(3)S(4)(CN)3]2- (2) and [(Tp)2Mo(2)Fe(6)S(8)(CN)4]4- (5), respectively. Reduction of 2 with KC(14)H(10) yields [(Tp)MoFe(3)S(4)(CN)3]3- (3). Clusters were isolated in approximately 70-90% yields as Et(4)N+ or Bu(4)N+ salts; clusters 3 and 5 contain all-ferrous cores, and 3 is the first [MoFe(3)S(4)]1+ cluster isolated in substance. The structures of 2 and 3 are very similar; the volume of the reduced cluster core is slightly larger (2.5%), a usual effect upon reduction of cubane-type Fe(4)S(4) and MFe(3)S(4) clusters. Redox potentials and 57Fe isomer shifts of [(Tp)MoFe(3)S(4)L3]2-,3- and [(Tp)2Mo(2)Fe(6)S(8)L(4)]4-,3- clusters with L = CN-, PhS-, halide, and PEt3 are compared. Clusters with pi-donor ligands (L = halide, PhS) exhibit larger isomer shifts and lower (more negative) redox potentials, while pi-acceptor ligands (L = CN, PEt3) induce smaller isomer shifts and higher (less-negative) redox potentials. When the potentials of 3/2 and [(Tp)MoFe(3)S(4)(SPh)3]3-/2- are compared, cyanide stabilizes 3 by 270 mV versus the reduced thiolate cluster, commensurate with the 310 mV stabilization of [Fe(4)S(4)(CN)4]4- versus [Fe(4)S(4)(SPh)4]4- where four ligands differ. These results demonstrate the efficacy of cyanide stabilization of lower cluster oxidation states. (Tp = hydrotris(pyrazolyl)borate(1-)).

Confronting the surface temperature cold bias in AGCMs over the Tibetan Plateau and improving climate simulations

NASA Astrophysics Data System (ADS)

Wu, G. X.; Liu, Y.; Bao, Q.; Chen, X.; Li, J.

2017-12-01

One of the mid-term progresses of the NSFC- Key Research Program "Land-air Coupling over the Tibetan Plateau and Its Climate Impact " is presented. The elevated heating in summer and cooling in winter of the Tibetan Plateau significantly regulate the seasonal change of the atmospheric circulation and exert remarkable impacts on world climate. Recent studies have demonstrated that the majority of the Phase-5 Coupled Model Inter-comparison Project (CMIP5) models underestimate annual and seasonal mean surface air temperatures (Ta) over the Tibetan Plateau (TP). In addition, more than half of the models underestimate annual and seasonal mean surface temperatures (Ts) over the TP. These cold biases are larger over the western TP. By decomposing the Ts bias using the surface energy budget equation, it was demonstrated that this TP's cold bias can be attributed to various factors, in which the stronger bias in surface albedo (a-) and the weaker bias in clear-sky downward Longwave radiation (DLR) play the most significant roles. Since a- and DLR are respectively affected by snow coverage fraction at the ground surface and water vapor content in the atmosphere, these results then imply that the cold bias over the TP is caused by too large snow coverage fraction and too less water vapor content over the TP in the models. The FAMIL AGCM model developed at LASG also suffers from the similar cold bias over the TP. By introducing the 3D- Radiative Transfer Parameterization Over Mountains/Snow (Liou, 2013) into the model, the total solar radiation reaching the ground surface is increased during the daytime, resulting in more snowmelt and less snow coverage. Accordingly, surface albedo is decreased on the sunny side of the mountains, and the surface cold bias over mountain areas is decreased. It is shown that the improvement is sensitive to the model resolution: increased the horizontal resolution of Community Land Model version 4.0 (CLM 4.0) from nearly 200km (1.9o×2.5o) to about 25km (0.23o×0.31o) can significantly improve the parameterization effect and accuracy, with more notably improvement appearing in Spring. It is demonstrated that, by stimulating a Rossby wave and strengthen the precipitation in subtropical frontal zone of East Asia, the decrement of clod bias over the TP can greatly improve the climate simulations of the model.

Microencapsulation of Theobroma cacao L. waste extract: optimization using response surface methodology.

PubMed

Gabbay Alves, Taís Vanessa; Silva da Costa, Russany; Aliakbarian, Bahar; Casazza, Alessandro Alberto; Perego, Patrizia; Carréra Silva Júnior, José Otávio; Ribeiro Costa, Roseane Maria; Converti, Attilio

2017-03-01

The cocoa extract (Theobroma cacao L.) has a significant amount of polyphenols (TP) with potent antioxidant activity (AA). This study aims to optimise microencapsulation of the extract of cocoa waste using chitosan and maltodextrin. Microencapsulation tests were performed according to a Box-Behnken factorial design, and the results were evaluated by response surface methodology with temperature, maltodextrin concentration (MD) and extract flowrate (EF) as independent variables, and the fraction of encapsulated TP, TP encapsulation yield, AA, yield of drying and solubility index as responses. The optimum conditions were: inlet temperature of 170 °C, MD of 5% and EF of 2.5 mL/min. HPLC analysis identified epicatechin as the major component of both the extract and microparticles. TP release was faster at pH 3.5 than in water. These results as a whole suggest that microencapsulation was successful and the final product can be used as a nutrient source for aquatic animal feed. Highlights Microencapsulation is optimised according to a factorial design of the Box-Behnken type. Epicatechin is the major component of both the extract and microcapsules. The release of polyphenols from microcapsules is faster at pH 3.5 than in water.

Modeling a phosphorus credit trading program in an agricultural watershed.

PubMed

Corrales, Juliana; Naja, G Melodie; Bhat, Mahadev G; Miralles-Wilhelm, Fernando

2014-10-01

Water quality and economic models were linked to assess the economic and environmental benefits of implementing a phosphorus credit trading program in an agricultural sub-basin of Lake Okeechobee watershed, Florida, United States. The water quality model determined the effects of rainfall, land use type, and agricultural management practices on the amount of total phosphorus (TP) discharged. TP loadings generated at the farm level, reaching the nearby streams, and attenuated to the sub-basin outlet from all sources within the sub-basin, were estimated at 106.4, 91, and 85 mtons yr(-)(1), respectively. Almost 95% of the TP loadings reaching the nearby streams were attributed to agriculture sources, and only 1.2% originated from urban areas, accounting for a combined TP load of 87.9 mtons yr(-)(1). In order to compare a Least-Cost Abatement approach to a Command-and-Control approach, the most cost effective cap of 30% TP reduction was selected, and the individual allocation was set at a TP load target of 1.6 kg ha(-1) yr(-1) (at the nearby stream level). The Least-Cost Abatement approach generated a potential cost savings of 27% ($1.3 million per year), based on an optimal credit price of $179. Dairies (major buyer), ornamentals, row crops, and sod farms were identified as potential credit buyers, whereas citrus, improved pastures (major seller), and urban areas were identified as potential credit sellers. Almost 81% of the TP credits available for trading were exchanged. The methodology presented here can be adapted to deal with different forms of trading sources, contaminants, or other technologies and management practices. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unusual stoichiometry control in the atomic layer deposition of manganese borate films from manganese bis(tris(pyrazolyl)borate) and ozone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klesko, Joseph P.; Bellow, James A.; Saly, Mark J.

The atomic layer deposition (ALD) of films with the approximate compositions Mn{sub 3}(BO{sub 3}){sub 2} and CoB{sub 2}O{sub 4} is described using MnTp{sub 2} or CoTp{sub 2} [Tp = tris(pyrazolyl)borate] with ozone. The solid state decomposition temperatures of MnTp{sub 2} and CoTp{sub 2} are ∼370 and ∼340 °C, respectively. Preparative-scale sublimations of MnTp{sub 2} and CoTp{sub 2} at 210 °C/0.05 Torr afforded >99% recoveries with <0.1% nonvolatile residues. Self-limited ALD growth was demonstrated at 325 °C for MnTp{sub 2} or CoTp{sub 2} with ozone as the coreactant. The growth rate for the manganese borate process was 0.19 Å/cycle within the ALD window of 300–350 °C. The growth ratemore » for the cobalt borate process was 0.39–0.42 Å/cycle at 325 °C. X-ray diffraction of the as-deposited films indicated that they were amorphous. Atomic force microscopy of 35–36 nm thick manganese borate films grown within the 300–350 °C ALD window showed root mean square surface roughnesses of 0.4–0.6 nm. Film stoichiometries were assessed by x-ray photoelectron spectroscopy and time of flight-elastic recoil detection analysis. The differing film stoichiometries obtained from the very similar precursors MnTp{sub 2} and CoTp{sub 2} are proposed to arise from the oxidizing ability of the intermediate high valent manganese oxide layers and lack thereof for cobalt.« less

Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial.

PubMed

San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae-Hoon; Einsele, Hermann; Salwender, Hans; Sopala, Monika; Redhu, Suman; Paul, Sofia; Corrado, Claudia; Richardson, Paul G

2017-10-01

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd.

Facile green synthesis of functional nanoscale zero-valent iron and studies of its activity toward ultrasound-enhanced decolorization of cationic dyes.

PubMed

Wang, Xiangyu; Wang, Anqi; Ma, Jun; Fu, Minglai

2017-01-01

For the first time, an integrated green technology by coupling functional nanoscale zero-valent iron (NZVI) with ultrasound (US) was innovatively developed for the enhanced decolorization of malachite green (MG) and methylene blue (MB). The functional NZVI (TP-Fe) was successfully fabricated via a facile, one-step and environmentally-benign approach by directly introducing high pure tea polyphenol (TP), where TP contenting abundant epicatechin was employed as reductant, dispersant and capping agent. Note that neither additional extraction procedure nor protection gas was needed during the entire synthesis process. Affecting factors (including US frequency, initial pH, dye concentration, and reaction temperature) were investigated. Results show that TP-Fe exhibited enhanced activity, antioxidizability and stability over the reaction course, which could be attributed to the functionalization of TP on NZVI and the invigorating effect of US (i.e., improving the mass transfer rate, breaking up the aggregates of TP-Fe nanoparticles, and maintaining the TP-Fe surface activity). The kinetics for MG and MB decolorization by the TP-Fe/US system could be well described by a two-parameter pseudo-first-order decay model, and the activation energies of MG and MB decolorization in this new system were determined to be 21 kJ mol -1 and 24 kJ mol -1 , respectively. In addition, according to the identified reaction products, a possible mechanism associated with MG and MB decolorization with the TP-Fe/US system was proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Attenuation of dermal wounds via downregulating oxidative stress and inflammatory markers by protocatechuic acid rich n-butanol fraction of Trianthema portulacastrum Linn. in wistar albino rats.

PubMed

Yadav, Ekta; Singh, Deepika; Yadav, Pankajkumar; Verma, Amita

2017-12-01

Oxidative stress and inflammation contribute as a key factor for retarding the process of dermal wound healing. Trianthema portulcastrum Linn. (TP) leaves reported to possess antioxidant, antifungal, anti-inflammatory and antibacterial properties, which could make TP a promising wound healing agent. The current study was aimed to estimate the antioxidant potential of the fractionated hydroethanolic extract of TP leaves and evaluate wound healing activity by excision and incision wound models along with the assessment of possible underlying mechanism. Ethyl acetate, chloroform and n-butanol fractions of the hydroethanolic extract of TP leaves were examined for in vitro antioxidant ability by DPPH method. Strongest antioxidant activity bearing n-butanol fraction (nBuTP) was further analyzed quantitatively by High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). Wound healing potential of nBUTP using excision and incision wound model was studied. Wistar albino rats were randomly divided into four groups, containing six animals in each group; group I served as control treated with simple ointment base, group II was standard group, treated with povidone-iodine ointment USP (5%), group III treated with nBuTP 5% w/w ointment, and group IV treated with nBuTP 10%w/w ointment. All the groups were topically applied their respective ointments, once daily, till the complete healing achieved. Wound healing was assessed by analyzing % wound closure, hydroxyproline content, epithelialization period, tensile strength, enzymatic antioxidative status and inflammatory markers. Total phenolic and flavonoid content of the extract was estimated to be 112.32±1.12 and 84.42±0.47mg/g, respectively. HPLC-DAD of nBuTP confirmed the presence of chlorogenic acid (20.74±0.03), protocatechuic acid (34.45±0.02mg/g), caffeic acid (4.31±0.03mg/g) and ferulic acid (1.43±0.01mg/g). 5% and 10%w/w nBuTP ointment significantly accelerated the wound healing process dose-dependently in both wound models, evidenced by the faster rate of wound contraction, epithelialization, increased hydroxyproline content, high tensile strength, increased antioxidant enzyme activity, decreased the level of inflammatory markers compared to the control group. Histopathological studies also revealed the dose-dependant amelioration of wound healing by re-epithelialization, collagenation and vascularization of wounded skin sample in nBuTP treated groups. These results implicate potential medicinal value of nBuTP to heal dermal wounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Plume-stagnant slab-lithosphere interactions: Origin of the late Cenozoic intra-plate basalts on the East Eurasia margin

NASA Astrophysics Data System (ADS)

Kimura, Jun-Ichi; Sakuyama, Tetsuya; Miyazaki, Takashi; Vaglarov, Bogdan S.; Fukao, Yoshio; Stern, Robert J.

2018-02-01

Intra-plate basalts of 35-0 Ma in East Eurasia formed in a broad backarc region above the stagnant Pacific Plate slab in the mantle transition zone. These basalts show regional-scale variations in Nd-Hf isotopes. The basalts with the most radiogenic Nd-Hf center on the Shandong Peninsula with intermediate Nd-Hf at Hainan and Datong. The least radiogenic basalts occur in the perimeters underlain by the thick continental lithosphere. Shandong basalts possess isotopic signatures of the young igneous oceanic crust of the subducted Pacific Plate. Hainan and Datong basalts have isotopic signatures of recycled subduction materials with billions of years of storage in the mantle. The perimeter basalts have isotopic signatures similar to pyroxenite xenoliths from the subcontinental lithospheric mantle beneath East Eurasia. Hainan basalts exhibit the highest mantle potential temperature (Tp), while the Shandong basalts have the lowest Tp. We infer that a deep high-Tp plume interacted with the subducted Pacific Plate slab in the mantle transition zone to form a local low-Tp plume by entraining colder igneous oceanic lithosphere. We infer that the subducted Izanagi Plate slab, once a part of the Pacific Plate mosaic, broke off from the Pacific Plate slab at 35 Ma to sink into the lower mantle. The sinking Izanagi slab triggered the plume that interacted with the stagnant Pacific slab and caused subcontinental lithospheric melting. This coincided with formation of the western Pacific backarc marginal basins due to Pacific Plate slab rollback and stagnation.

Electron heating and Tp/Te variations during magnetic dipolarizations

NASA Astrophysics Data System (ADS)

Grigorenko, Elena; Kronberg, Elena; Daly, Patrick; Ganushkina, Natalia; Lavraud, Benoit; Sauvaud, Jean-Andre; Zelenyi, Lev

2017-04-01

The proton-to-electron temperature ratio (Tp/Te) in the plasma sheet (PS) of the Earth's magnetotail is studied by using 5 years of Cluster observations (2001-2005). The PS intervals are searched within a region defined with -19

Sensitivity studies on the impacts of Tibetan Plateau snowpack pollution on the Asian hydrological cycle and monsoon climate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Yun; Flanner, M G; Leung, Lai-Yung R

2011-03-02

The Tibetan Plateau (TP), the highest and largest plateau in the world, has long been identified to be critical in regulating the Asian monsoon climate and hydrological cycle. The snowpack and glaciers over the TP provide fresh water to billions of people in Asian countries, but the TP glaciers have been retreating extensively at a speed faster than any other part of the world. In this study a series of experiments with a global climate model are designed to simulate black carbon (BC) and dust in snow and their radiative forcing and to assess the relative impacts of anthropogenic COmore » 2 and carbonaceous particles in the atmosphere and snow, respectively, on the snowpack over the TP, as well as their subsequent impacts on the Asian monsoon climate and hydrological cycle. Results show a large BC content in snow over the TP, especially the southern slope, with concentration larger than 100 µk/kg. Because of the high aerosol content in snow and large incident solar radiation in the low latitude and high elevation, the TP exhibits the largest surface radiative forcing induced by aerosols (e.g. BC, Dust) in snow compared to other snow-covered regions in the world. The aerosol-induced snow albedo perturbations generate surface radiative forcing of 5-25 W m -2 during spring, with a maximum in April or May. BC-in-snow increases the surface air temperature by around 1.0°C averaged over the TP and reduces snowpack over the TP more than that induced by pre-industrial to present CO 2 increase and carbonaceous particles in the atmosphere during spring. As a result, runoff increases during late winter and early spring but decreases during late spring and early summer (i.e. a trend toward earlier melt dates). The snowmelt efficacy, defined as the snowpack reduction per unit degree of warming induced by the forcing agent, is 1-4 times larger for BC-in-snow than CO 2 increase during April-July, indicating that BC-in-snow more efficiently accelerates snowmelt because the increased net solar radiation induced by reduced albedo melts the snow more efficiently than snow melt due to warming in the air. The TP also influences the South (SAM) and East (EAM) Asian monsoon through its dynamical and thermal forcing. During boreal spring, aerosols are transported by the southwesterly and reach the higher altitude and/or deposited in the snowpack over the TP. While BC and OM in the atmosphere directly absorb sunlight and warm the air, the darkened snow surface polluted by BC absorbs more solar radiation and increases the skin temperature, which warms the air above by the increased sensible heat flux over the TP. Both effects enhance the upward motion of air and spur deep convection along the TP during pre-monsoon season, resulting in earlier onset of the SAM and increase of moisture, cloudiness and convective precipitation over northern India. BC-in-snow has a more significant impact on the EAM in July than CO 2 increase and carbonaceous particles in the atmosphere. Contributed by the significant increase of both sensible heat flux associated with the warm skin temperature and latent heat flux associated with increased soil moisture with long memory, the role of the TP as a heat pump is elevated from spring through summer as the land-sea thermal contrast increases to strengthen the EAM. As a result, both southern China and northern China become wetter, but central China (i.e. Yangtze River Basin) becomes drier - a near zonal anomaly pattern that is consistent with the dominant mode of precipitation variability in East Asia.« less

TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity.

PubMed

Tomasini, Richard; Seux, Mylène; Nowak, Jonathan; Bontemps, Caroline; Carrier, Alice; Dagorn, Jean-Charles; Pébusque, Marie-Josèphe; Iovanna, Juan L; Dusetti, Nelson J

2005-12-08

TP53INP1 is an alternatively spliced gene encoding two nuclear protein isoforms (TP53INP1alpha and TP53INP1beta), whose transcription is activated by p53. When overexpressed, both isoforms induce cell cycle arrest in G1 and enhance p53-mediated apoptosis. TP53INP1s also interact with the p53 gene and regulate p53 transcriptional activity. We report here that TP53INP1 expression is induced during experimental acute pancreatitis in p53-/- mice and in cisplatin-treated p53-/- mouse embryo fibroblasts (MEFs). We demonstrate that ectopic expression of p73, a p53 homologue, leads to TP53INP1 induction in p53-deficient cells. In turn, TP53INP1s alters the transactivation capacity of p73 on several p53-target genes, including TP53INP1 itself, demonstrating a functional association between p73 and TP53INP1s. Also, when overexpressed in p53-deficient cells, TP53INP1s inhibit cell growth and promote cell death as assessed by cell cycle analysis and colony formation assays. Finally, we show that TP53INP1s potentiate the capacity of p73 to inhibit cell growth, that effect being prevented when the p53 mutant R175H is expressed or when p73 expression is blocked by a siRNA. These results suggest that TP53INP1s are functionally associated with p73 to regulate cell cycle progression and apoptosis, independently from p53.

Five Different Piscidins from Nile Tilapia, Oreochromis niloticus: Analysis of Their Expressions and Biological Functions

PubMed Central

Peng, Kuan-Chieh; Lee, Shu-Hua; Hour, Ai-Ling; Pan, Chieh-Yu; Lee, Lin-Han; Chen, Jyh-Yih

2012-01-01

Piscidins are antimicrobial peptides (AMPs) that play important roles in helping fish resist pathogenic infections. Through comparisons of tilapia EST clones, the coding sequences of five piscidin-like AMPs (named TP1∼5) of Nile tilapia, Oreochromis niloticus, were determined. The complete piscidin coding sequences of TP1, -2, -3, -4, and -5 were respectively composed of 207, 234, 231, 270, and 195 bases, and each contained a translated region of 68, 77, 76, 89, and 64 amino acids. The tissue-specific, Vibrio vulnificus stimulation-specific, and Streptococcus agalactiae stimulation-specific expressions of TP2, -3, and -4 mRNA were determined by a comparative RT-PCR. Results of the tissue distribution analysis revealed high expression levels of TP2 mRNA in the skin, head kidneys, liver, and spleen. To study bacterial stimulation, S. agalactiae (SA47) was injected, and the TP4 transcript was upregulated by >13-fold (compared to the wild-type (WT) control, without injection) and was 60-fold upregulated (compared to the WT control, without injection) 24 h after the S. agalactiae (SA47) injection in the spleen and gills. Synthesized TP3 and TP4 peptides showed antimicrobial activities against several bacteria in this study, while the synthesized TP1, -2, and -5 peptides did not. The synthesized TP2, -3, and -4 peptides showed hemolytic activities and synthesized TP3 and TP4 peptides inhibited tilapia ovary cell proliferation with a dose-dependent effect. In summary, the amphiphilic α-helical cationic peptides of TP3 and TP4 may represent novel and potential antimicrobial agents for further peptide drug development. PMID:23226256

Removal and retention of phosphorus by periphyton from wastewater with high organic load.

PubMed

Cao, Jinxiang; Hong, Xiaoxing; Pei, Guofeng

2014-01-01

The total phosphorus (TP) removal efficiency from organic wastewater (pig farm and distillery wastewater) were estimated by using filamentous green algae (FGA) and benthic algal mats (BAM) treatment systems under laboratory conditions, and the contents of periphyton phosphorus fractions were determined by using a sequential extraction. The removal rates of TP reached 59-78% within the first 8 days of all treatment systems and could achieve average 80% during 30 day period, and the phosphorus removal rates by using BAM was higher than that of FGA. The ability of retention TP of periphyton enhanced gradually, the BAM TP contents were higher than that of FGA, the highest TP concentrations of BAM and FGA were 26.24 and 10.52 mg P g(-1)·dry weight. Inorganic phosphorus (IP) always exceeded 67.5% of TP, but the organic phosphorus fraction only made up less than 20% of TP. The calcium-binding phosphorus (Ca-P) was the dominant fraction and its relative contribution to TP was more than 40%. The TP was also strongly and positively correlated with the IP and Ca-P (p < 0.01) in periphyton. It showed that the periphyton had a potential ability of rapid phosphorus removing and remarkable retention from wastewater with high load phosphorus.

Evaluation of inhomogeneities of repolarization in patients with psoriasis vulgaris

PubMed Central

İnci, Sinan; Aksan, Gökhan; Nar, Gökay; Yüksel, Esra Pancar; Ocal, Hande Serra; Çapraz, Mustafa; Yüksel, Serkan; Şahin, Mahmut

2016-01-01

Introduction The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. Material and methods Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring. The QTd was defined as the difference between the maximum and minimum QT intervals. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave. The Tp-e interval was corrected for heart rate. The Tp-e/QT ratio was calculated using these measurements. Results There were no significant differences between the groups with respect to basal clinical and laboratory characteristics (p > 0.05). The Tp-e interval, the corrected Tp-e interval (cTp-e) and the Tp-e/QT ratio were also significantly higher in psoriasis patients compared to the control group (78.5 ±8.0 ms vs. 71.4 ±7.6 ms, p < 0.001, 86.3 ±13.2 ms vs. 77.6 ±9.0 ms, p < 0.001 and 0.21 ±0.02 vs. 0.19 ±0.02, p < 0.001 respectively). A significant correlation was detected between the cTp-e time and the Tp-e/QT ratio and the PASI score in the group of psoriatic patients (r = 0.51, p < 0.001; r = 0.59, p < 0.001, respectively). Conclusions In our study, we detected a significant increase in the Tp-e interval and the Tp-e/QT ratio in patients with psoriasis vulgaris. The Tp-e interval and the Tp-e/QT ratio may be predictors for ventricular arrhythmias in patients with psoriasis vulgaris. PMID:27904512

Evaluation of the Recombinant Protein TpF1 of Treponema pallidum for Serodiagnosis of Syphilis

PubMed Central

Jiang, Chuanhao; Zhao, Feijun; Xiao, Jinhong; Zeng, Tiebing; Yu, Jian; Ma, Xiaohua; Wu, Haiying

2013-01-01

Syphilis is a chronic infection caused by Treponema pallidum subsp. pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with the T. pallidum Nichols strain and T. pallidum clinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n = 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n = 30) and individuals with potentially cross-reactive infections, including Lyme disease (n = 30) and leptospirosis (n = 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of the T. pallidum particle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis. PMID:23945159

Biorefinery cascade processing for creating added value on tomato industrial by-products from Tunisia.

PubMed

Kehili, Mouna; Schmidt, Lisa Marie; Reynolds, Wienke; Zammel, Ayachi; Zetzl, Carsten; Smirnova, Irina; Allouche, Noureddine; Sayadi, Sami

2016-01-01

In today's consumer perception of industrial processes and food production, aspects like food quality, human health, environmental safety, and energy security have become the keywords. Therefore, much effort has been extended toward adding value to biowastes of agri-food industries through biorefinery processing approaches. This study focused, for the first time, on the valorization of tomato by-products of a Tunisian industry for the recovery of value-added compounds using biorefinery cascade processing. The process integrated supercritical CO 2 extraction of carotenoids within the oil fractions from tomato seeds (TS) and tomato peels (TP), followed by a batch isolation of protein from the residues. The remaining lignocellulosic matter from both fractions was then submitted to a liquid hot water (LHW) hydrolysis. Supercritical CO 2 experiments extracted 5.79% oleoresin, 410.53 mg lycopene/kg, and 31.38 mg β-carotene/kg from TP and 26.29% oil, 27.84 mg lycopene/kg, and 5.25 mg β-carotene/kg from TS, on dry weights. Protein extraction yields, nearing 30% of the initial protein contents equal to 13.28% in TP and 39.26% in TS, revealed that TP and TS are a rich source of essential amino acids. LHW treatment run at 120-200 °C, 50 bar for 30 min showed that a temperature of 160 °C was the most convenient for cellulose and hemicellulose hydrolysis from TP and TS, while keeping the degradation products low. Results indicated that tomato by-products are not only a green source of lycopene-rich oleoresin and tomato seed oil (TSO) and of protein with good nutritional quality but also a source of lignocellulosic matter with potential for bioethanol production. This study would provide an important reference for the concept and the feasibility of the cascade fractionation of valuable compounds from tomato industrial by-products.Graphical abstractSchema of biorefinery cascade processing of tomato industrial by-products toward isolation of valuable fractions.

Clinical implications of genomic profiles in metastatic breast cancer with a focus on TP53 and PIK3CA, the most frequently mutated genes.

PubMed

Kim, Ji-Yeon; Lee, Eunjin; Park, Kyunghee; Park, Woong-Yang; Jung, Hae Hyun; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

2017-04-25

Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0.018 and p < 0.001, respectively). TP53 stopgain/loss and frameshift mutation was related to low expression of TP53 in contrast nonsynonymous mutation was related to high expression. The impact of TP53 mutation on clinical outcome varied with regard to ER status. In ER-positive BCs, wild type TP53 had a better prognosis than mutated TP53 (median overall survival (OS) (wild type vs. mutated): 88.5 ± 54.4 vs. 32.6 ± 10.7 (months), p = 0.002). In contrast, mutated TP53 had a protective effect in ER-negative BCs (median OS: 0.10 vs. 32.6 ± 8.2, p = 0.026). However, PIK3CA mutation did not affect patient survival. In gene expression analysis, CALM1, a potential regulator of AKT, was highly expressed in PIK3CA-mutated BCs. In conclusion, mutation of TP53 was associated with expression status and affect clinical outcome according to ER status in MBC. Although mutation of PIK3CA was not related to survival in this study, mutation of PIK3CA altered the expression of other genes and pathways including CALM1 and may be a potential predictive marker of PI3K inhibitor effectiveness.

Time series comparisons of satellite and rocketsonde temperatures in 1978-1979

NASA Technical Reports Server (NTRS)

Remsberg, Ellis E.; Bhatt, Praful P.; Schmidlin, Francis J.

1994-01-01

The Limb Infrared Monitor of the Stratosphere (LIMS) experiment on Nimbus 7 yielded temperature-versus-pressure (T(p)) profiles for each radiance scan. The present report describes time series comparisons between LIMS and rocketsonde T(p) values at rocketsonde station locations. Sample size has increased up to 665 by this new approach, leading to better statistics for a T(p) validation. The results indicate no clearly significant bias for LIMS versus Datasonde from 10 kPa at low and mid latitudes. There is a positive LIMS bias of 2 to 3 K in the upper stratosphere at high latitudes for the Northern Hemisphere in both winter and spring. LIMS is progressively colder than Datasonde from 0.4 kPa (about -3 K) to 0.1 kPa (about -9 K) at all latitudes. A similar comparison between LIMS and the more accurate falling sphere measurements reveals an equivalent mid-latitude LIMS bias at 0.4 kPa but a much smaller bias at 0.1 kPa (-4.6 K). Because the biases do not vary noticeably with season, it is concluded that they are not a function of atmospheric state. This result confirms the robustness of the LIMS temperature retrieval technique.

Future vegetation ecosystem response to warming climate over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Bao, Y.; Gao, Y.; Wang, Y.

2017-12-01

The amplified vegetation response to climate variability has been found over the Tibetan Plateau (TP) in recent decades. In this study, the potential impacts of 21st century climate change on the vegetation ecosystem over the TP are assessed based on the dynamic vegetation outputs of models from Coupled Model Intercomparison Project Phase 5 (CMIP5), and the sensitivity of the TP vegetation in response to warming climate was investigated. Models project a continuous and accelerating greening in future, especially in the eastern TP, which closely associates with the plant type upgrade due to the pronouncing warming in growing season.Vegetation leaf area index (LAI) increase well follows the global warming, suggesting the warming climate instead of co2 fertilization controlls the future TP plant growth. The warming spring may advance the start of green-up day and extend the growing season length. More carbon accumulation in vegetation and soil will intensify the TP carbon cycle and will keep it as a carbon sink in future. Keywords: Leaf Area Index (LAI), Climate Change, Global Dynamic Vegetation Models (DGVMs), CMIP5, Tibetan Plateau (TP)

Characterisation of single domain ATP-binding cassette protien homologues of Theileria parva.

PubMed

Kibe, M K; Macklin, M; Gobright, E; Bishop, R; Urakawa, T; ole-MoiYoi, O K

2001-09-01

Two distinct genes encoding single domain, ATP-binding cassette transport protein homologues of Theileria parva were cloned and sequenced. Neither of the genes is tandemly duplicated. One gene, TpABC1, encodes a predicted protein of 593 amino acids with an N-terminal hydrophobic domain containing six potential membrane-spanning segments. A single discontinuous ATP-binding element was located in the C-terminal region of TpABC1. The second gene, TpABC2, also contains a single C-terminal ATP-binding motif. Copies of TpABC2 were present at four loci in the T. parva genome on three different chromosomes. TpABC1 exhibited allelic polymorphism between stocks of the parasite. Comparison of cDNA and genomic sequences revealed that TpABC1 contained seven short introns, between 29 and 84 bp in length. The full-length TpABC1 protein was expressed in insect cells using the baculovirus system. Application of antibodies raised against the recombinant antigen to western blots of T. parva piroplasm lysates detected an 85 kDa protein in this life-cycle stage.

α-Terpineol reduces cancer pain via modulation of oxidative stress and inhibition of iNOS.

PubMed

Gouveia, Daniele Nascimento; Costa, Janara Santos; Oliveira, Marlange Almeida; Rabelo, Thallita Kelly; Silva, Ana Mara de Oliveira E; Carvalho, Adriana Andrade; Miguel-Dos-Santos, Rodrigo; Lauton-Santos, Sandra; Scotti, Luciana; Scotti, Marcus Tullius; Santos, Márcio Roberto Viana Dos; Quintans-Júnior, Lucindo José; Albuquerque Junior, Ricardo Luiz Cavalcanti De; Guimarães, Adriana Gibara

2018-06-11

α-Terpineol (TP) is present in a wide range of essential oils of the genus Eucalyptus, with recognized potential for a range of biological effects, such as analgesic. Hence, our study aimed to investigate the effect of TP on cancer pain induced by sarcoma 180 in Swiss mice. Our results showed that TP reduced significantly mechanical hyperalgesia and spontaneous and palpation-induced nociception, improved paw use without reducing tumor growth and grip strength. Importantly, no evident biochemical and hematological toxicity was oberved. Furthermore, TP increased the tissue antioxidant capacity due to ferric-reducing antioxidant power (FRAP) and glutathione (GSH). TP also reduced inducible nitric oxide synthase (iNOS) immunocontent in the tumors. Molecular docking estimated that TP binds within the same range of iNOS regions (other iNOS inhibitors), such as N-Nitroarginine methyl ester (L-NAME). These data provide strong evidence that TP may be an interesting candidate for the development of new safe analgesic drugs that are effective for cancer pain control. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Development in modeling Tibetan Plateau Land/Climate Interaction

NASA Astrophysics Data System (ADS)

Xue, Yongkang; Liu, Ye; li, qian; Maheswor Shrestha, Maheswor; Ma, Hsi-Yen; Cox, Peter; Sun, shufen; Koike, Toshio

2015-04-01

Tibetan Plateau (TP) plays an important role in influencing the continental and planetary scale climate, including East Asian and South Asian monsoon, circulation and precipitation over West Pacific and Indian Oceans. The numerical study has identified TP as the area with strongest land/atmosphere interactions over the midlatitude land. The land degradation there has also affected the monsoon precipitation in TP along the monsoon pathway. The water cycle there affects water sources for major Asian river systems, which include the Tarim, Amu Darya, Indus, Ganges, Brahmaputra, Irrawaddy, Salween, Mekong, Yellow, and Yangtze Rivers. Despite the importance of TP land process in the climate system, the TP land surface processes are poorly modeled due to lack of data available for model validation. To better understand, simulate, and project the role of Tibetan Plateau land surface processes, better parameterization of the Tibetan Land surface processes have been developed and evaluated. The recently available field measurement there and satellite observation have greatly helped this development. This paper presents these new developments and preliminary results using the newly developed biophysical/dynamic vegetation model, frozen soil model, and glacier model. In recent CMIP5 simulation, the CMIP5 models with dynamic vegetation model show poor performance in simulating the TP vegetation and climate. To better simulate the TP vegetation condition and its interaction with climate, we have developed biophysical/dynamic vegetation model, the Simplified Simple Biosphere Model version 4/Top-down Representation of Interactive Foliage and Flora Including Dynamics Model (SSiB4/TRIFFID), based on water, carbon, and energy balance. The simulated vegetation variables are updates, driven by carbon assimilation, allocation, and accumulation, as well as competition between plant functional types. The model has been validated with the station data, including those measured over the TP. The offline SSiB4/TRIFFID is integrated using the observed precipitation and reanalysis-based meteorological forcing from 1948 to 2008 with 1 degree horizontal resolution. The simulated vegetation conditions and surface hydrology are compared well with observational data with some bias, and shows strong decadal and interannual variabilities with a linear trend associated with the global warming. The TP region is covered by both discontinuous and sporadic permafrost with irregular snow layers above. A frozen soil model is developed to take the coupling effect of mass and heat transport into consideration and includes a detailed description of mass balances of volumetric liquid water, ice, as well as vapor content. It also considers contributions' of heat conduction to the energy balance. The model has been extensively tested using a number of TP station data, which included soil temperature and soil water measurements. The results suggest that it is important to include the frozen sol process to adequately simulate the surface energy balance during the freezing and thawing periods and surface temperature variability, including its diurnal variation. Issues in simulating permafrost process will also be addressed. To better understand the glacier variations under climate change scenarios, an integrated modeling system with an energy budget-based multilayer scheme for clean glaciers, a single-layer scheme for debris-covered glaciers and multilayer scheme for seasonal snow over glacier, soil and forest are developed within a distributed biosphere hydrological modeling framework (WEB-DHM-S model). Discharge simulations using this model show good agreement with observations for Hunza River Basin (13,733 km2) in the Karakoram region of Pakistan for three hydrologic years (2002-2004). Flow composition analysis reveals that the runoff regime is strongly controlled by the snow and glacier melt runoff (50% snowmelt and 33% glacier melt) and suggests that both topography and glacier hypsometry play key roles in glacier mass balance. This study provides a basis for potential application of such an integrated model to the entire Hindu-Kush-Karakoram-Himalaya region.

Separation of acid blue 25 from aqueous solution using water lettuce and agro-wastes by batch adsorption studies

NASA Astrophysics Data System (ADS)

Kooh, Muhammad Raziq Rahimi; Dahri, Muhammad Khairud; Lim, Linda B. L.; Lim, Lee Hoon; Chan, Chin Mei

2018-05-01

Three plant-based materials, namely water lettuce (WL), tarap peel (TP) and cempedak peel (CP), were used to investigate their potentials as adsorbents using acid blue 25 (AB25) dye as a model for acidic dye. The adsorbents were characterised using Fourier transform infrared spectroscopy, X-ray fluorescence and scanning electron microscope. Batch experiments involving parameters such as pH, temperature, contact time, and initial dye concentration were done to investigate the optimal conditions for the adsorption of AB25 onto the adsorbents. Thermodynamics study showed that the uptake of AB25 by the three adsorbents was feasible and endothermic in nature. Both the Langmuir and Freundlich isotherm models can be used to describe the adsorption process of AB25 onto WL and CP while pseudo-second-order fitted the kinetics data, suggesting that chemisorptions were majorly involved. The use of 0.1 M of NaOH showed the best results in regenerating of the WL, TP and CP's adsorption ability after AB25 treatment.

Optimisation of pressurised liquid extraction of antioxidants from black bamboo leaves.

PubMed

Shang, Ya Fang; Kim, Sang Min; Um, Byung-Hun

2014-07-01

To develop an efficient green extraction approach for recovering bioactive compounds from natural plants, the potential of using pressurised liquid extraction (PLE) was examined on black bamboo (Phyllostachys nigra) leaves, with ethanol/water as solvents. The superheated PLE process showed a higher recovery of most constituents and antioxidative activity, compared to reflux extraction, with a significantly improved recovery of the total phenolic (TP) and flavonoid (TF) content and DPPH radical scavenging ability. For a broad range of ethanol aqueous solutions and temperatures, 50% EtOH and 200°C (static time: 25min) gave the best performance, in terms of the TP and TF (75% EtOH) content yield and DPPH scavenging ability (25% EtOH). Under the optimised extraction conditions, eight main antioxidative compounds were isolated and identified with HPLC-ABTS(+) assay guidance and assessed for radical scavenging activity. The superheated extraction process for black bamboo leaves enhanced the antioxidant properties by increasing the extraction of the phenolic components. Copyright © 2013 Elsevier Ltd. All rights reserved.

Snowmelt in the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Zhang, F.

2016-12-01

Snow accumulation and melting are important hydrological processes in the Tibetan Plateau (TP). Qualification of snow dynamics is helpful for water resources management. In this study, a case study of snow and runoff modeling in a glaciated catchment in south Tibet was firstly conducted and showed that MODIS snow cover data can be successfully used for snow model calibration. Following the method, snow accumulation and melting in the TP was simulated using a distributed degree-day model through zonal calibration. The simulation results showed that the spatial pattern of snowmelt is basically in accordance with that of precipitation with discrepancy mainly introduced by elevation and temperature lapse. During 1979-2010, average annual precipitation and snowmelt in the TP was 394 and 80 mm/yr, respectively, indicating that about 1/5 of the precipitation in the TP supplied the rivers, lakes, and groundwater etc in the form of snowmelt. Seasonal snowmelt accounted for 35%, 37%, 26%, and 2% of the annual gross in spring, summer, fall, and winter, respectively, with net accumulation of snow in fall and winter added to the snowmelt in the following spring and summer. The overall changing trends of annual precipitation and snowmelt in the TP were 4.1 and 0.4 mm/yr, respectively, with the most intensive snowmelt increase of about 3.0 mm/yr in the upstream of Tarim river basin (UTA) but decrease of about -1.4 mm/yr in the upstream of Mekong river basin (UME) due to the interacting impacts of temperature and precipitation. Significant increasing trend of snowmelt in spring shown in the UTA may benefit the local water use for irrigation etc.

The Karakoram/Western Tibetan vortex: seasonal and year-to-year variability

NASA Astrophysics Data System (ADS)

Li, Xiao-Feng; Fowler, Hayley J.; Forsythe, Nathan; Blenkinsop, Stephen; Pritchard, David

2018-02-01

The "Karakoram Vortex" (KV), hereafter also referred to as the "Western Tibetan Vortex" (WTV), has recently been recognized as a large-scale atmospheric circulation system related to warmer (cooler) near-surface and mid-lower troposphere temperatures above the Karakoram in the western Tibetan Plateau (TP). It is characterized by a deep, anti-cyclonic (cyclonic) wind anomaly associated with higher (lower) geopotential height in the troposphere, during winter and summer seasons. In this study, we further investigate the seasonality and basic features of the WTV in all four seasons, and explore its year-to-year variability and influence on regional climate. We find the WTV accounts for the majority of year-to-year circulation variability over the WTP as it can explain over 50% ({R^2} ≥slant 0.5 ) variance of the WTP circulation on multiple levels throughout the troposphere, which declines towards the eastern side of the TP in most seasons. The WTV is not only more (less) active but also has a bigger (smaller) domain area, with a deeper (shallower) structure, in winter and spring (summer and autumn). We find that the WTV is sensitive to both the location and intensity of the Subtropical Westerly Jet (SWJ), but the relationship is highly dependent on the climatological mean location of SWJ axes relative to the TP in different seasons. We also show that the WTV significantly modulates surface and stratospheric air temperatures, north-south precipitation patterns and total column ozone surrounding the western TP. As such, the WTV has important implications for the understanding of atmospheric, hydrological and glaciological variability over the TP.

Experimental manipulation of TN:TP ratiossuppress cyanobacterial biovolume and microcystinconcentration in large-scale in situ mesocosms

USGS Publications Warehouse

Harris, Theodore D.; Wilhelm, Frank M.; Graham, Jennifer L.; Loftin, Keith A.

2014-01-01

A global dataset was compiled to examine relations between the total nitrogen to total phosphorus ratio (TN:TP) and microcystin concentration in lakes and reservoirs. Microcystin concentration decreased as TN:TP ratios increased, suggesting that manipulation of the TN:TP ratio may reduce microcystin concentrations. This relationship was experimentally tested by adding ammonium nitrate to increase the TN:TP ratio in large-scale (70 m3), in situ mesocosms located in a eutrophic reservoir that routinely experiences toxic blooms of cyanobacteria. At a TN:TP ratio >75:1, chlorophytes dominated the phytoplankton community in the mesocosms, while cyanobacterial biovolume was significantly reduced and microcystin was not detected. In contrast, the unmanipulated reservoir was dominated by cyanobacteria, and microcystin was detected. Secchi depths were 1.1 to 1.8 times greater in the mesocosms relative to the reservoir. Cladoceran zooplankton had a larger body size (0.14 mm on average) in the mesocosms compared to conspecifics in the reservoir, which was likely related to the higher quality food. Combined, these empirical and experimental data indicate that although nutrient addition is counterintuitive to current cyanobacteria management practices, increasing the TN:TP ratio by adding nitrogen may be a potential short-term management strategy to reduce cyanobacteria and cyanotoxins when other alternatives (e.g., phosphorus reduction) are not possible. Additional experimental studies with careful controls are needed to define best management practices and identify any potential unintended consequences before nitrogen addition is implemented as a lake and reservoir management practice.

Symmetric Electrode Spanning Narrows the Excitation Patterns of Partial Tripolar Stimuli in Cochlear Implants.

PubMed

Luo, Xin; Wu, Ching-Chih

2016-12-01

In cochlear implants (CIs), standard partial tripolar (pTP) mode reduces current spread by returning a fraction of the current to two adjacent flanking electrodes within the cochlea. Symmetric electrode spanning (i.e., separating both the apical and basal return electrodes from the main electrode by one electrode) has been shown to increase the pitch of pTP stimuli, when the ratio of intracochlear return current was fixed. To explain the pitch increase caused by symmetric spanning in pTP mode, this study measured the electrical potentials of both standard and symmetrically spanned pTP stimuli on a main electrode EL8 in five CI ears using electrical field imaging (EFI). In addition, the spatial profiles of evoked compound action potentials (ECAP) and the psychophysical forward masking (PFM) patterns were also measured for both stimuli. The EFI, ECAP, and PFM patterns of a given stimulus differed in shape details, reflecting the different levels of auditory processing and different ratios of intracochlear return current across the measurement methods. Compared to the standard pTP stimuli, the symmetrically spanned pTP stimuli significantly reduced the areas under the curves of the normalized EFI and PFM patterns, without shifting the pattern peaks and centroids (both around EL8). The more focused excitation patterns with symmetric spanning may have caused the previously reported pitch increase, due to an interaction between pitch and timbre perception. Being able to reduce the spread of excitation, pTP mode symmetric spanning is a promising stimulation strategy that may further increase spectral resolution and frequency selectivity with CIs.

[Inversion Model and Daily Variation of Total Phosphorus Concentrations in Taihu Lake Based on GOCI Data].

PubMed

Du, Cheng-gong; Li, Yun-mei; Wang, Qiao; Zhu, Li; Lü, Heng

2016-03-15

The TP concentration is an important index of water quality and an important influencing factor of eutrophication and algae blooms. Remote sensing technology has advantages of wide scope and high time limited efficacy. Monitoring the concentration of TP by satellite remote sensing is important for the study of water quality and eutrophication. In situ datasets collected during the three times of experiments in Taihu Lake between 2013 and 2014 were used to develop the TP inversion model based on GOCI data. The GOCI data in spring, summer, autumn and winter in 2014 were selected to analyze the time and space changes of TP concentration in Taihu Lake. The results showed that the TP algorithm was built up based on the variables, which was to use the eight band combination of GOCI data as variable, and build model using Multi factor linear regression method. The algorithm achieved more accurate TP estimation with R² = 0.898, MAPE = 14.296%, RMSE = 0.026 mg · L⁻¹. Meantime, a analysis on the precision of the model by using the measured sample points and the synchronous satellite images with MAPE = 33.642%, 22.551%, RMSE = 0.076 mg · L⁻¹, 0.028 mg · L⁻¹ on August 5, 2014 and October 24, 2014. Through the analysis of the 30 images on the four days of the four seasons, it showed that the absolute concentration of total phosphorus was different in different seasons. But temporal and spatial distribution of total phosphorus concentration was similar in the morning and afternoon. In spatial distribution, the TP concentration in Meiliang Bay, Zhushan Bay, Gonghu Bay, Xiaomei Port and Changdou Port in the southwest coast was at a continuously high position. The TP concentration change in different regions was influenced by wind direction, wind speed and other factors. The TP concentration highest in the morning, and then gradually decreased, this phenomenon reflected that the TP concentration was affected by temperature and light.

Effect of rye bread enriched with tomato pomace on fat absorption and lipid metabolism in rats fed a high-fat diet.

PubMed

Bajerska, Joanna; Chmurzynska, Agata; Mildner-Szkudlarz, Sylwia; Drzymała-Czyż, Sławomira

2015-07-01

Tomato pomace (TP), obtained as a residue of tomato processing, was used to enrich rye bread (RB). The sensory profile of this functional bread (RB+TP) was characterised, and its fat absorption and lipid metabolism properties in high-fat-fed rats were studied. Intake of the HF diet containing RB, RB+TP, or TP alone increased faecal energy and fat excretion, but did not affect animal growth or visceral fat weight. Both RB and RB+TP diminished the negative impact of the HF diet, lowering the atherogenic index of plasma (AIP) and the total liver lipid contents by 31.6% and 24%, respectively. The experimental diets had no effect on liver S-adenosylhomocysteine (SAH) concentrations or on the S-adenosylmethionine (SAM) to SAH ratio, though the lowest SAM levels were observed in the HF+TP group. No significant differences were detected in blood homocysteine, triglycerides, glucose or insulin levels. Although RB+TP incorporated into a HF diet may lead to a decrease in AIP and total liver lipid content, this effect does not depend on the components of TP, but rather on the RB ingredients. However, pure TP, in the doses used in this study, may potentially play a role in the energy balance via faecal loss of lipids. © 2014 Society of Chemical Industry.

Dioxygen activation by non-adiabatic oxidative addition to a single metal center [O 2 activation by non-adiabatic oxidative addition to a single metal center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akturk, Eser S.; Yap, Glenn P. A.; Theopold, Klaus H.

2015-10-16

A chromium(I) dinitrogen complex reacts rapidly with O 2 to form the mononuclear dioxo complex [Tp tBu,MeCr V(O) 2] (Tp tBu,Me=hydrotris(3- tert-butyl-5-methylpyrazolyl)borate), whereas the analogous reaction with sulfur stops at the persulfido complex [Tp tBu,MeCr III(S 2)]. The transformation of the putative peroxo intermediate [Tp tBu,MeCr III(O 2)] (S= 3/ 2) into [Tp tBu,MeCr V(O) 2] (S= 1/ 2) is spin-forbidden. The minimum-energy crossing point for the two potential energy surfaces has been identified. Finally, although the dinuclear complex [(Tp tBu,MeCr) 2(μ-O) 2] exists, mechanistic experiments suggest that O 2 activation occurs on a single metal center, by an oxidativemore » addition on the quartet surface followed by crossover to the doublet surface.« less

Linking Atmospheric Pollution to Cryospheric Changes over the Third Pole

NASA Astrophysics Data System (ADS)

Kang, S.; Zhang, Q.; Ji, Z.; Li, Y.; Chen, J.; Zhang, G.; Li, C.; Cong, Z.; Chen, P.; Guo, J.; Huang, J.; Tripathee, L.; Rupakheti, D.; Li, X.; Zhang, Y.; Panday, A. K.; Rupakheti, M.

2016-12-01

Known as "the Third Pole" (TP), the Tibetan Plateau and surrounding mountains hold the largest aggregate of glaciers outside the pole regions. Recent monitoring and projection indicated an accelerated glacier decline and increasing glacier runoff. The long-range transport of South Asian atmospheric pollutants, including light absorbing impurities (LAIs) such as black carbon (BC) and mineral dust (MD), can absorb the solar radiation in the atmosphere and reduce albedo after being deposited onto the cryosphere, thereby promoting glacier and snow melt. A coordinated atmospheric pollution monitoring network has been launched covering the TP with emphasis on trans-Himalayan transects since 2013. TSP were collected for 24h at an interval of 3-6 days. BC/OC, polycyclic aromatic hydrocarbons (PAHs) and heavy metals were measured. Results reveal a consistent decrease in almost all analyzed parameters from south to north across the Himalayas. Geochemical signatures of carbonaceous aerosols indicate dominant sources of biomass burning and vehicle exhaust, in line with results of PAHs. Integrated analysis of satellite images and air mass trajectories suggest that the trans-boundary air pollution occurred episodically and concentrated in pre-monsoon seasons via upper air circulation, through-valley wind, and local convection. Simulation results showed that carbonaceous aerosols produced positive/negative shortwave radiative forcing in the atmosphere/ground surface. Aerosols increased surface air temperatures by 0.1-0.5° over the TP and decreased temperatures in South Asia during the monsoon season. Surface snow/ice samples were collected from benchmark glaciers to estimate the impacts of LAIs on glacier melt with model assistance. BC (37%) and MD (32%) contribute to the summer melting of Laohugou Glacier in the northern TP. MD (38%) contributed more glacier melt than BC (11%) on Zhadang Glacier in the southern TP. In the southeastern TP, BC and MD contribute to 30% of the total glacier melt, up to 350 mm w.e. yr-1. The monitoring network and ongoing studies point to trans-boundary pollution as an increasing stressor for the TP environment, and highlighted the link between atmospheric pollution and cryospheric changes as well as other surface ecosystems over high mountain regions.

Data Assimilation Experiments using Quality Controlled AIRS Version 5 Temperature Soundings

NASA Technical Reports Server (NTRS)

SUsskind, Joel

2008-01-01

The AIRS Science Team Version 5 retrieval algorithm has been finalized and is now operational at the Goddard DAAC in the processing (and reprocessing) of all AIRS data. The AIRS Science Team Version 5 retrieval algorithm contains two significant improvements over Version 4: 1) Improved physics allows for use of AIRS observations in the entire 4.3 pm C02 absorption band in the retrieval of temperature profile T(p) during both day and night. Tropospheric sounding 15 pm C02 observations are now used primarily in the generation of cloud cleared radiances Ri. This approach allows for the generation of accurate values of Ri and T(p) under most cloud conditions. 2) Another very significant improvement in Version 5 is the ability to generate accurate case-by-case, level-by-level error estimates for the atmospheric temperature profile, as well as for channel-by- channel error estimates for Ri. These error estimates are used for quality control of the retrieved products. We have conducted forecast impact experiments assimilating AIRS temperature profiles with different levels of quality control using the NASA GEOS-5 data assimilation system. Assimilation of quality controlled T(p) resulted in significantly improved forecast skill compared to that obtained from analyses obtained when all data used operationally by NCEP, except for AIRS data, is assimilated. We also conducted an experiment assimilating AIRS radiances uncontaminated by clouds, as done Operationally by ECMWF and NCEP. Forecasts resulting from assimilated AIRS radiances were of poorer quality than those obtained assimilating AIRS temperatures.

Southern Hemisphere origins for interannual variations of Tibetan Plateau snow cover in boreal summer

NASA Astrophysics Data System (ADS)

Wu, Z.

2017-12-01

The climate response to the Tibetan Plateau (TP) snow cover (TPSC) has been receiving extensive concern. However, relatively few studies have devoted to revealing the potential factors that can contribute to the TPSC variability on the interannual time scale. Especially during the boreal summer, snow cover can persist over the TP at high elevations, which exerts profound influences on the local and remote climate change. The present study finds that May Southern Hemisphere (SH) annular mode (SAM), the dominating mode of atmospheric circulation variability in the SH extratropics, exhibits a significant positive relationship with the boreal summer TPSC interannual variability. Observational analysis and numerical experiments manifest that the signal of May SAM can be "prolonged" by a meridional Indian Ocean tripole (IOT) sea surface temperature anomaly (SSTA) via atmosphere-ocean interaction. The IOT SSTA pattern persists into the following summer and excites anomalous local-scale zonal vertical circulation. Subsequently, a positive (or negative) tropical dipole rainfall (TDR) mode is induced with deficient (or sufficient) precipitation in tropical western Indian Ocean and sufficient (or deficient) precipitation in eastern Indian Ocean-Maritime continent. Rossby wave source diagnosis reveals that the wave energies, generated by the latent heat release of the TDR mode, propagate northward into western TP. As a response, abnormal cyclonic circulation and upward movement are triggered and prevail over western TP, providing favorable dynamical conditions for more TPSC, and vice versa. Hence, the IOT SSTA plays an "ocean bridge" role and the TDR mode acts as an "atmosphere bridge" role in the process of May SAM impacting the following summer TPSC variability. The results of our work may provide new insight about the cross-equatorial propagation of the SAM influence. Keywords Southern Hemisphere annular mode; Tibetan Plateau snow cover; Rossby wave source

Potential Application of Shallow Bed Wetland Roof systems for green urban cities

NASA Astrophysics Data System (ADS)

Bui, X. T.

2016-12-01

This study aims to investigate the growth, nutrient uptake, domestic wastewater treatment, green (leaf) area and heat reduction of four shallow subsurface flow wetland roof (WR) systems with four different new local plants. Selected species included Cyperus Javanicus Hot (WR1), Eleusine Indica (L.) Gaertn (WR2), Struchium Sparganophorum (L.) Kuntze (WR3) and Kyllinga Brevifolia Rottb (WR4). These systems were operated during 61 days at hydraulic loading rates of 353 - 403 m3/ha.day. The biomass growth of 4.9-73.7g fresh weight/day, and 0.8-11.4 g dry weight/day were observed. The nutrient accumulation according to dry biomass achieved 0.25-2.14% of total nitrogen (TN) and 0.13-1.07% of total phosphorus (TP). The average COD, TN and TP removal was 61-79%; 54-81% and 62-83%, which corresponding to 27-33 kg COD/ha.day, 10-14 kg TN/ha.day and 0.4-0.5 kg TP/ha.day, respectively. The WR4 system achieved the highest COD and TN removal among the WRs. The TP removal efficiency showed an insignificant difference for the systems. Consequently, the treated water quality complied with the Vietnam standard limits (QCVN 14:2008, level B). The green area of the four plants varied between 63-92 m2 green leaf/m2 WR. The WR4 was the highest green area. Moreover, the results also showed the temperature under the flat roof was 1-3°C lower than that of the ambient air. In summary, wetland roof is a promising technology, which not only owns the effective domestic wastewater treatment capacity, but also contributes to green urban with several above benefits.

Short circuit of water vapor and polluted air to the global stratosphere by convective transport over the Tibetan Plateau

PubMed Central

Fu, Rong; Hu, Yuanlong; Wright, Jonathon S.; Jiang, Jonathan H.; Dickinson, Robert E.; Chen, Mingxuan; Filipiak, Mark; Read, William G.; Waters, Joe W.; Wu, Dong L.

2006-01-01

During boreal summer, much of the water vapor and CO entering the global tropical stratosphere is transported over the Asian monsoon/Tibetan Plateau (TP) region. Studies have suggested that most of this transport is carried out either by tropical convection over the South Asian monsoon region or by extratropical convection over southern China. By using measurements from the newly available National Aeronautics and Space Administration Aura Microwave Limb Sounder, along with observations from the Aqua and Tropical Rainfall-Measuring Mission satellites, we establish that the TP provides the main pathway for cross-tropopause transport in this region. Tropospheric moist convection driven by elevated surface heating over the TP is deeper and detrains more water vapor, CO, and ice at the tropopause than over the monsoon area. Warmer tropopause temperatures and slower-falling, smaller cirrus cloud particles in less saturated ambient air at the tropopause also allow more water vapor to travel into the lower stratosphere over the TP, effectively short-circuiting the slower ascent of water vapor across the cold tropical tropopause over the monsoon area. Air that is high in water vapor and CO over the Asian monsoon/TP region enters the lower stratosphere primarily over the TP, and it is then transported toward the Asian monsoon area and disperses into the large-scale upward motion of the global stratospheric circulation. Thus, hydration of the global stratosphere could be especially sensitive to changes of convection over the TP. PMID:16585523

Assimilation of Quality Controlled AIRS Temperature Profiles using the NCEP GFS

NASA Technical Reports Server (NTRS)

Susskind, Joel; Reale, Oreste; Iredell, Lena; Rosenberg, Robert

2013-01-01

We have previously conducted a number of data assimilation experiments using AIRS Version-5 quality controlled temperature profiles as a step toward finding an optimum balance of spatial coverage and sounding accuracy with regard to improving forecast skill. The data assimilation and forecast system we used was the Goddard Earth Observing System Model , Version-5 (GEOS-5) Data Assimilation System (DAS), which represents a combination of the NASA GEOS-5 forecast model with the National Centers for Environmental Prediction (NCEP) operational Grid Point Statistical Interpolation (GSI) global analysis scheme. All analyses and forecasts were run at a 0.5deg x 0.625deg spatial resolution. Data assimilation experiments were conducted in four different seasons, each in a different year. Three different sets of data assimilation experiments were run during each time period: Control; AIRS T(p); and AIRS Radiance. In the "Control" analysis, all the data used operationally by NCEP was assimilated, but no AIRS data was assimilated. Radiances from the Aqua AMSU-A instrument were also assimilated operationally by NCEP and are included in the "Control". The AIRS Radiance assimilation adds AIRS observed radiance observations for a select set of channels to the data set being assimilated, as done operationally by NCEP. In the AIRS T(p) assimilation, all information used in the Control was assimilated as well as Quality Controlled AIRS Version-5 temperature profiles, i.e., AIRS T(p) information was substituted for AIRS radiance information. The AIRS Version-5 temperature profiles were presented to the GSI analysis as rawinsonde profiles, assimilated down to a case-by-case appropriate pressure level p(sub best) determined using the Quality Control procedure. Version-5 also determines case-by-case, level-by-level error estimates of the temperature profiles, which were used as the uncertainty of each temperature measurement. These experiments using GEOS-5 have shown that forecasts resulting from analyses using the AIRS T(p) assimilation system were superior to those from the Radiance assimilation system, both with regard to global 7 day forecast skill and also the ability to predict storm tracks and intensity.

A multi-scale automatic observatory of soil moisture and temperature served for satellite product validation in Tibetan Plateau

NASA Astrophysics Data System (ADS)

Tang, S.; Dong, L.; Lu, P.; Zhou, K.; Wang, F.; Han, S.; Min, M.; Chen, L.; Xu, N.; Chen, J.; Zhao, P.; Li, B.; Wang, Y.

2016-12-01

Due to the lack of observing data which match the satellite pixel size, the inversion accuracy of satellite products in Tibetan Plateau(TP) is difficult to be evaluated. Hence, the in situ observations are necessary to support the calibration and validation activities. Under the support of the Third Tibetan Plateau Atmospheric Scientific Experiment (TIPEX-III) projec a multi-scale automatic observatory of soil moisture and temperature served for satellite product validation (TIPEX-III-SMTN) were established in Tibetan Plateau. The observatory consists of two regional scale networks, including the Naqu network and the Geji network. The Naqu network is located in the north of TP, and characterized by alpine grasslands. The Geji network is located in the west of TP, and characterized by marshes. Naqu network includes 33 stations, which are deployed in a 75KM*75KM region according to a pre-designed pattern. At Each station, soil moisture and temperature are measured by five sensors at five soil depths. One sensor is vertically inserted into 0 2 cm depth to measure the averaged near-surface soil moisture and temperature. The other four sensors are horizontally inserted at 5, 10, 20, and 30 cm depths, respectively. The data are recorded every 10 minutes. A wireless transmission system is applied to transmit the data in real time, and a dual power supply system is adopted to keep the continuity of the observation. The construction of Naqu network has been accomplished in August, 2015, and Geji network will be established before Oct., 2016. Observations acquired from TIPEX-III-SMTN can be used to validate satellite products with different spatial resolution, and TIPEX-III-SMTN can also be used as a complementary of the existing similar networks in this area, such as CTP-SMTMN (the multiscale Soil Moistureand Temperature Monitoring Network on the central TP) . Keywords: multi-scale soil moisture soil temperature, Tibetan Plateau Acknowledgments: This work was jointly supported by CMA Special Fund for Scientific Research in the Public Interest (Grant No. GYHY201406001, GYHY201206008-01), and Climate change special fund (QHBH2014)'

Storage of Fruits and Vegetables in Refrigerator Increases their Phenolic Acids but Decreases the Total Phenolics, Anthocyanins and Vitamin C with Subsequent Loss of their Antioxidant Capacity

PubMed Central

Patel, Nilesh J.; Talati, Jayant G.

2017-01-01

It is of paramount importance for consumers, scientists and industrialists to understand how low-temperature storage of food items affects their bioactive compounds and properties. This study evaluated the effects of cold storage on total phenolics (TP), phenolic acids profile (PA), total anthocyanins (TA), total ascorbic acid (Vit. C) and antioxidant activity (AA) of 19 fruits and vegetables, collected from local Indian markets and stored in refrigerator (4 °C) during 15 days. Content of TP was highest in dill and amaranth and decreased (up to 29.67%) with storage. Leafy vegetables (amaranth, dill, onion, fenugreek and spinach) contained higher amounts of the 12 PA revealed by UPLC-UV; ellagic, gallic, sinapic and vanillic acids levels were the highest; chlorogenic acid (ρ = 0.423), syringic acid (ρ = 0.403) and sinapic acid (ρ = 0.452) mostly correlated with TP; and the PA increased during storage. Highest contents of Vit C estimated by AOAC, DCPIP and DNP methods were found in amaranth, dill and pomegranate, and decreased with storage. Pomegranate showed highest TA levels and low-temperature storage did not significantly increase TA, which was the largest contributor of TP in fruits and vegetables (ρ = 0.661). Storage induced a drastic decrease of AA, which mostly correlated with TP (ρ = 0.808, 0.690 and 0.458 for DPPH, ABTS and FRAP assays, respectively). Spearman’s correlation confirmed by principal component analysis demonstrated that dill, pomegranate and amaranth had the highest overall antioxidant capacity, whereas orange juice and carrot showed the lowest. The results provide support for a key-role of TP, followed by Vit. C and TA in antioxidant capacity of fruits and vegetables, which could be interesting dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress. PMID:28737734

Storage of Fruits and Vegetables in Refrigerator Increases their Phenolic Acids but Decreases the Total Phenolics, Anthocyanins and Vitamin C with Subsequent Loss of their Antioxidant Capacity.

PubMed

Galani, Joseph H Y; Patel, Jalpesh S; Patel, Nilesh J; Talati, Jayant G

2017-07-24

It is of paramount importance for consumers, scientists and industrialists to understand how low-temperature storage of food items affects their bioactive compounds and properties. This study evaluated the effects of cold storage on total phenolics (TP), phenolic acids profile (PA), total anthocyanins (TA), total ascorbic acid (Vit. C) and antioxidant activity (AA) of 19 fruits and vegetables, collected from local Indian markets and stored in refrigerator (4 °C) during 15 days. Content of TP was highest in dill and amaranth and decreased (up to 29.67%) with storage. Leafy vegetables (amaranth, dill, onion, fenugreek and spinach) contained higher amounts of the 12 PA revealed by UPLC-UV; ellagic, gallic, sinapic and vanillic acids levels were the highest; chlorogenic acid (ρ = 0.423), syringic acid (ρ = 0.403) and sinapic acid (ρ = 0.452) mostly correlated with TP; and the PA increased during storage. Highest contents of Vit C estimated by AOAC, DCPIP and DNP methods were found in amaranth, dill and pomegranate, and decreased with storage. Pomegranate showed highest TA levels and low-temperature storage did not significantly increase TA, which was the largest contributor of TP in fruits and vegetables (ρ = 0.661). Storage induced a drastic decrease of AA, which mostly correlated with TP (ρ = 0.808, 0.690 and 0.458 for DPPH, ABTS and FRAP assays, respectively). Spearman's correlation confirmed by principal component analysis demonstrated that dill, pomegranate and amaranth had the highest overall antioxidant capacity, whereas orange juice and carrot showed the lowest. The results provide support for a key-role of TP, followed by Vit. C and TA in antioxidant capacity of fruits and vegetables, which could be interesting dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress.

Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

PubMed

Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

2016-02-01

Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

Formation Conditions of Basalts at Gale Crater, Mars from ChemCam Analyses

NASA Astrophysics Data System (ADS)

Filiberto, J.; Bridges, J.; Dasgupta, R.; Edwards, P.; Schwenzer, S. P.; Wiens, R. C.

2015-12-01

Surface igneous rocks shed light onto the chemistry, tectonic, and thermal state of planetary interiors. For the purpose of comparative planetology, therefore, it is critical to fully utilize the compositional diversity of igneous rocks for different terrestrial planets. For Mars, igneous float rocks and conglomerate clasts at Gale Crater, as analyzed by ChemCam [1] using a new calibration [2], have a larger range in chemistry than have been analyzed at any other landing site or within the Martian meteorite collection [3, 4]. These rocks may reflect different conditions of melting within the Martian interior than any previously analyzed basalts. Here we present new formation conditions for basaltic and trachybasalt/dioritic rocks at Gale Crater from ChemCam analyses following previous procedures [5, 6]. We then compare these estimates of basalt formation with previous estimates for rocks from the Noachian (Gusev Crater, Meridiani Planum, and a clast in the NWA 7034 meteorite [5, 6]), Hesperian (surface volcanics [7]), and Amazonian (surface volcanics and shergottites [7-8]), to calculate an average mantle potential temperature for different Martian epochs and investigate how the interior of Mars has changed through time. Finally, we will compare Martian mantle potential temperatures with petrologic estimate of cooling for the Earth. Our calculated estimate for the mantle potential temperature (TP) of rocks at Gale Crater is 1450 ± 45 °C which is within error of previous estimates for Noachian aged rocks [5, 6]. The TP estimates for the Hesperian and Amazonian, based on orbital analyses of the crust [7], are lower in temperature than the estimates for the Noachian. Our results are consistent with simple convective cooling of the Martian interior. [1] Wiens R. et al. (2012) Space Sci Rev 170. 167-227. [2] Anderson R. et al. (2015) LPSC. Abstract #7031. [3] Schmidt M.E. et al. (2014) JGRP 2013JE004481. [4] Sautter V. et al. (2014) JGRP 2013JE004472. [5] Filiberto J. and Dasgupta R. (2011) EPSL 304. 527-537. [6] Filiberto J. and Dasgupta R. (2015) JGRP 2014JE004745. [7] Baratoux D. et al. (2011) Nature 472. 338-341. [8] Musselwhite D.S. et al. (2006) MaPS 41. 1271-1290.

Performance Evaluation of a Novel Chemiluminescence Assay Detecting Treponema Pallidum Antibody as a Syphilis Screening Method.

PubMed

Chen, Qixia; An, Jingna; Rao, Chenli; Wang, Tingting; Li, Dongdong; Feng, Shu; Tao, Chuanmin

2016-01-01

Syphilis is a major concern to global public health with increasing incidence. So its screening test should have sufficient sensitivity and specificity. We evaluated the performance of the Lumipulse G TP-N assay detection for syphilis screening and compared it with the InTec ELISA test kit for TP, which is widely used. Samples of several patient groups including 133 clinical and serologically characterized syphilitic sera, 175 samples containing potentially interfering agents, and 2290 unselected samples submitted for routine screening were detected by both the Lumipulse G TP-N assay and the InTec ELISA test kit for TP. Inconsistent samples were confirmed by RecomLine Treponema IgG, IgM immunoblot. Coefficient of variations of the Lumipulseo G TP-N assay at both levels were below 5% and of the InTec ELISA test kit for TP both over 5%. The sensitivity of the Lumipulse G TP-N assay and the InTec ELISA test kit for TP were 100% for all stages of syphilis. The two methods had consistent analytical specificity of 100% (95% CI: 97.21 - 100.00), while the clinical specificity was 100% (95% CI: 99.79 - 100.00) and 99.82% (95% CI: 99.51 - 99.94), respectively. Between them, Spearman's correlation coefficient was 0.455 and kappa value was 0.986. The overall sensitivity and specificity of the Lumipulse G TP-N assay was higher than the InTec ELISA test kit for TP (sensitivity: 100.0 versus 99.5, specificity: 100.0 versus 99.8). The automated Lumipulse G TP-N assay demonstrated excellent diagnostic sensitivity and specificity when evaluated as a screening test for syphilis. Thus, it can be an alternative to the treponemal screening test.

The Long Noncoding RNA TP73-AS1 Interacted with miR-124 to Modulate Glioma Growth by Targeting Inhibitor of Apoptosis-Stimulating Protein of p53.

PubMed

Xiao, Shuai; Wang, Rensheng; Wu, Xiangwei; Liu, Wen; Ma, Shanshan

2018-02-01

P73 antisense RNA 1T (non-protein coding), known as TP73-AS1 or PDAM, is a long noncoding RNA (lncRNA), which may regulate apoptosis by regulation of p53-dependent antiapoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In this study, the effect of TP73-AS1 in human brain glioma cell lines and clinical tumor samples was detected so as to reveal its role and function. In this study, TP73-AS1 was specifically upregulated in brain glioma cell lines and promoted glioma cell growth through targeting miR-124. TP73-AS1 knocking down suppressed human brain glioma cell proliferation, invasion, and metastasis in vitro. The inhibitory effect of TP73-AS1 knocking down on glioma cell proliferation and invasion could partly be restored by miR-124 inhibition. In addition, miR-124-dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) regulation was required in TP73-AS1-induced brain glioma cell growth. Data from this study revealed that TP73-AS1 inhibited the brain glioma growth and metastasis as a competing endogenous RNA (ceRNA) through miR-124-dependent iASPP regulation. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting brain glioma proliferation and metastasis and a potential target for human brain glioma treatment.

Phase-coexistence and thermal hysteresis in samples comprising adventitiously doped MnAs nanocrystals: programming of aggregate properties in magnetostructural nanomaterials.

PubMed

Zhang, Yanhua; Regmi, Rajesh; Liu, Yi; Lawes, Gavin; Brock, Stephanie L

2014-07-22

Small changes in the synthesis of MnAs nanoparticles lead to materials with distinct behavior. Samples prepared by slow heating to 523 K (type-A) exhibit the characteristic magnetostructural transition from the ferromagnetic hexagonal (α) to the paramagnetic orthorhombic (β) phase of bulk MnAs at Tp = 312 K, whereas those prepared by rapid nucleation at 603 K (type-B) adopt the β structure at room temperature and exhibit anomalous magnetic properties. The behavior of type-B nanoparticles is due to P-incorporation (up to 3%), attributed to reaction of the solvent (trioctylphosphine oxide). P-incorporation results in a decrease in the unit cell volume (∼1%) and shifts Tp below room temperature. Temperature-dependent X-ray diffraction reveals a large region of phase-coexistence, up to 90 K, which may reflect small differences in Tp from particle-to-particle within the nearly monodisperse sample. The large coexistence range coupled to the thermal hysteresis results in process-dependent phase mixtures. As-prepared type-B samples exhibiting the β structure at room temperature convert to a mixture of α and β after the sample has been cooled to 77 K and rewarmed to room temperature. This change is reflected in the magnetic response, which shows an increased moment and a shift in the temperature hysteresis loop after cooling. The proportion of α present at room temperature can also be augmented by application of an external magnetic field. Both doped (type-B) and undoped (type-A) MnAs nanoparticles show significant thermal hysteresis narrowing relative to their bulk phases, suggesting that formation of nanoparticles may be an effective method to reduce thermal losses in magnetic refrigeration applications.

Pseudogap Behavior of the Nuclear Spin-Lattice Relaxation Rate in FeSe Probed by 77Se-NMR

NASA Astrophysics Data System (ADS)

Shi, Anlu; Arai, Takeshi; Kitagawa, Shunsaku; Yamanaka, Takayoshi; Ishida, Kenji; Böhmer, Anna E.; Meingast, Christoph; Wolf, Thomas; Hirata, Michihiro; Sasaki, Takahiko

2018-01-01

We conducted 77Se-nuclear magnetic resonance studies of the iron-based superconductor FeSe in magnetic fields of 0.6 to 19 T to investigate the superconducting and normal-state properties. The nuclear spin-lattice relaxation rate divided by the temperature (T1T)-1 increases below the structural transition temperature Ts but starts to be suppressed below T*, well above the superconducting transition temperature Tc(H), resulting in a broad maximum of (T1T)-1 at Tp(H). This is similar to the pseudogap behavior in optimally doped cuprate superconductors. Because T* and Tp(H) decrease in the same manner as Tc(H) with increasing H, the pseudogap behavior in FeSe is ascribed to superconducting fluctuations, which presumably originate from the theoretically predicted preformed pair above Tc(H).

Structural, Bioinformatic, and In Vivo Analyses of Two Treponema pallidum Lipoproteins Reveal a Unique TRAP Transporter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deka, Ranjit K.; Brautigam, Chad A.; Goldberg, Martin

2012-05-25

Treponema pallidum, the bacterial agent of syphilis, is predicted to encode one tripartite ATP-independent periplasmic transporter (TRAP-T). TRAP-Ts typically employ a periplasmic substrate-binding protein (SBP) to deliver the cognate ligand to the transmembrane symporter. Herein, we demonstrate that the genes encoding the putative TRAP-T components from T. pallidum, tp0957 (the SBP), and tp0958 (the symporter), are in an operon with an uncharacterized third gene, tp0956. We determined the crystal structure of recombinant Tp0956; the protein is trimeric and perforated by a pore. Part of Tp0956 forms an assembly similar to those of 'tetratricopeptide repeat' (TPR) motifs. The crystal structure ofmore » recombinant Tp0957 was also determined; like the SBPs of other TRAP-Ts, there are two lobes separated by a cleft. In these other SBPs, the cleft binds a negatively charged ligand. However, the cleft of Tp0957 has a strikingly hydrophobic chemical composition, indicating that its ligand may be substantially different and likely hydrophobic. Analytical ultracentrifugation of the recombinant versions of Tp0956 and Tp0957 established that these proteins associate avidly. This unprecedented interaction was confirmed for the native molecules using in vivo cross-linking experiments. Finally, bioinformatic analyses suggested that this transporter exemplifies a new subfamily of TPATs (TPR-protein-associated TRAP-Ts) that require the action of a TPR-containing accessory protein for the periplasmic transport of a potentially hydrophobic ligand(s).« less

TpUB05, a Homologue of the Immunodominant Plasmodium falciparum Protein UB05, Is a Marker of Protective Immune Responses in Cattle Experimentally Vaccinated against East Coast Fever

PubMed Central

Dinga, Jerome Nyhalah; Wamalwa, Mark; Njimoh, Dieudonné Lemuh; Njahira, Moses N.; Djikeng, Appolinaire; Skilton, Rob; Titanji, Vincent Pryde Kehdingha; Pellé, Roger

2015-01-01

Introduction East Coast fever, a devastating disease of cattle, can be controlled partially by vaccination with live T. parva sporozoites. The antigens responsible for conferring immunity are not fully characterized. Recently it was shown that the P. falciparum immunodominant protein UB05 is highly conserved in T. parva, the causative agent of East Coast fever. The aim of the present investigation was to determine the role of the homologue TpUB05 in protective immunity to East Coast fever. Methods The cloning, sequencing and expression of TpUB05 were done according to standard protocols. Bioinformatics analysis of TpUB05 gene was carried out using algorithms found in the public domain. Polyclonal antiserum against recombinant TpUB05 were raised in rabbits and used for further analysis by Western blotting, ELISA, immunolocalization and in vitro infection neutralization assay. The ability of recombinant TpUB05 (r-TpUB05) to stimulate bovine PBMCs ex-vivo to produce IFN-γ or to proliferate was tested using ELISpot and [3H]-thymidine incorporation assays, respectively. Results All the 20 cattle immunised by the infection and treatment method (ITM) developed significantly higher levels of TpUB05 specific antibodies (p<0.0001) compared to the non-vaccinated ones. Similarly, r-TpUB05 highly stimulated bovine PMBCs from 8/12 (67%) of ITM-immunized cattle tested to produce IFN-γ and proliferate (p< 0.029) as compared to the 04 naїve cattle included as controls. Polyclonal TpUB05 antiserum raised against r-TpUB05 also marginally inhibited infection (p < 0.046) of bovine PBMCs by T. parva sporozoites. In further experiments RT-PCR showed that the TpUB05 gene is expressed by the parasite. This was confirmed by immunolocalization studies which revealed TpUB05 expression by schizonts and piroplasms. Bioinformatics analysis also revealed that this antigen possesses two transmembrane domains, a N-glycosylation site and several O-glycosylation sites. Conclusion It was concluded that TpUB05 is a potential marker of protective immunity in ECF worth investigating further. PMID:26053064

TpUB05, a Homologue of the Immunodominant Plasmodium falciparum Protein UB05, Is a Marker of Protective Immune Responses in Cattle Experimentally Vaccinated against East Coast Fever.

PubMed

Dinga, Jerome Nyhalah; Wamalwa, Mark; Njimoh, Dieudonné Lemuh; Njahira, Moses N; Djikeng, Appolinaire; Skilton, Rob; Titanji, Vincent Pryde Kehdingha; Pellé, Roger

2015-01-01

East Coast fever, a devastating disease of cattle, can be controlled partially by vaccination with live T. parva sporozoites. The antigens responsible for conferring immunity are not fully characterized. Recently it was shown that the P. falciparum immunodominant protein UB05 is highly conserved in T. parva, the causative agent of East Coast fever. The aim of the present investigation was to determine the role of the homologue TpUB05 in protective immunity to East Coast fever. The cloning, sequencing and expression of TpUB05 were done according to standard protocols. Bioinformatics analysis of TpUB05 gene was carried out using algorithms found in the public domain. Polyclonal antiserum against recombinant TpUB05 were raised in rabbits and used for further analysis by Western blotting, ELISA, immunolocalization and in vitro infection neutralization assay. The ability of recombinant TpUB05 (r-TpUB05) to stimulate bovine PBMCs ex-vivo to produce IFN-γ or to proliferate was tested using ELISpot and [3H]-thymidine incorporation assays, respectively. All the 20 cattle immunised by the infection and treatment method (ITM) developed significantly higher levels of TpUB05 specific antibodies (p<0.0001) compared to the non-vaccinated ones. Similarly, r-TpUB05 highly stimulated bovine PMBCs from 8/12 (67%) of ITM-immunized cattle tested to produce IFN-γ and proliferate (p< 0.029) as compared to the 04 naїve cattle included as controls. Polyclonal TpUB05 antiserum raised against r-TpUB05 also marginally inhibited infection (p < 0.046) of bovine PBMCs by T. parva sporozoites. In further experiments RT-PCR showed that the TpUB05 gene is expressed by the parasite. This was confirmed by immunolocalization studies which revealed TpUB05 expression by schizonts and piroplasms. Bioinformatics analysis also revealed that this antigen possesses two transmembrane domains, a N-glycosylation site and several O-glycosylation sites. It was concluded that TpUB05 is a potential marker of protective immunity in ECF worth investigating further.

An 80-year summer temperature history from the Xiao Dongkemadi ice core in the central Tibetan Plateau and its association with atmospheric circulation

NASA Astrophysics Data System (ADS)

Li, Xiangying; Ding, Yongjian; Yu, Zhongbo; Mika, Sillanpää; Liu, Shiyin; Shangguan, Donghui; Lu, Chengyang

2015-02-01

The climate significance of oxygen isotopes from the central Tibetan Plateau (cTP) ice cores is a debated issue because of large scale atmospheric circulation. A high-resolution δ18O record was recovered from the Xiao Dongkemadi (XD) ice core, which expanded the spatial coverage of δ18O data in this region. Annual average δ18O correlated significantly with nearby MJJAS air temperatures, suggesting the δ18O can be used as a proxy to reconstruct regional climate change. The reconstructed temperature anomaly is related to the regional and global warming trends, and the greater warming amplitude since 1970s is related to the elevation dependency of the warming signal. The close relationship of the warming to variations in glacier mass balances and discharge reveal that recent warming has led to obvious glacier shrinkage and runoff increase. Correlation analysis suggests that monsoon and westerly moisture substantially influence the cTP ice core records, along with an increase in their level of contribution to the XD core accumulation in recent decades, and confirms a teleconnection of regional climate of the cTP ice cores with climate parameters in the Indian and North Atlantic Oceans.

Kinetic and thermodynamic selectivity of intermolecular C-H activation at [Tp'Rh(PMe3)]. How does the ancillary ligand affect the metal-carbon bond strength?

PubMed

Jiao, Yunzhe; Morris, James; Brennessel, William W; Jones, William D

2013-10-30

Tp'Rh(PMe3)(CH3)H was synthesized as a precursor to produce the coordinatively unsaturated fragment [Tp'Rh(PMe3)], which reacts with benzene, mesitylene, 3,3-dimethyl-1-butene, 2-methoxy-2-methylpropane, 2-butyne, acetone, pentane, cyclopentane, trifluoroethane, fluoromethane, dimethyl ether, and difluoromethane at ambient temperature to give only one product in almost quantitative yield in each case. All of the complexes Tp'Rh(PMe3)(R)H were characterized by NMR spectroscopy, and their halogenated derivatives were fully characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The active species [Tp'Rh(PMe3)] was also able to activate the alkynyl C-H bond of terminal alkynes to give activation products of the type Tp'Rh(PMe3)(C≡CR)H (R = t-Bu, SiMe3, hexyl, CF3, Ph, p-MeOC6H4, and p-CF3C6H4). The measured relative rhodium-carbon bond strengths display two linear correlations with the corresponding carbon-hydrogen bond strengths, giving a slope of 1.54 for α-unsubstituted hydrocarbons and a slope of 1.71 for substrates with α-substitution. Similar trends of energy correlations were established by DFT calculated metal-carbon bond strengths for the same groups of substrates.

Terpinen-4-ol inhibits colorectal cancer growth via reactive oxygen species

PubMed Central

Nakayama, Ken; Murata, Soichiro; Ito, Hiromu; Iwasaki, Kenichi; Villareal, Myra Orlina; Zheng, Yun-Wen; Matsui, Hirofumi; Isoda, Hiroko; Ohkohchi, Nobuhiro

2017-01-01

Terpinen-4-ol (TP4O) is the main component of the essential oil extracted from Melaleuca alternifolia, known as the tea tree, of the botanical family Myrtaceae. The anticancer effects of TP4O have been reported in several cancer cell lines. Previous reports have demonstrated that TP4O exerts anticancer effects by inducing apoptotic cell death in several cell lines; however, the underlying molecular mechanisms of these effects remain unclear. In the present study, the anticancer effects of TP4O against the colorectal cancer (CRC) cell lines HCT116 and RKO were evaluated using WST-8 and bromodeoxyuridine assays. The mechanism of cell death was investigated by the measurement of caspase-3/7, Annexin V and lactate dehydrogenase release. Reactive oxygen species (ROS) levels induced by TP4O were evaluated by electron spin resonance and quantitative measurement of dihydroethidium. Localization of the ROS derived from mitochondria was observed by confocal inverted microscopy. Protein levels of ROS scavengers were assessed by western blotting analysis. To confirm the role of ROS, cell viability was measured in the presence of antioxidant reagents. In an in vivo xenograft model of ICR-SCID mice implanted with HCT116 cells, 200 mg/kg TP4O was injected locally, and tumor growth was compared with that of the control. TP4O induced apoptotic cell death in HCT116 and RKO cells in a dose-dependent manner, and TP4O also increased the levels of ROS generated by mitochondria. TP4O-induced cell death was rescued by administration of antioxidant regents. In vivo, TP4O inhibited the proliferation of HCT116 xenografts compared with that of the control group. The results of the present study suggest that TP4O induces apoptosis in CRC cells through ROS generation. Furthermore, TP4O is potentially useful for the development of novel therapies against CRC. PMID:28781645

Enhanced Climatic Warming Over the Tibetan Plateau Due to Doubling CO2: A Model Study

NASA Technical Reports Server (NTRS)

Chen, Baode; Chao, Winston C.; Liu, Xiaodong; Lau, William K. M. (Technical Monitor)

2001-01-01

A number of studies have presented the evidences that surface climate change associated with global warming at high elevation sites shows more pronounced warming than at low elevations, i.e. an elevation dependency of climatic warming pointed out that snow-albedo feedback may be responsible for the excessive warming in the Swiss Alps. From an ensemble of climate change experiments of increasing greenhouse gases and aerosols using an air-sea coupled climate model, Eyre and Raw (1999) found a marked elevation dependency of the simulated surface screen temperature increase over the Rocky Mountains. Using almost all available instrumental records, Liu and Chen (2000) showed that the main portion of the Tibetan Plateau (TP) has experienced significant ground temperature warming since the middlebrows, especially in winter, and that there is a tendency for the warming trend to increase with elevation in the TP as well as its surrounding areas. In this paper, we will investigate the mechanism of elevation dependency of climatic warming in the TP by using a high-resolution regional climate model.

Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy.

PubMed

Romero, M T; Cooper, M L; Komisaruk, B R; Bodnar, R J

1988-01-01

Both gender-specific and gonadectomy-specific effects have been observed for the analgesic responses following continuous and intermittent cold-water swims (CCWS and ICWS respectively): female rats display significantly less analgesia than males, and gonadectomized rats display significantly less analgesia than sham-operated controls. The present study evaluated the effects of steroid replacement therapy with testosterone propionate (TP: 2 mg/kg, SC) upon CCWS and ICWS analgesia on the tail-flick and jump tests and hypothermia in sham-operated or gonadectomized male and female rats. Thirty days following surgery, rats received either no treatment, a sesame oil vehicle or TP for 14 days prior to, and then during testing. Relative to the no treatment condition, repeated vehicle injections in sham-operated rats eliminated the gender-specific, but did not affect the gonadectomy-specific effects upon CCWS and ICWS analgesia. TP reversed the deficits in CCWS and ICWS analgesia observed in both castrated and ovariectomized rats on both pain tests. TP only potentiated CCWS analgesia in sham-operated males on the tail-flick test. TP potentiated CCWS and ICWS hypothermia in gonadectomized rats and in male sham-operated rats. These data indicate that gonadal steroids play a major modulatory role in the etiology of swim analgesia, and that the observed gender effects are sensitive to possible adaptational variables.

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

PubMed

Chen, Xia; Sun, Chang-Kai; Han, Guo-Zhu; Peng, Jin-Yong; Li, Ying; Liu, Yan-Xia; Lv, Yuan-Yuan; Liu, Ke-Xin; Zhou, Qin; Sun, Hui-Jun

2009-04-21

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

Potential scenarios for broadening stakeholder involvement in the implementing geological disposal technology platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martell, Meritxell; Bergmans, Anne

This paper analyses the potential for the involvement of different types of stakeholders in the Implementing Geological Disposal Technology Platform (IGD-TP). This analysis was conducted as part of the InSOTEC project, a three-year (2011- 2014) collaborative research project funded under the 7. Euratom Framework Programme (Grant Agreement nr. 269906). In our analysis, we consider the extent to which the IGDTP's practice as regards to stakeholder involvement matches its discourse, and what potential for improvement exists given its structural organisation as a European Technology Platform (ETPs). Technology Platforms (TPs) can be understood as knowledge networks, deliberately set up to influence (research)more » policy in a specific domain. We therefore use knowledge networks as a conceptual approach and look at the IGD-TP as a complex network which includes actors, knowledge and practices across different countries, focusing on a very specific topic (i.e. implementing geological disposal). We compare the way different stakeholders are involved in the IGD-TP to the practice of other ETPs, and explore how the IGD-TP is viewed by its members and by outsiders to the platform Applying Callon's framework of knowledge co-production (1999) we come to define different degrees of interaction between science, society and policy in view of defining research and development (R and D) priorities [1]. Subsequently we describe how these interactions could be conceptualised and interpreted for the IGD-TP. The current approach of the IGDTP can be mainly understood as classical model involving mainly expert stakeholders and scientists. Where there seems to be a good representation among IGD-TP members of industry, research institutes, and some members of the academic community this is not the case for other types of stakeholders, such as public authorities or civil society. At this stage, the overall approach of the IGD-TP would seem to restrict the scope of stakeholder involvement, as it narrows participation down to uniquely technology experts, hindering socio-technical manifestations. Our analysis nevertheless shows that there is room for engaging with a broader range of stakeholders in the field of radioactive waste management, if this is the intention of the IGD-TP. However, this would require a commitment to developing a common knowledge base including other stakeholders through a process of mutual adjustment and negotiation. (authors)« less

Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles.

PubMed

Hou, Jian; Sun, E; Zhang, Zhen-Hai; Wang, Jing; Yang, Lei; Cui, Li; Ke, Zhong-Cheng; Tan, Xiao-Bin; Jia, Xiao-Bin; Lv, Huixia

2017-11-01

The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0.265 ± 0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09 ± 0.09% and 95.67 ± 2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78 ± 0.14 mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC 50 values of PTX-TP-M (3.14 ± 0.85 and 8.28 ± 1.02 μg/mL) were lower than those of PTX solution (5.21 ± 0.93 and 14.53 ± 1.96 μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.

Improving Forecast Skill by Assimilation of Quality Controlled AIRS Version 5 Temperature Soundings

NASA Technical Reports Server (NTRS)

Susskind, Joel; Reale, Oreste

2009-01-01

The AIRS Science Team Version 5 retrieval algorithm has been finalized and is now operational at the Goddard DAAC in the processing (and reprocessing) of all AIRS data. The AIRS Science Team Version 5 retrieval algorithm contains two significant improvements over Version 4: 1) Improved physics allows for use of AIRS observations in the entire 4.3 micron CO2 absorption band in the retrieval of temperature profile T(p) during both day and night. Tropospheric sounding 15 micron CO2 observations are now used primarily in the generation of cloud cleared radiances R(sub i). This approach allows for the generation of accurate values of R(sub i) and T(p) under most cloud conditions. 2) Another very significant improvement in Version 5 is the ability to generate accurate case-by-case, level-by-level error estimates for the atmospheric temperature profile, as well as for channel-by-channel error estimates for R(sub i). These error estimates are used for Quality Control of the retrieved products. We have conducted forecast impact experiments assimilating AIRS temperature profiles with different levels of Quality Control using the NASA GEOS-5 data assimilation system. Assimilation of Quality Controlled T(p) resulted in significantly improved forecast skill compared to that obtained from analyses obtained when all data used operationally by NCEP, except for AIRS data, is assimilated. We also conducted an experiment assimilating AIRS radiances uncontaminated by clouds, as done operationally by ECMWF and NCEP. Forecast resulting from assimilated AIRS radiances were of poorer quality than those obtained assimilating AIRS temperatures.

Tension pneumocephalus following suboccipital sitting craniotomy in the pediatric population.

PubMed

Daszkiewicz, P; Dziedzic, D

Sitting craniotomy often results in entrapment of air in fluid-filled intracranial cavities. Gas under pressure exerts a deleterious effect on adjacent nervous tissue, resulting in clinical deterioration. To assess the incidence of tension pneumocephalus (TP) and to define risk factors associated therewith. Analysis included 100 consecutive patients (57 boys, 43 girls, mean age 9.7 y) undergoing suboccipital sitting craniotomy since 2012 to 2014. In our material (n=100) TP was seen in 7 cases, asymptomatic pneumocephalus (AP) in 77 and no pneumocephalus (NP) in 16. Tumor types encountered were typical for pediatric population. In the TP group (n=7) the ratio of low-grade to high-grade tumors was 5:2, in the AP group (n=77) 2:1 and in the NP group (n=16) 1:1. Preoperative hydrocephalus was present in 21 cases (21%, mean incidence), thereof 3 in the TP group (3/7; 42.8%), 12 in AP group (12/77; 15.5%) and 6 in the NP group (6/16; 37.5%). All TP patients received an emergency external drainage, thereof 4 required a permanent ventriculo-peritoneal shunt (57.1%), while AP and NP patients combined (n=93) required a permanent shunt in 4 cases only (4.3%). TP-associated morbidity (n=2) consisted in a significant deterioration of neurological condition. TP is a relatively rare but potentially serious complication of suboccipital sitting craniotomy. Risk factors for TP are low-grade tumor and pre-existing long-standing hydrocephalus. TP requires emergency decompression by temporary external drainage. TP patients significantly more often require a permanent CSF shunt. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

TP53 Mutational Status Is a Potential Marker for Risk Stratification in Wilms Tumour with Diffuse Anaplasia

PubMed Central

Chagtai, Tasnim; Popov, Sergey D.; Sebire, Neil J.; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R.; Grundy, Paul; Dome, Jeffrey S.; Pritchard-Jones, Kathy

2014-01-01

Purpose The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. Patients and Methods We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. PMID:25313908

TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia.

PubMed

Maschietto, Mariana; Williams, Richard D; Chagtai, Tasnim; Popov, Sergey D; Sebire, Neil J; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R; Grundy, Paul; Dome, Jeffrey S; Pritchard-Jones, Kathy

2014-01-01

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

Mitochondrial phylogeny, divergence history and high-altitude adaptation of grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) inhabiting the Tibetan Plateau.

PubMed

Yuan, Ming-Long; Zhang, Qi-Lin; Zhang, Li; Jia, Cheng-Lin; Li, Xiao-Peng; Yang, Xing-Zhuo; Feng, Run-Qiu

2018-05-01

Grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) are the most important pests in alpine meadows of the Tibetan Plateau (TP) and have well adapted to high-altitude environments. To further understand the evolutionary history and their adaptation to the TP, we newly determined seven complete TP Gynaephora mitogenomes. Compared to single genes, whole mitogenomes provided the best phylogenetic signals and obtained robust results, supporting the monophyly of the TP Gynaephora species and a phylogeny of Arctiinae + (Aganainae + Lymantriinae). Incongruent phylogenetic signals were found among single mitochondrial genes, none of which recovered the same phylogeny as the whole mitogenome. We identified six best-performing single genes using Shimodaira-Hasegawa tests and found that the combinations of rrnS and either cox1 or cox3 generated the same phylogeny as the whole mitogenome, indicating the phylogenetic potential of these three genes for future evolutionary studies of Gynaephora. The TP Gynaephora species were estimated to radiate on the TP during the Pliocene and Quaternary, supporting an association of the diversification and speciation of the TP Gynaephora species with the TP uplifts and associated climate changes during this time. Selection analyses revealed accelerated evolutionary rates of the mitochondrial protein-coding genes in the TP Gynaephora species, suggesting that they accumulated more nonsynonymous substitutions that may benefit their adaptation to high altitudes. Furthermore, signals of positive selection were detected in nad5 of two Gynaephora species with the highest altitude-distributions, indicating that this gene may contribute to Gynaephora's adaptation to divergent altitudes. This study adds to the understanding of the TP Gynaephora evolutionary relationships and suggests a link between mitogenome evolution and ecological adaptation to high-altitude environments in grassland caterpillars. Copyright © 2018 Elsevier Inc. All rights reserved.

Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.

PubMed

Yang, Jing; Sun, Lixin; Wang, Lu; Hassan, Hozeifa M; Wang, Xuan; Hylemon, Phillip B; Wang, Tao; Zhou, Huiping; Zhang, Luyong; Jiang, Zhenzhou

2017-01-01

Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo . The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro . The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.

Synthesis, characterization, and electrochemistry of cis-oxothio- and cis-bis(thio)tungsten(VI) complexes of hydrotris(3,5-dimethylpyrazol-1-yl)borate.

PubMed

Eagle, A A; Tiekink, E R; George, G N; Young, C G

2001-08-27

The complexes TpWO2X react with sulfiding agents such as B2S3 or P4S10 to give the oxothio- and bis(thio)tungsten(VI) complexes TpWOSX (X = Cl(-)) and TpWS2X [X = Cl(-), S2PPh2(-); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate]. The reaction of TpWS2Cl with (i) PPh3 in pyridine and (ii) dimethyl sulfoxide affords TpWOSCl in good overall yield. The chloro complexes undergo metathesis with alkali metal salts to yield species of the type TpWOSX and TpWS2X [X = OPh(-), SPh(-), SePh(-), (-)-mentholate]. The diamagnetic complexes exhibit NMR spectra indicative of C(1) (TpWOSX) or C(s) (TpWS2X) symmetry and IR spectra consistent with terminal oxo and thio ligation (nu(W=O), 940-925 cm(-1); nu(W=S) or nu(WS2), 495-475 cm(-1)). Crystals of (R,S)-TpWOS[(-)-mentholate] are monoclinic, space group P2(1), with a = 11.983(2) A, b = 18.100(3) A, c = 13.859(3) A, beta = 91.60(2) degrees, V = 3004.6(8) A(3), and Z = 4. Crystals of TpWS2(OPh)-CH2Cl2 are orthorhombic, space group Pbca, with a = 16.961(4) A, b = 33.098(7) A, c = 9.555(2) A, V = 5364(2) A(3), and Z = 8. The mononuclear, distorted-octahedral tungsten centers are coordinated by a tridentate Tp ligand, an alkoxy or aryloxy ligand, and two terminal chalcogenide ligands. The average W=O and W=S distances are 1.726(7) and 2.125(2) A, respectively, and the O=W=S and S=W=S angles 102.9(3) and 102.9(1) degrees, respectively. The tungsten and sulfur X-ray absorption spectra of TpWOSCl and TpWS2Cl are consistent with the presence of terminal pi-bonded thio ligands in both complexes. The thio complexes generally undergo a reversible one-electron reduction at potentials significantly more positive than their oxo analogues. The chemical, spectroscopic, and electrochemical properties of the complexes are heavily influenced by the presence of W=S pi frontier orbitals.

Tpeak - Tend and Tpeak - Tend /QT ratio as markers of ventricular arrhythmia risk in cardiac resynchronization therapy patients.

PubMed

Barbhaiya, Chirag; Po, Jose Ricardo F; Hanon, Sam; Schweitzer, Paul

2013-01-01

Cardiac resynchronization therapy (CRT) increases transmural dispersion of repolarization (TDR) and can be pro-arrhythmic. However, overall arrhythmia risk was not increased in large-scale CRT clinical trials. Increased TDR as measured by T(peak ) -T(end) (TpTe) was associated with arrhythmia risk in CRT in a single-center study. This study investigates whether QT interval, TpTe, and TpTe/QT ratio are associated with ventricular arrhythmias in patients with CRT-defibrillator (CRT-D). Post-CRT-D implant electrocardiograms of 128 patients (age 71.3 years ± 10.3) with at least 2 months of follow-up at our institution's device clinic (mean follow-up of 28.5 months ± 17) were analyzed for QT interval, TpTe, and TpTe/QT ratio. Incidence of ventricular arrhythmias was determined based on routine and directed device interrogations. Appropriate implantable cardioverter-defibrillator therapy for sustained ventricular tachycardia or ventricular fibrillation was delivered in 18 patients (14%), and nonsustained ventricular tachycardia (NSVT) was detected but did not require therapy in 58 patients (45%). Patients who received appropriate defibrillator therapy had increased TpTe/QT ratio (0.24 ± 0.03 ms vs 0.20 ± 0.04, P = 0.0002) and increased TpTe (105.56 ± 20.36 vs 87.82 ± 22.32 ms, P = 0.002), and patients with NSVT had increased TpTe/QT ratio (0.22 ± 0.04 vs 0.20 ± 0.04, P = 0.016). Increased QT interval was not associated with risk of ventricular arrhythmia. The relative risk for appropriate defibrillator therapy of T(p) T(e) /QT ratio ≥ 0.25 was 3.24 (P = 0.016). Increased TpTe and increased TpTe/QT ratio are associated with increased incidence of ventricular arrhythmias in CRT-D. The utility of TpTe interval and TpTe/QT ratio as potentially modifiable risk factors for ventricular arrhythmias in CRT requires further study. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis

PubMed Central

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting

2015-01-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 “borderline” samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. PMID:25972403

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis.

PubMed

An, Jingna; Chen, Qixia; Liu, Qianqian; Rao, Chenli; Li, Dongdong; Wang, Tingting; Tao, Chuanmin; Wang, Lanlan

2015-07-01

The resurgence of syphilis in recent years has become a serious threat to public health worldwide, and the serological detection of specific antibodies against Treponema pallidum remains the most reliable method for laboratory diagnosis of syphilis. This study examined the performance of the recently launched HISCL anti-Treponema pallidum (anti-TP) assay as a screening test for syphilis in a high-volume laboratory. The HISCL anti-TP assay was tested in 300 preselected syphilis-positive samples, 704 fresh syphilis-negative samples, 48 preselected potentially interfering samples, and 30 "borderline" samples and was compared head to head with the commercially available Lumipulse G TP-N. In this study, the HISCL anti-TP assay was in perfect agreement with the applied testing algorithms with an overall agreement of 100%, comparable to that of Lumipulse G TP-N (99.63%). The sensitivity and specificity of the HISCL anti-TP assay were 100% (95% confidence interval [CI], 98.42% to 100%) and 100% (95% CI, 99.37% to 100%), respectively. Considering the excellent ease of use and automation, high throughput, and its favorable sensitivity and specificity, the HISCL anti-TP assay may represent a new choice for syphilis screening in high-volume laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.

PubMed

Wagle, Neil; Xian, Jun; Shishova, Ekaterina Y; Wei, Jie; Glicksman, Marcie A; Cuny, Gregory D; Stein, Ross L; Cohen, David E

2008-12-01

Phosphatidylcholine transfer protein (PC-TP, also referred to as StarD2) is a highly specific intracellular lipid-binding protein that catalyzes the transfer of phosphatidylcholines between membranes in vitro. Recent studies have suggested that PC-TP in vivo functions to regulate fatty acid and glucose metabolism, possibly via interactions with selected other proteins. To begin to address the relationship between activity in vitro and biological function, we undertook a high-throughput screen to identify small-molecule inhibitors of the phosphatidylcholine transfer activity of PC-TP. After adapting a fluorescence quench assay to measure phosphatidylcholine transfer activity, we screened 114,752 compounds of a small-molecule library. The high-throughput screen identified 14 potential PC-TP inhibitors. Of these, 6 compounds exhibited characteristics consistent with specific inhibition of PC-TP activity, with IC(50) values that ranged from 4.1 to 95.0muM under conditions of the in vitro assay. These compounds should serve as valuable reagents to elucidate the biological function of PC-TP. Because mice with homozygous disruption of the PC-TP gene (Pctp) are sensitized to insulin action and relatively resistant to the development of atherosclerosis, these inhibitors may also prove to be of value in the management of diabetes and atherosclerotic cardiovascular diseases.

Painful Heat Reveals Hyperexcitability of the Temporal Pole in Interictal and Ictal Migraine States

PubMed Central

Moulton, E. A.; Becerra, L.; Maleki, N.; Pendse, G.; Tully, S.; Hargreaves, R.; Burstein, R.

2011-01-01

During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy. PMID:20562317

7-Deazapurine containing DNA: efficiency of c7GdTP, c7AdTP and c7IdTP incorporation during PCR-amplification and protection from endodeoxyribonuclease hydrolysis.

PubMed Central

Seela, F; Röling, A

1992-01-01

The enzymatic synthesis of 7-deazapurine nucleoside containing DNA (501 bp) is performed by PCR-amplification (Taq polymerase) using a pUC18 plasmid DNA as template and the triphosphates of 7-deaza-2'-deoxyguanosine (c7Gd), -adenosine (c7Ad) and -inosine (c7Id). c7GdTP can fully replace dGTP resulting in a completely modified DNA-fragment of defined size and sequence. The other two 7-deazapurine triphosphates (c7AdTP) and (c7IdTP) require the presence of the parent purine 2'-deoxyribonucleotides. In purine/7-deazapurine nucleotide mixtures Taq polymerase prefers purine over 7-deazapurine nucleotides but accepts c7GdTP much better than c7AdTP or c7IdTP. As incorporation of 7-deazapurine nucleotides represents a modification of the major groove of DNA it can be used to probe DNA/protein interaction. Regioselective phosphodiester hydrolysis of the modified DNA-fragments was studied with 28 endodeoxyribonucleases. c7Gd is able to protect the DNA from the phosphodiester hydrolysis in more than 20 cases, only a few enzymes (Mae III, Rsa I, Hind III, Pvu II or Taq I) do still hydrolyze the modified DNA. c7Ad protects DNA less efficiently, as this DNA could only be modified in part. The absence of N-7 as potential binding position or a geometric distortion of the recognition duplex caused by the 7-deazapurine base can account for protection of hydrolysis. Images PMID:1738604

Role of antimony in the charge transport mechanisms for La0.67Ca0.33Mn1-xSbxO3 manganites

NASA Astrophysics Data System (ADS)

Kataria, B. R.; Solanki, Pankaj; Pandya, D. D.; Solanki, P. S.; Shah, N. A.

2018-07-01

Single phasic La0.67Ca0.33Mn1-xSbxO3 (LCMSO; x = 0.00, 0.02, 0.04, 0.06, 0.08 and 0.10) samples were characterized by performing temperature and magnetic field dependent resistance measurements. Present study, mainly, aims for the better understanding of possible charge conduction mechanisms responsible for the low temperature resistivity and high temperature [well above metal to insulator transition temperature (TP)] semiconducting regions. Variation in resistivity and TP with Sb5+ content (x) and applied magnetic field has been discussed in the light of the modifications in structural and magnetic lattices of smaller diamagnetic Sb5+ doped LCMSO system. Various models and mechanisms have been theoretical employed to fit obtained experimental resistivity data for the low temperature resistivity and semiconducting regions of all LCMSO manganites. It is found that low temperature resistivity minima follows the coulomb blockade model while charge conduction in the semiconducting region obeys the variable range hopping (VRH) mechanism. Variation in low temperature blocking energy, activation energy in semiconducting region and magnetoresistance (MR) with Sb5+ content (x) and applied magnetic field has been discussed in detail.

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiang; Zhao, Fang

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit themore » expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.« less

ROS Modifiers and NOX4 Affect the Expression of the Survivin-Associated Radio-Adaptive Response.

PubMed

Murley, Jeffrey S; Arbiser, Jack L; Weichselbaum, Ralph R; Grdina, David J

2018-04-13

The survivin-associated radio-adaptive response can be induced following exposure to ionizing radiation in the dose range from 5 to 100 mGy, and its magnitude of expression is dependent upon the TP53 mutational status of cells and ROS signaling. The purpose of the study was to investigate the potential role of ROS in the development of the survivin-associated adaptive response. Utilizing human colon carcinoma HCT116 TP53 wild type (WT) and HCT116 isogenic TP53 null mutant (Mut) cell cultures, the roles of inter- and intracellular ROS signaling on expression of the adaptive response as evidenced by changes in intracellular translocation of survivin measured by ELISA, and cell survival determined by a standard colony forming assay were investigated using ROS modifying agents that include emodin, N-acetyl-l-cysteine (NAC), fulvene-5, honokiol, metformin and rotenone. The role of NADPH oxidase 4 (NOX4) in the survivin-associated adaptive response was investigated by transfecting HCT116 cells, both WT and Mut, with two different NOX4 siRNA oligomers and Western blotting. A dose of 5 mGy or a 15min exposure to 50µM of the ROS producing drug emodin were equally effective in inducing a pro-survival adaptive response in TP53 WT and a radio-sensitization adaptive response in TP53 Mut HCT116 cells. Each response was associated with a corresponding translocation of survivin into the cytoplasm or nucleus, respectively. Exposure to 10mM NAC completely inhibited both responses. Exposure to 10µM honokiol induced responses similar to those observed following NAC exposure in TP53 WT and Mut cells. The mitochondrial complex 1 inhibitor rotenone was effective in reducing both cytoplasmic and nuclear survivin levels, but was ineffective in altering the expression of the adaptive response in either TP53 WT or Mut cells. In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio-sensitization and vice versa, respectively. These changes were accompanied by corresponding reversals in the translocation of survivin to the nuclei of TP53 WT and to the cytoplasm of TP53 Mut cells. The potential role of NOX4 in the expression of the survivin-associated adaptive response was investigated by transfecting HCT116 cells with NOX4 siRNA oligomers to inhibit NOX4 expression. Under these conditions NOX4 expression was inhibited by about 50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin-associated adaptive responses as was observed following metformin and fulvene-5 treatment. Exposure to 5 mGy resulted in enhanced NOX4 expression by about 40% in both TP53 WT and Mut cells, in contrast to only a 1 to 2% increase following a 2Gy only exposure. Utilizing mixed cultures of HCT116 TP53 WT and isogenic null Mut cells, as few as 10% TP53 Mut cells were sufficient to control the expression of the remaining 90% WT cells and resulted in an overall radio-sensitization response accompanied by the nuclear translocation of survivin characteristic of homogeneous TP53 Mut populations. Copyright © 2018. Published by Elsevier Inc.

Origin of geochemical mantle components: Role of spreading ridges and thermal evolution of mantle

NASA Astrophysics Data System (ADS)

Kimura, Jun-Ichi; Gill, James B.; van Keken, Peter E.; Kawabata, Hiroshi; Skora, Susanne

2017-02-01

We explore the element redistribution at mid-ocean ridges (MOR) using a numerical model to evaluate the role of decompression melting of the mantle in Earth's geochemical cycle, with focus on the formation of the depleted mantle component. Our model uses a trace element mass balance based on an internally consistent thermodynamic-petrologic computation to explain the composition of MOR basalt (MORB) and residual peridotite. Model results for MORB-like basalts from 3.5 to 0 Ga indicate a high mantle potential temperature (Tp) of 1650-1500°C during 3.5-1.5 Ga before decreasing gradually to ˜1300°C today. The source mantle composition changed from primitive (PM) to depleted as Tp decreased, but this source mantle is variable with an early depleted reservoir (EDR) mantle periodically present. We examine a two-stage Sr-Nd-Hf-Pb isotopic evolution of mantle residues from melting of PM or EDR at MORs. At high-Tp (3.5-1.5 Ga), the MOR process formed extremely depleted DMM. This coincided with formation of the majority of the continental crust, the subcontinental lithospheric mantle, and the enriched mantle components formed at subduction zones and now found in OIB. During cooler mantle conditions (1.5-0 Ga), the MOR process formed most of the modern ocean basin DMM. Changes in the mode of mantle convection from vigorous deep mantle recharge before ˜1.5 Ga to less vigorous afterward is suggested to explain the thermochemical mantle evolution.

An Aircraft-Based Upper Troposphere Lower Stratosphere O3, CO, and H2O Climatology for the Northern Hemisphere

NASA Technical Reports Server (NTRS)

Tilmes, S.; Pan, L. L.; Hoor, P.; Atlas, E.; Avery, M. A.; Campos, T.; Christensen, L. E.; Diskin, G. S.; Gao, R.-S.; Herman, R. L.;

Map the Permafrost and its Affected Soils and Vegetation on the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Zhao, L.; Sheng, Y.; Pang, Q.; Zou, D.; Wang, Z.; Li, W.; Wu, X.; Yue, G.; Fang, H.; Zhao, Y.

2015-12-01

Great amount of literatures had been published to deal with the actual distribution and changes of permafrost on the Tibetan Plateau (TP) on the basis of observed ground temperature dataset along Qinghai-Xizang Highway and/or Railway (QXH/R) during the last several decades. But there is very limited data available in the eastern part of the QXH/R and almost no observation in the western part of QXH/R not only for the observed permafrost data, but also for the dataset on ground surface conditions, such as soil and vegetation, which are used as model parameters, initial variables, or benchmark data sets for calibration, validation, and comparison in various Earth System Models (ESMs). To evaluate the status of permafrost and its environmental conditions, such as the distribution and thermal state of permafrost, soil and vegetation on the TP, detailed investigation on permafrost were conducted in 5 regions with different climatic and geologic conditions over the whole plateau from 2009 to 2013, and more than 100 ground temperatures (GTs) monitoring boreholes were drilled and equipped with thermistors, of which 10 sites were equipped with automatic meteorological stations. Geophysical prospecting methods, such as ground penetrating radar (GPR) and electromagnetic prospecting, were used in the same time to detect the permafrost distribution and thicknesses. The monitoring data revealed that the thermal state of permafrost was well correlated with elevation, and regulated by annual precipitation, local geological, geomorphological and hydrological conditions through heat exchanges between ground and atmosphere. Different models, including GTs statistical model, Common Land Surface Model (CoLM), Noah land surface model and TTOP models, were used to map the permafrost in 5 selected regions and the whole TP, while the investigated and monitored data were used as calibration and validation for all models. Finally, we compiled the permafrost map of the TP, soil and vegetation map within the permafrost regions on the TP. We also compiled the soil organic carbon density map of permafrost affected soils on the TP. An overview on permafrost thickness, GTs, ice content was statistically summarized based on investigation data.

Total Pancreatectomy and Islet Auto-Transplantation in Children for Chronic Pancreatitis. Indication, Surgical Techniques, Post Operative Management and Long-Term Outcomes

PubMed Central

Chinnakotla, Srinath; Bellin, Melena D.; Schwarzenberg, Sarah J.; Radosevich, David M.; Cook, Marie; Dunn, Ty B.; Beilman, Gregory J.; Freeman, Martin L.; Balamurugan, A.N.; Wilhelm, Josh; Bland, Barbara; Jimenez-Vega, Jose M; Hering, Bernhard J.; Vickers, Selwyn M.; Pruett, Timothy L.; Sutherland, David E.R.

2014-01-01

Objective Describe the surgical technique, complications and long term outcomes of total pancreatectomy and islet auto transplantation (TP-IAT) in a large series of pediatric patients. Summary Background Data Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, while islet auto transplantation (IAT) potentially can prevent or minimize TP-related diabetes. Methods Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic or surgical treatment between 1989–2012. Results Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (p =<0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (p=0.032), lack of prior Puestow (p=0.018), lower body surface area (p=0.048), IEQ per Kg Body Weight (p=0.001) and total IEQ (100,000) (0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT:(1) male gender, (2) lower body surface area and the (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (OR = 2.62; p value < 0.001). Conclusions TP-IAT provides sustained pain relief and improved quality of life. The β cell function is dependent on islet yield. TP-IAT is an effective therapy for children with painful pancreatitis that fail medical and or endoscopic management PMID:24509206

Scenario analysis of the impacts of socioeconomic development on phosphorous export and loading from the Dongting Lake watershed, China.

PubMed

Hou, Ying; Chen, Weiping; Liao, Yuehua; Luo, Yueping

2017-12-01

Socioeconomic development in lake watersheds is closely related with lake nutrient pollution. As the second largest freshwater lake in China, the Dongting Lake has been experiencing an increase in nutrient loading and a growing risk of eutrophication. This study aimed to reveal the likely impacts of the socioeconomic development of the Dongting Lake watershed on the phosphorous pollution in the lake. We estimated the contributions from different sources and sub-watersheds to the total phosphorous (TP) export and loading from the Dongting Lake watershed under two most likely socioeconomic development scenarios. Moreover, we predicted the likely permissible and actual TP loadings to the Dongting Lake. Under both two scenarios, three secondary sub-watersheds-the upper and lower reaches of the Xiang River watershed and the Dongting Lake Area-are expected to dominate the contribution to the TP export from the Dongting Lake watershed in 2020. Three primary sub-watersheds-the Dongting Lake Area, the Xiang River, and the Yuan River watersheds-are predicted to be the major contributors to the TP loading from the entire watershed. The two scenarios are expected to have a slight difference in TP export and lake TP loading. Livestock husbandry is expected to be the predominant anthropogenic TP source in each of the sub-watersheds under both scenarios. Compared to 2010, permissible TP loading is not expected to increase but actual TP loading is predicted to grow significantly in 2020. Our study provides methodologies to identify the key sources and regions of lake nutrient loading from watersheds with complex socioeconomic context, and to reveal the potential influences of socioeconomic development on nutrient pollution in lake watersheds.

Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase

PubMed Central

Kim, Hye-Lin; Jung, Yunu; Kang, JongWook; Jeong, Mi-Young; Sethi, Gautam; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH. PMID:27880726

Intrinsic crystal phase separation in the antiferromagnetic superconductor Rb(y)Fe(2-x)Se2: a diffraction study.

PubMed

Yu Pomjakushin, V; Krzton-Maziopa, A; Pomjakushina, E V; Conder, K; Chernyshov, D; Svitlyk, V; Bosak, A

2012-10-31

The crystal and magnetic structures of the superconducting iron-based chalcogenides Rb(y)Fe(2-x)Se(2) have been studied by means of single-crystal synchrotron x-ray and high-resolution neutron powder diffraction in the temperature range 2-570 K. The ground state of the crystal is an intrinsically phase-separated state with two distinct-by-symmetry phases. The main phase has the iron vacancy ordered √5 × √5 superstructure (I4/m space group) with AFM ordered Fe spins. The minority phase does not have √5 × √5-type of ordering and has a smaller in-plane lattice constant a and larger tetragonal c-axis and can be well described by assuming the parent average vacancy disordered structure (I4/mmm space group) with the refined stoichiometry Rb(0.60(5))(Fe(1.10(5))Se)(2). The minority phase amounts to 8-10% mass fraction. The unit cell volume of the minority phase is 3.2% smaller than the one of the main phase at T = 2 K and has quite different temperature dependence. The minority phase merges with the main vacancy ordered phase on heating above the phase separation temperature T(P) = 475 K. The spatial dimensions of the phase domains strongly increase above T(P) from 1000 to >2500 Å due to the integration of the regions of the main phase that were separated by the second phase at low temperatures. Additional annealing of the crystals at a temperature T = 488 K, close to T(P), for a long time drastically reduces the amount of the minority phase.

Efficacy of the antimicrobial peptide TP4 against Helicobacter pylori infection: in vitro membrane perturbation via micellization and in vivo suppression of host immune responses in a mouse model

PubMed Central

Narayana, Jayaram Lakshmaiah; Huang, Han-Ning; Wu, Chang-Jer; Chen, Jyh-Yih

2015-01-01

Helicobacter pylori infection is marked by a strong association with various gastric diseases, including gastritis, ulcers, and gastric cancer. Antibiotic treatment regimens have low success rates due to the rapid occurrence of resistant H. pylori strains, necessitating the development of novel anti-H. pylori strategies. Here, we investigated the therapeutic potential of a novel peptide, Tilapia Piscidin 4 (TP4), against multidrug resistant gastric pathogen H. pylori, based on its in vitro and in vivo efficacy. TP4 inhibited the growth of both antibiotic-sensitive and -resistant H. pylori (CagA+, VacA+) via membrane micelle formation, which led to membrane depolarization and extravasation of cellular constituents. During colonization of gastric tissue, H. pylori infection maintains high T regulatorysubsets and a low Th17/Treg ratio, and results in expression of both pro- and anti-inflammatory cytokines. Treatment with TP4 suppressed Treg subset populations and pro- and anti-inflammatory cytokines. TP4 restored the Th17/Treg balance, which resulted in early clearance of H. pylori density and recovery of gastric morphology. Toxicity studies demonstrated that TP4 treatment has no adverse effects in mice or rabbits. The results of this study indicate that TP4 may be an effective and safe monotherapeutic agent for the treatment of multidrug resistant H. pylori infections. PMID:26002554

In vitro antioxidant and in vivo photoprotective effect of pistachio (Pistacia vera L., variety Bronte) seed and skin extracts.

PubMed

Martorana, Maria; Arcoraci, Teresita; Rizza, Luisa; Cristani, Mariateresa; Bonina, Francesco Paolo; Saija, Antonina; Trombetta, Domenico; Tomaino, Antonio

2013-03-01

Pistachio (Pistacia vera L.) nuts are a rich source of phenolic compounds, known for their high antioxidant activity, and contained not only in the seeds but also in the skin. A pistachio cultivar of high quality is typical of Bronte, Sicily, Italy. The purpose of our study was to investigate the chemical composition and antioxidant properties of two polyphenol-rich extracts from skins (TP) and decorticated seeds (SP) of Bronte pistachios, and to verify the potential use of these extracts for topical photoprotective products. Chemical analysis showed that the TP and SP extracts contain high levels of phenolic compounds, but the TP extract is about ten times richer in phenols than the SP extract, being anthocyanins the most abundant compounds found in the TP extract. Both these extracts, and especially the TP extract, possess good radical scavenger/antioxidant properties, as shown in a series of in vitro assays carried out using homogenous and non-homogenous chemical environment. Furthermore both the TP extract and, although at a lower degree, the SP extract reduce, when topically applied, UV-B-induced skin erythema in human volunteers. These findings suggest that extracts from Bronte TP and SP could be successfully employed as photoprotective ingredients in topical cosmetic and pharmaceutical formulations. Copyright © 2013 Elsevier B.V. All rights reserved.

Multiple stressor effects on biological quality elements in the Ebro River: Present diagnosis and predicted responses.

PubMed

Herrero, Albert; Gutiérrez-Cánovas, Cayetano; Vigiak, Olga; Lutz, Stefanie; Kumar, Rohini; Gampe, David; Huber-García, Verena; Ludwig, Ralf; Batalla, Ramon; Sabater, Sergi

2018-07-15

Multiple abiotic stressors affect the ecological status of water bodies. The status of waterbodies in the Ebro catchment (NE Spain) is evaluated using the biological quality elements (BQEs) of diatoms, invertebrates and macrophytes. The multi-stressor influence on the three BQEs was evaluated using the monitoring dataset available from the catchment water authority. Nutrient concentrations, especially total phosphorus (TP), affected most of the analyzed BQEs, while changes in mean discharge, water temperature, or river morphology did not show significant influences. Linear statistical models were used to evaluate the change of water bodies' ecological status under different combinations of future socioeconomic and climate scenarios. Changes in land use, rainfall, water temperature, mean discharge, TP and nitrate concentrations were modeled according to the future scenarios. These revealed an evolution of the abiotic stressors that could lead to a general decrease in the ecosystem quality of water bodies within the Ebro catchment. This deterioration was especially evidenced on the diatoms and invertebrate biological indices, mainly because of the foreseen increase in TP concentrations. Water bodies located in the headwaters were seen as the most sensitive to future changes. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

The Processing and Mechanical Properties of High Temperature/High Performance Composites. Book 1, Section 1: Coatings and Interfaces

DTIC Science & Technology

1989-10-15

Cut Prestressed Film H.M. Jensen on a Substrate J.W. Hutchinson K.S. Kim 8. Measuring the Strength and Stiffness T.P. Weihs of Thin Film Materials by...for Thin Films T.P. Weihs Using Micro-Cantilever Beams J.C. Bravman W.D. Nix 10. Analysis of Elastic and Plastic Deformation A.K. Bhattacharya...Associated with Indentation Testing of Thin W.D. Nix Films on Substrates 11. Finite Elenent Simulidion of Indentation A.K. 13hattacharya Experimnents W.D

Evolution of surface sensible heat over the Tibetan Plateau under the recent global warming hiatus

NASA Astrophysics Data System (ADS)

Zhu, Lihua; Huang, Gang; Fan, Guangzhou; Qu, Xia; Zhao, Guijie; Hua, Wei

2017-10-01

Based on regular surface meteorological observations and NCEP/DOE reanalysis data, this study investigates the evolution of surface sensible heat (SH) over the central and eastern Tibetan Plateau (CE-TP) under the recent global warming hiatus. The results reveal that the SH over the CE-TP presents a recovery since the slowdown of the global warming. The restored surface wind speed together with increased difference in ground-air temperature contribute to the recovery in SH. During the global warming hiatus, the persistent weakening wind speed is alleviated due to the variation of the meridional temperature gradient. Meanwhile, the ground surface temperature and the difference in ground-air temperature show a significant increasing trend in that period caused by the increased total cloud amount, especially at night. At nighttime, the increased total cloud cover reduces the surface effective radiation via a strengthening of atmospheric counter radiation and subsequently brings about a clear upward trend in ground surface temperature and the difference in ground-air temperature. Cloud-radiation feedback plays a significant role in the evolution of the surface temperature and even SH during the global warming hiatus. Consequently, besides the surface wind speed, the difference in ground-air temperature becomes another significant factor for the variation in SH since the slowdown of global warming, particularly at night.

Novel Regenerative Peptide TP508 Mitigates Radiation-Induced Gastrointestinal Damage By Activating Stem Cells and Preserving Crypt Integrity

PubMed Central

Kantara, Carla; Moya, Stephanie M.; Houchen, Courtney W.; Umar, Shahid; Ullrich, Robert L.; Singh, Pomila; Carney, Darrell H.

2015-01-01

In recent years, increasing threats of radiation exposure and nuclear disasters have become a significant concern for the United States and countries worldwide. Exposure to high doses of radiation triggers a number of potentially lethal effects. Among the most severe is the gastrointestinal (GI) toxicity syndrome caused by the destruction of the intestinal barrier, resulting in bacterial translocation, systemic bacteremia, sepsis and death. The lack of effective radioprotective agents capable of mitigating radiation-induced damage has prompted a search for novel countermeasures that can mitigate the effects of radiation post-exposure, accelerate tissue repair in radiation-exposed individuals, and prevent mortality. We report that a single injection of regenerative peptide TP508 (rusalatide acetate, Chrysalin®) 24h after lethal radiation exposure (9Gy, LD100/15) appears to significantly increase survival and delay mortality by mitigating radiation-induced intestinal and colonic toxicity. TP508 treatment post-exposure prevents the disintegration of gastrointestinal crypts, stimulates the expression of adherens junction protein E-cadherin, activates crypt cell proliferation, and decreases apoptosis. TP508 post-exposure treatment also up-regulates the expression of DCLK1 and LGR5 markers of stem cells that have been shown to be responsible for maintaining and regenerating intestinal crypts. Thus, TP508 appears to mitigate the effects of GI toxicity by activating radioresistant stem cells and increasing the stemness potential of crypts to maintain and restore intestinal integrity. These results suggest that TP508 may be an effective emergency nuclear countermeasure that could be delivered within 24h post-exposure to increase survival and delay mortality, giving victims time to reach clinical sites for advanced medical treatment. PMID:26280221

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo.

PubMed

Zhang, Li; Wang, Tengteng; Li, Qiang; Huang, Jing; Xu, Hao; Li, Jinlong; Wang, Yongjun; Liang, Qianqian

2016-01-01

Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is -35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

Is Xpert MTB/RIF appropriate for diagnosing tuberculous pleurisy with pleural fluid samples? A systematic review.

PubMed

Huo, Zhen-Yu; Peng, Li

2018-06-25

Tuberculous pleurisy (TP) presents a diagnostic problem due to the limitations of traditional diagnostic methods. Different studies with the Xpert MTB/RIF assay have drawn variable conclusions about its values in TP diagnosis. We conducted a meta-analysis to assess whether the Xpert MTB/RIF assay is appropriate for the diagnosis of TP using pleural fluid samples. A systematic search of four literature databases in English and Chinese language was performed to identify studies involving the use of Xpert MTB/RIF in patients with TP confirmed by plural biopsy and/or mycobacterial culture. Pooled sensitivity, specificity and accordance proportion were calculated, and the forest plots were generated to assess the accuracy of Xpert MTB/RIF for TP diagnosis. We identified 23 studies meeting our inclusion criteria. The pooled sensitivity and specificity of Xpert MTB/RIF were 30% (95% CI: 21-42%, I 2  = 87.93%) and 99% (95% CI: 97-100%, I 2  = 96.20%), respectively, and the area under the SROC curve (AUC) of Xpert MTB/RIF was 0.86 (95% CI: 0.83-0.89). Compared with drug susceptibility testing (DST), the pooled accordance rate of Xpert MTB/RIF in detecting rifampicin-susceptible cases and rifampicin-resistant cases was 99% (95% CI: 95-104%, I 2  = 8.7%) and 94% (95% CI: 86-102%), respectively. Our analysis suggests that the Xpert MTB/RIF assay is of limited value as a screening test for TP but has a high potential for confirming TP diagnosis and differentiating TP from non-TB diseases using pleural fluid samples.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Topping, R.J.; Stone, M.P.; Brush, C.K.

The {sup 1}H NMR spectrum of the tetradeoxynucleotide d(TpCpGpA) was examined as a function of temperature, pH, and concentration. At pH 7 and above the solution conformation for this oligodeoxynucleotide appears to be a mixture of random coil and Watson-Crick duplex. At 25{degree}C, a pH titration of d(TpCpGaA) shown that distinct conformational changes occur as the pH is lowered below 7.0. These conformational changes are reversible upon readjusting the pH to neutrality, indicating the presence of a pH-dependent set of conformational equilibria. At 25{degree}C, the various conformational state in the mixture are in rapid exchange on the NMR time scale.more » Examination of the titration curve shown the presence of distinct conformational states at pH greater than 7, and between pH 4 and pH 5. When the pH titration is repeated at 5{degree}C, the conformational equilibria are in slow exchange on the NMR time scale; distinct signals from each conformational state are observable. The stable conformational state present between pH 4 and pH 5 represents an ordered conformation of d(TpCpGpA) which dissociates to a less ordered structure upon raising the temperature. The ordered conformation differs from the Watson-Crick helix, as is shown from nuclear Overhauser enhancement experiments, as well as chemical shift data. These results indicate that their ordered conformation is similar to the conformation of d(TpCpGpA) observed between pH 4 and pH 5. In the present case it is likely that stabilization of an ordered duplex conformation for d(TpCpGpA) is achieved by protonation of cytosine. A possible model which could explain the data involves formation of Hoogsteen C{sup +}:G base pairs.« less

Spatio-temporal variability of vertical gradients of major meteorological observations around the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Guo, X.; Wang, L.; Tian, L.

2015-12-01

The near-surface air temperature lapse rate (TLR), wind speed gradient (WSG), and precipitation gradient (PG) provide crucial parameters used in models of mountain climate and hydrology. The complex mountain terrain and vast area of the Tibetan Plateau (TP) make such factors particularly important. With daily data from 161 meteorological stations over the past 43 years (1970-2012), we analyse the spatio-temporal variations of TLRs, WSGs, and PGs over and around TP, derived using linear regression methods and dividing the study area into zones based on spatial variations. Results of this study include: (1) The observed TLR varies from -0.46 to -0.73 ∘C (100 m) -1, with averaged TLRs of -0.60,-0.62, and -0.59 ∘C (100 m) -1 for Tmax, Tmin,and Tmean , respectively. The averaged TLR is slightly less than the global mean of -0.65 ∘C (100 m) -1 . The spatial variability of TLR relates to climate conditions, wherein the TLR increases in dry conditions and in cold months (October-April), while it lessens in humid regions and during warm months (May-September). (2) The estimated annual WSG ranges from 0.07 to 0.17m s -1 (100 m) -1. Monthly WSGs show a marked seasonal shift, in which higher WSGs can be explained by the high intensity of prevailing wind. (3) Positive summer PGs vary from 12.08 in the central TP to 26.14 mm (100 m) -1 in northeastern Qinghai and the southern TP, but a reverse gradient prevails in Yunnan and parts of Sichuan Province. (4) The regional warming over TP is more evident in winter, and Tmin demonstrated the most prominent warming compared with Tmax and Tmean. Environments at high elevations experience more rapid changes in temperatures (Tmax, Tmin,and Tmean) than those at low elevations, which is especially true in winter and for Tmin. Furthermore, inter-annual variation of TLRs is linked to elevation-dependent warming.

Evaluation of Wound Healing Potential of Topical Formulation of Leaf Juice of Tridax Procumbens L. in Mice

PubMed Central

Yaduvanshi, B.; Mathur, Rajani; Mathur, S. R.; Velpandian, T.

2011-01-01

Tridax procumbens L. (Compositae) is a common weed that grows in the rice fields of India. Traditionally the juice from leaves of Tridax procumbens has been used for healing dermal wound. However, in experimental studies, equivocal pro and anti-healing action of T. procumbens has been demonstrated. The present study evaluates the effect of topical ointment formulation of the leaf juice of T. procumbens using excision wound model in mice. Excision wounds (4 mm, i.d.) were inflicted on depilated back of mice. Ointment formulation of TP (50 mg of either 1 or 4 mg/g) was applied twice daily for 4 days on the dermal wound. Similarly, control group was treated with VEGF ointment (50 mg of 1 μg/g). The parameters observed were re-epithelization, vascularity, fibroblast number, collagen content. The healing exerted by TP (1 mg/g) was comparable to VEGF (1 μg/g). On the other hand, TP (4 mg/g) induced inflammation, edematous tissue and decreased vascularity. Taken together, the results imply that TP possesses dose dependent pro-healing potential, and its high dose exerts inflammatory reaction. PMID:22457556

Evaluation of wound healing potential of topical formulation of leaf juice of tridax procumbens L. In mice.

PubMed

Yaduvanshi, B; Mathur, Rajani; Mathur, S R; Velpandian, T

2011-05-01

Tridax procumbens L. (Compositae) is a common weed that grows in the rice fields of India. Traditionally the juice from leaves of Tridax procumbens has been used for healing dermal wound. However, in experimental studies, equivocal pro and anti-healing action of T. procumbens has been demonstrated. The present study evaluates the effect of topical ointment formulation of the leaf juice of T. procumbens using excision wound model in mice. Excision wounds (4 mm, i.d.) were inflicted on depilated back of mice. Ointment formulation of TP (50 mg of either 1 or 4 mg/g) was applied twice daily for 4 days on the dermal wound. Similarly, control group was treated with VEGF ointment (50 mg of 1 μg/g). The parameters observed were re-epithelization, vascularity, fibroblast number, collagen content. The healing exerted by TP (1 mg/g) was comparable to VEGF (1 μg/g). On the other hand, TP (4 mg/g) induced inflammation, edematous tissue and decreased vascularity. Taken together, the results imply that TP possesses dose dependent pro-healing potential, and its high dose exerts inflammatory reaction.

Expanding the indications of pancreas transplantation alone.

PubMed

Mehrabi, Arianeb; Golriz, Mohammad; Adili-Aghdam, Fatemeh; Hafezi, Mohammadreza; Ashrafi, Maryam; Morath, Christian; Zeier, Martin; Hackert, Thilo; Schemmer, Peter

2014-11-01

Total pancreatectomy (TP) is associated with postoperative endocrine and exocrine insufficiency. Especially, insulin therapy reduces quality of life and may lead to long-term complications. We review the literature with regard to the potential option of pancreas transplantation alone (PTA) after TP in patients with chronic pancreatitis or benign tumors. A MEDLINE search (1958-2013) using the terminologies pancreas transplantation, pancreas transplantation alone, total pancreatectomy, morbidity, mortality, insulin therapy, and quality of life was performed. In addition, the current book and congress publications were reviewed. Total pancreatectomy after benign and borderline tumors as well as chronic pancreatitis is continuously increasing. Despite improvement of exogenous insulin therapy, more than 50% of these patients experience severe glucose control problems, which cause up to 50% long-term mortality. Pancreas transplantation alone can cure both endocrine and exocrine insufficiency and reduce the associated risks. The 3-year graft and patient survival rates after PTA are up to 73% and 100%, respectively. Pancreas transplantation alone after TP in patients with pancreatitis or benign tumors improves the recipient's quality of life and reduces long-term mortality. Considering the amount of available organs and potential candidates, PTA can be a treatment option for patients after TP with chronic pancreatitis or benign tumors.

The complementary relationship (CR) approach aids evapotranspiration estimation in the data scarce region of Tibetan Plateau: symmetric and asymmetric perspectives

NASA Astrophysics Data System (ADS)

Ma, N.; Zhang, Y.; Szilagyi, J.; Xu, C. Y.

2015-12-01

While the land surface latent and sensible heat release in the Tibetan Plateau (TP) could greatly influence the Asian monsoon circulation, the actual evapotranspiration (ETa) information in the TP has been largely hindered by its extremely sparse ground observation network. Thus the complementary relationship (CR) theory lends great potential in estimating the ETa since it relies on solely routine meteorological observations. With the in-situ energy/water flux observation over the highest semiarid alpine steppe in the TP, the modifications of specific components within the CR were first implemented. We found that the symmetry of the CR could be achieved for dry regions of TP when (i) the Priestley-Taylor coefficient, (ii) the slope of the saturation vapor pressure curve and (iii) the wind function were locally calibrated by using the ETa observations in wet days, an estimate of the wet surface temperature and the Monin-Obukhov Similarity (MOS) theory, respectively. In this way, the error of the simulated ETa by the symmetric AA model could be decreased to a large extent. Besides, the asymmetric CR was confirmed in TP when the D20 above-ground and/or E601B sunken pan evaporation (Epan) were used as a proxy of the ETp. Thus daily ETa could also be estimated by coupling D20 above-ground and/or E601B sunken pans through CR. Additionally, to overcome the modification of the specific components in the CR, we also evaluated the Nonlinear-CR model and the Morton's CRAE model. The former does not need the pre-determination of the asymmetry of CR, while the latter does not require the wind speed data as input. We found that both models are also able to simulate the daily ETa well provided their parameter values have been locally calibrated. The sensitivity analysis shows that, if the measured ETa data are absence to calibrate the models' parameter values, the Nonlinear-CR model may be a particularly good way for estimating ETabecause of its mild sensitivity to the parameter values making possible to employ published parameter values derived under similar climatic and land cover conditions. The CRAE model should also be highlighted in the TP since the special topography make the wind speed data suffer large uncertainties when the advanced geo-statistical method was used to spatially interpolate the point-based meteorological records.

Spring Soil Temperature Anomalies over Tibetan Plateau and Summer Droughts/Floods in East Asia

NASA Astrophysics Data System (ADS)

Xue, Y.; Li, W.; LI, Q.; Diallo, I.; Chu, P. C.; Guo, W.; Fu, C.

2017-12-01

Recurrent extreme climate events, such as droughts and floods, are important features of the climate of East Asia, especially over the Yangtze River basin. Many studies have attributed these episodes to variability and anomaly of global sea surface temperatures (SST) anomaly. In addition, snow in the Tibetan Plateau has also been considered as one of the factors affecting the Asian monsoon variability. However, studies have consistently shown that SST along is unable to explain the extreme climate events fully and snow has difficulty to use as a predictor. Remote effects of observed large-scale land surface temperature (LST) and subsurface temperature variability in Tibetan Plateau (TP) on East Asian regional droughts/floods, however, have been largely ignored. We conjecture that a temporally filtered response to snow anomalies may be preserved in the LST anomaly. In this study, evidence from climate observations and model simulations addresses the LST/SUBT effects. The Maximum Covariance Analysis (MCA) of observational data identifies that a pronounce spring LST anomaly pattern over TP is closely associated with precipitation anomalies in East Asia with a dipole pattern, i.e., negative/positive TP spring LST anomaly is associated with the summer drought/flood over the region south of the Yangtze River and wet/dry conditions to the north of the Yangtze River. Climate models were used to demonstrate a causal relationship between spring cold LST anomaly in the TP and the severe 2003 drought over the southern part of the Yangtze River in eastern Asia. This severe drought resulted in 100 x 106 kg crop yield losses and an economic loss of 5.8 billion Chinese Yuan. The modeling study suggests that the LST effect produced about 58% of observed precipitation deficit; while the SST effect produced about 32% of the drought conditions. Meanwhile, the LST and SST effects also simulated the observed flood over to the north of the Yangtze River. This suggests that inclusion of this LST effect is essential to make reliable East Asian drought/flood predictions.

Observed soil temperature trends associated with climate change in the Tibetan Plateau, 1960-2014

NASA Astrophysics Data System (ADS)

Fang, Xuewei; Luo, Siqiong; Lyu, Shihua

2018-01-01

Soil temperature, an important indicator of climate change, has rarely explored due to scarce observations, especially in the Tibetan Plateau (TP) area. In this study, changes observed in five meteorological variables obtained from the TP between 1960 and 2014 were investigated using two non-parametric methods, the modified Mann-Kendall test and Sen's slope estimator method. Analysis of annual series from 1960 to 2014 has shown that surface (0 cm), shallow (5-20 cm), deep (40-320 cm) soil temperatures (ST), mean air temperature (AT), and precipitation (P) increased with rates of 0.47 °C/decade, 0.36 °C/decade, 0.36 °C/decade, 0.35 °C/decade, and 7.36 mm/decade, respectively, while maximum frozen soil depth (MFD) as well as snow cover depth (MSD) decreased with rates of 5.58 and 0.07 cm/decade. Trends were significant at 99 or 95% confidence level for the variables, with the exception of P and MSD. More impressive rate of the ST at each level than the AT indicates the clear response of soil to climate warming on a regional scale. Monthly changes observed in surface ST in the past decades were consistent with those of AT, indicating a central place of AT in the soil warming. In addition, with the exception of MFD, regional scale increasing trend of P as well as the decreasing MSD also shed light on the mechanisms driving soil trends. Significant negative-dominated correlation coefficients (α = 0.05) between ST and MSD indicate the decreasing MSD trends in TP were attributable to increasing ST, especially in surface layer. Owing to the frozen ground, the relationship between ST and P is complicated in the area. Higher P also induced higher ST, while the inhibition of freeze and thaw process on the ST in summer. With the increasing AT, P accompanied with the decreasing MFD, MSD should be the major factors induced the conspicuous soil warming of the TP in the past decades.

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

PubMed Central

Fang, Xia; Xiu, Bing; Yang, Zhizhang; Qiu, Weizhe; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Suhong; Yi, Xianghua; Liang, Aibin; Zeng, Yu

2017-01-01

Abstract Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear. Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan–Meier curves with log rank test, and Cox's proportional hazards regression model. PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients’ gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1+ TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients’ survival time. Besides, PD-1 expression, patients’ age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance. PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients. PMID:28403071

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.

PubMed

Fang, Xia; Xiu, Bing; Yang, Zhizhang; Qiu, Weizhe; Zhang, Long; Zhang, Suxia; Wu, Yunjin; Zhu, Xuyou; Chen, Xue; Xie, Suhong; Yi, Xianghua; Liang, Aibin; Zeng, Yu

2017-04-01

Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Molecular cloning and characterization of leucine aminopeptidase gene from Taenia pisiformis.

PubMed

Zhang, Shaohua; Cai, Xuepeng; Luo, Xuenong; Wang, Shuai; Guo, Aijiang; Hou, Junling; Wu, Run

2018-03-01

Leucine aminopeptidase (LAP, EC: 3.4.11.1) is an important metalloexopeptidase that catalyze the hydrolysis of amino-terminal leucine residues from polypeptides and proteins. In this study, a full length of cDNA encoding leucine aminopeptidase of Taenia pisiformis (TpLAP) was cloned by rapid amplification of cDNA-ends using the polymerase chain reaction (RACE-PCR) method. The full-length cDNA of the TpLAP gene is 1823 bp and contains a 1569 bp ORF encoding 533 amino acids with a putative mass of 56.4 kDa. TpLAP contains two characteristic motifs of the M17LAP family in the C-terminal sequence: the metal binding site 265-[VGKG]-271 and the catalytic domain motif 351-[NTDAEGRL]-357. The soluble GST-TpLAP protein was expressed in Escherichia coli Transetta (DE3) and four specific anti-TpLAP monoclonal antibodies (mAbs) were prepared. In enzymatic assays, the optimal activity was observed at pH 9.5 at 45 °C. GST-TpLAP displayed a hydrolyzing activity for the Leu-pNA substrate with a maximum activity of 46 U/ml. The enzymatic activity was significantly enhanced by Mn 2+ and completely inhibited by 20 nM bestatin and 0.15 mM EDTA. The native TpLAP was detected specifically in ES components of adult T. pisiformis by western blotting using anti-TpLAP mAb as a probe. Quantitative real-time PCR revealed that the TpLAP gene was expressed at a high level in adult worm tissues, especially in the gravid proglottids (50.71-fold). Immunolocalization analysis showed that TpLAP was located primarily in the subtegumental parenchyma zone and the uterine wall of adult worms. Our results indicate that TpLAP is a new member of the M17LAP family and can be considered as a stage-differentially expressed protein. These findings might provide new insights into the study of the mechanisms of growth, development and survival of T. pisiformis in the final host and have potential value as an attractive target for drug therapy or vaccine intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Remote sensing estimation of the total phosphorus concentration in a large lake using band combinations and regional multivariate statistical modeling techniques.

PubMed

Gao, Yongnian; Gao, Junfeng; Yin, Hongbin; Liu, Chuansheng; Xia, Ting; Wang, Jing; Huang, Qi

2015-03-15

Remote sensing has been widely used for ater quality monitoring, but most of these monitoring studies have only focused on a few water quality variables, such as chlorophyll-a, turbidity, and total suspended solids, which have typically been considered optically active variables. Remote sensing presents a challenge in estimating the phosphorus concentration in water. The total phosphorus (TP) in lakes has been estimated from remotely sensed observations, primarily using the simple individual band ratio or their natural logarithm and the statistical regression method based on the field TP data and the spectral reflectance. In this study, we investigated the possibility of establishing a spatial modeling scheme to estimate the TP concentration of a large lake from multi-spectral satellite imagery using band combinations and regional multivariate statistical modeling techniques, and we tested the applicability of the spatial modeling scheme. The results showed that HJ-1A CCD multi-spectral satellite imagery can be used to estimate the TP concentration in a lake. The correlation and regression analysis showed a highly significant positive relationship between the TP concentration and certain remotely sensed combination variables. The proposed modeling scheme had a higher accuracy for the TP concentration estimation in the large lake compared with the traditional individual band ratio method and the whole-lake scale regression-modeling scheme. The TP concentration values showed a clear spatial variability and were high in western Lake Chaohu and relatively low in eastern Lake Chaohu. The northernmost portion, the northeastern coastal zone and the southeastern portion of western Lake Chaohu had the highest TP concentrations, and the other regions had the lowest TP concentration values, except for the coastal zone of eastern Lake Chaohu. These results strongly suggested that the proposed modeling scheme, i.e., the band combinations and the regional multivariate statistical modeling techniques, demonstrated advantages for estimating the TP concentration in a large lake and had a strong potential for universal application for the TP concentration estimation in large lake waters worldwide. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characteristics of mesospheric gravity waves over the southeastern Tibetan Plateau region

NASA Astrophysics Data System (ADS)

Li, Qinzeng; Xu, Jiyao; Liu, Xiao; Yuan, Wei; Chen, Jinsong

2016-09-01

The Tibetan Plateau (TP), known as "Third Pole" of the Earth, has important influences on global climates and local weather. An important objective in present study is to investigate how orographic features of the TP affect the geographical distributions of gravity wave (GW) sources. Three-year OH airglow images (November 2011 to October 2014) from Qujing (25.6°N, 103.7°E) were used to study the characteristics of GWs over the southeastern TP region. Along with the almost concurrent and collocated meteor radar wind measurements and temperature data from SABER/TIMED satellite, the propagation conditions of three types of GWs (freely propagating, ducted, or evanescent) were estimated. Most of GWs exhibited ducted or evanescent characteristics. Almost all GWs propagate southeastward in winter. The GW propagation directions in winter are significantly different from other airglow imager observations at northern middle latitudes. Wind data and convective precipitation fields from the European Centre for Medium-Range Weather Forecasts reanalysis data are used to study the sources of GWs on the edge of the TP. Using backward ray-tracing analysis, we find that most of the mesospheric freely propagating GWs are located in or near the large wind shear intensity region ( 10 km- 17 km) on the southeastern edge of the TP in spring and winter. The averaged value of momentum flux is 11.6 ± 5.2 m2/s2 in winter and 7.5 ± 3.1 m2/s2 in summer. This work will provide valuable information for the GW parameterization schemes in general circulation models in TP region.

Effect of water phase transition on dynamic ruptures with thermal pressurization: Numerical simulations with changes in physical properties of water

NASA Astrophysics Data System (ADS)

Urata, Yumi; Kuge, Keiko; Kase, Yuko

2015-02-01

Phase transitions of pore water have never been considered in dynamic rupture simulations with thermal pressurization (TP), although they may control TP. From numerical simulations of dynamic rupture propagation including TP, in the absence of any water phase transition process, we predict that frictional heating and TP are likely to change liquid pore water into supercritical water for a strike-slip fault under depth-dependent stress. This phase transition causes changes of a few orders of magnitude in viscosity, compressibility, and thermal expansion among physical properties of water, thus affecting the diffusion of pore pressure. Accordingly, we perform numerical simulations of dynamic ruptures with TP, considering physical properties that vary with the pressure and temperature of pore water on a fault. To observe the effects of the phase transition, we assume uniform initial stress and no fault-normal variations in fluid density and viscosity. The results suggest that the varying physical properties decrease the total slip in cases with high stress at depth and small shear zone thickness. When fault-normal variations in fluid density and viscosity are included in the diffusion equation, they activate TP much earlier than the phase transition. As a consequence, the total slip becomes greater than that in the case with constant physical properties, eradicating the phase transition effect. Varying physical properties do not affect the rupture velocity, irrespective of the fault-normal variations. Thus, the phase transition of pore water has little effect on dynamic ruptures. Fault-normal variations in fluid density and viscosity may play a more significant role.

Non-isothermal crystallization kinetics of ternary Se90Te10-xPbx glasses

NASA Astrophysics Data System (ADS)

Atyia, H. E.; Farid, A. S.

2016-02-01

Ternary Se90Te10-xPbx with (x=2 and 6 at%) glass compositions have been prepared using a melt quenching technique and performed the non-isothermal kinetics by differential thermal analysis (DTA) at various heating rates. The glassy state of the studied samples has been characterized using x-ray diffraction analysis. The glass transition temperature Tg, the onset temperature of crystallization Tc and the peak temperature of crystallization Tp are found to be composition and heating rate dependent. From heating rate dependence of Tg and Tp, the glass transition activation energies Eg and the crystallization activation energies Ec have been determined according to different methods. The transformation mechanisms have been examined by the values of Avrami exponent n and dimensionality of growth m. Thermal stability and glass formation ability have been monitored through the calculation of the thermal stability S, temperature difference ΔT, Hurby parameter Hr, frequency factor Ko, crystallization rate factor K and fragility index F. The compositional dependence of the above-mentioned parameters indicate that, the stability of the studied glass samples decreases with increasing Pb at% content.

Synthesis and characterization of titanium dioxide-polypyrrole nanocomposites for the photodegradation of bromophenol blue

NASA Astrophysics Data System (ADS)

Buenviaje, Salvador C.; Usman, Ken Aldren S.; Payawan, Leon M.

2018-05-01

Titania (TiO2) nanoparticles were synthesized through sol-gel method and stabilized by polypyrrole through photopolymerization. The titania-polypyrrole (TP) nanocomposites were then characterized on the basis of particle size, stability, dispersity, band gap energy, and surface morphology. Using dynamic light scattering, TP products of varied mole ratios were found to be all nano in size with bare TiO2 having 66.6 nm and the rest with ˜90 nm. These materials were also found to be stable in water with Zeta potentials all above 25 mV. The band gap energies of TP products were precise and accurate relative to the 3.52 eV of bare TiO2 using ultraviolet-visible spectra. The particles were also monodisperse enough with ˜PDI values of 0.450. The TP material was also drop-casted on mica, and found to have cone-shaped peaks at 60 nm and almost uniform surface using atomic force microscopy. Photodegradation of bromophenol blue was also optimized and found to have 97.53% efficiency in the presence of TP as photocatalyst and at pH 7.

Evolution of the interfacial phases in Al2O3-Kovar® joints brazed using a Ag-Cu-Ti-based alloy

NASA Astrophysics Data System (ADS)

Ali, Majed; Knowles, Kevin M.; Mallinson, Phillip M.; Fernie, John A.

2017-04-01

A systematic investigation of the brazing of Al2O3 to Kovar® (Fe-29Ni-17Co wt.%) using the active braze alloy (ABA) Ag-35.25Cu-1.75Ti wt.% has been undertaken to study the chemical reactions at the interfaces of the joints. The extent to which silica-based secondary phases in the Al2O3 participate in the reactions at the ABA/Al2O3 interface has been clarified. Another aspect of this work has been to determine the influence of various brazing parameters, such as the peak temperature, Tp, and time at Tp, τ, on the resultant microstructure. As a consequence, the microstructural evolution of the joints as a function of Tp and τ is discussed in some detail. The formation of a Fe2Ti layer on the Kovar® and its growth, along with adjacent Ni3Ti particles in the ABA, dominate the microstructural developments at the ABA/Kovar® interface. The presence of Kovar® next to the ABA does not change the intrinsic chemical reactions occurring at the ABA/Al2O3 interface. However, the extent of these reactions is limited if the purity of the Al2O3 is high, and so it is necessary to have some silica-rich secondary phase in the Al2O3 to facilitate the formation of a Ti3Cu3O layer on the Al2O3. Breakdown of the Ti3Cu3O layer, together with fracture of the Fe2Ti layer and separation of this layer from the Kovar®, has been avoided by brazing at temperatures close to the liquidus temperature of the ABA for short periods of time, e.g., for Tp between 820 and 830 °C and τ between 2 and 8 min.

Effect of Mass Flow on Stack Eductor Performance.

DTIC Science & Technology

1984-06-01

absolute viscosity, lbf-sec/ft2 - density, Ibm/ft 3 "function of" ENGLISH LETTER SYMBOLS 2 A - area, in , ft B - atmospheric pressure, in Hg c - sonic... absolute temperature ratio T* - tertiary flow to primary flow absolute temperature t ratio - secondary -o primary mass flow rate ratio W* - tertiary to...secondary to primary absolute Tp temperature ratio TiL tertiary to primary absolute -TE temperature ratio secondary to primary flow density ratio

A more accurate detection of codon 72 polymorphism and LOH of the TP53 gene.

PubMed

Baccouche, Sami; Mabrouk, Imed; Said, Salem; Mosbah, Ali; Jlidi, Rachid; Gargouri, Ali

2003-01-10

The polymorphism at codon 72 of the TP53 gene has been extensively studied for its involvement in cancerogenesis and loss of heterozygosity (LOH) detection. Usually, the exon 4 of the TP53 gene is amplified by polymerase chain reaction (PCR) on DNA extracted from blood and tumor tissues, then digested by AccII. In the case of heterozygosity, the comparison of AccII profile from blood and tumor DNA PCR products allowed the identification of a potential LOH in the TP53 locus. This method can be hindered by a partial AccII digestion and/or DNA contamination of non-tumor cells. To circumvent these problems, we have developed a new approach by using the AccII restriction site between exon 4 and exon 6. The PCR amplification of exon 4-6, followed by AccII digestion allowed us to detect without ambiguity any LOH case.

Fire severity effects on ash extractable Total Phosphorous

NASA Astrophysics Data System (ADS)

Pereira, Paulo; Úbeda, Xavier; Martin, Deborah

2010-05-01

Phosphorous (P) is a crucial element to plant nutrition and limits vegetal production. The amounts of P in soil are lower and great part of this nutrient is absorbed or precipitated. It is well known that fire has important implications on P cycle, that can be lost throughout volatilization, evacuated with the smoke, but also more available to transport after organic matter mineralization imposed by the fire. The release of P depends on ash pH and their chemical and physical characteristics. Fire temperatures impose different severities, according to the specie affected and contact time. Fire severity is often evaluated by ash colour and this is a low-cost and excellent methodology to assess the fire effects on ecosystems. The aim of this work is study the ash properties physical and chemical properties on ash extractable Total Phosphorous (TP), collected in three wildfires, occured in Portugal, (named, (1) Quinta do Conde, (2) Quinta da Areia and (3) Casal do Sapo) composed mainly by Quercus suber and Pinus pinaster trees. The ash colour was assessed using the Munsell color chart. From all three plots we analyzed a total of 102 ash samples and we identified 5 different ash colours, ordered in an increasing order of severity, Very Dark Brown, Black, Dark Grey, Very Dark Grey and Light Grey. In order to observe significant differences between extractable TP and ash colours, we applied an ANOVA One Way test, and considered the differences significant at a p<0.05. The results showed that significant differences in the extractable TP among the different ash colours. Hence, to identify specific differences between each ash colour, we applied a post-hoc Fisher LSD test, significant at a p<0.05. The results obtained showed significant differences between the extractable TP from Very dark Brown and Black ash, produced at lower severities, in relation to Dark Grey, Very Dark Grey and Light Grey ash, generated at higher severities. The means of the first group were higher than the observed in the second one. This indicates that ash produced lower temperatures release in solution higher amounts of TP. These divergences occur due temperature of combustion, affected specie, ash pH values and CaCO3 content, which affects the quantity of this element in solution. Discussions about these effects will be accurate in the communication.

Climate Changes Documented in Ice Core Records from Third Pole Glaciers, with Emphasis on the Guliya Ice Cap in the Western Kunlun Mountains over the Last 100 Years

NASA Astrophysics Data System (ADS)

Thompson, L. G.; Yao, T.; Beaudon, E.; Mosley-Thompson, E.; Davis, M. E.; Kenny, D. V.; Lin, P. N.

2016-12-01

The Third Pole (TP) is a rapidly warming region containing 100,000 km2 of ice cover that collectively holds one of Earth's largest stores of freshwater that feeds Asia's largest rivers and helps sustain 1.5 billion people. Information on the accelerating warming in the region, its impact on the glaciers and subsequently on future water resources is urgently needed to guide mitigation and adaptation policies. Ice core histories collected over the last three decades across the TP demonstrate its climatic complexity and diversity. Here we present preliminary results from the flagship project of the Third Pole Environment Program, the 2015 Sino-American cooperative ice core drilling of the Guliya ice cap in the Kunlun Mountains in the western TP near the northern limit of the region influenced by the southwest monsoon. Three ice cores, each 51 meters in length, were recovered from the summit ( 6700 masl) while two deeper cores, one to bedrock ( 310 meters), were recovered from the plateau ( 6200 masl). Across the ice cap the net balance (accumulation) has increased annually by 2.3 cm of water equivalent from 1963-1992 to 1992-2015, and average oxygen isotopic ratios (δ18O) have enriched by 2‰. This contrasts with the recent ablation on the Naimona'nyi glacier located 540 km south of Guliya in the western Himalaya. Borehole temperatures in 2015 on the Guliya plateau have warmed substantially in the upper 30 meters of the ice compared to temperatures in 1992, when the first deep-drilling of the Guliya plateau was conducted. Compared with glaciers in the northern and western TP, the Himalayan ice fields are more sensitive to both fluctuations in the South Asian Monsoon and rising temperatures in the region. We examine the climatic changes of the last century preserved in ice core records from sites throughout the TP and compare them with those reconstructed for earlier warm epochs, such as the Medieval Climate Anomaly ( 950-1250 AD), the early Holocene "Hypsithermal" ( 5 to 9 kyr BP) and the Eemian (present only in Guliya). The latter epoch is the latest period when Earth may have been as warm as today and thus serves as an analog for the developing greenhouse world.

Application of a GCM Ensemble Seasonal Climate Forecasts to Crop Yield Prediction in East Africa

NASA Astrophysics Data System (ADS)

Ogutu, G.; Franssen, W.; Supit, I.; Hutjes, R. W. A.

2016-12-01

We evaluated the potential use of ECMWF System-4 seasonal climate forecasts (S4) for impacts analysis over East Africa. Using the 15 member, 7 months ensemble forecasts initiated every month for 1981-2010, we tested precipitation (tp), air temperature (tas) and surface shortwave radiation (rsds) forecast skill against the WATCH forcing Data ERA-Interim (WFDEI) re-analysis and other data. We used these forecasts as input in the WOFOST crop model to predict maize yields. Forecast skill is assessed using anomaly correlation (ACC), Ranked Probability Skill Score (RPSS) and the Relative Operating Curve Skill Score (ROCSS) for MAM, JJA and OND growing seasons. Predicted maize yields (S4-yields) are verified against historical observed FAO and nationally reported (NAT) yield statistics, and yields from the same crop model forced by WFDEI (WFDEI-yields). Predictability of the climate forecasts vary with season, location and lead-time. The OND tp forecasts show skill over a larger area up to three months lead-time compared to MAM and JJA. Upper- and lower-tercile tp forecasts are 20-80% better than climatology. Good tas forecast skill is apparent with three months lead-time. The rsds is less skillful than tp and tas in all seasons when verified against WFDEI but higher against others. S4-forecasts captures ENSO related anomalous years with region dependent skill. Anomalous ENSO influence is also seen in simulated yields. Focussing on the main sowing dates in the northern (July), equatorial (March-April) and southern (December) regions, WFDEI-yields are lower than FAO and NAT but anomalies are comparable. Yield anomalies are predictable 3-months before sowing in most of the regions. Differences in interannual variability in the range of ±40% may be related to sensitivity of WOFOST to drought stress while the ACCs are largely positive ranging from 0.3 to 0.6. Above and below-normal yields are predictable with 2-months lead time. We evidenced a potential use of seasonal climate forecasts with a crop simulation model to predict anomalous maize yields over East Africa. The findings open a window to better use of climate forecasts in food security early warning systems, and pre-season policy and farm management decisions.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells.

PubMed

Jung, Yunu; Park, Jinbong; Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-10-20

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake (Micrurus tener tener) venom.

PubMed

Vivas, Jeilyn; Ibarra, Carlos; Salazar, Ana M; Neves-Ferreira, Ana G C; Sánchez, Elda E; Perales, Jonás; Rodríguez-Acosta, Alexis; Guerrero, Belsy

2016-01-01

A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed. Copyright © 2015 Elsevier Inc. All rights reserved.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

PubMed Central

Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH. PMID:29152074

Magnetic and structural properties of nanoparticles of nickel oxide

NASA Astrophysics Data System (ADS)

Shim, Hyunja (Jenny)

In this dissertation, magnetic properties of NiO nanoparticles (NP) prepared by the sol-gel method in the size range D = 5 nm to 20 nm, with and without oleic acid (OA) coating, are reported. Transmission electron microscopy (TEM) studies show the morphology of the smaller particles to be primarily rod-like, changing over to nearly spherical shapes for D >10 nm. Average sizes D of NP determined by x-ray diffraction (XRD) are compared with the results from TEM. From the analysis of the XRD line intensities, the particle size dependence of the Debye-Waller factors for Ni and O atoms are derived. It is found that the Debye-Waller factors of nickel and oxygen atoms in smaller particles are larger than those in bulk NiO. For the coated and uncoated NiO nanorods of 5 nm diameter, variations of the magnetization M with temperature T (5 K to 370 K) and temperature variations of the EMR (electron magnetic resonance) spectra were measured to determine the respective blocking temperatures TB(m) and TB(EMR). The following differences are noted: (1) TB(m) is reduced from 230 K (uncoated) to 85 K(coated) for H = 25 Oe; (2) Decrease of TB(m) with H is weaker and the ratio TB(EMR)/T B(m) is smaller for the uncoated particles. These differences are due to stronger interparticle interaction present in the uncoated particles. Temperature variation (5 K-300 K) of the AC magnetic susceptibilities (chi' and chi") at various frequencies f (0.1-10,000 Hz) are reported for the coated and uncoated 5 nm diameter nanorods of NiO. Using the peak in chi' as the blocking temperature TB, it is observed that TB increases with increasing f. The data for the two samples fit the Vogel-Fulcher law: f = f0exp[-Ea/k(TB-T0)] with f 0 = 9.2 x 1011 Hz, Ea/k = 1085 K and T0 = 162 K (0 K) for the uncoated (coated) particles. This shows that T0 provides a good measure of the effects of interparticle interactions on magnetic relaxation and that these interactions are essentially eliminated with the OA coating. For all the particles, measurements of M versus T (5 K-370 K) in the zero-field cooled (ZFC) and field-cooled (FC) modes are used to determine the average blocking temperature TP. For the OA coated particles, TP increases with increase in size D as expected for superparamagnetic particles. However for the uncoated NP, TP decreases initially with increase in size for D < 10 nm; but for D > 10 nm, TP follows the same trend as for the coated NP. These differences are interpreted in terms of significant interparticle interaction. The data of M vs. the applied field H for T > TP are fit to the modified Langevin function: M = M0 L (muPH/kBT) + chiaH, to determine the magnetic moment muP per particle as a function of size D. The variation of muP with size D is interpreted in terms of the fraction of spins on the surface layer of the particles which contribute to mu P. It is observed that this fraction varies as 1/D reaching nearly 100 % for the 5 nm particles. From the temperature dependence of M0 and extrapolating to M0 → 0, the Neel temperatures TN for various sizes are determined. TN for NiO nanoparticles is found to decreases rapidly with decrease in size for D < 10 nm.

Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wenwen; Yang, Yanqin; Xiong, Zhewen

Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes. Our study aimed to investigate the role of GSK-3β in TP-induced cardiotoxicity. Inhibition of GSK-3β activity by SB 216763, a potent and selective GSK-3more » inhibitor, prominently ameliorated the detrimental effects in C57BL/6J mice with TP administration, which was associated with a correction of GSK-3β overactivity. Consistently, in TP-treated H9c2 cells, SB 216763 treatment counteracted GSK-3β overactivity, improved cell viability, and prevented apoptosis by modulating the expression of Bcl-2 family proteins. Mechanistically, GSK-3β interacted with and phosphorylated cyclophilin F (Cyp-F), a key regulator of mitochondrial permeability transition pore (mPTP). GSK-3β inhibition prevented the phosphorylation and activation of Cyp-F, and desensitized mPTP. Our findings suggest that pharmacological targeting of GSK-3β could represent a promising therapeutic strategy for protecting against cardiotoxicity induced by TP. - Highlights: • GSK-3β inhibition ameliorates TP-induced cardiotoxicity in vitro and in vivo. • GSK-3β controls Cyp-F activation, and regulates mPTP and apoptosis in H9c2 cells. • The protective effect is attributed to GSK-3β activity rather than to protein level. • GSK-3β may be a promising target against TP-induced cardiotoxicity.« less

Magnetic Flux Compression Reactor Concepts for Spacecraft Propulsion and Power (MSFC Center Director's Discretionary Fund; Project No. 99-24). Part 1

NASA Technical Reports Server (NTRS)

Litchford, R. J.; Robertson, G. A.; Hawk, C. W.; Turner, M. W.; Koelfgen, S.; Litchford, Ron J. (Technical Monitor)

2001-01-01

This technical publication (TP) examines performance and design issues associated with magnetic flux compression reactor concepts for nuclear/chemical pulse propulsion and power. Assuming that low-yield microfusion detonations or chemical detonations using high-energy density matter can eventually be realized in practice, various magnetic flux compression concepts are conceivable. In particular, reactors in which a magnetic field would be compressed between an expanding detonation-driven plasma cloud and a stationary structure formed from a high-temperature superconductor are envisioned. Primary interest is accomplishing two important functions: (1) Collimation and reflection of a hot diamagnetic plasma for direct thrust production, and (2) electric power generation for fusion standoff drivers and/or dense plasma formation. In this TP, performance potential is examined, major technical uncertainties related to this concept accessed, and a simple performance model for a radial-mode reactor developed. Flux trapping effectiveness is analyzed using a skin layer methodology, which accounts for magnetic diffusion losses into the plasma armature and the stationary stator. The results of laboratory-scale experiments on magnetic diffusion in bulk-processed type II superconductors are also presented.

Garnet peridotites from Williams kimberlites, north-central Montana, U.S.A

USGS Publications Warehouse

Hearn, B.C.; McGee, E.S.

1983-01-01

Two Williams kimberlites, 250x350m and 37x390m, in the eastern part of a swarm of 30 middle Eocene alnoitic diatremes in north-central Montana, USA, contain xenoliths of garnet-bearing lherzolites, harzburgites and dunites, in addition to spinel peridotites and upper and lower crustal amphibolites and granulites. Colluvial purple, red, and pink garnets are dominantly Mg- and Cr-rich, indicating their derivation From peridotites or megacrysts, and have CaO and Cr2O3 contents that fall in the lherzolite trend. Temperatures were calculated by the Lindsley-Dixon 20 kb method for lherzolites and by the O'Neill-Wood method for harzburgites and dunites, and pressures were calculated by the MacGregor method, or were assumed to be 50 kb for dunites. Most peridotites equilibrated at 1220-1350?C and 50-60 kb, well above a 44mW/m2 shield geotherm and on or at higher P than the graphite-diamond boundary. Four lherzolites are low T-P (830-990?C, 23-42 kb) and are close to the shield geotherm. All four low T-P lherzolites have coarse textures whereas the high T-P cluster has both coarse and porphyroclastic textures, indicating a range of conditions of deformation and recrystallization in a restricted high T-P range. The tiny size (0.01-0.2 mm) of granulated and euhedral olivines in several xenoliths shows that deformation was occurring just prior to incorporation in kimberlite and that ascent was rapid enough (40-70 km/hr) to retard Further coarsening of fine-grained olivine. For other high T-P peridotites, cessation of deformation and beginning of recrystallization before or during inclusion in kimberlite is suggested by larger (up to 3mm) euhedral olivines in a matrix of fine granulated olivine or by optical continuity of large and nearby small olivines. Two low T-P lherzolites contain distinctive, phlogopite-rimmed, 5-8mm clots of moderate-Cr garnet + Cr-spinel + Cr-diopside + enstatite that are inferred to have formed by reaction of an initial high-Cr garnet brought into the garnet + spinel stability Field. This suggests a reduction in pressure and temperature prior to inclusion in the kimberlite, followed by metasomatic introduction of phlogopite. These textural and compositional variations of peridotites seem most compatible with kimberlite generation and ascent during dynamic diapiric perturbation of the upper mantle.

Aquatic Nutrient Simulation Modules (NSMs) Developed for Hydrologic and Hydraulic Models

DTIC Science & Technology

2016-02-01

effect of temperature on algal growth unitless FOxpi oxygen attenuation for algal respiration unitless FOxb oxygen attenuation for benthic algal... effect of temperature below T0p on benthic algal growth 0C-2 ktb2 effect of temperature above T0p on benthic algal growth 0C-2 ka(T) oxygen ...Si Silica SOD Sediment Oxygen Demand SO4 TEMP Sulfate Water Temperature Simulation Module TN Total Nitrogen TP Total Phosphorous TIC Total

Northern Hemisphere Autumn and Winter Climate Responses to Realistic Tibetan Plateau and Mongolia Snow Anomalies

NASA Astrophysics Data System (ADS)

Wu, Q.; Yao, Y.; Liu, S.

2017-12-01

The impact of the Eurasian snow cover extent (SCE) on the Northern Hemisphere (NH) circulation is first investigated by applying a lagged maximum covariance analysis (MCA) to monthly satellite-derived SCE and NCEP reanalysis data. Wintertime atmospheric signals significantly correlated with persistently autumn-early winter SCE anomalies are found in the leading two MCA modes. The first MCA mode indicates the effect of Eurasian snow cover anomalies on the Arctic Oscillation/North Atlantic Oscillation (AO/NAO). The second MCA mode links a persistent dipole of autumn and winter SCE anomalies over the Tibetan Plateau (TP) and Mongolia with winter Pacific-North America (PNA)-like atmospheric variations. A modeling study further investigates atmospheric responses to above TP and Mongolia snow forcings using multiple ensemble transient integrations of the CAM4 and CLM4.0 models. Model boundary conditions are based on climatological sea ice extent (SIE) and sea surface temperature (SST), and satellite observations of SCE and snow water equivalent (SWE) over the TP and Mongolia from October to March in 1997/98 (heavy TP and light Mongolia snow) and 1984/85 (light TP and heavy Mongolia snow), with model derived SCE and SWE elsewhere. In various forcing experiments, the ensemble-mean difference between simulations with these two extreme snow states identifies local, distant, concurrent, and delayed climatic responses. The main atmospheric responses to a dipole of high TP and low Mongolia SCE persisting from October to March (versus the opposite extreme) are strong TP surface cooling, warming in the surrounding China and Mongolia region, and a winter positive PNA-like response. The localized response is maintained by persistent diabatic cooling or heating, and the remote PNA response results mainly from the increased horizontal eastward propagation of stationary Rossby wave energy due to persistent TP snow forcing and also a winter transient eddy feedback mechanism. With a less persistent dipole anomaly in autumn or winter only, local responses are similar depending on the specific anomalies, but the winter PNA-like response is nearly absent or noticeably reduced.

Mapping mesoscale variability of the Azores Current using TOPEX/POSEIDON and ERS 1 altimetry, together with hydrographic and Lagrangian measurements

NASA Astrophysics Data System (ADS)

Hernandez, Fabrice; Le Traon, Pierre-Yves; Morrow, Rosemary

1995-12-01

The SEMAPHORE mesoscale air/sea experiment was conducted in the Azores-Madeira region from July to November 1993. TOPEX/POSEIDON (T/P) and ERS 1 were flying simultaneously at that time. The main purposes of this paper are to evaluate the estimation of the oceanic mesoscale circulation from the two different sets of altimetric data (T/P and ERS 1) and to compare the results with in situ measurements provided by the SEMAPHORE hydrographic surveys and surface drifters (three expendable bathytermograph conductivity-temperature-depth surveys in a 500-km2 box and a set of 47 Lagrangian surface drifters drogued at 150 m). Comparisons are carried out through the maps obtained by objective analysis from the four data sets. The mapping accuracy of T/P, ERS 1, T/P and ERS 1 combined, and in situ data is investigated, as well as the sensitivity of the mapping to the correlation functions used. There is a good qualitative agreement between altimetric maps and corresponding drifter and hydrographic maps for the three hydrographic surveys. Correlations are about 0.8, and the regression fit is about 0.6-0.7; the lower values are due to the smooth climatology used to reference the altimetric maps. The correlation for time differences is better, with regression lines not significantly different from 1, especially when ERS 1 and T/P are combined. T/P mapping is almost as good as ERS 1 mapping, which was rather unexpected since the ERS 1 space-time sampling is better suited for the mesoscale. This may reflect the fact that the signal mapped by the hydrography and drifters does not contain the high frequency/wavenumber components. T/P and ERS 1 combined provide better results, although the improvement is not as large as expected, probably for the same reason.

Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau.

PubMed

Chen, Deliang; Tian, Yudong; Yao, Tandong; Ou, Tinghai

2016-08-24

This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302-480 km, while the annual precipitation showed smaller scales of 111-182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions.

Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau

NASA Astrophysics Data System (ADS)

Chen, Deliang; Tian, Yudong; Yao, Tandong; Ou, Tinghai

2016-08-01

This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302-480 km, while the annual precipitation showed smaller scales of 111-182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions.

Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau

PubMed Central

Chen, Deliang; Tian, Yudong; Yao, Tandong; Ou, Tinghai

2016-01-01

This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302–480 km, while the annual precipitation showed smaller scales of 111–182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions. PMID:27553388

Onset of the convection in a supercritical fluid.

PubMed

Meyer, H

2006-01-01

A model is proposed that leads to the scaled relation tp/tau D=Ftp(Ra-Rac) for the development of convection in a pure fluid in a Rayleigh-Bénard cell after the start of the heat current at t=0. Here tp is the time of the first maximum of the temperature drop DeltaT(t) across the fluid layer, the signature of rapidly growing convection, tau D is the diffusion relaxation time, and Rac is the critical Rayleigh number. Such a relation was first obtained empirically from experimental data. Because of the unknown perturbations in the cell that lead to convection development beyond the point of the fluid instability, the model determines tp/tau D within a multiplicative factor Psi square root Rac(HBL), the only fit parameter product. Here Rac(HBL), of the order 10(3), is the critical Rayleigh number of the hot boundary layer and Psi is a fit parameter. There is then good agreement over more than four decades of Ra-Rac between the model and the experiments on supercritical 3He at various heat currents and temperatures. The value of the parameter Psi, which phenomenologically represents the effectiveness of the perturbations, is discussed in connection with predictions by El Khouri and Carlès of the fluid instability onset time.

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

PubMed Central

Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

2016-01-01

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

Network dimensionality and ligand flexibility in lanthanide terephthalate hydrates

NASA Astrophysics Data System (ADS)

Zehnder, Ralph A.; Renn, Robert A.; Pippin, Ethan; Zeller, Matthias; Wheeler, Kraig A.; Carr, Jason A.; Fontaine, Nick; McMullen, Nathan C.

2011-01-01

Various lanthanide open framework materials incorporating the terephthalate (TP) entity were prepared using hydrothermal synthesis methods at a moderate temperature of 170 °C. The compounds Nd 2(TP) 3(H 2O) 4( 1), Er 2(TP) 3(H 2O) 4( 2), Yb 2(TP) 3(H 2O) 2( 3), Yb 2(TP) 3(H 2O) 6( 4), and Yb 2(TP) 3(H 2O) 8·2H 2O ( 5), were characterized by single crystal structural analysis and FT-IR spectroscopy. While compounds 1 and 2 have been reported before on the basis of powder X-ray diffraction, the structural characterization of any ytterbium terephthalate species is unprecedented. Compounds 1- 5 crystallize in triclinic settings with space group P-1. The compounds are compared with their previously reported Er and Tb-counterparts and the reduction of the dimensionality of the resulting networks from 3D over 2D to 1D with increasing level of hydration is discussed. Compounds 1, 2, and 3 with the lowest water content assemble in three-dimensional network lattices. Compounds 4 and 5, however, form 2D layered systems and 1D rod like chains, respectively, which are held together by hydrogen bonds originating from coordinating H 2O. The crystal lattices of the 3D networks experience higher levels of tension as can be seen by increasing out-of-plane torsion with regard to the terephthalate carboxylate groups. Moreover, there seems to be a correlation between the level of strain on the aromatic ligands and the reduction of the number of carboxylate oxygen atoms that are part of the coordination polyhedra.

GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer.

PubMed

Checa-Rojas, Alberto; Delgadillo-Silva, Luis Fernando; Velasco-Herrera, Martín Del Castillo; Andrade-Domínguez, Andrés; Gil, Jeovanis; Santillán, Orlando; Lozano, Luis; Toledo-Leyva, Alfredo; Ramírez-Torres, Alberto; Talamas-Rohana, Patricia; Encarnación-Guevara, Sergio

2018-04-24

The molecular processes and proteomic markers leading to tumor progression (TP) in cervical cancer (CC) are either unknown or only partially understood. TP affects metabolic and regulatory mechanisms that can be identified as proteomic changes. To identify which proteins are differentially expressed and to understand the mechanisms of cancer progression, we analyzed the dynamics of the tumor proteome in CC cell lines. This analysis revealed two proteins that are up-regulated during TP, GSTM3 and GSTP1. These proteins are involved in cell maintenance, cell survival and the cellular stress response via the NF-κB and MAP kinase pathways during TP. Furthermore, GSTM3 and GSTP1 knockdown showed that evasion of apoptosis was affected, and tumor proliferation was significantly reduced. Our data indicate the critical role of GST proteins in the regulation and progression of cervical cancer cells. Hence, we suggest GSTM3 and GSTP1 as novel biomarkers and potential therapeutic targets for treating cervical cancer. CC is particularly hazardous in the advanced stages, and there are few therapeutic strategies specifically targeting these stages. We performed analyses on CC tumor proteome dynamics and identified GSTM3 and GSTP1 as novel potential therapeutic targets. Knockdown of these proteins showed that they are involved in cell survival, cell proliferation and cellular evasion of apoptosis.

Evaluation of internal loading and water level changes: implications for phosphorus, algal production, and nuisance blooms in Kabetogama Lake, Voyageurs National Park, Minnesota

USGS Publications Warehouse

Christensen, Victoria G.; Maki, Ryan P.; Kiesling, Richard L.

2013-01-01

Hydrologic manipulations have the potential to exacerbate or remediate eutrophication in productive reservoirs. Dam operations at Kabetogama Lake, Minnesota, were modified in 2000 to restore a more natural water regime and improve water quality. The US Geological Survey and National Park Service evaluated nutrient, algae, and nuisance bloom data in relation to changes in Kabetogama Lake water levels. Comparison of the results of this study to previous studies indicates that chlorophyll a concentrations have decreased, whereas total phosphorus (TP) concentrations have not changed significantly since 2000. Water and sediment quality data were collected at Voyageurs National Park during 2008–2009 to assess internal phosphorus loading and determine whether loading is a factor affecting TP concentrations and algal productivity. Kabetogama Lake often was mixed vertically, except for occasional stratification measured in certain areas, including Lost Bay in the northeastern part of Kabetogama Lake. Stratification, higher bottom water and sediment nutrient concentrations than in other parts of the lake, and phosphorus release rates estimated from sediment core incubations indicated that Lost Bay is one of several areas that may be contributing to internal loading. Internal loading of TP is a concern because increased TP may cause excessive algal growth including potentially toxic cyanobacteria.

Evaluating water quality ecosystem services of wetlands under historic and future climate

NASA Astrophysics Data System (ADS)

Records, R.; Arabi, M.; Fassnacht, S. R.; Duffy, W.; Ahmadi, M.; Hegewisch, K.

2013-12-01

Potential hydrologic effects of climate change have been assessed extensively; however, possible impacts of changing climate on in-stream water quality at the watershed scale have received little study. We assessed potential impacts of climate change on water quantity and quality in the mountainous Sprague River watershed, Oregon, USA, where high total phosphorus (TP) and sediment loads are associated with lake eutrophication and mortality of endangered fish species. Additionally, we analyzed water quality impacts of wetland and riparian zone loss and gain under present-day climate and future climate scenarios. We utilized the hydrologic model Soil and Water Assessment Tool (SWAT) forced with six distinct climate scenarios derived from Coupled Model Intercomparison Project 5 (CMIP5) General Circulation Models to assess magnitude and direction of trends in streamflow, sediment and TP fluxes in the mid-21st century (2030-2059). Model results showed little significant trend in average annual streamflow under most climate scenarios, but trends in annual and monthly streamflow, sediment, and TP fluxes were more pronounced and were generally increasing. Results also suggest that future loss of present-day wetlands and riparian zones under land use or climatic change could result in substantial increases in sediment and TP loads at the Sprague River outlet.

Malignancy Risk Models for Oral Lesions

PubMed Central

Zarate, Ana M.; Brezzo, María M.; Secchi, Dante G.; Barra, José L.

2013-01-01

Objectives: The aim of this work was to assess risk habits, clinical and cellular phenotypes and TP53 DNA changes in oral mucosa samples from patients with Oral Potentially Malignant Disorders (OPMD), in order to create models that enable genotypic and phenotypic patterns to be obtained that determine the risk of lesions becoming malignant. Study Design: Clinical phenotypes, family history of cancer and risk habits were collected in clinical histories. TP53 gene mutation and morphometric-morphological features were studied, and multivariate models were applied. Three groups were estabished: a) oral cancer (OC) group (n=10), b) OPMD group (n=10), and c) control group (n=8). Results: An average of 50% of patients with malignancy were found to have smoking and drinking habits. A high percentage of TP53 mutations were observed in OC (30%) and OPMD (average 20%) lesions (p=0.000). The majority of these mutations were GC ? TA transversion mutations (60%). However, patients with OC presented mutations in all the exons and introns studied. Highest diagnostic accuracy (p=0.0001) was observed when incorporating alcohol and tobacco habits variables with TP53 mutations. Conclusions: Our results prove to be statistically reliable, with parameter estimates that are nearly unbiased even for small sample sizes. Models 2 and 3 were the most accurate for assessing the risk of an OPMD becoming cancerous. However, in a public health context, model 3 is the most recommended because the characteristics considered are easier and less costly to evaluate. Key words:TP53, oral potentially malignant disorders, risk factors, genotype, phenotype. PMID:23722122

Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa

PubMed Central

Yin, Honging; Deng, Yifeng; Wang, Huafu; Liu, Wugao; Zhuang, Xiyi; Chu, Weihua

2015-01-01

Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection. PMID:26548447

Naphthylacetic Acid and Tea Polyphenol Application Promote Biomass and Lipid Production of Nervonic Acid-Producing Microalgae.

PubMed

Xu, Feng; Fan, Yong; Miao, Fuhong; Hu, Guang-Rong; Sun, Juan; Yang, Guofeng; Li, Fu-Li

2018-01-01

Mychonastes afer HSO-3-1 is a potential producer of nervonic acid, which could be accumulated to 2-3% of dry cell weight. Improving the productivity of nervonic acid is critical to promote the commercialization of this product. In this study, 1-naphthylacetic acid (NAA) and tea polyphenol (TP) were selected as bioactive additives to stimulate the growth of M. afer . Supplementing NAA in the early growth stage and TP in the middle and late growth stage led to improved lipid accumulation in M. afer . The cultures supplemented with TP at the late growth stage maintained higher photosynthetic efficiency than the control groups without TP. Furthermore, the intracellular reactive oxygen species (ROS) accumulations in M. afer supplemented with 500 mg/L of TP was 63% lower than the control group. A linear relationship ( R 2 = 0.899) between the values of Fv/Fm and ROS accumulation was established. We hypothesize supplement of bioactive additives at different growth stage could promote the cell growth rate and nervonic acid productivity of M. afer by retrieving intracellular ROS level. Further analysis of photosynthetic system II (PSII) protein in M. afer cultured in presence of NAA and TP indicated the levels of D1 and D2 proteins, the core skeleton proteins of PSII, showed 33.3 and 25.6% higher than the control group. CP43 protein, a critical module in PSII repair cycle, decreased significantly. These implied that TP possesses the function of slowing down the damage of PSII by scavenging excess intracellular ROS.

TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines

NASA Technical Reports Server (NTRS)

Schwartz, J. L.; Jordan, R.; Liber, H.; Murnane, J. P.; Evans, H. H.

2001-01-01

Telomere shortening in telomerase-negative somatic cells leads to the activation of the TP53 protein and the elimination of potentially unstable cells. We examined the effect of TP53 gene expression on both telomere metabolism and chromosome stability in immortal, telomerase-positive cell lines. Telomere length, telomerase activity, and chromosome instability were measured in multiple clones isolated from three related human B-lymphoblast cell lines that vary in TP53 expression; TK6 cells express wild-type TP53, WTK1 cells overexpress a mutant form of TP53, and NH32 cells express no TP53 protein. Clonal variations in both telomere length and chromosome stability were observed, and shorter telomeres were associated with higher levels of chromosome instability. The shortest telomeres were found in WTK1- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability. The primary marker of instability was the presence of dicentric chromosomes. Aneuploidy and other stable chromosome alterations were also found in clones showing high levels of dicentrics. Polyploidy was found only in WTK1-derived cells. Both telomere length and chromosome instability fluctuated in the different cell populations with time in culture, presumably as unstable cells and cells with short telomeres were eliminated from the growing population. Our results suggest that transient reductions in telomere lengths may be common in immortal cell lines and that these alterations in telomere metabolism can have a profound effect on chromosome stability. Copyright 2000 Wiley-Liss, Inc.

Decreasing Phosphorus Loss in Tile-Drained Landscapes Using Flue Gas Desulfurization Gypsum.

PubMed

King, K W; Williams, M R; Dick, W A; LaBarge, G A

2016-09-01

Elevated phosphorus (P) loading from agricultural nonpoint-source pollution continues to impair inland waterbodies throughout the world. The application of flue gas desulfurization (FGD) gypsum to agricultural fields has been suggested to decrease P loading because of its high calcium content and P sorbing potential. A before-after control-impact paired field experiment was used to examine the water quality effects of successive FGD gypsum applications (2.24 Mg ha; 1 ton acre each) to an Ohio field with high soil test P levels (>480 ppm Mehlich-3 P). Analysis of covariance was used to compare event discharge, dissolved reactive P (DRP), and total P (TP) concentrations and loadings in surface runoff and tile discharge between the baseline period (86 precipitation events) and Treatment Period 1 (42 precipitation events) and Treatment Period 2 (84 precipitation events). Results showed that, after the first application of FGD gypsum, event mean DRP and TP concentrations in treatment field tile water were significantly reduced by 21 and 10%, respectively, and DRP concentrations in surface runoff were significantly reduced by 14%; however, no significant reductions were noted in DRP or TP loading. After the second application, DRP and TP loads were significantly reduced in surface runoff (DRP, 41%; TP 40%), tile discharge (DRP, 35%; TP, 15%), and combined (surface + tile) discharge (DRP, 36%; TP, 38%). These findings indicate that surface application of FGD gypsum can be used as a tool to address elevated P concentrations and loadings in drainage waters. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Rugged, Low Cost, Environmental Sensors for a Turbulent World

NASA Astrophysics Data System (ADS)

Schulz, B.; Sandell, C. T.; Wickert, A. D.

2017-12-01

Ongoing scientific research and resource management require a diverse range of high-quality and low-cost sensors to maximize the number and type of measurements that can be obtained. To accomplish this, we have developed a series of diversified sensors for common environmental applications. The TP-DownHole is an ultra-compact temperature and pressure sensor designed for use in CMT (Continuous Multi-channel Tubing) multi-level wells. Its 1 mm water depth resolution, 30 cm altitude resolution, and rugged design make it ideal for both water level measurements and monitoring barometric pressure and associated temperature changes. The TP-DownHole sensor has also been incorporated into a self-contained, fully independent data recorder for extreme and remote environments. This device (the TP-Solo) is based around the TP-DownHole design, but has self-contained power and data storage and is designed to collect data independently for up to 6 months (logging at once an hour), creating a specialized tool for extreme environment data collection. To gather spectral information, we have also developed a very low cost photodiode-based Lux sensor to measure spectral irradiance; while this does not measure the entire solar radiation spectrum, simple modeling to rescale the remainder of the solar spectrum makes this a cost-effective alternative to a thermopile pyranometer. Lastly, we have developed an instrumentation amplifier which is designed to interface a wide range of sensitive instruments to common data logging systems, such as thermopile pyranometers, thermocouples, and many other analog output sensors. These three instruments are the first in a diverse family aimed to give researchers a set of powerful and low-cost tools for environmental instrumentation.

Precipitation Kinetics of M23C6 Carbides in the Super304H Austenitic Heat-Resistant Steel

NASA Astrophysics Data System (ADS)

Zhou, Qingwen; Ping, Shaobo; Meng, Xiaobo; Wang, Ruikun; Gao, Yan

2017-12-01

The precipitation kinetics of M23C6 carbides in Super304H and TP304H steels were investigated using the selective-etching method, SEM backscattered electron images and Image-Pro-Plus 6.0 software. Precipitation-temperature-time (PTT) diagrams of M23C6 carbides in the as-received Super304H (fine grains), coarsened Super304H (coarse grains) and TP304H (coarse grains) steels all show the typical C-shaped character with nose temperature range from 800 to 850 °C. Compared with the TP304H steel, the same trend is found of the PTT curve of M23C6 carbides for both kinds of Super304H steels, but their start lines move to the right and finish lines to the left. The preferential formation of Nb(C,N) phase at grain boundaries in the Super304H steels inhibited the nucleation of M23C6 carbides in the early stage of precipitation, causing the right shift of the start line of PTT curve. The main reason for the left shift of the finish line of the two Super304H steels was the quicker growing and coarsening rate of M23C6 in the later precipitation stage due to their higher C content than in TP304H. For the difference in PPT curves between the two grain sizes of the Super304H steel, the lower diffusion rate of atoms in the coarse-grained Super304H steel may explain its righter finish line than the fine-grained counterpart, while the reason for its lefter start line is due to the higher solute segregation along coarse-grained boundaries.

Spatio-temporal variations of spring phenology of Plantago asiatica and Taraxacum mongolicum in the Tibetan Plateau from 2000 to 2011

NASA Astrophysics Data System (ADS)

Zheng, Z.; Zhu, W.

2016-12-01

Plant phenology is strongly controlled by climate and has become a sensitive bio-indicator to study the plant response to climate change. Since the high altitude, permafrost geography and harsh physical environment of the Tibetan Plateau (TP), the phenology shift in the TP was thought to be more sensitive than many other regions. However, the study of phenology in the TP was greatly limited by the lack of ground-observed phenological data. In this study, we collected the phonological records of first leaf date (FLD) and the first flowering date (FFD) of two herbaceous species (Plantago asiatica and Taraxacum mongolicum) both from 14 stations across the TP during 2000-2011 and analyzed the spatio-temporal variations of spring phenology. The results showed that the onset dates of FLD and FFD exhibited strong dependence on latitude, longitude and altitude because the onset dates of spring phenology occurred earlier at warmer locations. The sensitivities of spring phenology temperature varied among stations and earlier phenological events showed more negative temperature sensitivity except for the FFD of Taraxacum mongolicum. But the relationship between spring phenology and precipitation was not clear. Though the diverse trends of spring phenology of Plantago asiatica and Taraxacum mongolicum were found, the differences between the onset dates of FLD of the two species tended to increase (P < 0.05). However, the differences between the onset dates of FFD of the two species showed a reducing tendency (P < 0.01). These findings can help us to better understand the responses of plants to climate change in alpine ecosystem and provide information for phenology modelling.

PRIMELT3 MEGA.XLSM software for primary magma calculation: Peridotite primary magma MgO contents from the liquidus to the solidus

NASA Astrophysics Data System (ADS)

Herzberg, C.; Asimow, P. D.

2015-02-01

An upgrade of the PRIMELT algorithm for calculating primary magma composition is given together with its implementation in PRIMELT3 MEGA.xlsm software. It supersedes PRIMELT2.xls in correcting minor mistakes in melt fraction and computed Ni content of olivine, it identifies residuum mineralogy, and it provides a thorough analysis of uncertainties in mantle potential temperature and olivine liquidus temperature. The uncertainty analysis was made tractable by the computation of olivine liquidus temperatures as functions of pressure and partial melt MgO content between the liquidus and solidus. We present a computed anhydrous peridotite solidus in T-P space using relations amongst MgO, T and P along the solidus; it compares well with experiments on the solidus. Results of the application of PRIMELT3 to a wide range of basalts shows that the mantle sources of ocean islands and large igneous provinces were hotter than oceanic spreading centers, consistent with earlier studies and expectations of the mantle plume model.

High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans.

PubMed

Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

2009-01-31

To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis.

Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II.

PubMed

Bera, Hriday; Ojha, Probir kumar; Tan, Bee Jen; Sun, Lingyi; Dolzhenko, Anton V; Chui, Wai-Keung; Chiu, Gigi Ngar Chee

2014-05-06

In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 μM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Spatial and Temporal Variations of Water Quality and Trophic Status in Sembrong Reservoir, Johor

NASA Astrophysics Data System (ADS)

Intan Najla Syed Hashim, Syarifah; Hidayah Abu Talib, Siti; Salleh Abustan, Muhammad

2018-03-01

A study of spatial and temporal variations on water quality and trophic status was conducted to determine the temporal (average reading by month) and spatial variations of water quality in Sembrong reservoir and to evaluate the trophic status of the reservoir. Water samples were collected once a month from November 2016 to June 2017 in seventeen (17) sampling stations at Sembrong Reservoir. Results obtained on the concentration of dissolved oxygen (DO), water temperature, pH and secchi depth had no significant differences compared to Total Phosphorus (TP) and chlorophyll-a. The water level has significantly decreased the value of the water temperature, pH and TP. The water quality of Sembrong reservoir is classified in Class II which is suitable for recreational uses and required conventional treatment while TSI indicates that sembrong reservoir was in lower boundary of classical eutrophic (TSI > 50).

[Pilot-scale opposite folded plate hybrid anaerobic reactor (OFPHAR) in treatment of sewage].

PubMed

Han, Xiang-Kui; Ye, Chang-Bing; Zhuang, Jin-Peng; Bi, Dong; Wang, Lei

2008-11-01

Based on the theories of mass-transfer and two-double integrated staged multi-phase anaerobe (TSMPA), a pilot-scale opposite folded plate hybrid anaerobic reactor (OFPHAR) was designed to treat low concentration sewage. All the trial lasted 12 months and the results indicated that the optimal HRT was 6h. At this HRT, the COD, TP and TN removal rate were 78.58%, 35.15%, 39.17%, respectively, at 25 degrees C +/- 2 degrees C. The optimal rate of anaerobic section was 45%-65%. Controlled HRT = 6 h, the COD, TP and TN removal rate were 64.37%, 20.72%, 23.65%, respectively, and the specific methane production capacity were 1.85 mL/(g x h) when the temperature decreased to 7 degrees C. The results of trial indicated that apply this OFPHAR to treat low concentration sewage at low temperature in north China is feasible.

Kondo destruction in a quantum paramagnet with magnetic frustration

NASA Astrophysics Data System (ADS)

Zhang, Jiahao; Zhao, Hengcan; Lv, Meng; Hu, Sile; Isikawa, Yosikazu; Yang, Yi-feng; Si, Qimiao; Steglich, Frank; Sun, Peijie

2018-06-01

We report results of isothermal magnetotransport and susceptibility measurements at elevated magnetic fields B down to very low temperatures T on single crystals of the frustrated Kondo-lattice system CePdAl. They reveal a B*(T ) line within the paramagnetic part of the phase diagram. This line denotes a thermally broadened "small"-to-"large" Fermi-surface crossover which substantially narrows upon cooling. At B0 *=B*(T =0 ) =(4.6 ±0.1 ) T , this B*(T ) line merges with two other crossover lines, viz. Tp(B ) below and TFL(B ) above B0 *. Tp characterizes a frustration-dominated spin-liquid state, while TFL is the Fermi-liquid temperature associated with the lattice Kondo effect. Non-Fermi-liquid phenomena which are commonly observed near a "Kondo-destruction" quantum-critical point cannot be resolved in CePdAl. Our observations reveal a rare case where Kondo coupling, frustration, and quantum criticality are closely intertwined.

Field evidence for earlier leaf-out dates in alpine grassland on the eastern Tibetan Plateau from 1990 to 2006.

PubMed

Zhou, H K; Yao, B Q; Xu, W X; Ye, X; Fu, J J; Jin, Y X; Zhao, X Q

2014-08-01

Worldwide, many plant species are experiencing an earlier onset of spring phenophases due to climate warming. Rapid recent temperature increases on the Tibetan Plateau (TP) have triggered changes in the spring phenology of the local vegetation. However, remote sensing studies of the land surface phenology have reached conflicting interpretations about green-up patterns observed on the TP since the mid-1990s. We investigated this issue using field phenological observations from 1990 to 2006, for 11 dominant plants on the TP at the levels of species, families (Gramineae-grasses and Cyperaceae-sedges) and vegetation communities (alpine meadow and alpine steppe). We found a significant trend of earlier leaf-out dates for one species (Koeleria cristata). The leaf-out dates of both Gramineae and Cyperaceae had advanced (the latter significantly, starting an average of 9 days later per year than the former), but the correlation between them was significant. The leaf-out dates of both vegetation communities also advanced, but the pattern was only significant in the alpine meadow. This study provides the first field evidence of advancement in spring leaf phenology on the TP and suggests that the phenology of the alpine steppe can differ from that of the alpine meadow. These findings will be useful for understanding ecosystem responses to climate change and for grassland management on the TP. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Effect of water content and heating temperature on thermal properties of brown rice batter

NASA Astrophysics Data System (ADS)

Aboukzail, Jehan; Abdullah, Aminah; Ghani, Maaruf Abd

2015-09-01

The objectives of this research were to assess the effect of water content in the formulation (60%,80%, 100%, 105%, 110%, 120% flour basis) on starch gelatinization of brown rice batter, and to identify the effects of heat treatment at 50°C, 60°C, 70°C, 80°C on starch gelatinization and degree of starch gelatinization of brown rice batter and wheat dough. At 60% water content, there was no gelatinization of brown rice batter, but the batter was gelatinized by increasing the water content to 80%. No significant differences in onset (To) peak (Tp) and endest (Tend) temperature when the water content increased from 80% to 120%; however, enthalpy (ΔH) decreased when water content grew up. Heat treatment of brown rice batter at 60% water content made brown rice batter gelatinized. Starch gelatinization temperature To, Tend and ΔH did not have significant differences when temperature of heat treatment increased from 50°C to 80°C while Tp increased significantly (p<0.05) at 80°C. However, heat treatment had more effect on wheat dough compared to brown rice batter.

Lake seasonality across the Tibetan Plateau and their varying relationship with regional mass changes and local hydrology

NASA Astrophysics Data System (ADS)

Lei, Yanbin; Yao, Tandong; Yang, Kun; Sheng, Yongwei; Kleinherenbrink, Marcel; Yi, Shuang; Bird, Broxton W.; Zhang, Xiaowen; Zhu, La; Zhang, Guoqing

2017-01-01

The recent growth and deepening of inland lakes in the Tibetan Plateau (TP) may be a salient indicator of the consequences of climate change. The seasonal dynamics of these lakes is poorly understood despite this being potentially crucial for disentangling contributions from glacier melt and precipitation, which are all sensitive to climate, to lake water budget. Using in situ observations, satellite altimetry and gravimetry data, we identified two patterns of lake level seasonality. In the central, northern, and northeastern TP, lake levels are characterized by considerable increases during warm seasons and decreases during cold seasons, which is consistent with regional mass changes related to monsoon precipitation and evaporation. In the northwestern TP, however, lake levels exhibit dramatic increases during both warm and cold seasons, which deviate from regional mass changes. This appears to be more connected with high spring snowfall and large summer glacier melt. The variable lake level response to different drivers indicates heterogeneous sensitivity to climate change between the northwestern TP and other regions.

Organizational influence of the postnatal testosterone surge on the circadian rhythm of core body temperature of adult male rats.

PubMed

Zuloaga, Damian G; McGivern, Robert F; Handa, Robert J

2009-05-01

The suprachiasmatic nucleus (SCN) of the hypothalamus coordinates physiological and behavioral circadian rhythms such as activity, body temperature, and hormone secretion. Circadian rhythms coordinated by the SCN often show sex differences arising from both organizational and activational effects of gonadal hormones. In males, little is known about the organizational role of testosterone on the circadian regulation of core body temperature (CBT) in adulthood. To explore this, we castrated or sham-operated male rats on the day of birth, and at 4 months of age, implanted them with transmitters that measured CBT rhythms under a 12:12 light/dark cycle. This study revealed a significantly earlier rise in CBT during the light phase in neonatally castrated males. Subsequently, we found that treating neonatally castrated males with testosterone propionate (TP) in adulthood did not reverse the effect of neonatal castration, thus indicating an organizational role for testosterone. In contrast, a single injection of TP at the time of neonatal surgery, to mimic the postnatal surge of testosterone, coupled with TP treatment in adulthood, normalized the circadian rise in CBT. In a final study we examined CBT circadian rhythms in intact adult male and female rats and detected no differences in the rise of CBT during the light phase, although there was a greater overall elevation in female CBT. Together, results of these studies reveal an early organizational role of testosterone in males on the timing of the circadian rise of CBT, a difference that does not appear to reflect "defeminization".

Rapid formation and pollutant removal ability of aerobic granules in a sequencing batch airlift reactor at low temperature.

PubMed

Jiang, Yu; Shang, Yu; Wang, Hongyu; Yang, Kai

2016-12-01

The start-up of an aerobic granular sludge (AGS) reactor at low temperature was more difficult than at ambient temperature.The rapid formation and characteristics of AGS in a sequencing batch airlift reactor at low temperature were investigated. The nutrient removal ability of the system was also evaluated. It was found that compact granules with clear boundary were formed within 10 days and steady state was achieved within 25 days. The settling properties of sludge were improved with the increasing secretion of extracellular polymeric substances and removal performances of pollutants were enhanced along with granulation. The average removal efficiencies of COD, NH4(+)-N, total nitrogen (TN), total phosphorus (TP) after aerobic granules maturing were over 90.9%, 94.7%, 75.4%, 80.2%, respectively. The rise of temperature had little impact on pollutant biodegradation while the variation of dissolved oxygen caused obvious changes in TN and TP removal rates. COD concentrations of effluents were below 30 mg l(-1) in most cycles of operation with a wide range of organic loading rates (0.6-3.0 kg COD m(-3) d(-1)). The rapid granulation and good performance of pollutant reduction by the system might provide an alternate for wastewater treatment in cold regions.

Cross-plane electronic and thermal transport properties of p-type La0.67Sr0.33MnO3/LaMnO3 perovskite oxide metal/semiconductor superlattices

NASA Astrophysics Data System (ADS)

Jha, Pankaj; Sands, Timothy D.; Cassels, Laura; Jackson, Philip; Favaloro, Tela; Kirk, Benjamin; Zide, Joshua; Xu, Xianfan; Shakouri, Ali

2012-09-01

Lanthanum strontium manganate (La0.67Sr0.33MnO3, i.e., LSMO)/lanthanum manganate (LaMnO3, i.e., LMO) perovskite oxide metal/semiconductor superlattices were investigated as a potential p-type thermoelectric material. Growth was performed using pulsed laser deposition to achieve epitaxial LSMO (metal)/LMO (p-type semiconductor) superlattices on (100)-strontium titanate (STO) substrates. The magnitude of the in-plane Seebeck coefficient of LSMO thin films (<20 μV/K) is consistent with metallic behavior, while LMO thin films were p-type with a room temperature Seebeck coefficient of 140 μV/K. Thermal conductivity measurements via the photo-acoustic (PA) technique showed that LSMO/LMO superlattices exhibit a room temperature cross-plane thermal conductivity (0.89 W/m.K) that is significantly lower than the thermal conductivity of individual thin films of either LSMO (1.60 W/m.K) or LMO (1.29 W/m.K). The lower thermal conductivity of LSMO/LMO superlattices may help overcome one of the major limitations of oxides as thermoelectrics. In addition to a low cross-plane thermal conductivity, a high ZT requires a high power factor (S2σ). Cross-plane electrical transport measurements were carried out on cylindrical pillars etched in LSMO/LMO superlattices via inductively coupled plasma reactive ion etching. Cross-plane electrical resistivity data for LSMO/LMO superlattices showed a magnetic phase transition temperature (TP) or metal-semiconductor transition at ˜330 K, which is ˜80 K higher than the TP observed for in-plane resistivity of LSMO, LMO, or LSMO/LMO thin films. The room temperature cross-plane resistivity (ρc) was found to be greater than the in-plane resistivity by about three orders of magnitude. The magnitude and temperature dependence of the cross-plane conductivity of LSMO/LMO superlattices suggests the presence of a barrier with the effective barrier height of ˜300 meV. Although the magnitude of the cross-plane power factor is too low for thermoelectric applications by a factor of approximately 10-4—in part because the growth conditions chosen for this study yielded relatively high resistivity films—the temperature dependence of the resistivity and the potential for tuning the power factor by engineering strain, oxygen stoichiometry, and electronic band structure suggest that these epitaxial metal/semiconductor superlattices are deserving of further investigation.

T-p phase diagrams and the barocaloric effect in materials with successive phase transitions

NASA Astrophysics Data System (ADS)

Gorev, M. V.; Bogdanov, E. V.; Flerov, I. N.

2017-09-01

An analysis of the extensive and intensive barocaloric effect (BCE) at successive structural phase transitions in some complex fluorides and oxyfluorides was performed. The high sensitivity of these compounds to a change in the chemical pressure allows one to vary the succession and parameters of the transformations (temperature, entropy, baric coefficient) over a wide range and obtain optimal values of the BCE. A comparison of different types of schematic T-p phase diagrams with the complicated T( p) dependences observed experimentally shows that in some ranges of temperature and pressure the BCE in compounds undergoing successive transformations can be increased due to a summation of caloric effects associated with distinct phase transitions. The maximum values of the extensive and intensive BCE in complex fluorides and oxyfluorides can be realized at rather low pressure (0.1-0.3 GPa). In a narrow temperature range around the triple points conversion from conventional BCE to inverse BCE is observed, which is followed by a gigantic change of both \\vertΔ S_BCE\\vert and \\vertΔ T_AD\\vert .

Reduction potential, shadow prices, and pollution costs of agricultural pollutants in China.

PubMed

Tang, Kai; Gong, Chengzhu; Wang, Dong

2016-01-15

This paper analyses the reduction potential, shadow prices, and pollution costs of agricultural pollutants in China based on provincial panel data for 2001-2010. Using a parameterized quadratic form for the directional output distance function, we find that if agricultural sectors in all provinces were to produce on the production frontier, China could potentially reduce agricultural emissions of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) by 16.0%, 16.2%, and 20.4%, respectively. Additionally, our results show that the shadow price of TN increased rapidly and continuously, while that of COD and TP fluctuated for the whole period. For the whole country, the average shadow price of COD, TN, and TP are 8266 Yuan/tonne, 25,560 Yuan/tonne, and 10,160 Yuan/tonne, respectively. The regional shadow prices of agricultural pollutants are unbalanced. Furthermore, we show that the pollution costs from emissions of COD, TN, and TP are 6.09% of the annual gross output value of the agricultural sector and are highest in the Western and lowest in the Eastern provinces. Our estimates suggest that there is scope for further pollution abatement and simultaneous output expansion for China's agriculture if farmers promote greater efficiency in their production process. Policymakers are required to dynamically adjust the pollution tax rates and ascertain the initial permit price in an emission trading system. Policymakers should also consider the different pollution costs for each province when making the reduction allocations within the agricultural sector. Copyright © 2015 Elsevier B.V. All rights reserved.

Mars Ascent Vehicle-Propellant Aging

NASA Technical Reports Server (NTRS)

Dankanich, John; Rousseau, Jeremy; Williams, Jacob

2015-01-01

This project is to develop and test a new propellant formulation specifically for the Mars Ascent Vehicle (MAV) for the robotic Mars Sample Return mission. The project was initiated under the Planetary Sciences Division In-Space Propulsion Technology (ISPT) program and is continuing under the Mars Exploration Program. The two-stage, solid motor-based MAV has been the leading MAV solution for more than a decade. Additional studies show promise for alternative technologies including hybrid and bipropellant options, but the solid motor design has significant propellant density advantages well suited for physical constraints imposed while using the SkyCrane descent stage. The solid motor concept has lower specific impulse (Isp) than alternatives, but if the first stage and payload remain sufficiently small, the two-stage solid MAV represents a potential low risk approach to meet the mission needs. As the need date for the MAV slips, opportunities exist to advance technology with high on-ramp potential. The baseline propellant for the MAV is currently the carboxyl terminated polybutadiene (CTPB) based formulation TP-H-3062 due to its advantageous low temperature mechanical properties and flight heritage. However, the flight heritage is limited and outside the environments, the MAV must endure. The ISPT program competed a propellant formulation project with industry and selected ATK to develop a new propellant formulation specifically for the MAV application. Working with ATK, a large number of propellant formulations were assessed to either increase performance of a CTPB propellant or improve the low temperature mechanical properties of a hydroxyl terminated polybutadiene (HTPB) propellant. Both propellants demonstrated potential to increase performance over heritage options, but an HTPB propellant formulation, TP-H-3544, was selected for production and testing. The test plan includes propellant aging first at high vacuum conditions, representative of the Mars transit, followed by an additional year at simulated Mars surface conditions. The actual Mars surface environment is based on the igloo design, actively maintains the propellant at or above -40 degC, 95% carbon dioxide at Mars surface pressure. The NASA Marshall Space Flight Center (MSFC) Mars environment test facility is shown in figure 1 and located in the East Test area of Redstone Arsenal due to storage of live propellants. The facility consists of a vacuum chamber placed inside a large freezer unit. The facility includes pressure and temperature monitoring equipment in addition to a vacuum quality monitoring system spectrometer to record any outgassing products.

Optimization of Ultrasound-Assisted Extraction of phenolic compounds and anthocyanins from blueberry (Vaccinium ashei) wine pomace.

PubMed

He, Bo; Zhang, Ling-Li; Yue, Xue-Yang; Liang, Jin; Jiang, Jun; Gao, Xue-Ling; Yue, Peng-Xiang

2016-08-01

Ultrasound-Assisted Extraction (UAE) of total anthocyanins (TA) and phenolics (TP) from Blueberry Wine Pomace (BWP) was optimized using Response Surface Methodology (RSM). A Box-Behnken design was used to predict that the optimized conditions were an extraction temperature of 61.03°C, a liquid-solid ratio of 21.70mL/g and a sonication time of 23.67min. Using the modeled optimized conditions, the predicted and experimental yields of TA and TP were within a 2% difference. The yields of TA and TP obtained through the optimized UAE method were higher than those using a Conventional Solvent Extraction (CSE) method. Seven anthocyanins, namely delphinidin-3-O-glucoside, delphindin-3-O-arabinoside, petunidin-3-O-glucoside, cyanidin-3-O-arabinoside, cyanidin-3-O-glucoside, malvidin-3-O-glucoside and malvidin-3-O-arabinoside, were found in the BWP extract from both the UAE and CSE methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

Total pancreatectomy and islet autotransplantation in children for chronic pancreatitis: indication, surgical techniques, postoperative management, and long-term outcomes.

PubMed

Chinnakotla, Srinath; Bellin, Melena D; Schwarzenberg, Sarah J; Radosevich, David M; Cook, Marie; Dunn, Ty B; Beilman, Gregory J; Freeman, Martin L; Balamurugan, A N; Wilhelm, Josh; Bland, Barbara; Jimenez-Vega, Jose M; Hering, Bernhard J; Vickers, Selwyn M; Pruett, Timothy L; Sutherland, David E R

2014-07-01

Describe the surgical technique, complications, and long-term outcomes of total pancreatectomy and islet autotransplantation (TP-IAT) in a large series of pediatric patients. Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long-term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, whereas islet autotransplantation (IAT) potentially can prevent or minimize TP-related diabetes. Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic, or surgical treatment between 1989 and 2012. Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (P < 0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (P = 0.032), lack of prior Puestow procedure (P = 0.018), lower body surface area (P = 0.048), higher islet equivalents (IEQ) per kilogram body weight (P = 0.001), and total IEQ (100,000) (P = 0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT: (1) male sex, (2) lower body surface area, and (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (odds ratio = 2.62; P < 0.001). Total pancreatectomy and islet autotransplantation provides sustained pain relief and improved quality of life. The β-cell function is dependent on islet yield. Total pancreatectomy and islet autotransplantation is an effective therapy for children with painful pancreatitis that failed medical and/or endoscopic management.

Antiangiogenesis and gene aberration-related therapy may improve overall survival in patients with concurrent KRAS and TP53 hotspot mutant cancer

PubMed Central

Wang, Zhijie; Piha-Paul, Sarina; Janku, Filip; Subbiah, Vivek; Shi, Naiyi; Gong, Jing; Wathoo, Chetna; Shaw, Kenna; Hess, Kenneth; Broaddus, Russell; Naing, Aung; Hong, David; Tsimberidou, Apostolia M.; Karp, Daniel; Yao, James; Meric-Bernstam, Funda; Fu, Siqing

2017-01-01

Purpose Genetic alterations such as activating KRAS and/or inactivating TP53 are thought to be the most common drivers to tumorigenesis. Therefore, we assessed phase I cancer patients with KRAS+/TP53+ mutations. Results Approximately 8% of patients referred to phase I clinical trials harbored concurrent KRAS and TP53 mutations. Patients who received a phase I trial therapy (n = 57) had a median OS of 12 months, compared with 4.6 months in those who were not treated (n = 106; p = 0.003). KRAS G13 and TP53 R273 mutations were associated with poor overall survival (OS), while antiangiogenesis and gene aberration-related therapies were associated with prolonged OS. A prognostic model using neutrophilia, thrombocytosis, hypoalbuminemia, body mass index <30 kg/m2, and the absence of lung metastasis was established and validated. Phase I cancer patients in the low-risk group had a median OS of 16.6 months compared with 5.4 months in the high-risk group (p < 0.001). Untreated patients in the low-risk group had a median OS of 6.7 months compared with 3.6 months in the high-risk group (p = 0.033). Experimental Design We analyzed 163 consecutive patients with advanced KRAS+/TP53+ mutant cancer who were referred to phase I clinical trials, to identify molecular aberrations, clinical characteristics, survivals, and potentially effective treatment regimens. Conclusions This study provided preliminary evidence that besides modulation of the proinflammatory state, antiangiogensis and concomitant gene aberration-related therapies may improve the treatment of KRAS+/TP53+ mutant cancer. PMID:28430579

Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

PubMed Central

Yuan, Zhi-xiang; Jia, Lu; Lim, Lee Yong; Lin, Ju-chun; Shu, Gang; Zhao, Ling; Ye, Gang; Liang, Xiao-xia; Ji, Hongming; Fu, Hua-lin

2017-01-01

Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios – 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) – of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN. PMID:28848346

Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes.

PubMed

Yuan, Zhi-Xiang; Jia, Lu; Lim, Lee Yong; Lin, Ju-Chun; Shu, Gang; Zhao, Ling; Ye, Gang; Liang, Xiao-Xia; Ji, Hongming; Fu, Hua-Lin

2017-01-01

Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios - 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) - of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC 50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG 5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN.

Pharmacokinetic evaluation of the effects of ribavirin on zidovudine triphosphate formation: ACTG 5092s Study Team.

PubMed

Aweeka, F T; Kang, M; Yu, J-Y; Lizak, P; Alston, B; Chung, R T

2007-07-01

Ribavirin (RBV) is used for the treatment of hepatitis C virus (HCV) infection in subjects with HIV-1 infection who may require antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors including zidovudine (ZDV). We sought to investigate the potential antagonism between RBV and ZDV by evaluating the impact of RBV on the formation of intracellular ZDV triphosphate (TP) in HIV-infected patients receiving ZDV who were treated for HCV infection. Serial plasma and intracellular ZDV TP pharmacokinetics (PK) were determined in 14 subjects at entry (within 2 weeks prior to RBV administration) and at 8 weeks following initiation of RBV. Intracellular ZDV TP in peripheral blood mononuclear cells (PBMC) was quantified by a validated cartridge/liquid chromatography/tandem mass spectrometry method. PK exposure was estimated from the steady-state area under the concentration vs time curve (AUC(0-12 h)) in plasma and PBMC. Ribavirin did not have a statistically significant impact on ZDV TP AUC(0-12 h), plasma ZDV AUC(0-12 h) or the ratio of ZDV TP AUC(0-12 h) to plasma ZDV AUC(0-12 h), although there was a trend towards an increase post-RBV ratio compared with pre-RBV. There was extensive variability in the ZDV TP AUC(0-12 h). Ribavirin did not inhibit formation of ZDV TP in PBMC in 14 patients receiving ZDV as part of ART and RBV-based HCV therapy for 8 weeks. These results are consistent with those of a previously published limited study in seven subjects. These PK findings should be weighed carefully against emerging clinical reports of significant anaemia associated with combination ZDV and high-dose RBV therapy.

Evaluation of a novel Dot-ELISA assay utilizing a recombinant protein for the effective diagnosis of Taenia pisiformis larval infections.

PubMed

Chen, Lin; Yang, Deying; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

2014-08-29

Cysticercosis, caused by the larvae of Taenia pisiformis, is a common disease in domestic breeds of the rabbit Oryctolagus cuniculus that results in economic losses. At present, there is no convenient and effective method for the rapid detection of T. pisiformis larvae. Here, we developed and tested the efficacy of a Dot-ELISA assay for the diagnosis of T. pisiformis larval infections in rabbits, based on the expression of the recombinant fusion protein (rTp1) from the Tp1 gene. Rapid amplification of cDNA ends (RACE) was used to amplify the 3' ends of the Tp1 gene, based on the unigene similar to Ts1 gene (EU009656.1) which comes from transcriptome sequencing of T. pisiformis. The Tp1 gene was successfully amplified, cloned and expressed in BL21 (DE3). Western blot analysis revealed that the recombinant Tp1 protein is specifically recognized by rabbit T. pisiformis cysticercosis antisera. This purified recombinant fusion protein, rTp1, was probed by Dot-ELISA with sera from rabbits infected with T. pisiformis larvae and with other parasitic infections. Results showed that this Dot-ELISA assay had both high sensitivity (92.9-97.6%) and specificity (95.2-98.4%) to detect T. pisiformis larval infections. We also found very low levels of cross-reaction with other parasitic infections. This study has revealed that our novel Dot-ELISA assay utilizing the recombinant fusion protein, rTp1, has a strong potential for the effective diagnosis of T. pisiformis infections in rabbits. Copyright © 2014 Elsevier B.V. All rights reserved.

Preclinical toxicity evaluation of erythrocyte-encapsulated thymidine phosphorylase in BALB/c mice and beagle dogs: an enzyme-replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy.

PubMed

Levene, Michelle; Coleman, David G; Kilpatrick, Hugh C; Fairbanks, Lynette D; Gangadharan, Babunilayam; Gasson, Charlotte; Bax, Bridget E

2013-01-01

Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is currently under development as an enzyme replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder caused by a deficiency of thymidine phosphorylase. The rationale for the development of EE-TP is based on the pathologically elevated metabolites (thymidine and deoxyuridine) being able to freely diffuse across the erythrocyte membrane where the encapsulated enzyme catalyses their metabolism to the normal products. The systemic toxic potential of EE-TP was assessed when administered intermittently by iv bolus injection to BALB/c mice and Beagle dogs for 4 weeks. The studies consisted of one control group receiving sham-loaded erythrocytes twice weekly and two treated groups, one dosed once every 2 weeks and the other dosed twice per week. The administration of EE-TP to BALB/c mice resulted in thrombi/emboli in the lungs and spleen enlargement. These findings were also seen in the control group, and there was no relationship to the number of doses administered. In the dog, transient clinical signs were associated with EE-TP administration, suggestive of an immune-based reaction. Specific antithymidine phosphorylase antibodies were detected in two dogs and in a greater proportion of mice treated once every 2 weeks. Nonspecific antibodies were detected in all EE-TP-treated animals. In conclusion, these studies do not reveal serious toxicities that would preclude a clinical trial of EE-TP in patients with MNGIE, but caution should be taken for infusion-related reactions that may be related to the production of nonspecific antibodies or a cell-based immune response.

Texture Analysis of T1-Weighted and Fluid-Attenuated Inversion Recovery Images Detects Abnormalities That Correlate With Cognitive Decline in Small Vessel Disease.

PubMed

Tozer, Daniel J; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

2018-06-04

Magnetic resonance imaging may be useful to assess disease severity in cerebral small vessel disease (SVD), identify those individuals who are most likely to progress to dementia, monitor disease progression, and act as surrogate markers to test new therapies. Texture analysis extracts information on the relationship between signal intensities of neighboring voxels. A potential advantage over techniques, such as diffusion tensor imaging, is that it can be used on clinically obtained magnetic resonance sequences. We determined whether texture parameters (TP) were abnormal in SVD, correlated with cognitive impairment, predicted cognitive decline, or conversion to dementia. In the prospective SCANS study (St George's Cognition and Neuroimaging in Stroke), we assessed TP in 121 individuals with symptomatic SVD at baseline, 99 of whom attended annual cognitive testing for 5 years. Conversion to dementia was recorded for all subjects during the 5-year period. Texture analysis was performed on fluid-attenuated inversion recovery and T1-weighted images. The TP obtained from the SVD cohort were cross-sectionally compared with 54 age-matched controls scanned on the same magnetic resonance imaging system. There were highly significant differences in several TP between SVD cases and controls. Within the SVD population, TP were highly correlated to other magnetic resonance imaging parameters (brain volume, white matter lesion volume, lacune count). TP correlated with executive function and global function at baseline and predicted conversion to dementia, after controlling for age, sex, premorbid intelligence quotient, and magnetic resonance parameters. TP, which can be obtained from routine clinical images, are abnormal in SVD, and the degree of abnormality correlates with executive dysfunction and global cognition at baseline and decline during 5 years. TP may be useful to assess disease severity in clinically collected data. This needs testing in data clinically acquired across multiple sites. © 2018 The Authors.

Paramagnetic oxotungsten(V) complexes containing the hydrotris(3,5-dimethylpyrazol-1-yl)borate ligand.

PubMed

Sproules, Stephen; Eagle, Aston A; Taylor, Michelle K; Gable, Robert W; White, Jonathan M; Young, Charles G

2011-05-16

Sky-blue Tp*WOCl(2) has been synthesized from the high-yielding reaction of Tp*WO(2)Cl with boron trichloride in refluxing toluene. Dark-red Tp*WOI(2) was prepared via thermal decarbonylation followed by aerial oxidation of Tp*WI(CO)(3) in acetonitrile. From these precursors, an extensive series of mononuclear tungstenyl complexes, Tp*WOXY [X = Cl(-), Y = OPh(-), SPh(-); X = Y = OPh(-), 2-(n-propyl)phenolate (PP(-)), SPh(-), SePh(-); XY = toluene-3,4-dithiolate (tdt(2-)), quinoxaline-2,3-dithiolate (qdt(2-)), benzene-1,2-diselenolate (bds(2-)); Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate], was prepared by metathesis with the respective alkali-metal salt of X(-)/XY(2-) or (NHEt(3))(2)(qdt). The complexes were characterized by microanalysis, mass spectrometry, electrochemistry, IR, electron paramagnetic resonance (EPR), and electronic absorption spectroscopies, and X-ray crystallography (for X = Y = OPh(-), PP(-), SPh(-); XY = bds(2-)). The six-coordinate, distorted-octahedral tungsten centers are coordinated by terminal oxo [W≡O = 1.689(6)-1.704(3) Å], tridentate Tp*, and monodentate or bidentate O/S/Se-donor ligands. Spin Hamiltonian parameters derived from the simulation of fluid-solution X-band EPR spectra revealed that the soft-donor S/Se ligand complexes had larger g values and smaller (183)W hyperfine coupling constants than the less covalent hard-donor O/Cl species. The former showed low-energy ligand-to-metal charge-transfer bands in the near-IR region of their electronic absorption spectra. These oxotungsten(V) complexes display lower reduction potentials than their molybdenum counterparts, underscoring the preference of tungsten for higher oxidation states. Furthermore, the protonation of the pyrazine nitrogen atoms of the qdt(2-) ligand has been examined by spectroelectrochemistry; the product of the one-electron reduction of [Tp*WO(qdtH)](+) revealed usually intense low-energy bands.

Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations

PubMed Central

Kamitaki, Nolan; Mitchell, Jana; Avior, Yishai; Mello, Curtis; Kashin, Seva; Mekhoubad, Shila; Ilic, Dusko; Charlton, Maura; Saphier, Genevieve; Handsaker, Robert E.; Genovese, Giulio; Bar, Shiran; Benvenisty, Nissim; McCarroll, Steven A.; Eggan, Kevin

2017-01-01

Human pluripotent stem cells (hPSCs) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with acquisition of large copy number variants (CNVs) that provide mutant cells with a growth advantage in culture1–3. However, the nature, extent, and functional impact of other acquired genome sequence mutations in cultured hPSCs is not known. Here, we sequenced the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hESC) lines, including 26 lines prepared for potential clinical use4. We then applied computational strategies for identifying mutations present in a subset of cells5. Though such mosaic mutations were generally rare, we identified five unrelated hESC lines that carried six mutations in the TP53 gene that encodes the tumor suppressor P53. Notably, the TP53 mutations we observed are dominant negative and are the mutations most commonly seen in human cancers. We used droplet digital PCR to demonstrate that the TP53 mutant allelic fraction increased with passage number under standard culture conditions, suggesting that P53 mutation confers selective advantage. When we then mined published RNA sequencing data from 117 hPSC lines, we observed another nine TP53 mutations, all resulting in coding changes in the DNA binding domain of P53. Strikingly, in three lines, the allelic fraction exceeded 50%, suggesting additional selective advantage resulting from loss of heterozygosity at the TP53 locus. As the acquisition and favored expansion of cancer-associated mutations in hPSCs may go unnoticed during most applications, we suggest that careful genetic characterization of hPSCs and their differentiated derivatives should be carried out prior to clinical use. PMID:28445466

Polarity governed selective amplification of through plane proton shuttling in proton exchange membrane fuel cells.

PubMed

Gautam, Manu; Chattanahalli Devendrachari, Mruthyunjayachari; Thimmappa, Ravikumar; Raja Kottaichamy, Alagar; Pottachola Shafi, Shahid; Gaikwad, Pramod; Makri Nimbegondi Kotresh, Harish; Ottakam Thotiyl, Musthafa

2017-03-15

Graphene oxide (GO) anisotropically conducts protons with directional dominance of in plane ionic transport (σ IP) over the through plane (σ TP). In a typical H 2 -O 2 fuel cell, since the proton conduction occurs through the plane during its generation at the fuel electrode, it is indeed inevitable to selectively accelerate GO's σ TP for advancement towards a potential fuel cell membrane. We successfully achieved ∼7 times selective amplification of GO's σ TP by tuning the polarity of the dopant molecule in its nanoporous matrix. The coexistence of strongly non-polar and polar domains in the dopant demonstrated a synergistic effect towards σ TP with the former decreasing the number of water molecules coordinated to protons by ∼3 times, diminishing the effects of electroosmotic drag exerted on ionic movements, and the latter selectively accelerating σ TP across the catalytic layers by bridging the individual GO planes via extensive host guest H-bonding interactions. When they are decoupled, the dopant with mainly non-polar or polar features only marginally enhances the σ TP, revealing that polarity factors contribute to fuel cell relevant transport properties of GO membranes only when they coexist. Fuel cell polarization and kinetic analyses revealed that these multitask dopants increased the fuel cell performance metrics of the power and current densities by ∼3 times compared to the pure GO membranes, suggesting that the functional group factors of the dopants are of utmost importance in GO-based proton exchange membrane fuel cells.

Causes of spring vegetation greenness trends in the northern mid-high latitudes from 1982 to 2004

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Jiafu; Shi, Xiaoying; Thornton, Peter E

2012-01-01

The Community Land Model version 4 (CLM4) is applied to explore the spatial temporal patterns of spring (April May) vegetation growth trends over the northern mid high latitudes (NMH) (>25 N) between 1982 and 2004. During the spring season through the 23 yr period, both the satellite-derived and simulated normalized difference vegetation index (NDVI) anomalies show a statistically significant correlation and an overall greening trend within the study area. Consistently with the observed NDVI temperature relation, the CLM4 NDVI shows a significant positive association with the spring temperature anomaly for the NMH, North America and Eurasia. Large study areas experiencemore » temperature discontinuity associated with contrasting NDVI trends. Before and after the turning point (TP) of the temperature trends, climatic variability plays a dominant role, while the other environmental factors exert minor effects on the NDVI tendencies. Simulated vegetation growth is broadly stimulated by the increasing atmospheric CO2. Trends show that nitrogen deposition increases NDVI mostly in southeastern China, and decreases NDVI mainly in western Russia after the temperature TP. Furthermore, land use-induced NDVI trends vary roughly with the respective changes in land management practices (crop areas and forest coverage). Our results highlight how non-climatic factors mitigate or exacerbate the impact of temperature on spring vegetation growth, particularly across regions with intensive human activity.« less

SWAT Model Prediction of Phosphorus Loading in a South Carolina Karst Watershed with a Downstream Embayment

Treesearch

Devendra M. Amatya; Manoj K. Jha; Thomas M. Williams; Amy E. Edwards; Daniel R. Hitchcock

2013-01-01

The SWAT model was used to predict total phosphorus (TP) loadings for a 1555-ha karst watershed—Chapel Branch Creek (CBC)—which drains to a lake via a reservoir-like embayment (R-E). The model was first tested for monthly streamflow predictions from tributaries draining three potential source areas as well as the downstream R-E, followed by TP loadings using data...

GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer

PubMed Central

Checa-Rojas, Alberto; Delgadillo-Silva, Luis Fernando; Velasco-Herrera, Martín del Castillo; Andrade-Domínguez, Andrés; Gil, Jeovanis; Santillán, Orlando; Lozano, Luis; Toledo-Leyva, Alfredo; Ramírez-Torres, Alberto; Talamas-Rohana, Patricia; Encarnación-Guevara, Sergio

2018-01-01

The molecular processes and proteomic markers leading to tumor progression (TP) in cervical cancer (CC) are either unknown or only partially understood. TP affects metabolic and regulatory mechanisms that can be identified as proteomic changes. To identify which proteins are differentially expressed and to understand the mechanisms of cancer progression, we analyzed the dynamics of the tumor proteome in CC cell lines. This analysis revealed two proteins that are up-regulated during TP, GSTM3 and GSTP1. These proteins are involved in cell maintenance, cell survival and the cellular stress response via the NF-κB and MAP kinase pathways during TP. Furthermore, GSTM3 and GSTP1 knockdown showed that evasion of apoptosis was affected, and tumor proliferation was significantly reduced. Our data indicate the critical role of GST proteins in the regulation and progression of cervical cancer cells. Hence, we suggest GSTM3 and GSTP1 as novel biomarkers and potential therapeutic targets for treating cervical cancer. Significance CC is particularly hazardous in the advanced stages, and there are few therapeutic strategies specifically targeting these stages. We performed analyses on CC tumor proteome dynamics and identified GSTM3 and GSTP1 as novel potential therapeutic targets. Knockdown of these proteins showed that they are involved in cell survival, cell proliferation and cellular evasion of apoptosis. PMID:29774096

Wild 2 grains characterized combining MIR/FIR/Raman micro-spectroscopy and FE-SEM/EDS analyses

NASA Astrophysics Data System (ADS)

Ferrari, M.; Rotundi, A.; Rietmeijer, F. J. M.; Della Corte, V.; Baratta, G. A.; Brunetto, R.; Dartois, E.; Djouadi, Z.; Merouane, S.; Borg, J.; Brucato, J. R.; Le Sergeant d'Hendecourt, L.; Mennella, V.; Palumbo, M. E.; Palumbo, P.

We present the results of the analyses \\cite{Rotundi14} of two bulk terminal particles (TPs), C2112,7,171,0,0 (TP2) and C2112,9,171,0,0 (TP3), derived from the Jupiter-Family comet 81P/Wild 2 returned by the NASA Stardust mission \\cite{Brownlee06}. Each particle, embedded in a slab of silica aerogel, was pressed in a diamond cell. Aerogel is usually cause of problems when characterizing the minerals and organic materials present in the embedded particles. We overcame this common issue by means of the combination of FE-SEM/EDS, IR and Raman mu -spectroscopy, three non-destructive analytical techniques, which provided bulk mineralogical and organic information on TP2 and TP3. This approach proved to be a practical solution for preliminary characterization, i.e. scanning particles for chemical and mineralogical heterogeneity. Using this type of bulk characterization prior to more detailed studies, could be taken into account as a standard procedure to be followed for selecting Stardust particles-of-interest. TP2 and TP3 are dominated by Ca-free and low-Ca, Mg-rich, Mg,Fe-olivine. The presence of melilite in both particles is supported by IR mu -spectroscopy and corroborated by FE-SEM/EDS analyses, but is not confirmed by Raman mu -spectroscopy possibly because the amount of this mineral is too small to be detected. TP2 and TP3 show similar silicate mineral compositions, but Ni-free, low-Ni, sub-sulfur (Fe,Ni)S grains are present only in TP2. TP2 contains indigenous amorphous carbon hot spots, while no indigenous carbon was identified in TP3. These non-chondritic particles probably originated in a differentiated body. The presence of high temperature melilite group minerals (incl. gehlenite) in TP2 and TP3 reinforces the notion that collisionally-ejected refractory debris from differentiated asteroids may be common in Jupiter-Family comets. This raises the question whether similar debris and other clearly asteroidal particles could be present in Halley-type comets and, if so, which fraction of the dust in these comets is truly represented by non-processed silicates and organic material. The work done for Stardust samples is important to understand the similarities and differences among comets. In fact, the results of this study are relevant also for the ROSETTA mission that encountered the Jupiter-Family (J-F) comet 67P/Churyumov-Gerasimenko in August, 2014. At the time this mission was launched, our ideas of comet dust were biased by the findings of the Halley missions. The Stardust mission showed an unexpected richness of dust that originated from the inner solar system. Rosetta is confirming these results but also adding information, in particular on the presence of a primitive and unprocessed dust component \\cite{Fulle15}. The work was supported by PRIN2008/MIUR (Ministero dell'Istruzione dell'Università e della Ricerca), the Italian Space Agency (ASI), and MAE (Ministero degli Affari Esteri). The IAS team is grateful to the French space agency CNES for funding and supporting this work as well as to the CNRS PNP planetology program. FJMR was supported by grant NNX11AC36G through the NASA LARS Program. We thank the NASA Johnson Space Center/Astromaterials Curation laboratory for providing the samples.

Teucrium polium complex with molybdate enhance cultured islets secretory function.

PubMed

Mohseni Salehi Monfared, Seyed Sajad; Pournourmohammadi, Shirin

2010-02-01

Islet transplantation has become a promising treatment in the therapy of type 1 diabetes. Its function improvement, after isolation and before transplantation, is crucial because of their loss both in number and function of islets after isolation procedures. Trace elements sodium orthovanadate (SOV) and sodium molybdate (SM), as well as medicinal plant Teucrium polium L. (TP), showed and possessed high beneficial antioxidative potential and even hypoglycemic properties via their effect on islets. We evaluated the effect of these components in combination on cultured islet function in order to improve pancreatic islet transplantation. Rat pancreatic islets were cultured for 24 h then incubated with different concentrations of TP (0.01 and 0.1 mg/mL) alone and in combination with SOV (1 mM) or SM (1 mM). Insulin concentration in buffer media was measured as islet secretory function. Administration of TP (0.01 mg/mL), SM, and SOV alone or in combination with each other significantly increased insulin secretion at high glucose concentration (16.7 mM); insulin secretion was significantly greater in the group containing both TP and SM than other treated groups (p < 0.05). The combination of the mentioned trace elements especially molybdate with TP could improve islet cells function before transplantation.

IFNγ Enhances CD64-Potentiated Phagocytosis of Treponema pallidum Opsonized with Human Syphilitic Serum by Human Macrophages

PubMed Central

Hawley, Kelly L.; Cruz, Adriana R.; Benjamin, Sarah J.; La Vake, Carson J.; Cervantes, Jorge L.; LeDoyt, Morgan; Ramirez, Lady G.; Mandich, Daniza; Fiel-Gan, Mary; Caimano, Melissa J.; Radolf, Justin D.; Salazar, Juan C.

2017-01-01

Syphilis is a multi-stage, sexually transmitted disease caused by the spirochete Treponema pallidum (Tp). Considered broadly, syphilis can be conceptualized as a dualistic process in which spirochete-driven inflammation, the cause of clinical manifestations, coexists to varying extents with bacterial persistence. Inflammation is elicited in the tissues, along with the persistence of spirochetes to keep driving a robust immune response while evading host defenses; this duality is best exemplified during the florid, disseminated stage called secondary syphilis (SS). SS lesions typically contain copious amounts of spirochetes along with a mixed cellular infiltrate consisting of CD4+ T cells, CD8+ T cells, NK cells, plasma cells, and macrophages. In the rabbit model, Tp are cleared by macrophages via antibody-mediated opsonophagocytosis. Previously, we demonstrated that human syphilitic serum (HSS) promotes efficient uptake of Tp by human monocytes and that opsonophagocytosis of Tp markedly enhances cytokine production. Herein, we used monocyte-derived macrophages to study Tp–macrophage interactions ex vivo. In the absence of HSS, monocyte-derived macrophages internalized low numbers of Tp and secreted little cytokine (e.g., TNF). By contrast, these same macrophages internalized large numbers of unopsonized Borrelia burgdorferi and secreted robust levels of cytokines. Maturation of macrophages with M-CSF and IFNγ resulted in a macrophage phenotype with increased expression of HLA-DR, CD14, inducible nitric oxide synthase, TLR2, TLR8, and the Fcγ receptors (FcγR) CD64 and CD16, even in the absence of LPS. Importantly, IFNγ-polarized macrophages resulted in a statistically significant increase in opsonophagocytosis of Tp accompanied by enhanced production of cytokines, macrophage activation markers (CD40, CD80), TLRs (TLR2, TLR7, TLR8), chemokines (CCL19, CXCL10, CXCL11), and TH1-promoting cytokines (IL-12, IL-15). Finally, the blockade of FcγRs, primarily CD64, significantly diminished spirochetal uptake and proinflammatory cytokine secretion by IFNγ-stimulated macrophages. Our ex vivo studies demonstrate the importance of CD64-potentiated uptake of opsonized Tp and suggest that IFNγ-activated macrophages have an important role in the context of early syphilis. Our study results also provide an ex vivo surrogate system for use in future syphilis vaccine studies. PMID:29051759

Synthesis and coordination chemistry of TpC*MI complexes where M=Mg, Ca, Sr, Ba and Zn and TpC*=tris[3-(2-methoxy-1,1-dimethyl)pyrazolyl]hydroborate.

PubMed

Chisholm, Malcolm H; Gallucci, Judith C; Yaman, Gulsah

2009-01-14

Reactions involving MI2 where M=Mg, Ca, Sr, Ba or Zn and M'TpC* where M'=Na or Tl and TpC*=tris[3-methoxy-1,1-dimethyl)pyrazolyl]hydroborate in tetrahydrofuran are described leading to the isolation and characterization of the complexes TpC*MgI, , TpC*CaI, , TpC*SrI, , TpC*SrI(THF), , TpC*BaI, , TpC*BaI(pz*H), , where pz*H=3-(2-methoxyl-1,1-dimethyl)pyrazole, TpC*BaI.1/2toluene, and TpC*ZnI, . The compounds , , , , and have been characterized by single-crystal X-ray crystallography. Compounds and are isostructural and are salt-like containing kappa6-TpM+ cations and I- anions. In all other structures, the iodide is bound to the metal and TpC* is kappa6 bonded to the group 2 M(2+) ions. Reactions involving TpC*CaI, , and sodium or lithium alkoxides or amides failed to yield the amide or alkoxide calcium TpC* derivative, though related reactions involving TpC*ZnI, , and KOSiMe3 proceeded quantitatively to yield kappa3TpC*ZnOSiMe3, , which was also structurally characterized and shown to have the kappa3-TpC* bound ligand.

Evaluation of Tp-E Interval and Tp-E/QT Ratio in Patients with Aortic Stenosis.

PubMed

Yayla, Çağrı; Bilgin, Murat; Akboğa, Mehmet Kadri; Gayretli Yayla, Kadriye; Canpolat, Uğur; Dinç Asarcikli, Lale; Doğan, Mehmet; Turak, Osman; Çay, Serkan; Özeke, Özcan; Akyel, Ahmet; Yeter, Ekrem; Aydoğdu, Sinan

2016-05-01

The risk of syncope and sudden cardiac death due to ventricular arrhythmias increased in patients with aortic stenosis (AS). Recently, it was shown that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio can be novel indicators for prediction of ventricular arrhythmias and mortality. We aimed to investigate the association between AS and ventricular repolarization using Tp-e interval and Tp-e/QT ratio. Totally, 105 patients with AS and 60 control subjects were enrolled to this study. The severity of AS was defined by transthoracic echocardiographic examination. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly increased in parallel to the severity of AS (P < 0.001, P = 0.001, and P = 0.001, respectively). Also, it was shown that Tp-e/QTc ratio had significant positive correlation with mean aortic gradient (r = 0.192, P = 0.049). In multivariate logistic regression analysis, Tp-e/QTc ratio and left ventricular mass were found to be independent predictors of severe AS (P = 0.03 and P = 0.04, respectively). Our study showed that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were increased in patients with severe AS. Tp-e/QTc ratio and left ventricular mass were found as independent predictors of severe AS. © 2015 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rycyna, R.E.; Wallace, J.C.; Sharma, M.

Acetone-photosensitized UV irradiation of three thymine oligomers, d(TpT), d(TpTpT), and d(TpTpTpT), forms predominantly cis-syn cyclobutyl photodimers. C-18 reverse-phase high-performance liquid chromatography is used to purify the following positional isomers: d(TpT(p)T), d(T(p)TpT), d-(TpTpT(p)T), d(TpT(p)TpT), d(T(p)TpTpT), and d(T(p)TpT(p)T), where T(p)T represents the cis-syn photodimer. Conformational properties of the cis-syn dimers and adjacent thymine nucleotides have been investigated in solution by using /sup 1/H, /sup 13/C, and /sup 31/P NMR spectroscopy. These studies show that (1) the photodimer conformation in longer oligothymidylates is similar to that in the dinucleoside monophosphate and (2) the cis-syn dimer induces alterations to a greater degree on themore » 5' side than on the 3' side of the photodimer. Specifically, the photodimer distorts the exocyclic bonds epsilon (C3'-O3') in Tp- and ..gamma..(C5'-C4') in -pT(p)- on the 5' side and slightly alters the furanose equilibrium of the -pT nucleotide on the 3' side of the dimer.« less

Calorimetry of 25 Ah lithium/thionyl chloride cells

NASA Technical Reports Server (NTRS)

Johnson, C. J.; Dawson, S.

1991-01-01

Heat flow measurements of 25-Ah lithium thionyl chloride cells provided a method to calculate an effective thermal potential, E(TP) of 3.907 V. The calculation is useful to determine specific heat generation of this cell chemistry and design. The E(TP) value includes heat generation by electrochemical cell reactions, competitive chemical reactions, and resistance heating at the tabs, connectors, and leads. Heat flow was measured while applying electrical loads to the cell in an isothermal calorimeter set at 0, 20, and 60 C.

Enhanced Climatic Warming in the Tibetan Plateau Due to Double CO2: A Model Study

NASA Technical Reports Server (NTRS)

Chen, Baode; Chao, Winston C.; Liu, Xiao-Dong; Lau, William K. M. (Technical Monitor)

2001-01-01

The NCAR (National Center for Atmospheric Research) regional climate model (RegCM2) with time-dependent lateral meteorological fields provided by a 130-year transient increasing CO2 simulation of the NCAR Climate System Model (CSM) has been used to investigate the mechanism of enhanced ground temperature warming over the TP (Tibetan Plateau). From our model results, a remarkable tendency of warming increasing with elevation is found for the winter season, and elevation dependency of warming is not clearly recognized in the summer season. This simulated feature of elevation dependency of ground temperature is consistent with observations. Based on an analysis of surface energy budget, the short wave solar radiation absorbed at the surface plus downward long wave flux reaching the surface shows a strong elevation dependency, and is mostly responsible for enhanced surface warming over the TP. At lower elevations, the precipitation forced by topography is enhanced due to an increase in water vapor supply resulted from a warming in the atmosphere induced by doubling CO2. This precipitation enhancement must be associated with an increase in clouds, which results in a decline in solar flux reaching surface. At higher elevations, large snow depletion is detected in the 2xCO2run. It leads to a decrease in albedo, therefore more solar flux is absorbed at the surface. On the other hand, much more uniform increase in downward long wave flux reaching the surface is found. The combination of these effects (i.e. decrease in solar flux at lower elevations, increase in solar flux at higher elevation and more uniform increase in downward long wave flux) results in elevation dependency of enhanced ground temperature warming over the TP.

Effect of a Cooling Vest on Core Temperature in Athletes With and Without Spinal Cord Injury

PubMed Central

Trbovich, Michelle

2014-01-01

Background: It is well accepted that persons with spinal cord injury (SCI) have impaired ability to regulate core temperature due to impaired vasomotor and sudomotor activity below their level of injury. Impaired heat dissipation puts SCI athletes at great risk of exercise-induced hyperthermia (EIH) (>37.8°C). There is minimal evidence for efficacy of any specific cooling method in SCI athletes in a thermoneutral sport-specific setting. Objective: To evaluate the extent of EIH in persons with and without SCI and subsequently examine the effect of a cooling vest to attenuate rise in core body temperature (Tc). Methods: SCI (n = 17) and able-bodied (AB; n = 19) athletes participated in a 60-minute intermittent sprinting exercise in a thermoneutral (21.1°C-23.9°C) environment. Participants were separated according to their level of injury: tetraplegia defined as above T1 (TP; n = 6), high paraplegia defined as T5 through T1 (HP; n = 5), low paraplegia defined as T6 and below (LP; n = 6), and AB (n = 19). Tc was recorded at 15-minute intervals using an ingestible thermometer pill. This protocol was completed with a cooling vest (V) and without a cooling vest (NV). Results: All SCI and most AB athletes experienced EIH. After 60 minutes, Tc of TP athletes was significantly increased compared to HP (P = .03) and AB athletes (P = .007). There was no significant effect of the vest on Tc over time for any group. Conclusions: TP athletes have the highest risk of exercise-induced hyperthermia. The cooling vest does not significantly attenuate rise in Tc in SCI or AB athletes. PMID:24574824

Effect of a cooling vest on core temperature in athletes with and without spinal cord injury.

PubMed

Trbovich, Michelle; Ortega, Catherine; Schroeder, James; Fredrickson, Mark

2014-01-01

It is well accepted that persons with spinal cord injury (SCI) have impaired ability to regulate core temperature due to impaired vasomotor and sudomotor activity below their level of injury. Impaired heat dissipation puts SCI athletes at great risk of exercise-induced hyperthermia (EIH) (>37.8°C). There is minimal evidence for efficacy of any specific cooling method in SCI athletes in a thermoneutral sport-specific setting. To evaluate the extent of EIH in persons with and without SCI and subsequently examine the effect of a cooling vest to attenuate rise in core body temperature (Tc). SCI (n = 17) and able-bodied (AB; n = 19) athletes participated in a 60-minute intermittent sprinting exercise in a thermoneutral (21.1°C-23.9°C) environment. Participants were separated according to their level of injury: tetraplegia defined as above T1 (TP; n = 6), high paraplegia defined as T5 through T1 (HP; n = 5), low paraplegia defined as T6 and below (LP; n = 6), and AB (n = 19). Tc was recorded at 15-minute intervals using an ingestible thermometer pill. This protocol was completed with a cooling vest (V) and without a cooling vest (NV). All SCI and most AB athletes experienced EIH. After 60 minutes, Tc of TP athletes was significantly increased compared to HP (P = .03) and AB athletes (P = .007). There was no significant effect of the vest on Tc over time for any group. TP athletes have the highest risk of exercise-induced hyperthermia. The cooling vest does not significantly attenuate rise in Tc in SCI or AB athletes.

Growth and Proteome Response of Temperate and Polar Diatoms Thalassiosira pseudonana and Chaetoceros sp. to variations in Cobalt and Zinc: Identification of the High-Affinity Zinc Transporter and Potential for Use as a Biomarker

NASA Astrophysics Data System (ADS)

Kellogg, M. M.; Moran, D. M.; McIlvin, M. R.; Allen, A. E.; Saito, M. A.

2016-02-01

Marine diatoms such as the temperate Thalassiosira pseudonana (Tp) and the polar Chaetoceros sp (Ch) are known to be important contributors to marine primary productivity and the global carbon cycle. The nutritional use of zinc (Zn) in diatoms and the ability to substitute cobalt (Co) for Zn has been previously demonstrated to be of importance in their growth and biochemistry. We conducted physiological experiments with Zn and Co on these diatoms and analyzed their proteomic response. Growth studies involving Tp confirmed previous studies' findings showing Zn/Co substitution, while studies on Ch showed a toxic response to high Zn abundances. Proteome responses of Tp to Zn limitation identified a putative and previously unidentified transporter that was undetectable at high Zn concentration and became highly abundant at two lower Zn concentrations. The distribution of this protein in nature and its potential use as a Zn stress biomarker in diatoms will be discussed.

Unexpected stasis in a changing world: Lake nutrient and chlorophyll trends since 1990

USGS Publications Warehouse

Oliver, Samantha K.; Collins, Sarah M.; Soranno, Patricia A.; Wagner, Tyler; Stanley, Emily H.; Jones, John R.; Stow, Craig A.; Lottig, Noah R.

2017-01-01

The United States (U.S.) has faced major environmental changes in recent decades, including agricultural intensification and urban expansion, as well as changes in atmospheric deposition and climate—all of which may influence eutrophication of freshwaters. However, it is unclear whether or how water quality in lakes across diverse ecological settings has responded to environmental change. We quantified water quality trends in 2913 lakes using nutrient and chlorophyll (Chl) observations from the Lake Multi-Scaled Geospatial and Temporal Database of the Northeast U.S. (LAGOS-NE), a collection of preexisting lake data mostly from state agencies. LAGOS-NE was used to quantify whether lake water quality has changed from 1990 to 2013, and whether lake-specific or regional geophysical factors were related to the observed changes. We modeled change through time using hierarchical linear models for total nitrogen (TN), total phosphorus (TP), stoichiometry (TN:TP), and Chl. Both the slopes (percent change per year) and intercepts (value in 1990) were allowed to vary by lake and region. Across all lakes, TN declined at a rate of 1.1% year−1, while TP, TN:TP, and Chl did not change. A minority (7%–16%) of individual lakes had changing nutrients, stoichiometry, or Chl. Of those lakes that changed, we found differences in the geospatial variables that were most related to the observed change in the response variables. For example, TN and TN:TP trends were related to region-level drivers associated with atmospheric deposition of N; TP trends were related to both lake and region-level drivers associated with climate and land use; and Chl trends were found in regions with high air temperature at the beginning of the study period. We conclude that despite large environmental change and management efforts over recent decades, water quality of lakes in the Midwest and Northeast U.S. has not overwhelmingly degraded or improved.

Relations between total phosphorus and orthophosphorus concentrations and rainfall, surface-water discharge, and groundwater levels in Big Cypress Seminole Indian Reservation, Florida, 2014–16

USGS Publications Warehouse

McBride, W. Scott; Sifuentes, Dorothy F.

2018-02-06

The Seminole Tribe of Florida (the Tribe) is partnering with the U.S. Environmental Protection Agency to develop a numeric phosphorus criterion for the 52,000-acre Big Cypress Seminole Indian Reservation (BCSIR), which is located downgradient of the Everglades Agricultural Area, and of other public and private lands, in southeastern Hendry County and northwestern Broward County in southern Florida. The U.S. Geological Survey (USGS), in cooperation with the Tribe, used water-quality data collected between October 2014 and September 2016 by the Tribe and the South Florida Water Management District (SFWMD), along with data from rainfall gages, surface-water stage and discharge gages, and groundwater monitoring wells, to (1) examine the relations between local hydrology and measured total phosphorus (TP) and orthophosphorus (OP) concentrations and (2) identify explanatory variables for TP concentrations. Of particular concern were conditions when TP exceeded 10 parts per billion (ppb) (0.01 milligram per liter [mg/L]) given that the State of Florida and the Miccosukee Tribe of Indians Alligator Alley Reservation (located downstream of the BCSIR) have adopted a 10-ppb maximum TP criterion for surface waters.From October 2014 to September 2016, the Tribe collected 47–52 samples at each of nine water-quality sites for analysis of TP and OP, except at one site where 28 samples were collected. For all sites sampled, concentrations of TP (as phosphorus [P]) ranged from less than 0.002 mg/L (2 ppb) to a maximum of nearly 0.50 mg/L (500 ppb), whereas concentrations of OP (as P), the reactive form of inorganic phosphorus readily absorbed by plants and (or) abiotically absorbed, ranged from less than 0.003 mg/L (3 ppb) to a maximum of 0.24 mg/L (240 ppb). The median and interquartile ranges of concentrations of TP and OP in the samples collected in 2014–16 by the Tribe were similar to the median and interquartile ranges of concentrations in samples collected by the SFWMD at nearby sites during the same period. Differences in concentrations can likely be explained by differences in sample collection methods, sampling locations, sample collection time, and the hydrology during sampling or by the number of samples collected. A major limitation of this study was the short duration of sample collection, which covers a limited range of hydrologic conditions within the BCSIR.The effect of surface-water and groundwater hydrologic conditions on TP and OP concentrations was assessed by using rainfall data and surface-water stage and discharge records. The highest TP and OP concentrations occurred during peak surface-water flows in the canals following long dry periods. Concentrations of TP and OP increased internal to the BCSIR in the western half of the BCSIR during wet periods, but increased concentrations tended to lag behind rainfall events, likely because control structures upstream of sampling sites do not release flows until the water levels in the canals reach predetermined levels. This pattern may indicate that bed sediments in the canals contain high concentrations of phosphorus that becomes resuspended during high flows or that phosphorus salts that had accumulated on dry land during dry periods are carried into the canals by runoff. The largest TP spikes usually occurred at the beginning of high-flow events, but then quickly tapered off even when flows remained high.Groundwater flows were assessed in the BCSIR by using groundwater level observations from two preexisting USGS monitoring well clusters, each characterized by a shallow well installed in the surficial aquifer system and a deeper well installed in the intermediate aquifer system. Groundwater levels were evaluated with respect to surface-water levels and discharge in the BCSIR during the period of surface-water sampling. During dry conditions water levels in canals were often higher than groundwater levels in the surficial aquifer, indicating the potential for surface water to recharge the surficial aquifer. During wetter conditions, this trend reversed, and there was potential for shallow groundwater discharge into the canals.From October 2014 to September 2016, concentrations of TP tended to decrease as surface-water inflows moved across the BCSIR from north to south. In both the western and eastern halves of the reservation, the mean concentration of TP was lower in the surface-water outflows from the BCSIR than in the inflows. The mean concentration of TP in the inflows to the western reservation was 0.04 mg/L (40 ppb), whereas the mean concentration of TP in the outflows was 0.03 mg/L (30 ppb). In the eastern reservation, the mean concentration of TP in the inflows was 0.07 mg/L (70 ppb), whereas the mean concentration of TP in the outflows was 0.04 mg/L (40 ppb).TP and OP concentrations were evaluated relative to other water-quality parameters, including turbidity, suspended solids, nitrate plus nitrite, dissolved oxygen, pH, and specific conductance, to determine if any relations existed between TP and other variables. Weak relations were indicated for turbidity and suspended solids at two sites, which indicates that there may be a relation of increased TP to mobilization of sediment.

Diagnostic and model dependent uncertainty of simulated Tibetan permafrost area

NASA Astrophysics Data System (ADS)

Wang, W.; Rinke, A.; Moore, J. C.; Cui, X.; Ji, D.; Li, Q.; Zhang, N.; Wang, C.; Zhang, S.; Lawrence, D. M.; McGuire, A. D.; Zhang, W.; Delire, C.; Koven, C.; Saito, K.; MacDougall, A.; Burke, E.; Decharme, B.

2015-03-01

We perform a land surface model intercomparison to investigate how the simulation of permafrost area on the Tibetan Plateau (TP) varies between 6 modern stand-alone land surface models (CLM4.5, CoLM, ISBA, JULES, LPJ-GUESS, UVic). We also examine the variability in simulated permafrost area and distribution introduced by 5 different methods of diagnosing permafrost (from modeled monthly ground temperature, mean annual ground and air temperatures, air and surface frost indexes). There is good agreement (99-135 x 104 km2) between the two diagnostic methods based on air temperature which are also consistent with the best current observation-based estimate of actual permafrost area (101 x 104 km2). However the uncertainty (1-128 x 104 km2) using the three methods that require simulation of ground temperature is much greater. Moreover simulated permafrost distribution on TP is generally only fair to poor for these three methods (diagnosis of permafrost from monthly, and mean annual ground temperature, and surface frost index), while permafrost distribution using air temperature based methods is generally good. Model evaluation at field sites highlights specific problems in process simulations likely related to soil texture specification and snow cover. Models are particularly poor at simulating permafrost distribution using definition that soil temperature remains at or below 0°C for 24 consecutive months, which requires reliable simulation of both mean annual ground temperatures and seasonal cycle, and hence is relatively demanding. Although models can produce better permafrost maps using mean annual ground temperature and surface frost index, analysis of simulated soil temperature profiles reveals substantial biases. The current generation of land surface models need to reduce biases in simulated soil temperature profiles before reliable contemporary permafrost maps and predictions of changes in permafrost distribution can be made for the Tibetan Plateau.

Fate, mass balance, and transport of phosphorus in the septic system drainfields.

PubMed

Mechtensimer, Sara; Toor, Gurpal S

2016-09-01

Septic systems can be a potential source of phosphorus (P) in shallow groundwater. Our objective was to investigate the fate, mass balance, and transport of P in the drainfield of a drip-dispersal septic system. Drainfields were replicated in lysimeters (152.4 cm long, 91.4 cm wide, and 91.4 cm high). Leachate and effluent samples were collected over 67 events (n = 15 daily; n = 52 weekly flow-weighted) and analyzed for total P (TP), orthophosphate (PO4P), and other P (TP - PO4P). Mean TP was 15 mg L(-1) (84% PO4P; 16% other P) in the effluent and 0.16 mg L(-1) (47% PO4P, 53% other P) in the leachate. After one year, 46.8 g of TP was added with effluent and rainfall to each drainfield, of which, <1% leached, 3.8% was taken up by St. Augustine grass, leaving >95% in the drainfield. Effluent dispersal increased water extractable P (WEP) in the drainfield from <5 to >10 mg kg(-1). Using the P sorption maxima of sand (118 mg kg(-1)) and soil (260 mg kg(-1)), we estimated that ∼18% of the drainfield P sorption capacity was saturated after one year of effluent dispersal. We conclude that despite the low leaching potential of P dispersed with effluent in the first year of drainfield operation, a growing WEP pool in the drainfield and low P sorption capacity of Florida's sandy soils may have the potential to transport P to shallow groundwater in long-running septic systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Probiotic properties of native Lactobacillus spp. strains for dairy calves.

PubMed

Fernández, S; Fraga, M; Silveyra, E; Trombert, A N; Rabaza, A; Pla, M; Zunino, P

2018-04-10

The use of native microorganisms with probiotic capacity is an alternative tool for the treatment and prevention of several diseases that affect animals, such as neonatal calf diarrhoea. The selection of probiotic strains within a collection is based on different in vitro and in vivo assays, which predict their potential. The aim of this study was to characterise a group of native Lactobacillus spp. strains isolated from faeces of healthy calves using an in vitro approach and to assess their ability to colonise the gastrointestinal tract (GIT) of calves. Native Lactobacillus spp. strains were evaluated on their capacity to survive low pH conditions and bile salts presence, biofilm formation and adhesion to both mucus and Caco-2 cells. Based on the in vitro characterisation, four strains (Lactobacillus johnsonii TP1.1, Lactobacillus reuteri TP1.3B, L. johnsonii TP1.6 and Lactobacillus amylovorus TP8.7) were selected to evaluate their capacity to colonise and persist in the GIT of calves. The assessment of enteric persistence involved an in vivo assay with oral administration of probiotics and quantification in faeces of the administered bacterial species with real-time quantitative PCR (qPCR). The study was conducted using 15 calves (1-month-old) which were divided into five groups of three animals, four of which were treated with four different selected strains and one was the control group. Strains TP1.3B and TP1.6 managed to persist in treated animals until ten days after the end of the administration period, indicating that they could be promising candidates for the design of probiotics for calves.

Study on the paper substrate room temperature phosphorescence of theobromine, caffeine and theophylline and analytical application

NASA Astrophysics Data System (ADS)

Chuan, Dong; Yan-Li, Wei; Shao-Min, Shuang

2003-05-01

Paper substrate room temperature phosphorescence (RTP) of theobromine (TB), caffeine (CF) and theophylline (TP) were investigated. The method is based on fast speed quantitative filter paper as substrate and KI-NaAc as heavy atom perturber. Various factors affecting their RTP were discussed in detail. Under the optimum experimental conditions, the linear dynamic range, limit of detection (LOD), and relative standard deviation (R.S.D.) were 14.41˜576.54 ng per spot, 1.14 ng per spot, 4.8% for TB, 5.44˜699.08 ng per spot, 0.78 ng per spot, 1.56% for CF, 7.21˜360.34 ng per spot, 1.80 ng per spot, 3.80% for TP, respectively. The first analytical application for the determination of these compounds was developed. The recovery of standard samples added to commercial products chocolate, tea, coffee and aminophylline is in the range 92.80-106.08%. The proposed method was successfully applied to real sample analysis without separation.

Impact of titanium dioxide nanoparticles on the bacterial communities of biological activated carbon filter intended for drinking water treatment.

PubMed

Zhiyuan, Liu; Shuili, Yu; Heedeung, Park; Qingbin, Yuan; Guicai, Liu; Qi, Li

2016-08-01

Titanium dioxide nanoparticles (TiO2 NPs) are inevitably present in the aquatic environment owing to their increasing production and use. However, knowledge of the potential effects of TiO2 NPs on the treatment of drinking water is scarce. Herein, the effects of two types of anatase TiO2 NPs (TP1, 25 nm; TP2, 100 nm) on the bacterial community in a biological activated carbon (BAC) filter were investigated via quantitative polymerase chain reaction (Q-PCR) analysis, ATP quantification, and 454 pyrosequencing analysis. Both TP1 and TP2 significantly inhibited the bacterial ATP level (p < 0.01) and induced a decrease in the abundance of bacterial 16S rDNA gene copies at doses of 0.1 and 100 mg L(-1). Simultaneously, the diversity and evenness of the bacterial communities were considerably reduced. The relative abundances of bacteria annotated to OTUs from Nitrospira class and Betaproteobacteria class decreased upon TiO2 NP treatment, whereas those of Bacilli class and Gammaproteobacteria class increased. TiO2 NP size showed a greater effect on the bacterial composition than did the dose based on Bray-Curtis distances. These findings identified negative effects of TiO2 NPs on the bacterial community in the BAC filter. Given the fact that BAC filters are used widely in drinking water treatment plants, these results suggested a potential threat by TiO2 NP to drinking water treatment system.

Germline TP53 Mutations in Patients With Early-Onset Colorectal Cancer in the Colon Cancer Family Registry

PubMed Central

Yurgelun, Matthew B.; Masciari, Serena; Joshi, Victoria A.; Mercado, Rowena C.; Lindor, Noralane M.; Gallinger, Steven; Hopper, John L.; Jenkins, Mark A.; Buchanan, Daniel D.; Newcomb, Polly A.; Potter, John D.; Haile, Robert W.; Kucherlapati, Raju; Syngal, Sapna

2015-01-01

IMPORTANCE Li-Fraumeni syndrome, usually characterized by germline TP53 mutations, is associated with markedly elevated lifetime risks of multiple cancers, and has been linked to an increased risk of early-onset colorectal cancer. OBJECTIVE To examine the frequency of germline TP53 alterations in patients with early-onset colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter cross-sectional cohort study of individuals recruited to the Colon Cancer Family Registry (CCFR) from 1998 through 2007 (genetic testing data updated as of January 2015). Both population-based and clinic-based patients in the United States, Canada, Australia, and New Zealand were recruited to the CCFR. Demographic information, clinical history, and family history data were obtained at enrollment. Biospecimens were collected from consenting probands and families, including microsatellite instability and DNA mismatch repair immunohistochemistry results. A total of a 510 individuals diagnosed as having colorectal cancer at age 40 years or younger and lacking a known hereditary cancer syndrome were identified from the CCFR as being potentially eligible. Fifty-three participants were excluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47) or biallelic MUTYH mutations (n = 6). INTERVENTIONS Germline sequencing of the TP53 gene was performed. Identified TP53 alterations were assessed for pathogenicity using literature and international mutation database searches and in silico prediction models. MAIN OUTCOMES AND MEASURES Frequency of nonsynonymous germline TP53 alterations. RESULTS Among 457 eligible participants (314, population-based; 143, clinic-based; median age at diagnosis, 36 years [range, 15–40 years]), 6 (1.3%; 95%CI, 0.5%–2.8%) carried germline missense TP53 alterations, none of whom met clinical criteria for Li-Fraumeni syndrome. Four of the identified TP53 alterations have been previously described in the literature in probands with clinical features of Li-Fraumeni syndrome, and 2 were novel alterations. CONCLUSIONS AND RELEVANCE In a large cohort of patients with early-onset colorectal cancer, germline TP53 mutations were detected at a frequency comparable with the published prevalence of germline APC mutations in colorectal cancer. With the increasing use of multigene next-generation sequencing panels in hereditary cancer risk assessment, clinicians will be faced with the challenge of interpreting the biologic and clinical significance of germline TP53 mutations in families whose phenotypes are atypical for Li-Fraumeni syndrome. PMID:26086041

Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress

PubMed Central

McDade, Simon S.; Patel, Daksha; Moran, Michael; Campbell, James; Fenwick, Kerry; Kozarewa, Iwanka; Orr, Nicholas J.; Lord, Christopher J.; Ashworth, Alan A.; McCance, Dennis J.

2014-01-01

In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome-wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53-dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveal that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair. PMID:24823795

Li-Fraumeni syndrome: cancer risk assessment and clinical management.

PubMed

McBride, Kate A; Ballinger, Mandy L; Killick, Emma; Kirk, Judy; Tattersall, Martin H N; Eeles, Rosalind A; Thomas, David M; Mitchell, Gillian

2014-05-01

Carriers of germline mutations in the TP53 gene, encoding the cell-cycle regulator and tumour suppressor p53, have a markedly increased risk of cancer-related morbidity and mortality during both childhood and adulthood, and thus require appropriate and effective cancer risk management. However, the predisposition of such patients to multiorgan tumorigenesis presents a specific challenge for cancer risk management programmes. Herein, we review the clinical implications of germline mutations in TP53 and the evidence for cancer screening and prevention strategies in individuals carrying such mutations, as well as examining the potential psychosocial implications of lifelong management for a ubiquitous cancer risk. In addition, we propose an evidence-based framework for the clinical management of TP53 mutation carriers and provide a platform for addressing the management of other cancer predisposition syndromes that can affect multiple organs.

Water-Soluble Vitamin E-Tocopheryl Phosphate.

PubMed

Zingg, Jean-Marc

The hydrophobicity of vitamin E poses transport and metabolic challenges to regulate its bioavailability and to prevent its accumulation in lipid-rich tissues such as adipose tissue, brain, and liver. Water-soluble precursors of vitamin E (α-tocopherol, αT), such as its esters with acetate (αTA), succinate (αTS), or phosphate (αTP), have increased solubility in water and stability against reaction with free radicals, but they are rapidly converted during their uptake into the lipid-soluble vitamin E. Therefore, the bioavailability of these precursors as intact molecules is low; nevertheless, at least for αTS and αTP, the recent research has revealed unique regulatory effects on signal transduction and gene expression and the modulation of cellular events ranging from proliferation, survival/apoptosis, lipid uptake and metabolism, phagocytosis, long term potentiation, cell migration, telomere maintenance, and angiogenesis. Moreover, water-soluble derivatives of vitamin E including some based on αTP are increasingly used as components of nanocarriers for enhanced and targeted delivery of drugs and other molecules (vitamins, including αT and αTP itself, vitamin D3, carnosine, caffeine, docosahexaenoic acid (DHA), insulin) and cofactors such as coenzyme Q10. In this review, the chemical characteristics, transport, metabolic pathways, and molecular mechanisms of action of αTP in cells and tissues are summarized and put into perspective with its possible role in the prevention of a number of diseases. © 2018 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Thomas J.; Markillie, Lye MENG.

The thromboxane A{sub 2} (TXA{sub 2}) receptor (TP) is represented by two alternatively spliced forms, termed the platelet/placental (TP-P) and endothelial (TP-E) type receptors. Experimental evidence suggests that TP isoforms may be regulated by novel ligands termed the isoprostanes, which paradoxically act as TP agonists in smooth muscle and TP antagonists in platelet preparations. Here we have investigated whether prototypical isoprostanes (8-iso-PG{sub 2{sub {alpha}}} and 8-iso-PGE{sub 2}) regulate the activity of TP isoforms expressed in Chinese Hamster Ovary (CHO) cells using activator protein-1 (AP-1)-luciferase activity as a reporter. AP-1-luciferase activity was increased by a TP agonist (U46619) in CHO cellsmore » transfected with the human TP-P and TP-E receptors and this response was fully inhibited by TP antagonists (ISAP, SQ29,548). AP-1-luciferase activity was potently (nM) increased by 8-iso-PGE2 in CHO TP-P and TP-E cells, and this response was partially inhibited by cotreatment of cells with TP antagonists, while 8-iso-PGF{sub 2{sub {alpha}}} was without effect. Cyclooxygenase inhibitors did not abolish 8-iso-PGE{sub 2} mediated AP-1-luciferase activity, indicating that this response is not dependent on de novo TXA2 biosynthesis. Interestingly, 8-iso-PGE{sub 2}-mediated AP-1-luciferase activity was near maximal in naive cells between 1-10 nM concentrations, and this response was not inhibited by TP antagonist or reproduced by agonists for TP or EP1/EP3 receptors. These observations (1) support a role for novel ligands in the regulation of TP-dependent signaling, (2) indicate that TP-P and TP-E couple to AP-1, (3) provide further evidence that isoprostanes function as TP agonists in a cell-type specific fashion, and (4) indicate that additional targets regulated by 8-iso-PGE{sub 2} couple to AP-1.« less

Satellite-observed snow cover variations over the Tibetan Plateau for the period 2001-2014

NASA Astrophysics Data System (ADS)

Long, D.; Chen, X.

2016-12-01

Snow is an integral component of the global climate system. Owing to its high albedo and thermal and water storage properties, snow has important linkages and feedbacks through its influence on surface energy and moisture fluxes, clouds, precipitation, hydrology, and atmospheric circulation. As the "Roof of the World" and the "Third Pole" with the highest mountains in middle latitudes, the Tibetan Plateau (TP) is one of the most hot spots in climate change and hydrological studies, in which seasonal snow cover is a critical aspect. Unlike large-scale snow cover and regional-scale glaciers over other cryospheric regions, changes in snow cover over the TP has been largely unknown due mostly to the quality of observations. Based on improved MODIS daily snow cover products, this study aims to quantify the distribution and changes in snow cover over the TP for the period 2001 to 2014. Results show that the spatial distribution of changes in snow cover fraction (SCF) over the 14-year study period exhibited a general negative trend over the TP driven primarily by increasing land surface temperature (LST), except some areas of the upper Golden-Sanded River and upper Brahmaputra River basins. However, decreased LST and increased precipitation in the accumulation season (September to the following February) resulted in increased SCF in the accumulation season, coinciding with large-scale cold snaps and heavy snowfall events at middle latitudes. Detailed analyses of the intra-annual variability of SCF in the TP regions show an increase in SCF in the accumulation season but a decrease in SCF in the melting season (March to August), indicating that the intra-annual amplitude of SCF increased during the study period and more snow cover was released as snowmelt in the spring season.

Phosphorus retention in a newly constructed wetland receiving agricultural tile drainage water.

PubMed

Kynkäänniemi, Pia; Ulén, Barbro; Torstensson, Gunnar; Tonderski, Karin S

2013-01-01

One measure used in Sweden to mitigate eutrophication of waters is the construction of small wetlands (free water surface wetland for phosphorus retention [P wetlands]) to trap particulate phosphorus (PP) transported in ditches and streams. This study evaluated P retention dynamics in a newly constructed P wetland serving a 26-ha agricultural catchment with clay soil. Flow-proportional composite water samples were collected at the wetland inlet and outlet over 2 yr (2010-2011) and analyzed for total P (TP), dissolved P (DP), particulate P (PP), and total suspended solids (TSS). Both winters had unusually long periods of snow accumulation, and additional time-proportional water samples were frequently collected during snowmelt. Inflow TP and DP concentrations varied greatly (0.02-1.09 mg L) during the sampling period. During snowmelt in 2010, there was a daily oscillation in P concentration and water flow in line with air temperature variations. Outflow P concentrations were generally lower than inflow concentrations, with net P losses observed only in August and December 2010. On an annual basis, the wetland acted as a net P sink, with mean specific retention of 69 kg TP, 17 kg DP, and 30 t TSS ha yr, corresponding to a reduction in losses of 0.22 kg TP ha yr from the agricultural catchment. Relative retention was high (36% TP, 9% DP, and 36% TSS), indicating that small constructed wetlands (0.3% of catchment area) can substantially reduce P loads from agricultural clay soils with moderately undulating topography. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

[Ph(3)PCH(2)Ph](2)[Zn(3)(tp)(3)Cl(2)] and Ni(3)(tma)(2)(H(2)O)(8): two unusual claylike frameworks of metal-polycarboxylate coordination polymers (tp = terephthalate, tma = trimesate).

PubMed

Yang, Guo-Dong; Dai, Jing-Cao; Lian, Yun-Xia; Wu, Wen-Shi; Lin, Jian-Ming; Hu, Sheng-Min; Sheng, Tian-Lu; Fu, Zhi-Yong; Wu, Xin-Tao

2007-09-17

Two new compounds, [Ph3PCH2Ph]2[Zn3(tp)3Cl2] (1) and Ni3(tma)2(H2O)8 (2) (tp = terephthalate, tma = trimesate), are metal-polycarboxylate coordination polymers prepared by similar hydrothermal synthesis techniques. X-ray single-crystal structural analysis shows that both compounds crystallize in the 2D claylike lamellar architectures, in which 1 possesses the interlayer [Ph3PCH2Ph]+ exchangeable cation and has been confirmed by PXRD patterns. 1 (C74H56Cl2O12P2Zn3) belongs to monoclinic P21/c, Z = 2 (a = 18.956(1) A, b = 10.2697(5) A, c = 17.067(1) A, beta = 99.486(4) degrees ). 2 (C18H22O20Ni3) is attributed to triclinic P, Z = 1 (a = 6.6643(8) A, b = 9.622(1) A, c = 10.089(1) A, alpha = 112.675(2) degrees , beta = 94.007(1) degrees, gamma = 106.411(2) degrees ). Linear metal trinuclear clusters bridged by rigid linear tp ligands for 1 and trigonal tma ligands for 2 give rise to a novel 2D 6-linked (3,6) topological anionic network in 1 and an interesting 2D 3,6-linked molybdenite topological neutral network in 2, respectively. Both compounds exhibit intense fluorescent emission bands at 410 nm (lambda(exc) = 355 nm) for 1 and 398 nm (lambda(exc) = 300 nm) for 2 in the solid state at room temperature.

Photosynthetic capacity is negatively correlated with the concentration of leaf phenolic compounds across a range of different species

PubMed Central

Sumbele, Sally; Fotelli, Mariangela N.; Nikolopoulos, Dimosthenis; Tooulakou, Georgia; Liakoura, Vally; Liakopoulos, Georgios; Bresta, Panagiota; Dotsika, Elissavet; Adams, Mark A.; Karabourniotis, George

2012-01-01

Background and aims Phenolic compounds are the most commonly studied of all secondary metabolites because of their significant protective–defensive roles and their significant concentration in plant tissues. However, there has been little study on relationships between gas exchange parameters and the concentration of leaf phenolic compounds (total phenolics (TP) and condensed tannins (CT)) across a range of species. Therefore, we addressed the question: is there any correlation between photosynthetic capacity (Amax) and TP and CT across species from different ecosystems in different continents? Methodology A plethora of functional and structural parameters were measured in 49 plant species following different growth strategies from five sampling sites located in Greece and Australia. The relationships between several leaf traits were analysed by means of regression and principal component analysis. Principal results The results revealed a negative relationship between TP and CT and Amax among the different plant species, growth strategies and sampling sites, irrespective of expression (with respect to mass, area or nitrogen content). Principal component analysis showed that high concentrations of TP and CT are associated with thick, dense leaves with low nitrogen. This leaf type is characterized by low growth, Amax and transpiration rates, and is common in environments with low water and nutrient availability, high temperatures and high light intensities. Therefore, the high TP and CT in such leaves are compatible with the protective and defensive functions ascribed to them. Conclusions Our results indicate a functional integration between carbon gain and the concentration of leaf phenolic compounds that reflects the trade-off between growth and defence/protection demands, depending on the growth strategy adopted by each species. PMID:23050073

Photosynthetic capacity is negatively correlated with the concentration of leaf phenolic compounds across a range of different species.

PubMed

Sumbele, Sally; Fotelli, Mariangela N; Nikolopoulos, Dimosthenis; Tooulakou, Georgia; Liakoura, Vally; Liakopoulos, Georgios; Bresta, Panagiota; Dotsika, Elissavet; Adams, Mark A; Karabourniotis, George

2012-01-01

Phenolic compounds are the most commonly studied of all secondary metabolites because of their significant protective-defensive roles and their significant concentration in plant tissues. However, there has been little study on relationships between gas exchange parameters and the concentration of leaf phenolic compounds (total phenolics (TP) and condensed tannins (CT)) across a range of species. Therefore, we addressed the question: is there any correlation between photosynthetic capacity (A(max)) and TP and CT across species from different ecosystems in different continents? A plethora of functional and structural parameters were measured in 49 plant species following different growth strategies from five sampling sites located in Greece and Australia. The relationships between several leaf traits were analysed by means of regression and principal component analysis. The results revealed a negative relationship between TP and CT and A(max) among the different plant species, growth strategies and sampling sites, irrespective of expression (with respect to mass, area or nitrogen content). Principal component analysis showed that high concentrations of TP and CT are associated with thick, dense leaves with low nitrogen. This leaf type is characterized by low growth, A(max) and transpiration rates, and is common in environments with low water and nutrient availability, high temperatures and high light intensities. Therefore, the high TP and CT in such leaves are compatible with the protective and defensive functions ascribed to them. Our results indicate a functional integration between carbon gain and the concentration of leaf phenolic compounds that reflects the trade-off between growth and defence/protection demands, depending on the growth strategy adopted by each species.

A nanomagnetic study of phase transition in manganite thin films and ballistic magnetoresistance in magnetic nanocontacts

NASA Astrophysics Data System (ADS)

Chung, Seok-Hwan

This work focuses on two largely unexplored phenomena in micromagnetics: the temperature-driven paramagnetic insulator to ferromagnetic (FM) metallic phase transition in perovskite manganite and ballistic magnetoresistance in spin-polarized nanocontacts. To investigate the phase transition, an off-the-shelf commercial scanning force microscope was redesigned for operation at temperatures from 350 K to 100 K. This adaptation is elaborated in this thesis. Using this system, both ferromagnetic and charge-ordered domain structures of (La 1-xPrx)0.67Ca0.33MnO3 thin film were observed by magnetic force microscopy (MFM) and electric force microscopy (EFM) operated in the vicinity of the peak resistance temperature (Tp). Predominantly in-plane oriented FM domains of sub-micrometer size emerge below Tp and their local magnetic moment increased as the temperature is reduced. Charge-ordered insulating regions show a strong electrostatic interaction with an EFM tip at a few degrees above Tp and the interaction correlates well with the temperature dependence of resistivity of the film. Cross-correlation analysis between topography and magnetic structure on several substrates indicates FM domains form on the flat regions of the surface, while charge ordering occurs at surface protrusions. In the investigation of ballistic magnetoresistance, new results on half-metallic ferromagnets formed by atomic or nanometer contacts of CrO2-CrO 2 and CrO2-Ni are presented showing magnetoconductance as high as 400%. Analysis of the magnetoconductance versus conductance data for all materials known to exhibit so-called ballistic magnetoresistance strongly suggests that magnetoconductance of nanocontacts follows a universal mechanism. If the maximum magnetoconductance is normalized to unity and the conductance is scaled with the resistivity of the material, then all data points fall onto a universal curve independent of the contact material and the transport mechanism. The analysis has been applied to all available magnetoconductance data of magnetic nanocontacts in the literature. The results are in agreement with a theory that takes into account only the spin-scattering within a magnetic domain wall and are independent of whether the transport is ballistic or diffusive.

Effect of stock size, climate, predation, and trophic status on recruitment of alewives in Lake Ontario, 1978-2000

USGS Publications Warehouse

O'Gorman, Robert; Lantry, Brian F.; Schneider, Clifford P.

2004-01-01

The population of alewives Alosa pseudoharengus in Lake Ontario is of great concern to fishery managers because alewives are the principal prey of introduced salmonines and because alewives negatively influence many endemic fishes. We used spring bottom trawl catches of alewives to investigate the roles of stock size, climate, predation, and lake trophic status on recruitment of alewives to age 2 in Lake Ontario during 1978–2000. Climate was indexed from the temperature of water entering a south-shore municipal treatment plant, lake trophic status was indexed by the mean concentration of total phosphorus (TP) in surface water in spring, and predation was indexed by the product of the number of salmonines stocked and relative, first-year survival of Chinook salmonOncorhynchus tshawytscha. A Ricker-type parent–progeny model suggested that peak production of age-1 alewives could occur over a broad range of spawning stock sizes, and the fit of the model was improved most by the addition of terms for spring water temperature and winter duration. With the addition of the two climate terms, the Ricker model indicated that when water was relatively warm in spring and the winter was relatively short, peak potential production of young was nine times higher than when water temperature and winters were average, and 73 times higher than when water was cold in spring and winters were long. Relative survival from age 1 to recruitment at age 2 was best described by a multiple linear regression with terms for adult abundance, TP, and predation. Mean recruitment of age-2 fish in the 1978–1998 year-classes predicted by using the two models in sequence was only about 20% greater than the observed mean recruitment. Model estimates fit the measured data exceptionally well for all but the largest four year-classes, which suggests that the models will facilitate improvement in estimates of trophic transfer due to alewives.

Probing matrix and tumor mechanics with in situ calibrated optical trap based active microrheology

NASA Astrophysics Data System (ADS)

Staunton, Jack Rory; Vieira, Wilfred; Tanner, Kandice; Tissue Morphodynamics Unit Team

Aberrant extracellular matrix deposition and vascularization, concomitant with proliferation and phenotypic changes undergone by cancer cells, alter mechanical properties in the tumor microenvironment during cancer progression. Tumor mechanics conversely influence progression, and the identification of physical biomarkers promise improved diagnostic and prognostic power. Optical trap based active microrheology enables measurement of forces up to 0.5 mm within a sample, allowing interrogation of in vitro biomaterials, ex vivo tissue sections, and small organisms in vivo. We fabricated collagen I hydrogels exhibiting distinct structural properties by tuning polymerization temperature Tp, and measured their shear storage and loss moduli at frequencies 1-15k Hz at multiple amplitudes. Lower Tp gels, with larger pore size but thicker, longer fibers, were stiffer than higher Tp gels; decreasing strain increased loss moduli and decreased storage moduli at low frequencies. We subcutanously injected probes with metastatic murine melanoma cells into mice. The excised tumors displayed storage and loss moduli 40 Pa and 10 Pa at 1 Hz, increasing to 500 Pa and 1 kPa at 15 kHz, respectively.

Decomposability and convex structure of thermal processes

NASA Astrophysics Data System (ADS)

Mazurek, Paweł; Horodecki, Michał

2018-05-01

We present an example of a thermal process (TP) for a system of d energy levels, which cannot be performed without an instant access to the whole energy space. This TP is uniquely connected with a transition between some states of the system, that cannot be performed without access to the whole energy space even when approximate transitions are allowed. Pursuing the question about the decomposability of TPs into convex combinations of compositions of processes acting non-trivially on smaller subspaces, we investigate transitions within the subspace of states diagonal in the energy basis. For three level systems, we determine the set of extremal points of these operations, as well as the minimal set of operations needed to perform an arbitrary TP, and connect the set of TPs with thermomajorization criterion. We show that the structure of the set depends on temperature, which is associated with the fact that TPs cannot increase deterministically extractable work from a state—the conclusion that holds for arbitrary d level system. We also connect the decomposability problem with detailed balance symmetry of an extremal TPs.

Species interactions slow warming-induced upward shifts of treelines on the Tibetan Plateau

PubMed Central

Liang, Eryuan; Wang, Yafeng; Piao, Shilong; Lu, Xiaoming; Camarero, Jesús Julio; Zhu, Haifeng; Zhu, Liping; Ciais, Philippe; Peñuelas, Josep

2016-01-01

The alpine treeline is commonly regarded as being sensitive to climatic warming because regeneration and growth of trees at treeline generally are limited by low temperature. The alpine treelines of the Tibetan Plateau (TP) occur at the highest elevations (4,900 m above sea level) in the Northern Hemisphere. Ongoing climatic warming is expected to shift treelines upward. Studies of treeline dynamics at regional and local scales, however, have yielded conflicting results, indicating either unchanging treeline elevations or upward shifts. To reconcile this conflict, we reconstructed in detail a century of treeline structure and tree recruitment at sites along a climatic gradient of 4 °C and mean annual rainfall of 650 mm on the eastern TP. Species interactions interacted with effects of warming on treeline and could outweigh them. Densification of shrubs just above treeline inhibited tree establishment, and slowed upward movement of treelines on a time scale of decades. Interspecific interactions are major processes controlling treeline dynamics that may account for the absence of an upward shift at some TP treelines despite continued climatic warming. PMID:27044083

Species interactions slow warming-induced upward shifts of treelines on the Tibetan Plateau.

PubMed

Liang, Eryuan; Wang, Yafeng; Piao, Shilong; Lu, Xiaoming; Camarero, Jesús Julio; Zhu, Haifeng; Zhu, Liping; Ellison, Aaron M; Ciais, Philippe; Peñuelas, Josep

2016-04-19

The alpine treeline is commonly regarded as being sensitive to climatic warming because regeneration and growth of trees at treeline generally are limited by low temperature. The alpine treelines of the Tibetan Plateau (TP) occur at the highest elevations (4,900 m above sea level) in the Northern Hemisphere. Ongoing climatic warming is expected to shift treelines upward. Studies of treeline dynamics at regional and local scales, however, have yielded conflicting results, indicating either unchanging treeline elevations or upward shifts. To reconcile this conflict, we reconstructed in detail a century of treeline structure and tree recruitment at sites along a climatic gradient of 4 °C and mean annual rainfall of 650 mm on the eastern TP. Species interactions interacted with effects of warming on treeline and could outweigh them. Densification of shrubs just above treeline inhibited tree establishment, and slowed upward movement of treelines on a time scale of decades. Interspecific interactions are major processes controlling treeline dynamics that may account for the absence of an upward shift at some TP treelines despite continued climatic warming.

Use of multivariate analysis to suggest a new molecular classification of colorectal cancer

PubMed Central

Domingo, Enric; Ramamoorthy, Rajarajan; Oukrif, Dahmane; Rosmarin, Daniel; Presz, Michal; Wang, Haitao; Pulker, Hannah; Lockstone, Helen; Hveem, Tarjei; Cranston, Treena; Danielsen, Havard; Novelli, Marco; Davidson, Brian; Xu, Zheng-Zhou; Molloy, Peter; Johnstone, Elaine; Holmes, Christopher; Midgley, Rachel; Kerr, David; Sieber, Oliver; Tomlinson, Ian

2013-01-01

Abstract Molecular classification of colorectal cancer (CRC) is currently based on microsatellite instability (MSI), KRAS or BRAF mutation and, occasionally, chromosomal instability (CIN). Whilst useful, these categories may not fully represent the underlying molecular subgroups. We screened 906 stage II/III CRCs from the VICTOR clinical trial for somatic mutations. Multivariate analyses (logistic regression, clustering, Bayesian networks) identified the primary molecular associations. Positive associations occurred between: CIN and TP53 mutation; MSI and BRAF mutation; and KRAS and PIK3CA mutations. Negative associations occurred between: MSI and CIN; MSI and NRAS mutation; and KRAS mutation, and each of NRAS, TP53 and BRAF mutations. Some complex relationships were elucidated: KRAS and TP53 mutations had both a direct negative association and a weaker, confounding, positive association via TP53–CIN–MSI–BRAF–KRAS. Our results suggested a new molecular classification of CRCs: (1) MSI+ and/or BRAF-mutant; (2) CIN+ and/or TP53– mutant, with wild-type KRAS and PIK3CA; (3) KRAS- and/or PIK3CA-mutant, CIN+, TP53-wild-type; (4) KRAS– and/or PIK3CA-mutant, CIN–, TP53-wild-type; (5) NRAS-mutant; (6) no mutations; (7) others. As expected, group 1 cancers were mostly proximal and poorly differentiated, usually occurring in women. Unexpectedly, two different types of CIN+ CRC were found: group 2 cancers were usually distal and occurred in men, whereas group 3 showed neither of these associations but were of higher stage. CIN+ cancers have conventionally been associated with all three of these variables, because they have been tested en masse. Our classification also showed potentially improved prognostic capabilities, with group 3, and possibly group 1, independently predicting disease-free survival. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:23165447

SNP array profiling of childhood adrenocortical tumors reveals distinct pathways of tumorigenesis and highlights candidate driver genes.

PubMed

Letouzé, Eric; Rosati, Roberto; Komechen, Heloisa; Doghman, Mabrouka; Marisa, Laetitia; Flück, Christa; de Krijger, Ronald R; van Noesel, Max M; Mas, Jean-Christophe; Pianovski, Mara A D; Zambetti, Gerard P; Figueiredo, Bonald C; Lalli, Enzo

2012-07-01

Childhood adrenocortical tumors (ACT) are rare malignancies, except in southern Brazil, where a higher incidence rate is associated to a high frequency of the founder R337H TP53 mutation. To date, copy number alterations in these tumors have only been analyzed by low-resolution comparative genomic hybridization. We analyzed an international series of 25 childhood ACT using high-resolution single nucleotide polymorphism arrays to: 1) detect focal copy number alterations highlighting candidate driver genes; and 2) compare genetic alterations between Brazilian patients carrying the R337H TP53 mutation and non-Brazilian patients. We identified 16 significantly recurrent chromosomal alterations (q-value < 0.05), the most frequent being -4q34, +9q33-q34, +19p, loss of heterozygosity (LOH) of chromosome 17 and 11p15. Focal amplifications and homozygous deletions comprising well-known oncogenes (MYC, MDM2, PDGFRA, KIT, MCL1, BCL2L1) and tumor suppressors (TP53, RB1, RPH3AL) were identified. In addition, eight focal deletions were detected at 4q34, defining a sharp peak region around the noncoding RNA LINC00290 gene. Although non-Brazilian tumors with a mutated TP53 were similar to Brazilian tumors, those with a wild-type TP53 displayed distinct genomic profiles, with significantly fewer rearrangements (P = 0.019). In particular, three alterations (LOH of chromosome 17, +9q33-q34, and -4q34) were significantly more frequent in TP53-mutated samples. Finally, two of four TP53 wild-type tumors displayed as sole rearrangement a copy-neutral LOH of the imprinted region at 11p15, supporting a major role for this region in ACT development. Our findings highlight potential driver genes and cellular pathways implicated in childhood ACT and demonstrate the existence of different oncogenic routes in this pathology.

Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway.

PubMed

Hodroj, Mohammad Hassan; Jardaly, Achraf; Abi Raad, Sarah; Zouein, Annalise; Rizk, Sandra

2018-01-01

Topotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata , was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro. U937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways. Both TP and andrographolide showed an antiproliferative effect in a dose-dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression. The pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately.

Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway

PubMed Central

Hodroj, Mohammad Hassan; Jardaly, Achraf; Abi Raad, Sarah; Zouein, Annalise; Rizk, Sandra

2018-01-01

Background Topotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata, was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro. Materials and methods U937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways. Results Both TP and andrographolide showed an antiproliferative effect in a dose-dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression. Conclusion The pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately. PMID:29785137

Enhanced immune response and protective efficacy of a Treponema pallidum Tp92 DNA vaccine vectored by chitosan nanoparticles and adjuvanted with IL-2.

PubMed

Zhao, Feijun; Wu, Yimou; Zhang, Xiaohong; Yu, Jian; Gu, Weiming; Liu, Shuangquan; Zeng, Tiebing; Zhang, Yuejun; Wang, Shiping

2011-10-01

In this study, the immune-modulatory and protective efficacy of using an interleukin-2 (IL-2) expression plasmid as a genetic adjuvant and chitosan (CS) nanoparticles as vectors to enhance a Tp92 DNA vaccine candidate were investigated in a Treponema pallidum (Tp) rabbit challenge model. CS vectoring of pTp92 or pIL-2 were both demonstrated to augment anti-Tp92 antibody levels induced by pTp92 DNA vaccines. Interestingly, the combination of CS vectored Tp92 and pIL-2 led to the greatest enhancements of anti-Tp92 antibodies and T-cell proliferation (p < 0.05). At week 10 after the first immunization, 15 of the 18 rabbits in each group were challenged with Tp Nichols strain and monitored for skin lesions and ulcer lesions. Ratios of positive skin lesions and ratios of ulcer lesions in groups immunized with pTp92 were significantly lower than those of the empty vector or PBS groups (p < 0.05), demonstrating that pTp92 immunization elicited significant protective efficacy against the Tp Nichols strain challenge. CS vectored and pIL-2 adjuvanted pTp92 immunized animals exhibited the lowest rates of positive skin and ulcer lesions. Male New Zealand white rabbits were randomly assigned to groups (n = 18/group) and immunized intramuscularly with pTp92 based plasmid DNA constructs (100 μg of DNA/rabbit/immunization). Two weeks before Tp challenge (Week 8), three rabbits from each group were used to determine cytokine measurements and fifteen rabbits from each group were used for Tp challenge studies. Intramuscular injection of pTp92 induced strong humoral and cellular immune responses and conferred protection from Tp challenge in rabbits. The use of CS as a pTp92 vector or pIL-2 as an adjuvant achieved a superior level of protective efficacy against Tp challenge, however CS vectored, IL-2 adjuvanted pTp92 immunization conferred the highest level of protective efficacy.

Crystal growth, structural, optical, thermal, mechanical, laser damage threshold and electrical properties of triphenylphosphine oxide 4-nitrophenol (TP4N) single crystals for nonlinear optical applications

NASA Astrophysics Data System (ADS)

Karuppasamy, P.; Senthil Pandian, Muthu; Ramasamy, P.; Verma, Sunil

2018-05-01

The optically good quality single crystals of triphenylphosphine oxide 4-nitrophenol (TP4N) with maximum dimension of 15 × 10 × 5 mm3 were grown by slow evaporation solution technique (SEST) at room temperature. The cell dimensions of the grown TP4N crystal were confirmed by single crystal X-ray diffraction (SXRD) and the crystalline purity was confirmed and planes were indexed by powder X-ray diffraction (PXRD) analysis. Functional groups of TP4N crystal were confirmed by Fourier transform infrared (FTIR) spectral analysis. The optical transmittance of the grown crystal was determined by the UV-Vis NIR spectral analysis and it has good optical transparency in the entire visible region. The band tail (Urbach) energy of the grown crystal was analyzed and it appears to be minimum, which indicates that the TP4N has good crystallinity. The position of valence band (Ev) and conduction band (Ec) of the TP4N have been determined from the electron affinity energy (EA) and the ionization energy (EI) of its elements and using the optical band gap. The thermal behaviour of the grown crystal was investigated by thermogravimetric and differential thermal analysis (TG-DTA). Vickers microhardness analysis was carried out to identify the mechanical stability of the grown crystal and their indentation size effect (ISE) was explained by the Meyer's law (ML), Hays-Kendall's (HK) approach, proportional specimen resistance (PSR) model, modified PSR model (MPSR), elastic/plastic deformation (EPD) model and indentation induced cracking (IIC) model. Chemical etching study was carried out to find the etch pit density (EPD) of the grown crystal. Laser damage threshold (LDT) value was measured by using Nd:YAG laser (1064 nm). The dielectric permittivity (ε՛) and dielectric loss (tan δ) as a function of frequency was measured. The electronic polarizability (α) of the TP4N crystal was calculated. It is well matched to the value which was calculated from Clausius-Mossotti relation, Lorentz-Lorentz equation, optical band gap and coupled dipole method (CDM). The Z-scan technique was carried out using solid state laser (640 nm) to analyze the nonlinear optical properties of the TP4N crystal. It exhibits the self-defocusing and saturable absorbance effect during analysis of closed and open aperture respectively. The nonlinear optical parameters such as refractive index (n2), absorption coefficient (β) and the third order nonlinear optical susceptibility (χ(3)) were analyzed.

Ultrafast studies of organometallic photochemistry: The mechanism of carbon-hydrogen bond activation in solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bromberg, S.E.

1998-05-01

When certain organometallic compounds are photoexcited in room temperature alkane solution, they are able to break or activate the C-H bonds of the solvent. Understanding this potentially practical reaction requires a detailed knowledge of the entire reaction mechanism. Because of the dynamic nature of chemical reactions, time-resolved spectroscopy is commonly employed to follow the important events that take place as reactants are converted to products. For the organometallic reactions examined here, the electronic/structural characteristics of the chemical systems along with the time scales for the key steps in the reaction make ultrafast UV/Vis and IR spectroscopy along with nanosecond Step-Scanmore » FTIR spectroscopy the ideal techniques to use for this study. An initial study of the photophysics of (non-activating) model metal carbonyls centering on the photodissociation of M(CO){sub 6} (M = Cr, W, Mo) was carried out in alkane solutions using ultrafast IR spectroscopy. Next, picosecond UV/vis studies of the C-H bond activation reaction of Cp{sup *}M(CO){sub 2} (M = Rh, Ir), conducted in room temperature alkane solution, are described in an effort to investigate the origin of the low quantum yield for bond cleavage ({approximately}1%). To monitor the chemistry that takes place in the reaction after CO is lost, a system with higher quantum yield is required. The reaction of Tp{sup *}Rh(CO){sub 2} (Tp{sup *} = HB-Pz{sub 3}{sup *}, Pz{sup *} = 3,5-dimethylpyrazolyl) in alkanes has a quantum yield of {approximately}30%, making time resolved spectroscopic measurements possible. From ultrafast IR experiments, two subsequently formed intermediates were observed. The nature of these intermediates are discussed and the first comprehensive reaction mechanism for a photochemical C-H activating organometallic complex is presented.« less

A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal tumor development in ApcΔ14/+ mice.

PubMed

Nakanishi, Masako; Hanley, Matthew P; Zha, Ruochen; Igarashi, Yuichi; Hull, Mark A; Mathias, Gary; Sciavolino, Frank; Grady, James J; Rosenberg, Daniel W

2018-03-08

Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.

Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functional p53

PubMed Central

Gadhikar, Mayur A.; Sciuto, Maria Rita; Alves, Marcus Vinicius Ortega; Pickering, Curtis R.; Osman, Abdullah A.; Neskey, David M.; Zhao, Mei; Fitzgerald, Alison L.; Myers, Jeffrey N.; Frederick, Mitchell J

2014-01-01

Despite the use of multimodality therapy employing cisplatin to treat patients with advanced stage head and neck squamous cell carcinoma (HNSCC), there is an unacceptably high rate of treatment failure. TP53 is the most commonly mutated gene in HNSCC, and the impact of p53 mutation on response to cisplatin treatment is poorly understood. Here we show unambiguously that wild type TP53 (wtp53) is associated with sensitivity of HNSCC cells to cisplatin treatment while mutation or loss of TP53 is associated with cisplatin resistance. We also demonstrate that senescence is the major cellular response to cisplatin in wtp53 HNSCC cells and that cisplatin resistance in p53 null or mutant TP53 cells is due to their lack of senescence. Given the dependence on Chk1/2 kinases to mediate the DNA damage response in p53 deficient cells, there is potential to exploit this to therapeutic advantage through targeted inhibition of the Chk1/2 kinases. Treatment of p53 deficient HNSCC cells with the Chk inhibitor AZD7762 sensitizes them to cisplatin through induction of mitotic cell death. This is the first report demonstrating the ability of a Chk kinase inhibitor to sensitize TP53-deficient HNSCC to cisplatin in a synthetic lethal manner, which has significance given the frequency of TP53 mutations in this disease and because cisplatin has become part of standard therapy for aggressive HNSCC tumors. These pre-clinical data provide evidence that a personalized approach to the treatment of HNSCC based on Chk inhibition in p53 mutant tumors may be feasible. PMID:23839309

MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas

PubMed Central

Grünewald, Inga; Trautmann, Marcel; Busch, Alina; Bauer, Larissa; Huss, Sebastian; Schweinshaupt, Petra; Vollbrecht, Claudia; Odenthal, Margarete; Quaas, Alexander; Büttner, Reinhard; Meyer, Moritz F.; Beutner, Dirk; Hüttenbrink, Karl-Bernd; Wardelmann, Eva; Stenner, Markus; Hartmann, Wolfgang

2016-01-01

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs. 25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2. In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance. PMID:27662657

MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas.

PubMed

Grünewald, Inga; Trautmann, Marcel; Busch, Alina; Bauer, Larissa; Huss, Sebastian; Schweinshaupt, Petra; Vollbrecht, Claudia; Odenthal, Margarete; Quaas, Alexander; Büttner, Reinhard; Meyer, Moritz F; Beutner, Dirk; Hüttenbrink, Karl-Bernd; Wardelmann, Eva; Stenner, Markus; Hartmann, Wolfgang

2016-11-15

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs.25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2.In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance.

DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

PubMed

Dong, Xiaoqun; Li, Yanan; Hess, Kenneth R; Abbruzzese, James L; Li, Donghui

2011-01-01

DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

Pre-operative assessment of residual disease in locally advanced breast cancer patients: A sequential study by quantitative diffusion weighted MRI as a function of therapy.

PubMed

Agarwal, Khushbu; Sharma, Uma; Sah, Rani G; Mathur, Sandeep; Hari, Smriti; Seenu, Vurthaluru; Parshad, Rajinder; Jagannathan, Naranamangalam R

2017-10-01

The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated. DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADC WT ), solid tumor (ADC ST ), intra-tumoral necrosis (ADC Nec ) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins. Of 38 patients, 6 were pathological complete responders (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADC ST and ADC WT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating the heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR, indicating the presence of residual disease in these shells. Pre-surgery information may serve as a guide to define cancer free margins and the extent of residual disease which may be useful in planning breast conservation surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis

PubMed Central

Singh, Yadvir; Kohli, Sakshi; Ahmad, Javeed; Ehtesham, Nasreen Z.; Tyagi, Anil K.

2014-01-01

ABSTRACT Mycobacterial evolution involves various processes, such as genome reduction, gene cooption, and critical gene acquisition. Our comparative genome size analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes were bigger than those of opportunistic (OP) or totally pathogenic (TP) mycobacteria, with the TP genomes being smaller yet variable in size—their genomic plasticity reflected their ability to evolve and survive under various environmental conditions. From the 44 mycobacterial species, 13 species, representing TP, OP, and NP, were selected for genomic-relatedness analyses. Analysis of homologous protein-coding genes shared between Mycobacterium indicus pranii (NP), Mycobacterium intracellulare ATCC 13950 (OP), and Mycobacterium tuberculosis H37Rv (TP) revealed that 4,995 (i.e., ~95%) M. indicaus pranii proteins have homology with M. intracellulare, whereas the homologies among M. indicus pranii, M. intracellulare ATCC 13950, and M. tuberculosis H37Rv were significantly lower. A total of 4,153 (~79%) M. indicus pranii proteins and 4,093 (~79%) M. intracellulare ATCC 13950 proteins exhibited homology with the M. tuberculosis H37Rv proteome, while 3,301 (~82%) and 3,295 (~82%) M. tuberculosis H37Rv proteins showed homology with M. indicus pranii and M. intracellulare ATCC 13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP mycobacteria showed enzymatic plasticity between M. indicus pranii (NP) and M. intracellulare ATCC 13950 (OP), Mycobacterium avium 104 (OP), and M. tuberculosis H37Rv (TP). Mycobacterium tuberculosis seems to have acquired novel alternate pathways with possible roles in metabolism, host-pathogen interactions, virulence, and intracellular survival, and by implication some of these could be potential drug targets. PMID:25370496

Nutrient delivery to Lake Winnipeg from the Red-Assiniboine River Basin – A binational application of the SPARROW model

USGS Publications Warehouse

Benoy, Glenn A.; Jenkinson, R. Wayne; Robertson, Dale M.; Saad, David A.

2016-01-01

Excessive phosphorus (TP) and nitrogen (TN) inputs from the Red–Assiniboine River Basin (RARB) have been linked to eutrophication of Lake Winnipeg; therefore, it is important for the management of water resources to understand where and from what sources these nutrients originate. The RARB straddles the Canada–United States border and includes portions of two provinces and three states. This study represents the first binationally focused application of SPAtially Referenced Regressions on Watershed attributes (SPARROW) models to estimate loads and sources of TP and TN by jurisdiction and basin at multiple spatial scales. Major hurdles overcome to develop these models included: (1) harmonization of geospatial data sets, particularly construction of a contiguous stream network; and (2) use of novel calibration steps to accommodate limitations in spatial variability across the model extent and in the number of calibration sites. Using nutrient inputs for a 2002 base year, a RARB TP SPARROW model was calibrated that included inputs from agriculture, forests and wetlands, wastewater treatment plants (WWTPs) and stream channels, and a TN model was calibrated that included inputs from agriculture, WWTPs and atmospheric deposition. At the RARB outlet, downstream from Winnipeg, Manitoba, the majority of the delivered TP and TN came from the Red River Basin (90%), followed by the Upper Assiniboine River and Souris River basins. Agriculture was the single most important TP and TN source for each major basin, province and state. In general, stream channels (historically deposited nutrients and from bank erosion) were the second most important source of TP. Performance metrics for the RARB SPARROW model are similarly robust compared to other, larger US SPARROW models making it a potentially useful tool to address questions of where nutrients originate and their relative contributions to loads delivered to Lake Winnipeg.

Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

PubMed

Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

2015-02-01

Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes

PubMed Central

Santhosh, KT; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, AJ; Dakshinamurti, S

2011-01-01

BACKGROUND AND PURPOSE Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor–mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. EXPERIMENTAL APPROACH We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca2+ response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. KEY RESULTS Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. CONCLUSIONS AND IMPLICATIONS TP receptor sensitivity and EC50 for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca2+ mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. PMID:21385177

Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

PubMed

Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

2018-03-25

Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The low salinity effect at high temperatures

DOE PAGES

Xie, Quan; Brady, Patrick V.; Pooryousefy, Ehsan; ...

2017-04-05

The mechanism(s) of low salinity water flooding (LSWF) must be better understood at high temperatures and pressures if the method is to be applied in high T/P kaolinite-bearing sandstone reservoirs. We measured contact angles between a sandstone and an oil (acid number, AN = 3.98 mg KOH/g, base number, BN = 1.3 mg KOH/g) from a reservoir in the Tarim Field in western China in the presence of various water chemistries. We examined the effect of aqueous ionic solutions (formation brine, 100X diluted formation brine, and softened water), temperature (60, 100 and 140 °C) and pressure (20, 30, 40, andmore » 50 MPa) on the contact angle. We also measured the zeta potential of the oil/water and water/rock interfaces to calculate oil/brine/rock disjoining pressures. A surface complexation model was developed to interpret contact angle measurements and compared with DLVO theory predictions. Contact angles were greatest in formation water, followed by the softened water, and low salinity water at the same pressure and temperature. Contact angles increased slightly with temperature, whereas pressure had little effect. DLVO and surface complexation modelling predicted similar wettability trends and allow reasonably accurate interpretation of core-flood results. Water chemistry has a much larger impact on LSWF than reservoir temperature and pressure. As a result, low salinity water flooding should work in high temperature and high pressure kaolinite-bearing sandstone reservoirs.« less

The low salinity effect at high temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Quan; Brady, Patrick V.; Pooryousefy, Ehsan

The mechanism(s) of low salinity water flooding (LSWF) must be better understood at high temperatures and pressures if the method is to be applied in high T/P kaolinite-bearing sandstone reservoirs. We measured contact angles between a sandstone and an oil (acid number, AN = 3.98 mg KOH/g, base number, BN = 1.3 mg KOH/g) from a reservoir in the Tarim Field in western China in the presence of various water chemistries. We examined the effect of aqueous ionic solutions (formation brine, 100X diluted formation brine, and softened water), temperature (60, 100 and 140 °C) and pressure (20, 30, 40, andmore » 50 MPa) on the contact angle. We also measured the zeta potential of the oil/water and water/rock interfaces to calculate oil/brine/rock disjoining pressures. A surface complexation model was developed to interpret contact angle measurements and compared with DLVO theory predictions. Contact angles were greatest in formation water, followed by the softened water, and low salinity water at the same pressure and temperature. Contact angles increased slightly with temperature, whereas pressure had little effect. DLVO and surface complexation modelling predicted similar wettability trends and allow reasonably accurate interpretation of core-flood results. Water chemistry has a much larger impact on LSWF than reservoir temperature and pressure. As a result, low salinity water flooding should work in high temperature and high pressure kaolinite-bearing sandstone reservoirs.« less

The Golgi localization of phosphatidylinositol transfer protein beta requires the protein kinase C-dependent phosphorylation of serine 262 and is essential for maintaining plasma membrane sphingomyelin levels.

PubMed

van Tiel, Claudia M; Westerman, Jan; Paasman, Marten A; Hoebens, Martha M; Wirtz, Karel W A; Snoek, Gerry T

2002-06-21

Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262) was identified as the major site of phosphorylation and Ser(165) as a minor phosphorylation site. The phospholipid transfer activities of wild-type PI-TP beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell lysates was used to separate PI-TP beta from its phosphorylated form. After Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF 109203X, the phosphorylated form of wtPI-TP beta was strongly reduced. Immunolocalization showed that wtPI-TP beta was predominantly associated with the Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was distributed throughout the cell similar to what was observed for PI-TP beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI-TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma membrane upon degradation by sphingomyelinase. This implies that PKC-dependent association with the Golgi complex is a prerequisite for PI-TP beta to express its effect on sphingomyelin metabolism.

Nutlin‐3a selects for cells harbouring TP 53 mutations

PubMed Central

Hollstein, Monica; Arlt, Volker M.; Phillips, David H.

2016-01-01

TP53 mutations occur in half of all human tumours. Mutagen‐induced or spontaneous TP53 mutagenesis can be studied in vitro using the human TP53 knock‐in (Hupki) mouse embryo fibroblast (HUF) immortalisation assay (HIMA). TP53 mutations arise in up to 30% of mutagen‐treated, immortalised HUFs; however, mutants are not identified until TP53 sequence analysis following immortalisation (2–5 months) and much effort is expended maintaining TP53‐WT cultures. In order to improve the selectivity of the HIMA for HUFs harbouring TP53 mutations, we explored the use of Nutlin‐3a, an MDM2 inhibitor that leads to stabilisation and activation of wild‐type (WT) p53. First, we treated previously established immortal HUF lines carrying WT or mutated TP53 with Nutlin‐3a to examine the effect on cell growth and p53 activation. Nutlin‐3a induced the p53 pathway in TP53‐WT HUFs and inhibited cell growth, whereas most TP53‐mutated HUFs were resistant to Nutlin‐3a. We then assessed whether Nutlin‐3a treatment could discriminate between TP53‐WT and TP53‐mutated cells during the HIMA (n = 72 cultures). As immortal clones emerged from senescent cultures, each was treated with 10 µM Nutlin‐3a for 5 days and observed for sensitivity or resistance. TP53 was subsequently sequenced from all immortalised clones. We found that all Nutlin‐3a‐resistant clones harboured TP53 mutations, which were diverse in position and functional impact, while all but one of the Nutlin‐3a‐sensitive clones were TP53‐WT. These data suggest that including a Nutlin‐3a counter‐screen significantly improves the specificity and efficiency of the HIMA, whereby TP53‐mutated clones are selected prior to sequencing and TP53‐WT clones can be discarded. PMID:27813088

Amino-terminal residues of ΔNp63, mutated in ectodermal dysplasia, are required for its transcriptional activity.

PubMed

Lena, Anna Maria; Duca, Sara; Novelli, Flavia; Melino, Sonia; Annicchiarico-Petruzzelli, Margherita; Melino, Gerry; Candi, Eleonora

2015-11-13

p63, a member of the p53 family, is a crucial transcription factor for epithelial development and skin homeostasis. Heterozygous mutations in TP63 gene have been associated with human ectodermal dysplasia disorders. Most of these TP63 mutations are missense mutations causing amino acidic substitutions at p63 DNA binding or SAM domains that reduce or abolish the transcriptional activity of mutants p63. A significant number of mutants, however, resides in part of the p63 protein that apparently do not affect DNA binding and/or transcriptional activity, such as the N-terminal domain. Here, we characterize five p63 mutations at the 5' end of TP63 gene aiming to understand the pathogenesis of the diseases and to uncover the role of ΔNp63α N-terminus residues in determining its transactivation potential. Copyright © 2015 Elsevier Inc. All rights reserved.

Mutations in the evolutionarily highly conserved KEOPS complex genes cause nephrotic syndrome with microcephaly

PubMed Central

Braun, Daniela A.; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A.; Schanze, Denny; Ashraf, Shazia; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I. Chiara; Sanchez-Ferras, Oraly; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E.; Pabst, Werner L.; Warejko, Jillian; Daga, Ankana; LeBerre, Tamara Basta; Matejas, Verena; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T.; Gipson, Patrick E.; Hsu, Chyong-Hsin; Kari, Jameela A.; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okasha; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth; Rump, Patrick; Schnur, Rhonda E.; Shiihara, Takashi; Sinha, Manish; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A.; Tsai, Wen-Hui; Tsai, Jeng-Daw; Vester, Udo; Viskochil, David H.; Vatanavicharn, Nithiwat; Waxler, Jessica L.; Wolf, Matthias T.F.; Wong, Sik-Nin; Poduri, Annapurna; Truglio, Gessica; Mane, Shrikant; Lifton, Richard P.; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Calleweart, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

2018-01-01

Galloway-Mowat syndrome (GAMOS) is a severe autosomal-recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies. To date, mutations of WDR73 are the only known monogenic cause of GAMOS and in most affected individuals the molecular diagnosis remains elusive. We here identify recessive mutations of OSGEP, TP53RK, TPRKB, or LAGE3, encoding the 4 subunits of the KEOPS complex in 33 individuals of 30 families with GAMOS. CRISPR/Cas9 knockout in zebrafish and mice recapitulates the human phenotype of microcephaly and results in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibits cell proliferation, which human mutations fail to rescue, and knockdown of either gene activates DNA damage response signaling and induces apoptosis. OSGEP and TP53RK molecularly interact and co-localize with the actin-regulating ARP2/3 complex. Furthermore, knockdown of OSGEP and TP53RK induces defects of the actin cytoskeleton and reduces migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identify 4 novel monogenic causes of GAMOS, describe the first link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. PMID:28805828

RSRM TP-H1148 Main Grain Propellant Crack Initiation Evaluation

NASA Technical Reports Server (NTRS)

Earnest, Todd E.

2005-01-01

Pressurized TP-HI 148 propellant fracture toughness testing was performed to assess the potential for initiation of visually undetectable cracks in the RSRM forward segment transition region during motor ignition. Two separate test specimens were used in this evaluation. Testing was performed in cold-gas and hot-fire environments, and under both static and dynamic pressurization conditions. Analysis of test results demonstrates safety factors against initiation of visually undetectable cracks in excess of 8.0. The Reusable Solid Rocket Motor (RSRM) forward segment is cast with PBAN propellant (TP-HI 148) to form T an 1 1-point star configuration that transitions to a tapered center perforated bore (see Figure 1). The geometry of the transition region between the fin valleys and the bore causes a localized area of high strain during horizontal storage. Updated analyses using worst-case mechanical properties at 40 F and improved modeling techniques indicated a slight reduction in safety margins over previous predictions. Although there is no history of strain induced cracks or flaws in the transition region propellant, a proactive test effort was initiated to better understand the implications of the new analysis, primarily the resistance of TP-H1148 propellant to crack initiation' during RSRM ignition.

The anti-photoaging effect of antioxidant collagen peptides from silver carp (Hypophthalmichthys molitrix) skin is preferable to tea polyphenols and casein peptides.

PubMed

Zhang, Ling; Zheng, Yayao; Cheng, Xiaofeng; Meng, Mengfei; Luo, Yongkang; Li, Bo

2017-04-19

Applying antioxidants to attenuate skin photoaging has received great attention. In this study, antioxidant collagen peptides (ACPs) with different activities were prepared using different proteases, called high (HCP), medium (MCP) and low antioxidant collagen peptides (LCP). The effects of ACPs, tea polyphenols (TP) and casein peptides (CP) on the photoaged skin of mice were evaluated and compared. Ingestion of ACPs significantly alleviated UV-induced abnormal alterations of skin components and antioxidative indicators in both serum and skin (p < 0.05). In addition, HCP had the best effect on protecting skin from photoaging among the three collagen peptides, with no significant differences between MCP and LCP (p > 0.05). TP and CP, with higher antioxidant activity in vitro, only significantly increased hydroxyproline content (only in the TP group) and CAT activity and decreased protein carbonyl content at week 2, showing a much weaker effect than that of the ACP groups. The histological analysis result further demonstrates that ACPs exerted a stronger beneficial effect on normalizing skin structure and collagen arrangement than TP and CP. Accordingly, ACPs have potential for nutraceuticals as anti-skin-photoaging ingredients.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

PubMed

Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

2011-07-01

Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Tp-e Interval, Tp-e/QTc Ratio, and Fragmented QRS Are Correlated with the Severity of Liver Cirrhosis.

PubMed

Akboga, Mehmet Kadri; Yuksel, Mahmut; Balci, Kevser Gulcihan; Kaplan, Mustafa; Cay, Serkan; Gokbulut, Volkan; Yayla, Cagri; Ertem, Ahmet Goktug; Ayhan, Meral Akdogan; Topaloglu, Serkan; Aras, Dursun

2017-01-01

Arrhythmias and electrocardiographic changes are reported in several noncardiac diseases, including liver cirrhosis (LC). We intended to evaluate the interval from the peak to the end of the electrocardiographic T wave (Tp-e), Tp-e/QTc ratio, and fQRS as presumed markers of arrhythmias in LC. In this cross-sectional study, a total of 88 consecutive patients with LC according to clinical, biological, ultrasonographic, or histological criteria and 73 control subjects were enrolled. The severity of cirrhosis was classified according to Pugh-Child's classification and Model for End-Stage Liver Disease (MELD) score. Tp-e interval, Tp-e/QTc ratio, and fQRS rates were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QTc ratio and fQRS rates were significantly increased in parallel to the severity of LC (P < 0.001, P < 0.001, and P = 0.003, respectively). In correlation analysis, Pugh-Child stage showed a significantly positive correlation with Tp-e interval (r = 0.462, P < 0.001), QTc interval (r = 0.373, P < 0.001), Tp-e/QTc ratio (r = 0.352, P < 0.001), and fQRS (r = 0.407, P < 0.001). Furthermore, Tp-e interval (r = 0.414, P < 0.001) and Tp-e/QTc ratio (r = 0.426, P< 0.001) had significant positive correlation with MELD score. Our study demonstrated that Tp-e interval, Tp-e/QTc ratios, and fQRS rates were significantly increased in parallel to the severity of LC. Thus, these findings may implicate that Tp-e interval, Tp-e/QTc ratio, and fQRS may be novel and useful indicators for prediction of arrhythmias in LC. © 2016 Wiley Periodicals, Inc.

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

PubMed Central

Piskorz, Anna M.; Biggs, Heather; Addley, Helen; Freeman, Sue; Moyle, Penelope; Sala, Evis; Sayal, Karen; Hosking, Karen; Gounaris, Ioannis; Earl, Helena M.; Rosenfeld, Nitzan; Brenton, James D.

2016-01-01

Background Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). Methods and Findings We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%–22%) compared to 0.7% (IQR 0.3%–2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28–54) compared with a median time to nadir of 84 d (IQR 42–116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07–0.67, p = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%–92%) and 88% specificity (95% CI 64%–99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. Conclusions In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment. PMID:27997533

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

PubMed

Parkinson, Christine A; Gale, Davina; Piskorz, Anna M; Biggs, Heather; Hodgkin, Charlotte; Addley, Helen; Freeman, Sue; Moyle, Penelope; Sala, Evis; Sayal, Karen; Hosking, Karen; Gounaris, Ioannis; Jimenez-Linan, Mercedes; Earl, Helena M; Qian, Wendi; Rosenfeld, Nitzan; Brenton, James D

2016-12-01

Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, p = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.

An Innovative Concept for Testing Rutting Susceptibility of Asphalt Mixture

NASA Astrophysics Data System (ADS)

Mohseni, Alaeddin; Azari, Haleh

Currently, flow number (FN) is being used for measuring permanent deformation resistance of asphalt mixtures. The provisional AASHTO TP 79-10 test method specifies the requirements of the FN test; however, there are undefined levels of test variables, such as temperature, axial stress, and confinement. Therefore, agreeable FN criteria that can reliably discriminate between various mixtures have not been established yet. As the asphalt industry continues to develop more sophisticated mixtures (Warm Mix, RAP and RAS), the FN value has failed to capture the true complexity of the asphalt mixtures. These shortcomings and the unpredictable testing time of the FN test have affected its usefulness for evaluating high temperature performance of asphalt mixtures. A new test procedure for evaluation of rutting susceptibility of asphalt mixtures is being proposed. The new procedure is conducted at one temperature and multiple stresses on the same replicate in three increments of 500 cycles, which only takes 33 minutes to complete. The property of the test is the permanent strain due to the last cycle of each test increment (Minimum Strain Rate, or MSR). A master curve is developed by plotting the MSR values versus parameter TP, which is a product of Temperature and Pressure. The MSR master curve represents the unit rutting damage (rut per axle) of asphalt mixtures at any stress and temperature and can be used in laboratory for material characterization, mix design verification, ranking of the mixtures, or for pavement design applications to predict rut depth for project climate and design traffic.

Nutrient bioassimilation capacity of aquacultured oysters: quantification of an ecosystem service.

PubMed

Higgins, Colleen B; Stephenson, Kurt; Brown, Bonnie L

2011-01-01

Like many coastal zones and estuaries, the Chesapeake Bay has been severely degraded by cultural eutrophication. Rising implementation costs and difficulty achieving nutrient reduction goals associated with point and nonpoint sources suggests that approaches supplemental to source reductions may prove useful in the future. Enhanced oyster aquaculture has been suggested as one potential policy initiative to help rid the Bay waters of excess nutrients via harvest of bioassimilated nutrients. To assess this potential, total nitrogen (TN), total phosphorous (TP), and total carbon (TC) content were measured in oyster tissue and shell at two floating-raft cultivation sites in the Chesapeake Bay. Models were developed based on the common market measurement of total length (TL) for aquacultured oysters, which was strongly correlated to the TN (R2 = 0.76), TP (R2 = 0.78), and TC (R2 = 0.76) content per oyster tissue and shell. These models provide resource managers with a tool to quantify net nutrient removal. Based on model estimates, 10(6) harvest-sized oysters (76 mm TL) remove 132 kg TN, 19 kg TP, and 3823 kg TC. In terms of nutrients removed per unit area, oyster harvest is an effective means of nutrient removal compared with other nonpoint source reduction strategies. At a density of 286 oysters m(-2), assuming no mortality, harvest size nutrient removal rates can be as high as 378 kg TN ha(-1), 54 kg TP ha(-1), and 10,934 kg TC ha(-1) for 76-mm oysters. Removing 1 t N from the Bay would require harvesting 7.7 million 76-mm TL cultivated oysters.

A Valuable Tool in Predicting Poor Outcome due to Sepsis in Pediatric Intensive Care Unit: Tp-e/QT Ratio.

PubMed

Ozdemir, Rahmi; Isguder, Rana; Kucuk, Mehmet; Karadeniz, Cem; Ceylan, Gokhan; Katipoglu, Nagehan; Yilmazer, Murat Muhtar; Yozgat, Yilmaz; Mese, Timur; Agin, Hasan

2016-10-01

To assess the feasibility of 12-lead electrocardiographic (ECG) measures such as P wave dispersion (PWd), QT interval, QT dispersion (QTd), Tp-e interval, Tp-e/QT and Tp-e/QTc ratio in predicting poor outcome in patients diagnosed with sepsis in pediatric intensive care unit (PICU). Ninety-three patients diagnosed with sepsis, severe sepsis or septic shock and 103 age- and sex-matched healthy children were enrolled into the study. PWd, QT interval, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were obtained from a 12-lead electrocardiogram. PWd, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were significantly higher in septic patients compared with the controls. During the study period, 41 patients had died. In multivariate logistic regression analyses, only Tp-e/QT ratio was found to be an independent predictor of mortality. The ECG measurements can predict the poor outcome in patients with sepsis. The Tp-e/QT ratio may be a valuable tool in predicting mortality for patients with sepsis in the PICU. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fluorescence and computational studies of thymidine phosphorylase affinity toward lipidated 5-FU derivatives

NASA Astrophysics Data System (ADS)

Lettieri, R.; D'Abramo, M.; Stella, L.; La Bella, A.; Leonelli, F.; Giansanti, L.; Venanzi, M.; Gatto, E.

2018-04-01

Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

Development of an engineered soil bacterium enabling to convert both insoluble inorganic and organic phosphate into plant available phosphate and its use as a biofertilizer.

PubMed

Liu, Lili; Du, Wenya; Luo, Wenyu; Su, Yi; Hui, Jiejie; Ma, Shengwu

2015-05-01

Phosphorus (P) is one of the most important nutrient elements for plant growth and metabolism. We previously isolated a P-solubilizing bacterium 9320-SD with the ability to utilize inorganic P and convert it into plant-available P. The present study aims to enhance the P-solubilizing capacity of 9320-SD, as our long-term goal is to develop a more effective P-solubilizing bacterial strain for use as a biofertilizer. In this end, we introduced a bacterial phytase encoding gene into 9320-SD. One randomly selected transformant, SDLiuTP02, was examined for recombinant protein expression and phytase activity, and assessed for its ability to promote plant growth. Our results indicate that SDLiuTP02 is capable of expressing high levels of phytase activity. Importantly, corn seedlings treated with the SDLiuTP02 cell culture exhibited increased rates of photosynthesis, transpiration, and stomatal conductance as well as increased growth rate under laboratory conditions and increased growth rate in pot assays compared to seedlings treated with cell cultures of the parental strain 9320-SD. Field experiments further indicated that application of SDLiuTP02 promoted a greater growth rate in young cucumber plant and a higher foliar chlorophyll level in chop suey greens when compared to 9320-SD treated controls. These results indicate that SDLiuTP02 has the potential to be a more effective P biofertilizer to increase agricultural productivity.

Stereochemistry-Dependent Proton Conduction in Proton Exchange Membrane Fuel Cells.

PubMed

Thimmappa, Ravikumar; Devendrachari, Mruthyunjayachari Chattanahalli; Kottaichamy, Alagar Raja; Tiwari, Omshanker; Gaikwad, Pramod; Paswan, Bhuneshwar; Thotiyl, Musthafa Ottakam

2016-01-12

Graphene oxide (GO) is impermeable to H2 and O2 fuels while permitting H(+) shuttling, making it a potential candidate for proton exchange membrane fuel cells (PEMFC), albeit with a large anisotropy in their proton transport having a dominant in plane (σIP) contribution over the through plane (σTP). If GO-based membranes are ever to succeed in PEMFC, it inevitably should have a dominant through-plane proton shuttling capability (σTP), as it is the direction in which proton gets transported in a real fuel-cell configuration. Here we show that anisotropy in proton conduction in GO-based fuel cell membranes can be brought down by selectively tuning the geometric arrangement of functional groups around the dopant molecules. The results show that cis isomer causes a selective amplification of through-plane proton transport, σTP, pointing to a very strong geometry angle in ionic conduction. Intercalation of cis isomer causes significant expansion of GO (001) planes involved in σTP transport due to their mutual H-bonding interaction and efficient bridging of individual GO planes, bringing down the activation energy required for σTP, suggesting the dominance of a Grotthuss-type mechanism. This isomer-governed amplification of through-plane proton shuttling resulted in the overall boosting of fuel-cell performance, and it underlines that geometrical factors should be given prime consideration while selecting dopant molecules for bringing down the anisotropy in proton conduction and enhancing the fuel-cell performance in GO-based PEMFC.

Evaluating stocking efficacy in an ecosystem undergoing oligotrophication

USGS Publications Warehouse

Kao, Yu-Chun; Rogers, Mark W.; Bunnell, David B.

2018-01-01

Oligotrophication has negatively affected fisheries production in many freshwater ecosystems and could conceivably reduce the efficacy of stockings used to enhance fisheries. In Lake Michigan, offshore oligotrophication has occurred since the 1970s, owing to reductions in total phosphorus (TP) inputs and nearshore sequestration of TP by nonindigenous dreissenid mussels. We evaluated simultaneous effects of stock enhancement and oligotrophication on salmonine species (Chinook salmon Oncorhynchus tshawytscha, lake trout Salvelinus namaycush, and steelhead O. mykiss) that support valuable recreational fisheries. We employed a novel application of an Ecopath with Ecosim model by conducting a full factorial simulation experiment. Our design included multiple levels of salmonine stocking, consumption by invasive quagga mussels (Dreissena bugensis), and TP that were informed by manager interests. Under all levels of TP and quagga mussel consumption, our results showed that stock enhancement could still increase salmonine biomass, but positive responses were stronger for lake trout and steelhead than Chinook salmon. Simulations showed that quagga mussel consumption has deleterious effects on pelagic-oriented prey fishes and Chinook salmon, which feed almost exclusively on the pelagic-oriented alewife (Alosa pseudoharengus). In summary, results from our simulation experiment suggested that lake trout and steelhead are better suited to the current ecosystem than Chinook salmon, and therefore, stock enhancement provides the highest gains for these two species. Furthermore, simulated biomass of all recreational salmonine species increased with increasing TP, indicating the need for managers to consider how potential future oligotrophication will limit the carrying capacity of salmonine biomass in Lake Michigan

Regional interpretation of water-quality monitoring data

USGS Publications Warehouse

Smith, Richard A.; Schwarz, Gregory E.; Alexander, Richard B.

1997-01-01

We describe a method for using spatially referenced regressions of contaminant transport on watershed attributes (SPARROW) in regional water-quality assessment. The method is designed to reduce the problems of data interpretation caused by sparse sampling, network bias, and basin heterogeneity. The regression equation relates measured transport rates in streams to spatially referenced descriptors of pollution sources and land-surface and stream-channel characteristics. Regression models of total phosphorus (TP) and total nitrogen (TN) transport are constructed for a region defined as the nontidal conterminous United States. Observed TN and TP transport rates are derived from water-quality records for 414 stations in the National Stream Quality Accounting Network. Nutrient sources identified in the equations include point sources, applied fertilizer, livestock waste, nonagricultural land, and atmospheric deposition (TN only). Surface characteristics found to be significant predictors of land-water delivery include soil permeability, stream density, and temperature (TN only). Estimated instream decay coefficients for the two contaminants decrease monotonically with increasing stream size. TP transport is found to be significantly reduced by reservoir retention. Spatial referencing of basin attributes in relation to the stream channel network greatly increases their statistical significance and model accuracy. The method is used to estimate the proportion of watersheds in the conterminous United States (i.e., hydrologic cataloging units) with outflow TP concentrations less than the criterion of 0.1 mg/L, and to classify cataloging units according to local TN yield (kg/km2/yr).

Effect of CO2 Enrichment on Synthesis of Some Primary and Secondary Metabolites in Ginger (Zingiber officinale Roscoe)

PubMed Central

Ghasemzadeh, Ali; Jaafar, Hawa Z. E.

2011-01-01

The effect of two different CO2 concentrations (400 and 800 μmol mol−1) on the photosynthesis rate, primary and secondary metabolite syntheses and the antioxidant activities of the leaves, stems and rhizomes of two Zingiber officinale varieties (Halia Bentong and Halia Bara) were assessed in an effort to compare and validate the medicinal potential of the subterranean part of the young ginger. High photosynthesis rate (10.05 μmol CO2 m−2s−1 in Halia Bara) and plant biomass (83.4 g in Halia Bentong) were observed at 800 μmol mol−1 CO2. Stomatal conductance decreased and water use efficiency increased with elevated CO2 concentration. Total flavonoids (TF), total phenolics (TP), total soluble carbohydrates (TSC), starch and plant biomass increased significantly (P ≤ 0.05) in all parts of the ginger varieties under elevated CO2 (800 μmol mol−1). The order of the TF and TP increment in the parts of the plant was rhizomes > stems > leaves. More specifically, Halia Bara had a greater increase of TF (2.05 mg/g dry weight) and TP (14.31 mg/g dry weight) compared to Halia Bentong (TF: 1.42 mg/g dry weight; TP: 9.11 mg/g dry weight) in average over the whole plant. Furthermore, plants with the highest rate of photosynthesis had the highest TSC and phenolics content. Significant differences between treatments and species were observed for TF and TP production. Correlation coefficient showed that TSC and TP content are positively correlated in both varieties. The antioxidant activity, as determined by the ferric reducing/antioxidant potential (FRAP) activity, increased in young ginger grown under elevated CO2. The FRAP values for the leaves, rhizomes and stems extracts of both varieties grown under two different CO2 concentrations (400 and 800 μmol mol−1) were significantly lower than those of vitamin C (3107.28 μmol Fe (II)/g) and α-tocopherol (953 μmol Fe (II)/g), but higher than that of BHT (74.31 μmol Fe (II)/g). These results indicate that the plant biomass, primary and secondary metabolite synthesis, and following that, antioxidant activities of Malaysian young ginger varieties can be enhanced through controlled environment (CE) and CO2 enrichment. PMID:21541046

Use of Bio-Amp, a commercial bio-additive for the treatment of grease trap wastewater containing fat, oil, and grease.

PubMed

Tang, Hao L; Xie, Yuefeng F; Chen, Yen-Chih

2012-11-01

This research investigated the application of Bio-Amp, a commercial bio-additive for the treatment of fat, oil, and grease (FOG) in a grease trap, and evaluated potential impacts of treated effluent on downstream collection system and treatment processes. Results show that after Bio-Amp treatment, FOG deposit formation was reduced by 40%, implicating a potential reduction of sewer line blockages. Chemical oxygen demand (COD), total nitrogen (TN), total phosphorus (TP) and total fatty acids were reduced by 39%, 33%, 56%, and 59%, respectively, which represents an overall loading reduction of 9% COD, 5% TN and 40% TP received by the treatment plant from all the dining halls. On the other hand, readily biodegradable COD fractions significantly increased, which implies a potential improvement on Bio-P removal. Overall, the results showed that application of Bio-Amp in grease trap provides potential reduction of sewer line blockages, and can also alleviate downstream treatment burden. Copyright © 2012 Elsevier Ltd. All rights reserved.

Glucagon-Secreting Alpha Cell Selective Two-Photon Fluorescent Probe TP-α: For Live Pancreatic Islet Imaging.

PubMed

Agrawalla, Bikram Keshari; Chandran, Yogeswari; Phue, Wut-Hmone; Lee, Sung-Chan; Jeong, Yun-Mi; Wan, Si Yan Diana; Kang, Nam-Young; Chang, Young-Tae

2015-04-29

Two-photon (TP) microscopy has an advantage for live tissue imaging which allows a deeper tissue penetration up to 1 mm comparing to one-photon (OP) microscopy. While there are several OP fluorescence probes in use for pancreatic islet imaging, TP imaging of selective cells in live islet still remains a challenge. Herein, we report the discovery of first TP live pancreatic islet imaging probe; TP-α (Two Photon-alpha) which can selectively stain glucagon secreting alpha cells. Through fluorescent image based screening using three pancreatic cell lines, we discovered TP-α from a TP fluorescent dye library TPG (TP-Green). In vitro fluorescence test showed that TP-α have direct interaction and appear glucagon with a significant fluorescence increase, but not with insulin or other hormones/analytes. Finally, TP-α was successfully applied for 3D imaging of live islets by staining alpha cell directly. The newly developed TP-α can be a practical tool to evaluate and identify live alpha cells in terms of localization, distribution and availability in the intact islets.

The hollow fibre assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells

PubMed Central

Temmink, O H; Prins, H-J; van Gelderop, E; Peters, G J

2006-01-01

The Hollow Fibre Assay (HFA) is usually applied as an early in vivo model for anti-cancer drug screening, but is potentially an excellent model for short-term in vivo pharmacodynamic studies. We used the model to study the in vivo role of thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) in the cytotoxicity and pharmacodynamics of TAS-102 in colon cancer cells. TAS-102 is a new oral drug formulation, which is composed of trifluorothymidine (TFT) and thymidine phosphorylase inhibitor (TPI), which prevents TFT degradation. We compared the activity with Xeloda (capecitabine), which is activated by TP into 5FU. Hollow fibres filled with human Colo320 or Colo320TP1 colorectal cancer cells with deficient or high TP expression, respectively, were implanted subcutaneously (s.c.) at both flanks of BALB/c mice. The mice were treated orally over 5 days with TAS-102, TFT alone, 5′DFUR±TPI or capecitabine at their maximum tolerated dose (MTD). The cells were retrieved from the fibres and assayed for growth (MTT assay), cell cycle distribution (flow cytometry) and apoptosis induction (FragEL method). TAS-102 induced considerable growth inhibition (50%, P<0.01) to both cell lines, which was completely abolished in the absence of TPI. Capecitabine and its metabolite 5′DFUR reduced proliferation of Colo320TP1 cells in the fibres significantly (down to 25–40%), but much less in Colo320 cells, whereas addition of TPI reduced the effect of 5′DFUR, although not completely. These differences in cytotoxic effects were reflected in the pharmacodynamic evaluation. TAS-102 induced a G2M-phase arrest (from 25 to 40%) and apoptosis (>8-fold), which was more pronounced in Colo320 than in Colo320TP1. Again, omission of TPI neutralised the effect of TAS-102. Similarly, 5′DFUR and capecitabine induced a significant G2M-phase arrest (up to 45%) in the Colo320TP1 cell line, but less pronounced in the parental Colo320. Addition of TPI to 5′DFUR reduced this effect to control levels. Also induction of apoptosis was reduced in the presence of TPI. The data demonstrated that the HFA is excellently suited for studying short-term pharmacodynamic effects of fluoropyrimidines in vivo. TAS-102 is only effective in inducing cytotoxicity when systemic TPI is present, but acts against both low and high TP expressing colon cancer cells, while 5′DFUR needs cellular TP to exert significant activity. PMID:17179993

Factors Associated with the Development of Tertiary Peritonitis in Critically Ill Patients.

PubMed

Ballus, Josep; Lopez-Delgado, Juan C; Sabater-Riera, Joan; Perez-Fernandez, Xose L; Betbese, Antoni J; Roncal, Joan A

2017-07-01

Critically ill surgical patients remain at a high risk of adverse outcomes as a result of secondary peritonitis (SP). The risk is even higher if tertiary peritonitis (TP) develops. Factors related to the development of TP, however, are scarce in the literature. The main aim of our study was to identify factors associated with the development of TP in patients with SP in the intensive care unit (ICU), and also to report differences in microbiologic patterns and antibiotic therapy in patients with the two conditions. A prospective, observational study was conducted at our institution from 2010 to 2014. Baseline characteristics on admission, outcomes, microbiologic results, and antibiotic therapy were recorded for analysis. We included 343 patients with SP, of whom TP developed in 185 (53.9%). Almost two-thirds (64.4%) were male; mean age was 63.7 ± 14.3 years, and mean APACHE was 19.4 ± 7.8. In-hospital death was 42.6% (146). Multivariable analysis showed that longer ICU stay (odds ratio [OR]: 1.019; 95% confidence interval [CI]: 1.004-1.034; p = 0.010), urgent operation on hospital admission (OR: 3.247; 95% CI: 1.392-7.575; p = 0.006), total parenteral nutrition (TPN) (OR: 3.079; 95% CI: 1.535-6.177; p = 0.002) and stomach-duodenum as primary infection site (OR: 4.818; 95% CI: 1.429-16.247; p = 0.011) were factors associated with the development of TP, whereas patients with localized peritonitis were less prone to have TP develop (OR: 0.308; 95% CI: 0.152-0.624; p = 0.001). Higher incidences of Candida spp. (OR: 1.275; 95% CI: 1.096-1.789; p = 0.016), Enterococcus faecium (OR: 1.085; 95% CI: 1.018-1.400; p = 0.002), and Enterococcus spp. (OR: 1.370; 95% CI: 1.139-1.989; p = 0.047) were found in TP, and higher rates of cephalosporin use in SP (OR: 3.51; 95% CI: 1.139-10.817; p = 0.035). Complicated peritonitis remains a cause of a high numbers of deaths in the ICU. The need for TPN, urgent operation on hospital admission, and particularly surgical procedures in the proximal gastrointestinal tract were factors associated with development of TP and may potentially help to identify patients with SP at risk for development of TP. Physicians should be aware concerning multi-drug-resistant germs when treating these patients.

Evaluation of Tp-Te Interval and Tp-Te/QT Ratio in Patients with Coronary Slow Flow Tp-Te/QT Ratio and Coronary Slow Flow.

PubMed

Tenekecioglu, Erhan; Karaagac, Kemal; Yontar, Osman Can; Agca, Fahriye Vatansever; Ozluk, Ozlem Arican; Tutuncu, Ahmet; Arslan, Burhan; Yilmaz, Mustafa

2015-06-01

Coronary slow flow (CSF) phenomenon is described by angiographically normal coronary arteries with delayed opacification of the distal vasculature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-Te) may correspond to the transmural dispersion of the repolarization and that increased Tp-Te interval and Tp-Te/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate the ventricular repolarization by using Tp-Te interval and Tp-Te/QT ratio in patients with CSF. This study included 50 CSF patients (40 male, mean age 48.6±12.5 years) and 40 control individuals (23 male, mean age 47.8±12.5 years). Tp-Te interval and Tp-Te/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared in groups. Baseline characteristics of the study groups were comparable. In electrocardiographic parameters analysis, QT and corrected QT were similar in CSF patients compared to the controls (357±35.2 vs 362±38.0 milliseconds and 419±25.8 vs 430±44.2 milliseconds, all p value >0.05). Tp-Te interval, Tp-Te/QT and Tp-Te/QTc ratio were significantly higher in CSF patients (85±13.7 vs 74±9.9 milliseconds and 0.24±0.03 vs 0.20±0.02 and 0.20±0.03 vs 0.17±0.02 all p value <0.001). Our study revealed that QTd, Tp-Te interval and Tp-Te/QT ratio are prolonged in patients with CSF.

Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

PubMed

Demirtaş, K; Yayla, Ç; Yüksel, M; Açar, B; Ünal, S; Ertem, A G; Kaplan, M; Akpinar, M Y; Kiliç, Z M Y; Kayaçetin, E

2017-11-01

Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval (64.2±11.0 vs. 44.5±6.0; p<0.001), Tp-e/QT ratio (0.18±0.02 vs. 0.13±0.02; p<0.001) and Tp-e/QTc ratio (0.16±0.02 vs. 0.11±0.01; p<0.001) were significantly higher in patients with celiac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, p<0.001). Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with celiac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Platelet dysfunction associated with the novel Trp29Cys thromboxane A₂ receptor variant.

PubMed

Mumford, A D; Nisar, S; Darnige, L; Jones, M L; Bachelot-Loza, C; Gandrille, S; Zinzindohoue, F; Fischer, A-M; Mundell, S J; Gaussem, P

2013-03-01

Genetic variations that affect the structure of the thromboxane A2 receptor (TP receptor) provide insights into the function of this key platelet and vascular receptor, but are very rare in unselected populations. To determine the functional consequences of the TP receptor Trp29Cys (W29C) substitution. We performed a detailed phenotypic analysis of an index case (P1) with reduced platelet aggregation and secretion responses to TP receptor pathway activators, and a heterozygous TP receptor W29C substitution. An analysis of the variant W29C TP receptor expressed in heterologous cells was performed. Total TP receptor expression in platelets from P1 was similar to that of controls, but there was reduced maximum binding and reduced affinity of binding to the TP receptor antagonist [(3) H]SQ29548. HEK293 cells transfected with W29C TP receptor cDNA showed similar total TP receptor expression to wild-type (WT) controls. However, the TP receptor agonist U46619 was less potent at inducing rises in cytosolic free Ca(2+) in HEK293 cells expressing the W29C TP receptor than in WT controls, indicating reduced receptor function. Immunofluorescence microscopy and cell surface ELISA showed intracellular retention and reduced cell surface expression of the W29C TP receptor in HEK293 cells. Consistent with the platelet phenotype, both maximum binding and the affinity of binding of [(3) H]SQ29548 to the W29C TP receptor were reduced compared to WT controls. These findings extend the phenotypic description of the very rare disorder TP receptor deficiency, and show that the W29C substitution reduces TP receptor function by reducing surface receptor expression and by disrupting ligand binding. © 2012 International Society on Thrombosis and Haemostasis.

Landscape prediction and mapping of game fish biomass, an ecosystem service of Michigan rivers

USGS Publications Warehouse

Esselman, Peter C.; Stevenson, R Jan; Lupi, Frank; Riseng, Catherine M.; Wiley, Michael J.

2015-01-01

The increased integration of ecosystem service concepts into natural resource management places renewed emphasis on prediction and mapping of fish biomass as a major provisioning service of rivers. The goals of this study were to predict and map patterns of fish biomass as a proxy for the availability of catchable fish for anglers in rivers and to identify the strongest landscape constraints on fish productivity. We examined hypotheses about fish responses to total phosphorus (TP), as TP is a growth-limiting nutrient known to cause increases (subsidy response) and/or decreases (stress response) in fish biomass depending on its concentration and the species being considered. Boosted regression trees were used to define nonlinear functions that predicted the standing crops of Brook Trout Salvelinus fontinalis, Brown Trout Salmo trutta, Smallmouth Bass Micropterus dolomieu, panfishes (seven centrarchid species), and Walleye Sander vitreus by using landscape and modeled local-scale predictors. Fitted models were highly significant and explained 22–56% of the variation in validation data sets. Nonlinear and threshold responses were apparent for numerous predictors, including TP concentration, which had significant effects on all except the Walleye fishery. Brook Trout and Smallmouth Bass exhibited both subsidy and stress responses, panfish biomass exhibited a subsidy response only, and Brown Trout exhibited a stress response. Maps of reach-specific standing crop predictions showed patterns of predicted fish biomass that corresponded to spatial patterns in catchment area, water temperature, land cover, and nutrient availability. Maps illustrated predictions of higher trout biomass in coldwater streams draining glacial till in northern Michigan, higher Smallmouth Bass and panfish biomasses in warmwater systems of southern Michigan, and high Walleye biomass in large main-stem rivers throughout the state. Our results allow fisheries managers to examine the biomass potential of streams, describe geographic patterns of fisheries, explore possible nutrient management targets, and identify habitats that are candidates for species management.

New perspective on spring vegetation phenology and global climate change based on Tibetan Plateau tree-ring data

PubMed Central

Yang, Bao; He, Minhui; Shishov, Vladimir; Tychkov, Ivan; Vaganov, Eugene; Rossi, Sergio; Ljungqvist, Fredrik Charpentier; Bräuning, Achim; Grießinger, Jussi

2017-01-01

Phenological responses of vegetation to climate, in particular to the ongoing warming trend, have received much attention. However, divergent results from the analyses of remote sensing data have been obtained for the Tibetan Plateau (TP), the world’s largest high-elevation region. This study provides a perspective on vegetation phenology shifts during 1960–2014, gained using an innovative approach based on a well-validated, process-based, tree-ring growth model that is independent of temporal changes in technical properties and image quality of remote sensing products. Twenty composite site chronologies were analyzed, comprising about 3,000 trees from forested areas across the TP. We found that the start of the growing season (SOS) has advanced, on average, by 0.28 d/y over the period 1960–2014. The end of the growing season (EOS) has been delayed, by an estimated 0.33 d/y during 1982–2014. No significant changes in SOS or EOS were observed during 1960–1981. April–June and August–September minimum temperatures are the main climatic drivers for SOS and EOS, respectively. An increase of 1 °C in April–June minimum temperature shifted the dates of xylem phenology by 6 to 7 d, lengthening the period of tree-ring formation. This study extends the chronology of TP phenology farther back in time and reconciles the disparate views on SOS derived from remote sensing data. Scaling up this analysis may improve understanding of climate change effects and related phenological and plant productivity on a global scale. PMID:28630302

Tank Pressure Control Experiment: Thermal Phenomena in Microgravity. Video 3 of 4

NASA Technical Reports Server (NTRS)

1996-01-01

The report presents the results of the flight experiment Tank Pressure Control Experiment/Thermal Phenomena (TPCE/TP) performed in the microgravity environment of the space shuttle. TPCE/TP, flown on the Space Transportation System STS-52, was a second flight of the Tank Pressure Control Experiment (TPCE). The experiment used Freon 113 at near saturation conditions. The test tank was filled with liquid to about 83 percent by volume. The experiment consisted of 21 tests. Each test generally started with a heating phase to increase the tank pressure and to develop temperature stratification in the fluid, followed by a fluid mixing phase for the tank pressure reduction and fluid temperature equilibration. The heating phase provided pool boiling data from large (relative to bubble sizes) heating surfaces (0.1046 m by 0.0742 m) at low heat fluxes (0.23 to 1.16 kW/m(exp 2)). The system pressure and the bulk liquid subcooling varied from 39 to 78 kPa and 1 to 3 deg C, respectively. The boiling process during the entire heating period, as well a jet-induced mixing process for the first 2 min. of the mixing period, was also recorded on video. Analyses of data from the two flight experiments (TPCE and TPCE/TP) and their comparison with the results obtained in drop tower experiments suggest that as Bond number approaches zero the flow pattern produced by an axial jet and the mixing time can be predicted by the Weber number. This is video 3 of 4.

Tank Pressure Control Experiment: Thermal Phenomena in Microgravity. Video 4 of 4

NASA Technical Reports Server (NTRS)

1996-01-01

The report presents the results of the flight experiment Tank Pressure Control Experiment/Thermal Phenomena (TPCE/TP) performed in the microgravity environment of the space shuttle. TPCE/TP, flown on the Space Transportation System STS-52, was a second flight of the Tank Pressure Control Experiment (TPCE). The experiment used Freon 113 at near saturation conditions. The test tank was filled with liquid to about 83 percent by volume. The experiment consisted of 21 tests. Each test generally started with a heating phase to increase the tank pressure and to develop temperature stratification in the fluid, followed by a fluid mixing phase for the tank pressure reduction and fluid temperature equilibration. The heating phase provided pool boiling data from large (relative to bubble sizes) heating surfaces (0.1046 m by 0.0742 m) at low heat fluxes (0.23 to 1.16 kW/m(exp 2)). The system pressure and the bulk liquid subcooling varied from 39 to 78 kPa and 1 to 3 deg C, respectively. The boiling process during the entire heating period, as well a jet-induced mixing process for the first 2 min. of the mixing period, was also recorded on video. Analyses of data from the two flight experiments (TPCE and TPCE/TP) and their comparison with the results obtained in drop tower experiments suggest that as Bond number approaches zero the flow pattern produced by an axial jet and the mixing time can be predicted by the Weber number. This is video 4 of 4.

Tank Pressure Control Experiment: Thermal Phenomena in Microgravity. Video 1 of 4

NASA Technical Reports Server (NTRS)

1996-01-01

The report presents the results of the flight experiment Tank Pressure Control Experiment/Thermal Phenomena (TPCE/TP) performed in the microgravity environment of the space shuttle. TPCE/TP, flown on the Space Transportation System STS-52, was a second flight of the Tank Pressure Control Experiment (TPCE). The experiment used Freon 113 at near saturation conditions. The test tank was filled with liquid to about 83 percent by volume. The experiment consisted of 21 tests. Each test generally started with a heating phase to increase the tank pressure and to develop temperature stratification in the fluid, followed by a fluid mixing phase for the tank pressure reduction and fluid temperature equilibration. The heating phase provided pool boiling data from large (relative to bubble sizes) heating surfaces (0.1046 m by 0.0742 m) at low heat fluxes (0.23 to 1.16 kW/m(exp 2)). The system pressure and the bulk liquid subcooling varied from 39 to 78 kPa and 1 to 3 deg C, respectively. The boiling process during the entire heating period, as well a jet-induced mixing process for the first 2 min. of the mixing period, was also recorded on video. Analyses of data from the two flight experiments (TPCE and TPCE/TP) and their comparison with the results obtained in drop tower experiments suggest that as Bond number approaches zero the flow pattern produced by an axial jet and the mixing time can be predicted by the Weber number. This is video 1 of 4.

Tank Pressure Control Experiment: Thermal Phenomena in Microgravity. Video 2 of 4

NASA Technical Reports Server (NTRS)

1996-01-01

The report presents the results of the flight experiment Tank Pressure Control Experiment/Thermal Phenomena (TPCE/TP) performed in the microgravity environment of the space shuttle. TPCE/TP, flown on the Space Transportation System STS-52, was a second flight of the Tank Pressure Control Experiment (TPCE). The experiment used Freon 113 at near saturation conditions. The test tank was filled with liquid to about 83 percent by volume. The experiment consisted of 21 tests. Each test generally started with a heating phase to increase the tank pressure and to develop temperature stratification in the fluid, followed by a fluid mixing phase for the tank pressure reduction and fluid temperature equilibration. The heating phase provided pool boiling data from large (relative to bubble sizes) heating surfaces (0.1046 m by 0.0742 m) at low heat fluxes (0.23 to 1.16 kW/m(exp 2)). The system pressure and the bulk liquid subcooling varied from 39 to 78 kPa and 1 to 3 deg C, respectively. The boiling process during the entire heating period, as well a jet-induced mixing process for the first 2 min. of the mixing period, was also recorded on video. Analyses of data from the two flight experiments (TPCE and TPCE/TP) and their comparison with the results obtained in drop tower experiments suggest that as Bond number approaches zero the flow pattern produced by an axial jet and the mixing time can be predicted by the Weber number. This is video 2 of 4.

New perspective on spring vegetation phenology and global climate change based on Tibetan Plateau tree-ring data

NASA Astrophysics Data System (ADS)

Yang, Bao; He, Minhui; Shishov, Vladimir; Tychkov, Ivan; Vaganov, Eugene; Rossi, Sergio; Charpentier Ljungqvist, Fredrik; Bräuning, Achim; Grießinger, Jussi

2017-07-01

Phenological responses of vegetation to climate, in particular to the ongoing warming trend, have received much attention. However, divergent results from the analyses of remote sensing data have been obtained for the Tibetan Plateau (TP), the world’s largest high-elevation region. This study provides a perspective on vegetation phenology shifts during 1960-2014, gained using an innovative approach based on a well-validated, process-based, tree-ring growth model that is independent of temporal changes in technical properties and image quality of remote sensing products. Twenty composite site chronologies were analyzed, comprising about 3,000 trees from forested areas across the TP. We found that the start of the growing season (SOS) has advanced, on average, by 0.28 d/y over the period 1960-2014. The end of the growing season (EOS) has been delayed, by an estimated 0.33 d/y during 1982-2014. No significant changes in SOS or EOS were observed during 1960-1981. April-June and August-September minimum temperatures are the main climatic drivers for SOS and EOS, respectively. An increase of 1 °C in April-June minimum temperature shifted the dates of xylem phenology by 6 to 7 d, lengthening the period of tree-ring formation. This study extends the chronology of TP phenology farther back in time and reconciles the disparate views on SOS derived from remote sensing data. Scaling up this analysis may improve understanding of climate change effects and related phenological and plant productivity on a global scale.

[Cellular uptake of TPS-L-carnitine synthesised as transporter-based renal targeting prodrug].

PubMed

Li, Li; Zhu, Di; Sun, Xun

2012-11-01

To synthesize transporter-based renal targeting prodrug TPS-L-Carnitine and to determine its cellular uptake in vitro. Triptolide (TP) was conjugated with L-carnitine using succinate as the linker to form TPS-L-Carnitine, which could be specifically recognized by OCTN2, a cationic transporter with high affinity to L-Carnitine and is highly expressed on the apical membrane of renal proximal tubule cells. Cellular uptake assays of the prodrug and its parent drug were performed on HK-2 cells, a human proximal tubule cell line, in different temperature, concentration and in the presence of competitive inhibitors. TPS-L-Carnitine was taken up into HK-2 cells in a saturable and temperature- and concentration-dependent manner. The uptake process could be inhibited by the competitive inhibitors. The uptake of TPS-L-Carnitine was significantly higher than that of TP at 37 degrees C in the same drug concentration. TPS-L-Carnitine was taken through endocytosis mediated by transporter. TPS-L-Carnitine provides a good renal targeting property and lays the foundation for further studies in vivo.

Application of response surface methodology to optimize pressurized liquid extraction of antioxidant compounds from sage (Salvia officinalis L.), basil (Ocimum basilicum L.) and thyme (Thymus vulgaris L.).

PubMed

Hossain, M B; Brunton, N P; Martin-Diana, A B; Barry-Ryan, C

2010-12-01

The present study optimized pressurized liquid extraction (PLE) conditions using Dionex ASE® 200, USA to maximize the antioxidant activity [Ferric ion Reducing Antioxidant Power (FRAP)] and total polyphenol content (TP) of the extracts from three spices of Lamiaceae family (sage, basil and thyme). Optimal conditions with regard to extraction temperature (66-129 °C) and solvent concentration (32-88% methanol) were identified using response surface methodology (RSM). For all three spices, results showed that 129 °C was the optimum temperature with regard to antioxidant activity. Optimal methanol concentrations with respect to the antioxidant activity of sage and basil extracts were 58% and 60% respectively. Thyme showed a different trend with regard to methanol concentration and was optimally extracted at 33%. Antioxidant activity yields of the optimal PLE were significantly (p < 0.05) higher than solid/liquid extracts. Predicted models were highly significant (p < 0.05) for both total phenol (TP) and FRAP values in all the spices with high regression coefficients (R(2)) ranging from 0.651 to 0.999.

Smoking Cessation among Low-Socioeconomic Status and Disadvantaged Population Groups: A Systematic Review of Research Output.

PubMed

Courtney, Ryan J; Naicker, Sundresan; Shakeshaft, Anthony; Clare, Philip; Martire, Kristy A; Mattick, Richard P

2015-06-08

Smoking cessation research output should move beyond descriptive research of the health problem to testing interventions that can provide causal data and effective evidence-based solutions. This review examined the number and type of published smoking cessation studies conducted in low-socioeconomic status (low-SES) and disadvantaged population groups. A systematic database search was conducted for two time periods: 2000-2004 (TP1) and 2008-2012 (TP2). Publications that examined smoking cessation in a low-SES or disadvantaged population were coded by: population of interest; study type (reviews, non-data based publications, data-based publications (descriptive, measurement and intervention research)); and country. Intervention studies were coded in accordance with the Cochrane Effective Practice and Organisation of Care data collection checklist and use of biochemical verification of self-reported abstinence was assessed. 278 citations were included. Research output (i.e., all study types) had increased from TP1 27% to TP2 73% (χ²=73.13, p<0.001), however, the proportion of data-based research had not significantly increased from TP1 and TP2: descriptive (TP1=23% vs. TP2=33%) or intervention (TP1=77% vs. TP2=67%). The proportion of intervention studies adopting biochemical verification of self-reported abstinence had significantly decreased from TP1 to TP2 with an increased reliance on self-reported abstinence (TP1=12% vs. TP2=36%). The current research output is not ideal or optimal to decrease smoking rates. Research institutions, scholars and funding organisations should take heed to review findings when developing future research and policy.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

PubMed

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2014-03-01

Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively). Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

PubMed

Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

2013-04-12

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. METHODS: Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. RESULTS: In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively). CONCLUSIONS: Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

Evaluation of Electrocardiographic T-peak to T-end Interval in Subjects with Increased Epicardial Fat Tissue Thickness.

PubMed

Kaplan, Ozgur; Kurtoglu, Ertugrul; Nar, Gokay; Yasar, Erdogan; Gozubuyuk, Gokhan; Dogan, Cem; Boz, Ahmet Ugur; Hidayet, Sıho; Pekdemir, Hasan

2015-12-01

The association between periatrial adiposity and atrial arrhythmias has been shown in previous studies. However, there are not enough available data on the association between epicardial fat tissue (EFT) thickness and parameters of ventricular repolarization. Thus, we aimed to evaluate the association of EFT thickness with indices of ventricular repolarization by using T-peak to T-end (Tp-e) interval and Tp-e/QT ratio. The present study included 50 patients whose EFT thickness ≥ 9 mm (group 1) and 40 control subjects with EFT thickness < 9 mm (group 2). Transthoracic echocardiographic examination was performed in all participants. QT parameters, Tp-e intervals and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. QTd (41.1 ± 2.5 vs 38.6 ± 3.2, p < 0.001) and corrected QTd (46.7 ± 4.7 vs 43.7 ± 4, p = 0.002) were significantly higher in group 1 when compared to group 2. The Tp-e interval (76.5 ± 6.3, 70.3 ± 6.8, p < 0.001), cTp-e interval (83.1 ± 4.3 vs. 76±4.9, p < 0.001), Tp-e/QT (0.20 ± 0.02 vs. 0.2 ± 0.02, p < 0.001) and Tp-e/QTc ratios (0.2 ± 0.01 vs. 0.18 ± 0.01, p < 0.001) were increased in group 1 in comparison to group 2. Significant positive correlations were found between EFT thickness and Tp-e interval (r = 0.548, p < 0.001), cTp-e interval (r = 0.259, p = 0.01), and Tp-e/QT (r = 0.662, p < 0.001) and Tp-e/QTc ratios (r = 0.560, p < 0.001). The present study shows that Tp-e and cTp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in subjects with increased EFT, which may suggest an increased risk of ventricular arrhythmia.

Interaction of Ester-Functionalized Ionic Liquids with Atomically-Defined Cobalt Oxides Surfaces: Adsorption, Reaction and Thermal Stability.

PubMed

Xu, Tao; Waehler, Tobias; Vecchietti, Julia; Bonivardi, Adrian; Bauer, Tanja; Schwegler, Johannes; Schulz, Peter S; Wasserscheid, Peter; Libuda, Joerg

2017-12-06

Hybrid materials consisting of ionic liquid (ILs) films on supported oxides hold a great potential for applications in electronic and energy materials. In this work, we have performed surface science model studies scrutinizing the interaction of ester-functionalized ILs with atomically defined Co 3 O 4 (111) and CoO(100) surfaces. Both supports are prepared under ultra-high vacuum (UHV) conditions in form of thin films on Ir(100) single crystals. Subsequently, thin films of three ILs, 3-butyl-1-methyl imidazolium bis(trifluoromethyl-sulfonyl) imide ([BMIM][NTf 2 ]), 3-(4-methoxyl-4-oxobutyl)-1-methylimidazolium bis(trifluoromethyl-sulfonyl) imide ([MBMIM][NTf 2 ]), and 3-(4-isopropoxy-4-oxobutyl)-1-methylimidazolium bis(trifluoromethyl-sulfonyl) imide ([IPBMIM][NTf 2 ]), were deposited on these surfaces by physical vapor deposition (PVD). Time-resolved and temperature-programmed infrared reflection absorption spectroscopy (TR-IRAS, TP-IRAS) were applied to monitor in situ the adsorption, film growth, and thermally induced desorption. By TP-IRAS, we determined the multilayer desorption temperature of [BMIM][NTf 2 ] (360±5 K), [MBMIM][NTf 2 ] (380 K) and [IPBMIM][NTf 2 ] (380 K). Upon deposition below the multilayer desorption temperature, all three ILs physisorb on both cobalt oxide surfaces. However, strong orientation effects are observed in the first monolayer, where the [NTf 2 ] - ion interacts with the surface through the SO 2 groups and the CF 3 groups point towards the vacuum. For the two functionalized ILs, the [MBMIM] + and [IPBMIM] + interact with the surface Co 2+ ions of both surfaces via the CO group of their ester function. A very different behavior is found, if the ILs are deposited above the multilayer desorption temperature (400 K). While for [BMIM][NTf 2 ] and [MBMIM][NTf 2 ] a molecularly adsorbed monolayer film is formed, [IPBMIM][NTf 2 ] undergoes a chemical transformation on the CoO(100) surface. Here, the ester group is cleaved and the cation is chemically linked to the surface by formation of a surface carboxylate. The IL-derived species in the monolayer desorb at temperatures around 500 to 550 K. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adsorption, polymerization and decomposition of acetaldehyde on clean and carbon-covered Rh(111) surfaces

NASA Astrophysics Data System (ADS)

Kovács, Imre; Farkas, Arnold Péter; Szitás, Ádám; Kónya, Zoltán; Kiss, János

2017-10-01

The adsorption and dissociation of acetaldehyde were investigated on clean and carbon-covered Rh(111) single crystal surfaces by electron energy loss spectroscopy (EELS), temperature programmed desorption (TPD), high-resolution electron energy loss spectroscopy (HREELS) and work function (Δφ) measurements. Acetaldehyde is a starting material for the catalytic production of many important chemicals and investigation of its reactions motivated by environmental purposes too. The adsorption of acetaldehyde on clean Rh(111) surface produced various types of adsorption forms. η1-(O)-CH3CHOa and η2-(O,C)-CH3CHOa are developing and characterized by HREELS. η1-CH3CHOa partly desorbed at Tp = 150 K, another part of these species are incorporated in trimer and linear 2D polimer species. The desorption of trimers (at amu 132) were observed in TPD with a peak maximum at Tp = 225 K. Above this temperature acetaldehyde either desorbed or bonded as a stable surface intermediate (η2-CH3CHOa) on the rhodium surface. The molecules decomposed to adsorbed products, and only hydrogen and carbon monoxide were analyzed in TPD. Surface carbon decreased the uptake of adsorbed acetaldehyde, inhibited the formation of polymers, nevertheless, it induced the Csbnd O bond scission and CO formation with 40-50 K lower temperature after higher acetaldehyde exposure.

Effects of pH, Temperature, Dissolved Oxygen, and Flow Rate on Phosphorus Release Processes at the Sediment and Water Interface in Storm Sewer

PubMed Central

Li, Haiyan; Li, Mingyi; Zhang, Xiaoran

2013-01-01

The effects of pH, temperature, dissolved oxygen (DO), and flow rate on the phosphorus (P) release processes at the sediment and water interface in rainwater pipes were investigated. The sampling was conducted in a residential storm sewer of North Li Shi Road in Xi Cheng District of Beijing on August 3, 2011. The release rate of P increased with the increase of pH from 8 to 10. High temperature is favorable for the release of P. The concentration of total phosphorus (TP) in the overlying water increased as the concentration of DO decreased. With the increase of flow rate from 0.7 m s−1 to 1.1 m s−1, the concentration of TP in the overlying water increased and then tends to be stable. Among all the factors examined in the present study, the flow rate is the primary influence factor on P release. The cumulative amount of P release increased with the process of pipeline runoff in the rainfall events with high intensities and shorter durations. Feasible measures such as best management practices and low-impact development can be conducted to control the P release on urban sediments by slowing down the flow rate. PMID:24349823

Strain and order-parameter coupling in Ni-Mn-Ga Heusler alloys from resonant ultrasound spectroscopy

NASA Astrophysics Data System (ADS)

Salazar Mejía, C.; Born, N.-O.; Schiemer, J. A.; Felser, C.; Carpenter, M. A.; Nicklas, M.

2018-03-01

Resonant ultrasound spectroscopy and magnetic susceptibility experiments have been used to characterize strain coupling phenomena associated with structural and magnetic properties of the shape-memory Heusler alloy series Ni50 +xMn25 -xGa25 (x =0 , 2.5, 5.0, and 7.5). All samples exhibit a martensitic transformation at temperature TM and ferromagnetic ordering at temperature TC, while the pure end member (x =0 ) also has a premartensitic transition at TP M, giving four different scenarios: TC>TP M>TM,TC>TM without premartensitic transition, TC≈TM , and TC

Comparative reactivity of TpRu(L)(NCMe)Ph (L = CO or PMe3): impact of ancillary ligand l on activation of carbon-hydrogen bonds including catalytic hydroarylation and hydrovinylation/oligomerization of ethylene.

PubMed

Foley, Nicholas A; Lail, Marty; Lee, John P; Gunnoe, T Brent; Cundari, Thomas R; Petersen, Jeffrey L

2007-05-30

Complexes of the type TpRu(L)(NCMe)R [L = CO or PMe3; R = Ph or Me; Tp = hydridotris(pyrazolyl)borate] initiate C-H activation of benzene. Kinetic studies, isotopic labeling, and other experimental evidence suggest that the mechanism of benzene C-H activation involves reversible dissociation of acetonitrile, reversible benzene coordination, and rate-determining C-H activation of coordinated benzene. TpRu(PMe3)(NCMe)Ph initiates C-D activation of C6D6 at rates that are approximately 2-3 times more rapid than that for TpRu(CO)(NCMe)Ph (depending on substrate concentration); however, the catalytic hydrophenylation of ethylene using TpRu(PMe3)(NCMe)Ph is substantially less efficient than catalysis with TpRu(CO)(NCMe)Ph. For TpRu(PMe3)(NCMe)Ph, C-H activation of ethylene, to ultimately produce TpRu(PMe3)(eta3-C4H7), is found to kinetically compete with catalytic ethylene hydrophenylation. In THF solutions containing ethylene, TpRu(PMe3)(NCMe)Ph and TpRu(CO)(NCMe)Ph separately convert to TpRu(L)(eta3-C4H7) (L = PMe3 or CO, respectively) via initial Ru-mediated ethylene C-H activation. Heating mesitylene solutions of TpRu(L)(eta3-C4H7) under ethylene pressure results in the catalytic production of butenes (i.e., ethylene hydrovinylation) and hexenes.

Diagnostic and model dependent uncertainty of simulated Tibetan permafrost area

USGS Publications Warehouse

Wang, A.; Moore, J.C.; Cui, Xingquan; Ji, D.; Li, Q.; Zhang, N.; Wang, C.; Zhang, S.; Lawrence, D.M.; McGuire, A.D.; Zhang, W.; Delire, C.; Koven, C.; Saito, K.; MacDougall, A.; Burke, E.; Decharme, B.

2016-01-01

 We perform a land-surface model intercomparison to investigate how the simulation of permafrost area on the Tibetan Plateau (TP) varies among six modern stand-alone land-surface models (CLM4.5, CoLM, ISBA, JULES, LPJ-GUESS, UVic). We also examine the variability in simulated permafrost area and distribution introduced by five different methods of diagnosing permafrost (from modeled monthly ground temperature, mean annual ground and air temperatures, air and surface frost indexes). There is good agreement (99 to 135  ×  104 km2) between the two diagnostic methods based on air temperature which are also consistent with the observation-based estimate of actual permafrost area (101  × 104 km2). However the uncertainty (1 to 128  ×  104 km2) using the three methods that require simulation of ground temperature is much greater. Moreover simulated permafrost distribution on the TP is generally only fair to poor for these three methods (diagnosis of permafrost from monthly, and mean annual ground temperature, and surface frost index), while permafrost distribution using air-temperature-based methods is generally good. Model evaluation at field sites highlights specific problems in process simulations likely related to soil texture specification, vegetation types and snow cover. Models are particularly poor at simulating permafrost distribution using the definition that soil temperature remains at or below 0 °C for 24 consecutive months, which requires reliable simulation of both mean annual ground temperatures and seasonal cycle, and hence is relatively demanding. Although models can produce better permafrost maps using mean annual ground temperature and surface frost index, analysis of simulated soil temperature profiles reveals substantial biases. The current generation of land-surface models need to reduce biases in simulated soil temperature profiles before reliable contemporary permafrost maps and predictions of changes in future permafrost distribution can be made for the Tibetan Plateau.

Diagnostic and model dependent uncertainty of simulated Tibetan permafrost area

NASA Astrophysics Data System (ADS)

Wang, W.; Rinke, A.; Moore, J. C.; Cui, X.; Ji, D.; Li, Q.; Zhang, N.; Wang, C.; Zhang, S.; Lawrence, D. M.; McGuire, A. D.; Zhang, W.; Delire, C.; Koven, C.; Saito, K.; MacDougall, A.; Burke, E.; Decharme, B.

2016-02-01

We perform a land-surface model intercomparison to investigate how the simulation of permafrost area on the Tibetan Plateau (TP) varies among six modern stand-alone land-surface models (CLM4.5, CoLM, ISBA, JULES, LPJ-GUESS, UVic). We also examine the variability in simulated permafrost area and distribution introduced by five different methods of diagnosing permafrost (from modeled monthly ground temperature, mean annual ground and air temperatures, air and surface frost indexes). There is good agreement (99 to 135 × 104 km2) between the two diagnostic methods based on air temperature which are also consistent with the observation-based estimate of actual permafrost area (101 × 104 km2). However the uncertainty (1 to 128 × 104 km2) using the three methods that require simulation of ground temperature is much greater. Moreover simulated permafrost distribution on the TP is generally only fair to poor for these three methods (diagnosis of permafrost from monthly, and mean annual ground temperature, and surface frost index), while permafrost distribution using air-temperature-based methods is generally good. Model evaluation at field sites highlights specific problems in process simulations likely related to soil texture specification, vegetation types and snow cover. Models are particularly poor at simulating permafrost distribution using the definition that soil temperature remains at or below 0 °C for 24 consecutive months, which requires reliable simulation of both mean annual ground temperatures and seasonal cycle, and hence is relatively demanding. Although models can produce better permafrost maps using mean annual ground temperature and surface frost index, analysis of simulated soil temperature profiles reveals substantial biases. The current generation of land-surface models need to reduce biases in simulated soil temperature profiles before reliable contemporary permafrost maps and predictions of changes in future permafrost distribution can be made for the Tibetan Plateau.

Depopulation of highly excited singlet states of DNA model compounds: quantum yields of 193 and 245 nm photoproducts of pyrimidine monomers and dinucleoside monophosphates.

PubMed

Gurzadyan, G G; Görner, H

1996-02-01

Formation of uracil and orotic acid photodimers, uridine and 5'-UMP photohydrates, TpT photodimers and (6-4)photoproducts, dCpT photohydrates and (6-4)photoproducts and UpU, CpC and CpU photohydrates were studied in neutral deoxygenated aqueous solution at room temperature upon irradiation at either 193 or 254 nm. The photoproducts were identified and quantified and the contribution from photoionization to substrate decomposition, using lambda irr = 193 nm, was separated. The ratio of the quantum yields of respective stable products, eta = phi 193/phi 254, is indicative of the yield of internal conversion from the second to the first excited singlet state, S2-->S1. For the observed photodimers eta decreases from 0.94 for uracil to 0.7 for TpT and further to 0.55 for orotic acid. For the (6-4)photoproducts of TpT and dCpT eta = 0.5-0.8 and for the photohydrates in the cases of UpU, CpC, CpU and dCpT eta ranges from 0.55 to 1.

Reductive dechlorination of atrazine catalyzed by metalloporphyrins.

PubMed

Nelkenbaum, Elza; Dror, Ishai; Berkowitz, Brian

2009-03-01

Atrazine (2-chloro-4-(ethylamine)-6-(isopropylamine)-s-triazine) is a widely used herbicide which is considered a persistent groundwater contaminant. Its selective transformation mediated by cobalt or nickel porphyrins was studied in aqueous solutions at room temperature and ambient pressure. Several metalloporphyrins were examined as catalysts for the reaction and all yielded the same reaction, transforming atrazine solely to the seldomly reported form 2,4-bis(ethylamine)-6-methyl-s-triazine. The reaction involves dechlorination and migration of a methyl group to yield a symmetric product. Nickel 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP) was activated by nanosized zero-valent iron (nZVI) while cobalt porphyrins (TMPyP, 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine-(TP(OH)P) and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl)tetrakis (benzenesulfonic acid)-(TBSP)) were activated by titanium(III) citrate as the electron donor. The effect of pH on atrazine transformation was demonstrated for the catalytic system of TP(OH)P-Co/Ti(III) citrate. Finally, a comparison of the reactivities of cobalt TMPyP and TP(OH)P was given and the differences discussed.

Bullae

MedlinePlus

Habif TP. Principles of diagnosis and anatomy. In: Habif TP, ed. Clinical Dermatology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 1. Habif TP. Vesicular and bullous diseases. In: Habif TP, ed. ...

Brassinosteroids Improve Quality of Summer Tea (Camellia sinensis L.) by Balancing Biosynthesis of Polyphenols and Amino Acids.

PubMed

Li, Xin; Ahammed, Golam J; Li, Zhi-Xin; Zhang, Lan; Wei, Ji-Peng; Shen, Chen; Yan, Peng; Zhang, Li-Ping; Han, Wen-Yan

2016-01-01

Summer grown green tea is less popular due to bitterness and high astringency, which are attributed to high levels of tea polyphenols (TP) and low levels of amino acids (AA) in tea leaves (Camellia sinensis L.). Brassinosteroids (BRs), a group of steroidal plant hormones can regulate primary and secondary metabolism in a range of plant species under both normal and stress conditions. However, specific effects of BRs on the photosynthesis of tea plants and the quality of summer green tea are largely unknown. Here we show that 24-epibrassinolide (EBR), a bioactive BR, promoted photosynthesis in tea plants in a concentration-dependent manner. Stimulation in photosynthesis by EBR resulted in an increased summer tea yield. Although all tested concentrations (0.01, 0.05, 0.1, 0.5, and 1.0 ppm) of EBR increased concentrations of TP and AA, a moderate concentration (0.5 ppm) caused the highest decrease in TP to AA ratio, an important feature of quality tea. Time-course analysis using 0.5 ppm EBR as foliar spray revealed that TP or AA concentration increased as early as 3 h after EBR application, reaching the highest peak at 24 h and that remained more or less stable. Importantly, such changes in TP and AA concentration by EBR resulted in a remarkably decreased but stable TP to AA ratio at 24 h and onward. Furthermore, concentrations of catechins and theanine increased, while that of caffeine remained unaltered following treatment with EBR. EBR improved activity of phenylalanine ammonia-lyase (PAL) and glutamine: 2-oxoglutarate aminotransferase (GOGAT) enzymes involved in catechins and theanine biosynthesis, respectively. Transcript analysis revealed that transcript levels of CsPAL and CsGS peaked as early as 6 h, while that of CsGOGAT peaked at 12 h following application of EBR, implying that EBR increased the concentration of TP and AA by inducing their biosynthesis. These results suggest a positive role of BR in enhancing green tea quality, which might have potential implication in improving quality of summer tea.

Current and future assessments of soil erosion by water on the Tibetan Plateau based on RUSLE and CMIP5 climate models.

PubMed

Teng, Hongfen; Liang, Zongzheng; Chen, Songchao; Liu, Yong; Viscarra Rossel, Raphael A; Chappell, Adrian; Yu, Wu; Shi, Zhou

2018-04-18

Soil erosion by water is accelerated by a warming climate and negatively impacts water security and ecological conservation. The Tibetan Plateau (TP) has experienced warming at a rate approximately twice that observed globally, and heavy precipitation events lead to an increased risk of erosion. In this study, we assessed current erosion on the TP and predicted potential soil erosion by water in 2050. The study was conducted in three steps. During the first step, we used the Revised Universal Soil Equation (RUSLE), publicly available data, and the most recent earth observations to derive estimates of annual erosion from 2002 to 2016 on the TP at 1-km resolution. During the second step, we used a multiple linear regression (MLR) model and a set of climatic covariates to predict rainfall erosivity on the TP in 2050. The MLR was used to establish the relationship between current rainfall erosivity data and a set of current climatic and other covariates. The coefficients of the MLR were generalised with climate covariates for 2050 derived from the fifth phase of the Coupled Model Intercomparison Project (CMIP5) models to estimate rainfall erosivity in 2050. During the third step, soil erosion by water in 2050 was predicted using rainfall erosivity in 2050 and other erosion factors. The results show that the mean annual soil erosion rate on the TP under current conditions is 2.76tha -1 y -1 , which is equivalent to an annual soil loss of 559.59×10 6 t. Our 2050 projections suggested that erosion on the TP will increase to 3.17tha -1 y -1 and 3.91tha -1 y -1 under conditions represented by RCP2.6 and RCP8.5, respectively. The current assessment and future prediction of soil erosion by water on the TP should be valuable for environment protection and soil conservation in this unique region and elsewhere. Copyright © 2018 Elsevier B.V. All rights reserved.

Brassinosteroids Improve Quality of Summer Tea (Camellia sinensis L.) by Balancing Biosynthesis of Polyphenols and Amino Acids

PubMed Central

Li, Xin; Ahammed, Golam J.; Li, Zhi-Xin; Zhang, Lan; Wei, Ji-Peng; Shen, Chen; Yan, Peng; Zhang, Li-Ping; Han, Wen-Yan

2016-01-01

Summer grown green tea is less popular due to bitterness and high astringency, which are attributed to high levels of tea polyphenols (TP) and low levels of amino acids (AA) in tea leaves (Camellia sinensis L.). Brassinosteroids (BRs), a group of steroidal plant hormones can regulate primary and secondary metabolism in a range of plant species under both normal and stress conditions. However, specific effects of BRs on the photosynthesis of tea plants and the quality of summer green tea are largely unknown. Here we show that 24-epibrassinolide (EBR), a bioactive BR, promoted photosynthesis in tea plants in a concentration-dependent manner. Stimulation in photosynthesis by EBR resulted in an increased summer tea yield. Although all tested concentrations (0.01, 0.05, 0.1, 0.5, and 1.0 ppm) of EBR increased concentrations of TP and AA, a moderate concentration (0.5 ppm) caused the highest decrease in TP to AA ratio, an important feature of quality tea. Time-course analysis using 0.5 ppm EBR as foliar spray revealed that TP or AA concentration increased as early as 3 h after EBR application, reaching the highest peak at 24 h and that remained more or less stable. Importantly, such changes in TP and AA concentration by EBR resulted in a remarkably decreased but stable TP to AA ratio at 24 h and onward. Furthermore, concentrations of catechins and theanine increased, while that of caffeine remained unaltered following treatment with EBR. EBR improved activity of phenylalanine ammonia-lyase (PAL) and glutamine: 2-oxoglutarate aminotransferase (GOGAT) enzymes involved in catechins and theanine biosynthesis, respectively. Transcript analysis revealed that transcript levels of CsPAL and CsGS peaked as early as 6 h, while that of CsGOGAT peaked at 12 h following application of EBR, implying that EBR increased the concentration of TP and AA by inducing their biosynthesis. These results suggest a positive role of BR in enhancing green tea quality, which might have potential implication in improving quality of summer tea. PMID:27625668

Cardiopulmonary responses of intratracheally instilled tire particles and constituent metal components

USGS Publications Warehouse

Gottipolu, R.R.; Landa, E.R.; Schladweiler, M.C.; McGee, J.K.; Ledbetter, A.D.; Richards, J.H.; Wallenborn, G.J.; Kodavanti, U.P.

2008-01-01

Tire and brake wear particles contain transition metals, and contribute to near-road PM. We hypothesized that acute cardiopulmonary injury from respirable tire particles (TP) will depend on the amount of soluble metals. Respirable fractions of two types of TP (TP1 and TP2) were analyzed for water and acid-leachable metals using ICP-AES. Both TP types contained a variety of transition metals, including zinc (Zn), copper (Cu), aluminum, and iron. Zn and Cu were detected at high levels in water-soluble fractions (TP2 > TP1). Male Wistar Kyoto rats (12-14 wk) were intratracheally instilled, in the first study, with saline, TP1 or TP2 (5 mg/kg), and in the second study, with soluble Zn, Cu (0.5 ??mol/kg), or both. Pulmonary toxicity and cardiac mitochondrial enzymes were analyzed 1 d, 1 wk, or 4 wk later for TP and 4 or 24 h later for metals. Increases in lavage fluid markers of inflammation and injury were observed at d 1 (TP2 > TP1), but these changes reversed by wk 1. No effects on cardiac enzymes were noted with either TP. Exposure of rats to soluble Zn and Cu caused marked pulmonary inflammation and injury but temporal differences were apparent (Cu effects peaked at 4 h and Zn at 24 h). Instillation of Zn, Cu, and Zn+ Cu decreased the activity of cardiac aconitase, isocitrate dehydrogenase, succinate dehydrogenase, cytochrome-c-oxidase and superoxide dismutase suggesting mitochondrial oxidative stress. The observed acute pulmonary toxicity of TP could be due to the presence of water soluble Zn and Cu. At high concentrations these metals may induce cardiac oxidative stress. Copyright ?? Informa Healthcare USA, Inc.

An Aggressive Surgical Approach Leads to Improved Survival in Patients With Gallbladder Cancer

PubMed Central

Dixon, Elijah; Vollmer, Charles M.; Sahajpal, Ajay; Cattral, Mark; Grant, David; Doig, Christopher; Hemming, Al; Taylor, Bryce; Langer, Bernard; Greig, Paul; Gallinger, Steven

2005-01-01

Objective: To determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Summary Background Data: Many physicians express a relatively nihilistic approach to the treatment of gallbladder cancer; consensus among surgeons regarding the indications for a radical surgical approach has not been reached. Methods: A retrospective review of all patients with gallbladder cancer admitted during the past 12 years was conducted. Ninety-nine patients were identified. Cases treated during the 12-year period 1990 to 2002 were divided into 2 time-period (TP) cohorts, those treated in the first 6 years (TP1, N = 35) and those treated in the last 6 years (TP2, N = 64). Results: Disease stratification by stage and other demographic features were similar in the 2 time periods. An operation with curative intent was performed on 38 patients. Nine (26%) R0 resections were performed in TP1 and 24 (38%) in TP2. The number of liver resections, as well as the frequency of extrahepatic biliary resections, was greater in TP2 (P < 0.04). In both time periods, an R0 resection was associated with improved survival (P < 0.02 TP1, P < 0.0001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P < 0.03), with a median survival of 9 months in TP1 and 17 months in TP2. The median 5-year survival in TP1 was 7%, and 35% in TP2. The surgical mortality rate for the entire cohort was 2%, with a 49% morbidity rate. Conclusions: A margin-negative, R0 resection leads to improved survival in patients with gallbladder cancer. PMID:15729060

Smoking Cessation among Low-Socioeconomic Status and Disadvantaged Population Groups: A Systematic Review of Research Output

PubMed Central

Courtney, Ryan J.; Naicker, Sundresan; Shakeshaft, Anthony; Clare, Philip; Martire, Kristy A.; Mattick, Richard P.

2015-01-01

Background: Smoking cessation research output should move beyond descriptive research of the health problem to testing interventions that can provide causal data and effective evidence-based solutions. This review examined the number and type of published smoking cessation studies conducted in low-socioeconomic status (low-SES) and disadvantaged population groups. Methods: A systematic database search was conducted for two time periods: 2000–2004 (TP1) and 2008–2012 (TP2). Publications that examined smoking cessation in a low-SES or disadvantaged population were coded by: population of interest; study type (reviews, non-data based publications, data-based publications (descriptive, measurement and intervention research)); and country. Intervention studies were coded in accordance with the Cochrane Effective Practice and Organisation of Care data collection checklist and use of biochemical verification of self-reported abstinence was assessed. Results: 278 citations were included. Research output (i.e., all study types) had increased from TP1 27% to TP2 73% (χ² = 73.13, p < 0.001), however, the proportion of data-based research had not significantly increased from TP1 and TP2: descriptive (TP1 = 23% vs. TP2 = 33%) or intervention (TP1 = 77% vs. TP2 = 67%). The proportion of intervention studies adopting biochemical verification of self-reported abstinence had significantly decreased from TP1 to TP2 with an increased reliance on self-reported abstinence (TP1 = 12% vs. TP2 = 36%). Conclusions: The current research output is not ideal or optimal to decrease smoking rates. Research institutions, scholars and funding organisations should take heed to review findings when developing future research and policy. PMID:26062037

TP53 dysfunction in CLL: Implications for prognosis and treatment.

PubMed

Te Raa, Gera D; Kater, Arnon P

2016-03-01

Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored. Copyright © 2016 Elsevier Ltd. All rights reserved.

SCPS-TP: A Satellite-Enhanced TCP

NASA Technical Reports Server (NTRS)

Scott, Keith; Torgerson, Leigh

2004-01-01

This viewgraph presentation reviews the Space Communications Protocol Standard Transport Protocol (SCPS-TP) which is a satellite enhanced Transport Control Protocol (TCP). The contents include: 1) Purpose; 2) Background; 3) Stressed Communication Environments; 4) SCPS-TP Features; 5) SCPS-TP Performance; 6) Performance Enhancing Proxies (PEPs); and 7) Ongoing and Future SCPS-TP Work.

Testosterone and muscle hypertrophy in female rats

NASA Technical Reports Server (NTRS)

Kuhn, F. E.; Max, S. R.

1985-01-01

The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common.

PubMed

Kashofer, Karl; Winter, Elke; Halbwedl, Iris; Thueringer, Andrea; Kreiner, Marisa; Sauer, Stefan; Regauer, Sigrid

2017-07-01

The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16 ink4a overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained. Thirty of 76 squamous cell carcinomas (43%; average 63 years) were HPV-negative with 8/33 squamous cell carcinomas being TP53 wild-type (24%; average 63 years). Twenty-five of 33 squamous cell carcinomas (76%; average 65 years) showed 32 different somatic TP53 mutations (23 missense mutations in exons 5-8, 6 nonsense, 1 frameshift and 2 splice-site mutations). Several hotspot mutations were detected multiple times (R175H, R248, R282, and R273). Eighteen of 19 squamous cell carcinomas with TP53 expression in immunohistochemistry had TP53 mutations. Fifty percent of TP53-negative squamous cell carcinomas showed mostly truncating loss-of-function TP53 mutations. Patients without mutations had longer survival (5 years: 86% vs 61%; 10 years: 60% vs 22%), but valid clinically relevant conclusions cannot be drawn due to different tumor stages and heterogeneous treatment of the cases presented in this study. Somatic TP53 mutations are a common feature in HPV-negative penile squamous cell carcinomas and offer an explanation for HPV-independent penile carcinogenesis. About half of HPV-negative penile cancers are driven by oncogenic activation of TP53, while a quarter is induced by loss of TP53 tumor suppressor function. Detection of TP53 mutations should be carried out by sequencing, as immunohistochemical TP53 staining could not identify all squamous cell carcinomas with TP53 mutations.

Prediction of utilizable true protein of mixed rations for sheep using an in vitro incubation technique.

PubMed

Li, Yuan-Xiao; Zhao, Guang-Yong

2007-04-01

The objective of the present experiment was to study the relationship between in vitro utilizable true protein (uTP) and in vivo-uTP of sheep rations by regression analysis. A further aim was to analyse if in vivo-uTP of mixed rations could be predicted by regression analysis between in vitro-uTP and in vivo-uTP, using N-retention of sheep as important evaluation criteria of protein value. Three adult male sheep (body weight [BW] 46 + 1.3 kg) fitted with rumen cannulas and simple T-type duodenal cannulas were fed with twelve typical rations with graded levels of crude protein and true protein in four experiments according a 3 x 3 Latin square design. Each experimental period included an adaptation (7 days), a N balance trial (4 days) and a collection of duodenal digesta (3 days). During collection of duodenal digesta, polyethylene glycol and chromium oxide were used as dual markers for the measurement of duodenal digesta flow and calculation of the in vivo-uTP of duodenal digesta. The in vitro-uTP of the rations was determined using the in vitro incubation technique of Zhao and Lebzien (2000). It was found that both in vitro-uTP intake and in vivo-uTP intake were significantly correlated with N-retention (p < 0.001) and that there was a significant linear relationship between the content of in vitro-uTP and in vivo-uTP in rations (p < 0.001). Therefore, it was concluded that the used in vitro incubation technique is suitable for the determination of in vitro-uTP of mixed rations for sheep, and that the amount of in vivo-uTP can be predicted by regression between in vitro-uTP and in vivo-uTP.

TP53 mutation and survival in aggressive B cell lymphoma.

PubMed

Zenz, Thorsten; Kreuz, Markus; Fuge, Maxi; Klapper, Wolfram; Horn, Heike; Staiger, Annette M; Winter, Doris; Helfrich, Hanne; Huellein, Jennifer; Hansmann, Martin-Leo; Stein, Harald; Feller, Alfred; Möller, Peter; Schmitz, Norbert; Trümper, Lorenz; Loeffler, Markus; Siebert, Reiner; Rosenwald, Andreas; Ott, German; Pfreundschuh, Michael; Stilgenbauer, Stephan

2017-10-01

TP53 is mutated in 20-25% of aggressive B-cell lymphoma (B-NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B-NHL, we investigated TP53 gene mutations within the RICOVER-60 trial. Of 1,222 elderly patients (aged 61-80 years) enrolled in the study and randomized to six or eight cycles of CHOP-14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index-Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B-symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event-free (EFS), progression-free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI-factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed. © 2017 UICC.

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines.

PubMed

Wierzbicki, Piotr M; Kogut-Wierzbicka, Marzena; Ruczynski, Jaroslaw; Siedlecka-Kroplewska, Kamila; Kaszubowska, Lucyna; Rybarczyk, Agnieszka; Alenowicz, Magdalena; Rekowski, Piotr; Kmiec, Zbigniew

2014-01-01

Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5-5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells.

TP53 codon 72 polymorphism and susceptibility to cervical cancer in the Chinese population: an update meta-analysis

PubMed Central

Li, Bing; Wang, Xin; Chen, Hong; Shang, Li-Xin; Wu, Nan

2015-01-01

Background: Although many epidemiologic studies investigated the TP53 codon 72 polymorphism and its association with cervical cancer (CC), definite conclusions cannot be drawn. Aim of the study: To evaluate the association between TP53 codon 72 polymorphism and risk of cervical cancer in the Chinese population. Methods: A computerized literature search was carried out in PubMed, Springer Link, Ovid, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database to collect relevant articles. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. Results: A total of 16 studies including 1684 CC cases and 1178 controls were involved in this meta-analysis. Overall, significant increased association was found between the Pro/Pro carriers and CC risk when all studies in Chinese population pooled into the meta-analysis (heterozygous model: OR = 1.22, 95% CI: 1.01-1.46). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Han and in hospital-based studies. Conclusion: Our results suggest that the TP53 codon 72 polymorphism may be potential biomarkers for CC risk in the Chinese population, especially for Han Chinese, and studies with wider spectrum of population are required for definite conclusions. PMID:26309559

Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin.

PubMed

Yuan, Zhi-xiang; Wu, Xiao-juan; Mo, Jingxin; Wang, Yan-li; Xu, Chao-qun; Lim, Lee Yong

2015-08-01

We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A299-585 (A299-585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A299-585 via a succinic acid spacer to give TPS-PF-A299-585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299-585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299-585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A299-585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A299-585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A299-585 to be a useful carrier for targeting TP to the kidney. Copyright © 2015 Elsevier B.V. All rights reserved.

Maximizing Aggregation of Organic Fluorophores to Prolong Fluorescence Lifetime for Two-Photon Fluorescence Lifetime Imaging.

PubMed

Hu, Wenbo; Guo, Lihong; Bai, Lei; Miao, Xiaofei; Ni, Yun; Wang, Qi; Zhao, Hui; Xie, Meng; Li, Lin; Lu, Xiaomei; Huang, Wei; Fan, Quli

2018-05-28

Two-photon fluorescence lifetime imaging (TP-FLIM) not only permits imaging deep inside the tissues with precise spatial manipulation but also circumvents tissue autofluorescence, holding tremendous promise in molecular imaging. However, the serious lack of suitable contrast agents with long fluorescence lifetime and efficient two-photon absorption (TPA) greatly limits the advance of TP-FLIM. This study reports a simple approach to fabricate water-soluble organic semiconducting nanoparticles [thioxanthone (TXO) NPs] with ultralong fluorescence lifetime and efficient TPA for in vivo TP-FLIM. The approach utilizes the aggregation of a specifically selected thermally activated delayed fluorescence (TADF) fluorophore to prolong its fluorescence lifetime. Encapsulating the TADF fluorophore within an amphiphilic copolymer not only maximizes its aggregation but also obtains TXO NPs with efficient TPA. Importantly, as-prepared TXO NPs exhibit a considerably long fluorescence lifetime at a magnitude of 4.2 µs, which is almost 1000 times larger than that of existing organic contrast agents. Moreover, such long fluorescence lifetime is almost oxygen-inert, readily realizing both in vitro and in vivo TP-FLIM. This work may set valuable guidance for designing organic semiconducting materials with ultralong fluorescence lifetimes to fulfill the potential of FLIM. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid northward shift of the Indian Monsoon on the Tibetan Plateau at the end of the Little Ice Age

NASA Astrophysics Data System (ADS)

Zhang, Xiaolong; Xu, Baiqing; Günther, Franziska; Witt, Roman; Wang, Mo; Xie, Ying; Zhao, Huabiao; Li, Jiule; Gleixner, Gerd

2017-09-01

Variations in the Indian Monsoon (IM) and Westerlies (WS) significantly affect the climate on the Tibetan Plateau (TP) and have widespread ecological and socioeconomic impacts on the whole of Asian society. So far, however, the rate and magnitude of changes in the IM have still remained unclear. Here we report for the first time that the IM rapidly shifted northward at the end of the Little Ice Age (LIA). We used sediment proxies for humidity and moisture sources from the Taro Co Lake, which is located in the transition zone between the WS and IM. Our comprehensive survey of climate records for the TP and its peripheral mountain ranges revealed that the northern boundary of the IM (i.e., the southern boundary of the WS) lay along the southern slope of the Gandise Range ( 29.5°N) in the late LIA. In contrast, it passed quickly over the Gandise Range by at least 1.5° in latitude at the end of the LIA. Our results suggest that this rapid climatic shift was potentially triggered by the counteracting effects of blocking by the TP and its marginal orography, which hindered the northward movement of the IM, and the pulling thermal gradient of the TP.

Evaluation of the AnnAGNPS Model for Predicting Runoff and Nutrient Export in a Typical Small Watershed in the Hilly Region of Taihu Lake.

PubMed

Luo, Chuan; Li, Zhaofu; Li, Hengpeng; Chen, Xiaomin

2015-09-02

The application of hydrological and water quality models is an efficient approach to better understand the processes of environmental deterioration. This study evaluated the ability of the Annualized Agricultural Non-Point Source (AnnAGNPS) model to predict runoff, total nitrogen (TN) and total phosphorus (TP) loading in a typical small watershed of a hilly region near Taihu Lake, China. Runoff was calibrated and validated at both an annual and monthly scale, and parameter sensitivity analysis was performed for TN and TP before the two water quality components were calibrated. The results showed that the model satisfactorily simulated runoff at annual and monthly scales, both during calibration and validation processes. Additionally, results of parameter sensitivity analysis showed that the parameters Fertilizer rate, Fertilizer organic, Canopy cover and Fertilizer inorganic were more sensitive to TN output. In terms of TP, the parameters Residue mass ratio, Fertilizer rate, Fertilizer inorganic and Canopy cover were the most sensitive. Based on these sensitive parameters, calibration was performed. TN loading produced satisfactory results for both the calibration and validation processes, whereas the performance of TP loading was slightly poor. The simulation results showed that AnnAGNPS has the potential to be used as a valuable tool for the planning and management of watersheds.

Temporal and spatial characteristics of the water pollutant concentration in Huaihe River Basin from 2003 to 2012, China.

PubMed

Dou, Ming; Zhang, Yan; Li, Guiqiu

2016-09-01

Based on the monitoring data of 78 monitoring stations from 2003 to 2012, five key water quality indexes (biochemical oxygen demand: BOD5, permanganate index: CODMn, dissolved oxygen: DO, ammonium nitrogen: NH3-N, and total phosphorus: TP) were selected to analyze their temporal and spatial characteristics in the highly disturbed Huaihe River Basin via Mann-Kendall trend analysis and boxplot analysis. The temporal and spatial variations of water pollutant concentrations in the Huaihe River Basin were investigated and analyzed to provide a scientific basis for water pollution control, water environment protection, and ecological restoration. The results indicated that the Yinghe River, Quanhe River, Honghe River, Guohe River, and Baohe River were the most seriously polluted rivers, followed by Hongze Lake, Luoma Lake, Yishuhe River, and Nansi Lake. BOD5, CODMn, and NH3-N were the major pollution indexes, for which the monitoring stations reported that more than 40 % of the water quality concentrations exceeded the class IV level. There were 21, 50, 36, and 21 monitoring stations that recorded significantly decreasing trends for BOD5, CODMn, NH3-N, and TP, respectively, and 39 monitoring stations showed a significantly increasing trend for DO. Moreover, the water quality concentrations had a certain concentricity and volatility according to boxplot analysis for the 20 monitoring stations. The majority of monitoring stations recorded a large fluctuation for the monitoring indexes in 2003 and 2004, which indicated that the water quality concentrations were unstable. According to the seasonal variations of the water quality concentrations in the mainstream of Huaihe River, the monthly variation trends of the BOD5, CODMn, DO, NH3-N, and TP concentrations were basically consistent among the seven monitoring stations. The BOD5, CODMn, NH3-N, and TP concentrations were affected by the change of the stream discharge; changes in DO and NH3-N concentrations were influenced by the regional environmental temperature, and the DO and NH3-N concentrations decreased when the water temperature increased.

Asteroseismology of ZZ Ceti stars with full evolutionary white dwarf models. II. The impact of AGB thermal pulses on the asteroseismic inferences of ZZ Ceti stars

NASA Astrophysics Data System (ADS)

De Gerónimo, F. C.; Althaus, L. G.; Córsico, A. H.; Romero, A. D.; Kepler, S. O.

2018-05-01

Context. The thermally pulsing phase on the asymptotic giant branch (TP-AGB) is the last nuclear burning phase experienced by most low- and intermediate-mass stars. During this phase, the outer chemical stratification above the C/O core of the emerging white dwarf (WD) is built up. The chemical structure resulting from progenitor evolution strongly impacts the whole pulsation spectrum exhibited by ZZ Ceti stars, which are pulsating C/O core white dwarfs located on a narrow instability strip at Teff 12 000 K. Several physical processes occurring during progenitor evolution strongly affect the chemical structure of these stars; those found during the TP-AGB phase are the most relevant for the pulsational properties of ZZ Ceti stars. Aims: We present a study of the impact of the chemical structure built up during the TP-AGB evolution on the stellar parameters inferred from asteroseismological fits of ZZ Ceti stars. Methods: Our analysis is based on a set of carbon-oxygen core white dwarf models with masses from 0.534 to 0.6463 M⊙ derived from full evolutionary computations from the ZAMS to the ZZ Ceti domain. We computed evolutionary sequences that experience different number of thermal pulses (TP). Results: We find that the occurrence or not of thermal pulses during AGB evolution implies an average deviation in the asteroseimological effective temperature of ZZ Ceti stars of at most 8% and on the order of ≲5% in the stellar mass. For the mass of the hydrogen envelope, however, we find deviations up to 2 orders of magnitude in the case of cool ZZ Ceti stars. Hot and intermediate temperature ZZ Ceti stars show no differences in the hydrogen envelope mass in most cases. Conclusions: Our results show that, in general, the impact of the occurrence or not of thermal pulses in the progenitor stars is not negligible and must be taken into account in asteroseismological studies of ZZ Ceti stars.

High-amplitude, centennial-scale climate oscillations during the last glacial in the western Third Pole as recorded in the Guliya ice cap

NASA Astrophysics Data System (ADS)

Thompson, L. G.; Yao, T.; Mosley-Thompson, E.; Wu, G.; Davis, M. E.; Tian, L.; Lin, P. N.

2015-12-01

The Guliya ice cap, located in the Kunlun Mountains in the western Third Pole (TP) region near the northern limit of the southwest monsoon influence, may be the only non-polar ice field that provides detailed histories of climate and environment over the last glacial cycle. A continuous climate record from an ice core drilled in 1992 contains Eemian ice, and basal temperatures measured that year confirmed that the record was not being removed from the bottom. The δ18O record throughout Marine Isotope Stage 2 (MIS2) displays the occurrence of high-amplitude (~20‰) episodes of ~200-year periodicity, and the aerosol records suggest snow cover, regional vegetation and fire frequency that vary in synchrony. These oscillations might reflect the movement of the northernmost penetration of the monsoon precipitation through the Late Glacial Stage, which is restricted by the topographic barrier posed by the Kunlun range, and might also reflect solar-driven nonlinearities in the climate system such as sudden shifts in the jet stream. Recent model simulations suggest that glacial cooling over China was significantly amplified by stationary waves, and the Guliya MIS2 oscillations could reflect cyclical variability in these waves. These results are supported by clumped isotope thermometry of carbonates from the Chinese Loess Plateau, which indicate a 6 to 7oC decrease in Last Glacial Maximum summer temperatures. These studies will lead to a better understanding of the mechanisms driving such high-frequency, high-amplitude oscillations. A review of the 2015 Sino-American cooperative ice core drilling program on Guliya is presented. This program will serve as a flagship for the TP Environment Program, an international, multidisciplinary collaboration among professionals and students in 14 countries designed to investigate environmental changes across the TP. The rapidly warming TP contains ~46,000 glaciers that collectively hold one of Earth's largest stores of fresh water that feeds Asia's largest rivers and helps sustain 1.5 billion people. Information on the accelerating warming of these glaciers and the impact on future water resources in this important region is urgently needed to help guide mitigation and adaptation policies.

The 72Pro Variant of the Tumor Protein 53 Is Associated with an Increased Breast Cancer Risk in the Moroccan Population.

PubMed

Ayoubi, Salah Eddine; Elkarroumi, Mohamed; El Khachibi, Meryam; Hassani Idrissi, Hind; Ayoubi, Hasnaa; Ennachit, Simohamed; Arazzakou, Mounia; Nadifi, Sellama

2018-06-25

The purpose of our case control study is to explore the potential association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism (rs1042522) with the risk of breast cancer (BC) development in the Moroccan population. The study population consisted of 125 female patients with confirmed BC and 126 healthy controls. DNA samples were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay method using BstUI restriction enzyme. We showed that the homozygous genotype of TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2, 95% CI 1.07-4.54, p = 0.03). The dominant and additive models of TP53 Pro allele were also correlated to the risk of BC (OR 2.13, 95% CI 1.07-4.23, p = 0.02 and OR 1.49, 95% CI 1.03-2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72 variant was associated with protection against BC, either in the homozygous genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22-0.93, p = 0.03; OR 0.46, 95% CI 0.23-0.92, p = 0.029 and OR 0.67, 95% CI 0.46-0.97, p = 0.03, respectively). Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population. © 2018 S. Karger AG, Basel.

The Tp0684 (MglB-2) Lipoprotein of Treponema pallidum: A Glucose-Binding Protein with Divergent Topology.

PubMed

Brautigam, Chad A; Deka, Ranjit K; Liu, Wei Z; Norgard, Michael V

2016-01-01

Treponema pallidum, the bacterium that causes syphilis, is an obligate human parasite. As such, it must acquire energy, in the form of carbon sources, from the host. There is ample evidence that the principal source of energy for this spirochete is D-glucose acquired from its environment, likely via an ABC transporter. Further, there is genetic evidence of a D-glucose chemotaxis system in T. pallidum. Both of these processes may be dependent on a single lipidated chemoreceptor: Tp0684, also called TpMglB-2 for its sequence homology to MglB of Escherichia coli. To broaden our understanding of this potentially vital protein, we determined a 2.05-Å X-ray crystal structure of a soluble form of the recombinant protein. Like its namesake, TpMglB-2 adopts a bilobed fold that is similar to that of the ligand-binding proteins (LBPs) of other ABC transporters. However, the protein has an unusual, circularly permuted topology. This feature prompted a series of biophysical studies that examined whether the protein's topological distinctiveness affected its putative chemoreceptor functions. Differential scanning fluorimetry and isothermal titration calorimetry were used to confirm that the protein bound D-glucose in a cleft between its two lobes. Additionally, analytical ultracentrifugation was employed to reveal that D-glucose binding is accompanied by a significant conformational change. TpMglB-2 thus appears to be fully functional in vitro, and given the probable central importance of the protein to T. pallidum's physiology, our results have implications for the viability and pathogenicity of this obligate human pathogen.

Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer.

PubMed

Knappskog, Stian; Chrisanthar, Ranjan; Løkkevik, Erik; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Leirvaag, Beryl; Miletic, Hrvoje; Lønning, Per E

2012-03-15

Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy. We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5). Our data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer.

Insights in nutrient sources and transport from high-frequency monitoring at the outlet pumping station of an agricultural lowland polder catchment

NASA Astrophysics Data System (ADS)

Rozemeijer, J.; Van der Grift, B.; Broers, H. P.; Berendrecht, W.; Oste, L.; Griffioen, J.

2015-12-01

In this study, we present new insights in nutrient sources and transport processes in an agricultural-dominated lowland water system based on high-frequency monitoring technology. Starting in October 2014, we have collected semi-continuous measurements of the TP and NO3 concentrations, conductivity and water temperature at a large scale pumping station at the outlet of a 576 km2 polder catchment. The semi-continuous measurements complement a water quality monitoring program at six locations within the drainage area based on conventional monthly or biweekly grab sampling. The NO3 and TP concentrations at the pumping station varied between 0.5 and 10 mgN/L and 0.1 and 0.5 mgP/L. The seasonal trends and short scale concentration dynamics clearly indicated that most of the NO3 loads at the pumping station originated from subsurface drain tubes that were active after intensive rainfall events during the winter months. A transfer function-noise model of hourly NO3 concentrations reveals that a large part of the dynamics in NO3 concentrations during the winter months can be predicted using rainfall data. In February however, NO3 concentrations were higher than predicted due to direct losses after the first manure application. The TP concentration almost doubled during operation of the pumping station. This highlights resuspension of particulate P from channel bed sediments induced by the higher flow velocities during pumping. Rainfall events that caused peaks in NO3 concentrations did not result in TP concentration peaks. Direct effects of run-off, with an association increase in the TP concentration and decrease of the NO3concentration, was only observed during rainfall event at the end of a freeze-thaw cycle. The high-frequency monitoring at the outlet of an agricultural-dominated lowland water system in combination with low-frequency monitoring within the area provided insight in nutrient sources and transport processes that are highly relevant for water quality management.

[Evaluation of the Performance of Two Kinds of Anti-TP Enzyme-Linked Immunosorbent Assay].

PubMed

Gao, Nan; Huang, Li-Qin; Wang, Rui; Jia, Jun-Jie; Wu, Shuo; Zhang, Jing; Ge, Hong-Wei

2018-06-01

To evaluate the accuracy and precision of 2 kinds of anti-treponema pallidum (anti-TP) ELISA reagents in our laboratory for detecting the anti-TP in voluntary blood donors, so as to provide the data support for use of ELISA reagents after introduction of chemiluminescene immunoassay (CLIA). The route detection of anti-TP was performed by using 2 kinds of ELISA reagents, then 546 responsive positive samples detected by anti-TP ELISA were collected, and the infections status of samples confirmed by treponema pallidum particle agglutination (TPPA) test was identified. The confirmed results of responsive samples detected by 2 kinds of anti-TP ELISA reagents were compared, the accuracy of 2 kinds of anti-TP ELISA reagents was analyzed by drawing ROC and comparing area under curve (AUC), and precision of 2 kinds of anti-TP ELISA reagents was compared by statistical analysis of quality control data from 7.1 2016 to 6.30 2017. There were no statistical difference in confirmed positive rate of responsive samples and weak positive samples between 2 kinds of anti-TP ELISA reagents. The responsive samples detected by 2 kinds of anti-TP ELISA reagents accounted for 85.53%(467/546) of all responsive samples, the positive rate confirmed by TPPA test was 82.87%. 44 responsive samples detected by anti-TP ELISA reagent A and 35 responsive samples detected by anti-TP ELISA reagent B were confirmed to be negative by TPPA test. Comparison of AUC showed that the accuracy of 2 kinds of anti-TP ELISA reagents was more high, the difference between 2 reagents was not statistically significant. The coefficient of variation (CV) of anti-TP ELISA reagent A and B was 14.98% and 18.04% respectively, which met the precision requirement of ELISA test. The accuracy and precision of 2 kinds of anti-TP ELISA reagents used in our laboratory are similar, and using any one of anti-TP ELISA reagents all can satisfy the requirements of blood screening.

Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

PubMed Central

Thanasai, Jongkonnee; Limpaiboon, Temduang; Jearanaikoon, Patcharee; Sripa, Banchob; Pairojkul, Chawalit; Tantimavanich, Srisurang; Miwa, Masanao

2010-01-01

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy. PMID:20355241

Recombinant Treponema pallidum Protein Tp0965 Activates Endothelial Cells and Increases the Permeability of Endothelial Cell Monolayer

PubMed Central

Zhang, Rui-Li; Zhang, Jing-Ping; Wang, Qian-Qiu

2014-01-01

The recombinant Treponema pallidum protein Tp0965 (rTp0965), one of the many proteins derived from the genome of T. pallidum subsp. pallidum, shows strong immunogenicity and immunoreactivity. In this study, we investigated the effects of rTp0965 on the endothelial barrier. Treatment of human umbilical vein endothelial cells (HUVECs) with rTp0965 resulted in increased levels of ICAM-1, E-selectin, and MCP-1 mRNA and protein expression. These increases contributed to the adhesion and chemataxis of monocytes (THP-1 cells) to HUVECs preincubated with rTp0965. In addition, rTp0965 induced reorganization of F-actin and decreased expression of claudin-1 in HUVECs. Interestingly, inhibition of the RhoA/ROCK signal pathway protected against rTp0965-induced higher endothelial permeability as well as transendothelial migration of monocytes. These data indicate that Tp0965 protein may play an important role in the immunopathogenesis of syphilis. PMID:25514584

Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

PubMed Central

Badal, Brateil; Solovyov, Alexander; Di Cecilia, Serena; Chan, Joseph Minhow; Chang, Li-Wei; Iqbal, Ramiz; Aydin, Iraz T.; Rajan, Geena S.; Chen, Chen; Abbate, Franco; Arora, Kshitij S.; Tanne, Antoine; Gruber, Stephen B.; Johnson, Timothy M.; Fullen, Douglas R.; Phelps, Robert; Bhardwaj, Nina; Bernstein, Emily; Ting, David T.; Brunner, Georg; Schadt, Eric E.; Greenbaum, Benjamin D.; Celebi, Julide Tok

2017-01-01

BACKGROUND. Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS. We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS. Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature (“epigenetic” cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of “viral mimicry” were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (“immune” clusters) were identified. CONCLUSION. The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell’s epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING. National Institutes of Health (CA154683, CA158557, CA177940, CA087497-13), Tisch Cancer Institute, Melanoma Research Foundation, the Dow Family Charitable Foundation, and the Icahn School of Medicine at Mount Sinai. PMID:28469092

Introducing TEX86 as a Water pH Proxy for Alkaline Lakes on the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Wang, M.; Tian, Q.; Li, X.; Liang, J.; Yue, H.; Hou, J.

2017-12-01

Lake water pH represents one of the most important indicators for lake evolution and factors influencing the evolution of aquatic ecosystem, however, which is less studied on the Tibetan Plateau (TP). Applicability of diatom assemblages, an effective proxy of lake water pH variation in freshwater lakes, is highly limited on the TP because the widespread distribution of alkaline lakes is unfavorable for preservation of diatom shells. Glycerol dialkyl glycerol tetraethers (GDGTs) are a series of specific membrane lipids biosynthesized by archaea and bacteria, which appear to be a promising method to reflect lake water pH variation. Here we present the distribution of iGDGTs compounds in surface sediments across the TP to discuss the effect of various environmental factors on iGDGTs distribution. The results show that TEX86 is a promising proxy for lake water pH in high-elevation alkaline lakes, as water pH appears to be the most important factor to affect the cyclization of iGDGTs. We proposed the water pH calibration for lakes (salinity<20g/L) on TP, pH=1.8176×TEX86+8.2376 (n=31, r=0.86, RMSE=0.24). To evaluate its performance, we applied the calibration at Bangong Co in western TP and reconstructed past changes in lake water pH. The TEX86-derived pH at Bangong Co varied from 8.69 to 9.49 since the last 16 kyr BP, which is generally consistent with precipitation isotope variation that was reconstructed from leaf wax D/H ratios in the same sediment core, suggesting the lake water pH was mainly controlled by local hydrology. We believe that TEX86 will be able to infer past water pH of alkaline lakes over TP and could be a potentially useful tool for reconstructing pH in alkaline lakes worldwide after regional calibrated.

Selenium as a Structural Surrogate of Sulfur: Template-Assisted Assembly of Five Types of Tungsten-Iron-Sulfur/Selenium Clusters and the Structural Fate of Chalcogenide Reactants

PubMed Central

Zheng, Bo; Chen, Xu-Dong; Zheng, Shao-Liang; Holm, R. H.

2012-01-01

Syntheses of five types of tungsten-iron-sulfur/selenium clusters–incomplete cubanes, single cubanes, edge-bridged double cubanes (EBDCs), PN-type clusters, and double-cuboidal clusters–have been devised based on the concept of template-assisted assembly. The template reactant is six-coordinate [(Tp*)WVIS3]1−, which in the assembly systems organizes FeII,III and sulfide/selenide into cuboidal [(Tp*)WFe2S3] or cubane [(Tp*)WFe3S3Q] units. With appropriate terminal iron ligation, these units are capable of independent existence or may be transformed into higher nuclearity species. Selenide is used as a surrogate for sulfide in cluster assembly in order to determine by X-ray structures the position occupied by an external chalcogenide nucleophile or an internal chalcogenide atom in product clusters. Specific incorporation of selenide is demonstrated by formation of [WFe3S3Se]2+,3+ cubane cores. Reductive dimerization of the cubane leads to the EBDC core [W2Fe6S6Se2]2+ containing μ4-Se sites. Reaction of these species with HSe− affords the PN-type cores [W2Fe6S6Se3]1+ in which selenide occupies μ6-Se and μ2-Se sites. Reaction of [(Tp*)WS3]1−, FeCl2, and Na2Se results in the double cuboidal [W2Fe4S6Se3]2+,0 core with μ2-Se and μ4-Se bridges. It is highly probable that in analogous sulfide-only assembly systems, external and internal sulfide reactants occupy corresponding positions in cluster products. The results further demonstrate the viability of template-assisted cluster synthesis inasmuch as the reduced (Tp*)WS3 unit is present in all clusters. Structures, zero-field Mössbauer data, and redox potentials are presented for all cluster types. (Tp* = tris(pyrazolyl)hydroborate(1−)) PMID:22424175

Nutrients removal from artificial bathroom greywater using Botryococcus sp. strain

NASA Astrophysics Data System (ADS)

Mohamed, RMSR; Al-Gheethi, AA; Wurochekke, AA; Maizatul, AY; Matias-Peralta, HM; Kassim, AH Mohd

2018-04-01

The discharge of untreated bathroom greywater directly into drain is a most common practice in the rural area. The uncontrolled discharge of greywater from the village houses escalates the pollution among Malaysian river and provide insanitary environment through mosquito and flies breeding grounds. Therefore, the current work aimed to investigate the potential of Botryococcus sp. for removing total nitrogen (TN), total phosphorus (TP) and total organic carbon (TOC) from artificial bathroom greywater and to determine the bio-kinetic removal rate for these parameters. The artificial bathroom greywater was prepared by using regular brands used in the community, the bathroom greywater quality was tested for BOD, COD, SS, pH, and Turbidity. The removal process was conducted in the lab scale with 108 cell mL-1 of Botryococcus sp. The removal of TN, TP and TOC was measured in interval of 3, 5 and 7 days. The results deduced that Botryococcus sp. removed 51.5% of TN, 49.5% of TP and 42.6% of TOC. Moreover, the bio-kinetic model studies, revealed that the specific removal rate of TN, TP and TOC have a significant relationship with initial concentration in the artificial greywater (R2 = 0.63, 0.95 and 0.95 respectively). The kinetic coefficient of greywater parameters removed by Botryococcus sp. was determined as k=0.357 mg TN 1 log10 cell mL-1 d-1 and km=31.33 mg L-1 (R2=0.73), k=4.58 mg TP 1 log10 cell mL-1 d-1 and km=283.86 mg L-1 (R2=0.95), k=7.9 mg TOC 1 log10 cell mL-1 d-1 and km=322.32 mg L-1 (R2=0.97). The bio-kinetic model indicated that more than 90% of TN, TP and TOC was taken place as a response for Botryococcus sp.

Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer.

PubMed

O'Sullivan, Aine G; Mulvaney, Eamon P; Kinsella, B Therese

2017-04-01

The prostanoid thromboxane (TX) A 2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA 2 /TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA 2 -TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA 2 /TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA 2 /TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA 2 /TP signalling axis in PCa, including potentially in CRPC. Copyright © 2017 Elsevier B.V. All rights reserved.

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

PubMed

Braun, Daniela A; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A; Schanze, Denny; Ashraf, Shazia; Ullmann, Jeremy F P; Hoogstraten, Charlotte A; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I Chiara; Sanchez-Ferras, Oraly; Hu, Jennifer F; Boschat, Anne-Claire; Sanquer, Sylvia; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E; Pabst, Werner L; Warejko, Jillian K; Daga, Ankana; Basta, Tamara; Matejas, Verena; Scharmann, Karin; Kienast, Sandra D; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T; Gaffney, Patrick M; Gipson, Patrick E; Hsu, Chyong-Hsin; Kari, Jameela A; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-Ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okashah; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Ozaltin, Fatih; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth R; Rump, Patrick; Schnur, Rhonda E; Shiihara, Takashi; Sinha, Manish D; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A; Tsai, Wen-Hui; Tsai, Jeng-Daw; Topaloglu, Rezan; Vester, Udo; Viskochil, David H; Vatanavicharn, Nithiwat; Waxler, Jessica L; Wierenga, Klaas J; Wolf, Matthias T F; Wong, Sik-Nin; Leidel, Sebastian A; Truglio, Gessica; Dedon, Peter C; Poduri, Annapurna; Mane, Shrikant; Lifton, Richard P; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Callewaert, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

2017-10-01

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

Polycyclic aromatic hydrocarbons in surface soil across the Tibetan Plateau: spatial distribution, source and air-soil exchange.

PubMed

Wang, Chuanfei; Wang, Xiaoping; Gong, Ping; Yao, Tandong

2014-01-01

There are limited data on polycyclic aromatic hydrocarbons (PAHs) in both the atmosphere and soil of the Tibetan Plateau (TP). Concentrations of PAHs were therefore measured in 13 XAD resin-based passive air samplers and 41 surface (0-5 cm) soil samples across the TP. The average concentration of atmospheric PAHs was 5.55 ng/m(3), which was lower than that reported for other background areas, but higher than the Arctic. Concentrations in the soils fell in a wide range from 5.54 to 389 ng/g, with an average of 59.9 ng/g. Elevation was found to play an important role in determining the spatial distribution of soil PAHs. The air-soil exchange state showed that the soils of the TP will likely remain as a sink for high molecular weight PAHs, but may become a potential "secondary source" for low molecular weight PAHs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phosphorous-doped TiO2 nanoparticles: synthesis, characterization, and visible photocatalytic evaluation on sulfamethazine degradation.

PubMed

Mendiola-Alvarez, Sandra Yadira; Hernández-Ramírez, Ma Aracely; Guzmán-Mar, Jorge Luis; Garza-Tovar, Lorena Leticia; Hinojosa-Reyes, Laura

2018-05-24

Mesoporous phosphorous-doped TiO 2 (TP) with different wt% of P (0.5, 1.0, and 1.5) was synthetized by microwave-assisted sol-gel method. The obtained materials were characterized by XRD with cell parameters refinement approach, Raman, BET-specific surface area analysis, SEM, ICP-OES, UV-Vis with diffuse reflectance, photoluminescence, FTIR, and XPS. The photocatalytic activity under visible light was evaluated on the degradation of sulfamethazine (SMTZ) at pH 8. The characterization of the phosphorous materials (TP) showed that incorporation of P in the lattice of TiO 2 stabilizes the anatase crystalline phase, even increasing the annealing temperature. The mesoporous P-doped materials showed higher surface area and lower average crystallite size, band gap, and particle size; besides, more intense bands attributed to O-H bond were observed by FTIR analysis compared with bare TiO 2 . The P was substitutionally incorporated in the TiO 2 lattice network as P 5+ replacing Ti 4+ to form Ti-O-P bonds and additionally present as PO 4 3-  on the TiO 2 surface. All these characteristics explain the observed superior photocatalytic activity on degradation (100%) and mineralization (32%) of SMTZ under visible radiation by TP catalysts, especially for P-doped TiO 2 1.0 wt% calcined at 450 °C (TP1.0-450). Ammonium, nitrate, and sulfate ions released during the photocatalytic degradation were quantified by ion chromatography; the nitrogen and sulfur mass balance evidenced the partial mineralization of this recalcitrant molecule.

Nuclear TP53: An unraveled function as transcriptional repressor of PINK1.

PubMed

Checler, Frédéric; Goiran, Thomas; Alves da Costa, Cristine

2018-05-11

The tumor suppressor TP53/p53 is a key protein in both neurodegenerative diseases and cancer. Thus, TP53-linked cell death appears exacerbated in several age-related neuropathologies, while TP53 mutation-associated phenotypes indicate a loss of function accounting for approximately half of cancers. Thus, TP53 plays a pivotal role in these phenotypically distinct pathologies, a hypothesis reinforced by recent epidemiological studies suggesting an opposite risk to develop one type of pathology relative to the other. Dysfunctions in mitophagic processes also occur in both types of pathologies and again, TP53 has been proposed as one of the regulators of this cellular process. The consensus view postulates that TP53 exerts both anti- and pro-autophagy functions that are directly driven by a specific subcellular localization. Thus, TP53 positively modulates autophagy via the transcriptional control of several genes while it is acknowledged that its anti-autophagy phenotype is exclusively linked to a transcription-independent cytosolic control of an AMPK-MTOR cascade. Our study indicates that TP53 can also downregulate the specialized autophagy-related mitophagy response via the transcriptional repression of PINK1. This is the first demonstration of an anti-mitophagic control by nuclear TP53.

Activation of heteroallenes by coordinatively unsaturated nickel(ii) alkyl complexes supported by the hydrotris(3-phenyl-5-methyl)pyrazolyl borate (Tp(Ph,Me)) ligand.

PubMed

Abubekerov, Mark; Eymann, Léonard Y M; Gianetti, Thomas L; Arnold, John

2016-10-07

Activation of sulfur containing heteroallenes by nickel(ii) alkyl complexes supported by the bulky hydrotris(3-phenyl-5-methylpyrazolyl)borate (Tp(Ph,Me)) ligand is described. Exposure of Tp(Ph,Me)NiCH2Ph (1a) and Tp(Ph,Me)NiCH2Si(CH3)3 (1b) to CS2 resulted in formation of the insertion products Tp(Ph,Me)Ni(η(2)-CS2)CH2Ph (2a) and Tp(Ph,Me)Ni(η(2)-CS2)CH2Si(CH3)3 (2b) in moderate yields. Reaction of 1a and MeNCS produced two species in a 1 : 1 ratio, identified as Tp(Ph,Me)Ni(η(2)-MeNC)CH2Ph (3) and Tp(Ph,Me)Ni(η(2)-MeNCS)SCH2Ph (4). Isolation of the unexpected insertion product (3) prompted an investigation into the activity of 1a-b in the presence of isocyanides (i.e.(t)BuNC), which resulted in isolation of Tp(Ph,Me)Ni(η(2-t)BuNC)CH2Ph (5a) and Tp(Ph,Me)Ni(η(2-t)BuNC)CH2Si(CH3)3 (5b). Similarly, reaction of 1a with OCS led to the isolation of a rare example of a Ni(i) carbonyl species Tp(Ph,Me)NiCO (6). Alternatively, complex 6 was also formed by exposure of 1a-b to an atmosphere of CO. Isolation of the intermediate species (Tp(Ph,Me)Ni(η(2)-CO)CH2TMS (7b) and Tp(Ph,Me)Ni(CO)(C(O)R, (8a-b) with R = Ph, TMS)) shed light on the formation of such species.

Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children's Oncology Group.

PubMed

Ooms, Ariadne H A G; Gadd, Samantha; Gerhard, Daniela S; Smith, Malcolm A; Guidry Auvil, Jaime M; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Huff, Vicki; Dome, Jeffrey S; Chi, Yueh-Yun; Tian, Jing; Geller, James I; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Walz, Amy L; van den Heuvel-Eibrink, Marry M; de Krijger, Ronald R; Ross, Nicole; Gastier-Foster, Julie M; Perlman, Elizabeth J

2016-11-15

To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs). All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. Following analysis of a single random sample, 57 DAWTs (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48 (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. Clin Cancer Res; 22(22); 5582-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children’s Oncology Group

PubMed Central

Ooms, Ariadne H.A.G.; Gadd, Samantha; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Huff, Vicki; Dome, Jeffrey S.; Chi, Yueh-Yun; Tian, Jing; Geller, James I.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Walz, Amy L.; van den Heuvel-Eibrink, Marry M.; de Krijger, Ronald R.; Ross, Nicole; Gastier-Foster, Julie M.; Perlman, Elizabeth J.

2016-01-01

Purpose To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumor (DAWT). Experimental Design All DAWTs registered on National Wilms Tumor Study-5 (n=118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. Results Following analysis of a single random sample, 57 DAWT (48%) demonstrated TP53 mutations, 13(11%) copy loss without mutation, and 48(41%) lacked both (defined as TP53-wildtype (wt)). Patients with Stage III/IV TP53-wt DAWTs (but not those with Stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWT showed 7(18%) to be TP53-wt: these demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in 6/7 tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. Conclusion These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. PMID:27702824

Electron temperatures within magnetic clouds between 2 and 4 AU: Voyager 2 observations

NASA Astrophysics Data System (ADS)

Sittler, E. C.; Burlaga, L. F.

1998-08-01

We have performed an analysis of Voyager 2 plasma electron observations within magnetic clouds between 2 and 4 AU identified by Burlaga and Behannon [1982]. The analysis has been confined to three of the magnetic clouds identified by Burlaga and Behannon that had high-quality data. The general properties of the plasma electrons within a magnetic cloud are that (1) the moment electron temperature anticorrelates with the electron density within the cloud, (2) the ratio Te/Tp tends to be >1, and (3) on average, Te/Tp~7.0. All three results are consistent with previous electron observations within magnetic clouds. Detailed analyses of the core and halo populations within the magnetic clouds show no evidence of either an anticorrelation between the core temperature TC and the electron density Ne or an anticorrelation between the halo temperature TH and the electron density. Within the magnetic clouds the halo component can contribute more than 50% of the electron pressure. The anticorrelation of Te relative to Ne can be traced to the density of the halo component relative to the density of the core component. The core electrons dominate the electron density. When the density goes up, the halo electrons contribute less to the electron pressure, so we get a lower Te. When the electron density goes down, the halo electrons contribute more to the electron pressure, and Te goes up. We find a relation between the electron pressure and density of the form Pe=αNeγ with γ~0.5.

Discordant Syphilis Immunoassays in Pregnancy: Perinatal Outcomes and Implications for Clinical Management.

PubMed

Mmeje, Okeoma; Chow, Joan M; Davidson, Lisette; Shieh, Jennifer; Schapiro, Jeffrey M; Park, Ina U

2015-10-01

The reverse sequence algorithm is often used for prenatal syphilis screening by high-volume laboratories, beginning with a treponemal test such as the chemiluminescence immunoassay (CIA), followed by testing of CIA-positive (CIA(+)) specimens with the rapid plasma reagin test (RPR). The clinical significance of discordant serology (CIA(+)/RPR(-)) for maternal and neonatal outcomes is unknown. From August 2007 to August 2010, all pregnant women at Kaiser Permanente Northern California with discordant treponemal serology underwent reflexive testing with Treponema pallidum particle agglutination assay (TP-PA) and were categorized as "TP-PA confirmed" (CIA(+)/RPR(-)/TP-PA(+)) or "isolated CIA positive" (CIA(+)/RPR(-)/TP-PA(-)). Demographic variables and clinical data were abstracted from the medical record and compared by TP-PA status. Of 194 pregnant women, 156 (80%) were CIA(+)/RPR(-)/TP-PA(-) and 38 (20%) were CIA(+)/RPR(-)/TP-PA(+). Among the 77 (49%) CIA(+)/RPR(-)/TP-PA(-) women who were retested, 53% became CIA(-). CIA(+)/RPR(-)/TP-PA(+) (n = 38) women were more likely to be older, have a prior history of sexually transmitted infections, and receive treatment for syphilis during pregnancy than women who were CIA(+)/RPR(-)/TP-PA(-) (all P < .005). Most pregnancies (189/194 [97.5%]) resulted in a live birth; there was no difference in birth outcomes according to TP-PA status and no stillbirths attributable to syphilis. Most pregnant women with discordant serology were CIA(+)/RPR(-)/TP-PA(-); more than half who were retested became CIA(-). CIA(+)/RPR(-)/TP-PA(-) serology in pregnancy is likely to be falsely positive. Reflexive testing of discordant specimens with TP-PA is important to stratify risk given the likelihood of false-positive results in this population. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

PubMed

Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

2014-12-24

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

Knockdown of long non-coding RNA TP73-AS1 inhibits osteosarcoma cell proliferation and invasion through sponging miR-142.

PubMed

Yang, Guangling; Song, Ruipeng; Wang, Limin; Wu, Xuejian

2018-07-01

Long non-coding RNA P73 antisense RNA 1 T (lncRNA TP73-AS1) has been shown to involve in the progression of numerous tumors. Nevertheless, the expression as well as the functional mechanisms of TP73-AS1 in osteosarcoma (OS) are still largely unknown. This study aimed to explore the roles and underlying mechanism of TP73-AS1 in OS progression. In thye present study, TP73-AS1 expression was significantly increased in OS tissues and cell lines. High TP73-AS1 expression was associated with poor overall survival of OS patients. TP73-AS1 knockdown suppressed OS cells proliferation and invasion in vitro as well as tumor growth in vivo. Furthermore, we identified that miR-142 could act as a direct target for TP73-AS1 and miR-142 inhibition reversed the suppression of OS cells proliferation and invasion induced by TP73-AS1 knockdown. In addition, we showed that TP73-AS1 could function as a sponge of miR-142 to positively regulate Rac1 in OS cells. Thus, our data suggested that TP73-AS1 served as an oncogenic lncRNA in OS progression, and could be regarded as an efficient therapeutic target in the treatment of OS. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Probing the Carbon-Hydrogen Activation of Alkanes Following Photolysis of Tp'Rh(CNR)(carbodiimide): A Computational and Time-Resolved Infrared Spectroscopic Study.

PubMed

Guan, Jia; Wriglesworth, Alisdair; Sun, Xue Zhong; Brothers, Edward N; Zarić, Snežana D; Evans, Meagan E; Jones, William D; Towrie, Michael; Hall, Michael B; George, Michael W

2018-02-07

Carbon-hydrogen bond activation of alkanes by Tp'Rh(CNR) (Tp' = Tp = trispyrazolylborate or Tp* = tris(3,5-dimethylpyrazolyl)borate) were followed by time-resolved infrared spectroscopy (TRIR) in the υ(CNR) and υ(B-H) spectral regions on Tp*Rh(CNCH 2 CMe 3 ), and their reaction mechanisms were modeled by density functional theory (DFT) on TpRh(CNMe). The major intermediate species were: κ 3 -η 1 -alkane complex (1); κ 2 -η 2 -alkane complex (2); and κ 3 -alkyl hydride (3). Calculations predict that the barrier between 1 and 2 arises from a triplet-singlet crossing and intermediate 2 proceeds over the rate-determining C-H activation barrier to give the final product 3. The activation lifetimes measured for the Tp*Rh(CNR) and Tp*Rh(CO) fragments with n-heptane and four cycloalkanes (C 5 H 10 , C 6 H 12 , C 7 H 14 , and C 8 H 16 ) increase with alkanes size and show a dramatic increase between C 6 H 12 and C 7 H 14 . A similar step-like behavior was observed previously with CpRh(CO) and Cp*Rh(CO) fragments and is attributed to the wider difference in C-H bonds that appear at C 7 H 14 . However, Tp'Rh(CNR) and Tp'Rh(CO) fragments have much longer absolute lifetimes compared to those of CpRh(CO) and Cp*Rh(CO) fragments, because the reduced electron density in dechelated κ 2 -η 2 -alkane Tp' complexes stabilizes the d 8 Rh(I) in a square-planar geometry and weakens the metal's ability for oxidative addition of the C-H bond. Further, the Tp'Rh(CNR) fragment has significantly slower rates of C-H activation in comparison to the Tp'Rh(CO) fragment for the larger cycloalkanes, because the steric bulk of the neopentyl isocyanide ligand hinders the rechelation in κ 2 -Tp'Rh(CNR)(cycloalkane) species and results in the C-H activation without the assistance of the rechelation.

Characterizing genomic differences of human cancer stratified by the TP53 mutation status.

PubMed

Wang, Mengyao; Yang, Chao; Zhang, Xiuqing; Li, Xiangchun

2018-06-01

The key roles of the TP53 mutation in cancer have been well established. TP53 is the most frequently mutated gene, and its inactivation is widespread among human cancer types. However, the landscape of genomic alterations in human cancers stratified by the TP53 mutation has not yet been described. We obtained somatic mutation and copy number change data of 6551 regular-mutated samples from the Cancer Genome Atlas (TCGA) and compared significantly mutated genes (SMGs), copy number alterations, mutational signatures and mutational strand asymmetries between cancer samples with and without the TP53 mutation. We identified 126 SMGs, 30 of which were statistically significant in both the TP53 mutant and wild-type groups. Several SMGs, such as VHL, SMAD4 and PTEN, showed a mutation bias towards the TP53 wild-type group, whereas ATRX, IDH1 and RB1 were more prevalent in the TP53 mutant group. Five mutational signatures were extracted from the combined TCGA dataset on which mutational asymmetry analysis was performed, revealing that the TP53 mutant group exhibited substantially greater replication and transcription biases. Furthermore, we found that alterations of multiple genes in a merged mutually exclusive network composed of BRAF, EGFR, PAK1, PIK3CA, PTEN, APC and TERT were related to shortened survival in the TP53 wild-type group. In summary, we characterized the genomic differences and similarities underlying human cancers stratified by the TP53 mutation and identified multi-gene alterations of a merged mutually exclusive network to be a poor prognostic factor for the TP53 wild-type group.

Selection of a Representative Subset of Global Climate Models that Captures the Profile of Regional Changes for Integrated Climate Impacts Assessment

NASA Technical Reports Server (NTRS)

Ruane, Alex C.; Mcdermid, Sonali P.

2017-01-01

We present the Representative Temperature and Precipitation (T&P) GCM Subsetting Approach developed within the Agricultural Model Intercomparison and Improvement Project (AgMIP) to select a practical subset of global climate models (GCMs) for regional integrated assessment of climate impacts when resource limitations do not permit the full ensemble of GCMs to be evaluated given the need to also focus on impacts sector and economics models. Subsetting inherently leads to a loss of information but can free up resources to explore important uncertainties in the integrated assessment that would otherwise be prohibitive. The Representative T&P GCM Subsetting Approach identifies five individual GCMs that capture a profile of the full ensemble of temperature and precipitation change within the growing season while maintaining information about the probability that basic classes of climate changes (relatively cool/wet, cool/dry, middle, hot/wet, and hot/dry) are projected in the full GCM ensemble. We demonstrate the selection methodology for maize impacts in Ames, Iowa, and discuss limitations and situations when additional information may be required to select representative GCMs. We then classify 29 GCMs over all land areas to identify regions and seasons with characteristic diagonal skewness related to surface moisture as well as extreme skewness connected to snow-albedo feedbacks and GCM uncertainty. Finally, we employ this basic approach to recognize that GCM projections demonstrate coherence across space, time, and greenhouse gas concentration pathway. The Representative T&P GCM Subsetting Approach provides a quantitative basis for the determination of useful GCM subsets, provides a practical and coherent approach where previous assessments selected solely on availability of scenarios, and may be extended for application to a range of scales and sectoral impacts.

Seasonal and life-phase related differences in growth in Scarus ferrugineus on a southern Red Sea fringing reef.

PubMed

Afeworki, Y; Videler, J J; Berhane, Y H; Bruggemann, J H

2014-05-01

Temporal trends in growth of the rusty parrotfish Scarus ferrugineus were studied on a southern Red Sea fringing reef that experiences seasonal changes in environmental conditions and benthic algal resources. Length increment data from tagging and recapture were compared among periods and sexes and modelled using GROTAG, a von Bertalanffy growth model. The growth pattern of S. ferrugineus was highly seasonal with a maximum occurring between April and June and a minimum between December and March. Body condition followed the seasonal variation in growth, increasing from April to June and decreasing from December to March. The season of maximum growth coincided with high irradiation, temperature increases and peak abundance of the primary food source, the epilithic algal community. There was a decline in growth rate during summer (July to October) associated with a combination of extreme temperatures and lowered food availability. There were strong sexual size dimorphism (SSD) and life-history traits. Terminal-phase (TP) males achieved larger asymptotic lengths than initial-phase individuals (IP) (L(∞) 34·55 v. 25·12 cm) with growth coefficients (K) of 0·26 and 0·38. The TPs were growing four times as fast as IPs of similar size. Three individuals changed from IP to TP while at liberty and grew eight times faster than IPs of similar size, suggesting that sex change in S. ferrugineus is accompanied by a surge in growth rate. The SSD in S. ferrugineus thus coincided with fast growth that started during sex change and continued into the TP. Faster growth during sex change suggests that the cost associated with sex change is limited. © 2014 The Fisheries Society of the British Isles.

Climate variability of heat wave and projection of warming scenario in Taiwan

NASA Astrophysics Data System (ADS)

Lin, C. Y.; Chien, Y. Y.; Su, C. J.

2017-12-01

This study examined the climate variability of heat wave (HW) according to air temperature and relative humidity to determine trends of variation and stress threshold in three major cities of Taiwan, Taipei (TP), Taichung (TC) and Kaohsiung (KH), during in the past four decades (1971-2010). According to data available, the wet-bulb globe temperature (WBGT) heat stress for the three studied cities was also calculated for the past (2003-2012) and simulated under the projected warming scenario for the end of this century (2075-2099) using ECHAM5/MPIOM-WRF (ECW) dynamic downscaling 5-km resolution Analysis showed that past decade (2001-2010) saw increase not only in number of HW days in all three cities but also the duration of each HW event in TP and KH. Simulation results revealed that ECW captures well the characteristics of data distribution in these three cities during 2003-2012. Under the A1B projection, ECW yielded higher WBGT in all three cities for 2075-2099. The WBGT in TP indicated that the heat stress for 50% of the days in July and August by 2075-2099 will be at danger level (WBGT ³ 31 °C). Even the median WBGT in TC and KH (30.91°C and 30.88°C, respectively), are close to 31°C. Hence, the heat stress in all three cities will either exceed or approach the danger level by the end of this century. Such projection under the global warming trend would necessitate adaptation and mitigation, and the huge impact of dangerous heat stress on public health merits urgent attention for Taiwan.

A new map of permafrost distribution on the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Zou, Defu; Zhao, Lin; Sheng, Yu; Chen, Ji; Hu, Guojie; Wu, Tonghua; Wu, Jichun; Xie, Changwei; Wu, Xiaodong; Pang, Qiangqiang; Wang, Wu; Du, Erji; Li, Wangping; Liu, Guangyue; Li, Jing; Qin, Yanhui; Qiao, Yongping; Wang, Zhiwei; Shi, Jianzong; Cheng, Guodong

2017-11-01

The Tibetan Plateau (TP) has the largest areas of permafrost terrain in the mid- and low-latitude regions of the world. Some permafrost distribution maps have been compiled but, due to limited data sources, ambiguous criteria, inadequate validation, and deficiency of high-quality spatial data sets, there is high uncertainty in the mapping of the permafrost distribution on the TP. We generated a new permafrost map based on freezing and thawing indices from modified Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperatures (LSTs) and validated this map using various ground-based data sets. The soil thermal properties of five soil types across the TP were estimated according to an empirical equation and soil properties (moisture content and bulk density). The temperature at the top of permafrost (TTOP) model was applied to simulate the permafrost distribution. Permafrost, seasonally frozen ground, and unfrozen ground covered areas of 1.06 × 106 km2 (0.97-1.15 × 106 km2, 90 % confidence interval) (40 %), 1.46 × 106 (56 %), and 0.03 × 106 km2 (1 %), respectively, excluding glaciers and lakes. Ground-based observations of the permafrost distribution across the five investigated regions (IRs, located in the transition zones of the permafrost and seasonally frozen ground) and three highway transects (across the entire permafrost regions from north to south) were used to validate the model. Validation results showed that the kappa coefficient varied from 0.38 to 0.78 with a mean of 0.57 for the five IRs and 0.62 to 0.74 with a mean of 0.68 within the three transects. Compared with earlier studies, the TTOP modelling results show greater accuracy. The results provide more detailed information on the permafrost distribution and basic data for use in future research on the Tibetan Plateau permafrost.

Mitigation and treatment of pollutants from railway and highway runoff by pocket wetland system; A case study.

PubMed

Senduran, Cem; Gunes, Kemal; Topaloglu, Duygu; Dede, Omer Hulusi; Masi, Fabio; Kucukosmanoglu, Ozen Arli

2018-08-01

This study performed in Sapanca Lake catchment area, used as a drinking water resource. Two highways located at northern and southern shores, and a railway at its south are significant sources of pollution. As a possible solution for protecting water quality a pocket wetland constructed and operated. Performances statistically interpreted by Spearman's Correlation test and univariate analysis of variance on collected data. The mean removal efficiencies obtaited were 52% (TSS), 4% (Nitrate), 26% (TN), -5% (TOC), 63% (TP), 4.5% (Chloride), 3% (Sulfate), 33% (Cr), 39% (Co), -19.5% (Ni), 7% (Cu), 55% (Zn), 36% (As), 38% (Cd) and 18% (Pb). TSS removal was in positive significant medium correlation with Co, Cu, Zn, and Pb removal respectively (p < 0.05). Other statistically significant positive high correlations calculated between removal efficiency of Nitrate-TN, Chloride-Sulfate, Cr-Co-Cu-As-Cd. According to ANOVA and Kruskal-Wallis test results, removal efficiencies of TSS and TOC partially affected by different temperature (p < 0.1 for TSS and p < 0.05 for TOC) and pH ranges (p < 0.1 for both removal efficiencies), TP removal efficiency significantly affected by different pH ranges (p < 0.001), and Chloride and Sulfate removal efficiencies were significantly (p < 0.001) affected by different temperature ranges. Regardless of geographical location and climatic factors, pocket wetland systems can be relied upon for minimizing heavy metals such as Cr, Co, Zn, As, Cd and Pb and critical pollutants such as TP and TSS caused by highway runoff. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia.

PubMed

Forero-Castro, Maribel; Robledo, Cristina; Benito, Rocío; Bodega-Mayor, Irene; Rapado, Inmaculada; Hernández-Sánchez, María; Abáigar, María; Maria Hernández-Sánchez, Jesús; Quijada-Álamo, Miguel; María Sánchez-Pina, José; Sala-Valdés, Mónica; Araujo-Silva, Fernanda; Kohlmann, Alexander; Luis Fuster, José; Arefi, Maryam; de Las Heras, Natalia; Riesco, Susana; Rodríguez, Juan N; Hermosín, Lourdes; Ribera, Jordi; Camos Guijosa, Mireia; Ramírez, Manuel; de Heredia Rubio, Cristina Díaz; Barragán, Eva; Martínez, Joaquín; Ribera, José M; Fernández-Ruiz, Elena; Hernández-Rivas, Jesús-María

2017-07-11

In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036). TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients.

Comparative analyses of nonpathogenic, opportunistic, and totally pathogenic mycobacteria reveal genomic and biochemical variabilities and highlight the survival attributes of Mycobacterium tuberculosis.

PubMed

Rahman, Syed Asad; Singh, Yadvir; Kohli, Sakshi; Ahmad, Javeed; Ehtesham, Nasreen Z; Tyagi, Anil K; Hasnain, Seyed E

2014-11-04

Mycobacterial evolution involves various processes, such as genome reduction, gene cooption, and critical gene acquisition. Our comparative genome size analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes were bigger than those of opportunistic (OP) or totally pathogenic (TP) mycobacteria, with the TP genomes being smaller yet variable in size--their genomic plasticity reflected their ability to evolve and survive under various environmental conditions. From the 44 mycobacterial species, 13 species, representing TP, OP, and NP, were selected for genomic-relatedness analyses. Analysis of homologous protein-coding genes shared between Mycobacterium indicus pranii (NP), Mycobacterium intracellulare ATCC 13950 (OP), and Mycobacterium tuberculosis H37Rv (TP) revealed that 4,995 (i.e., ~95%) M. indicaus pranii proteins have homology with M. intracellulare, whereas the homologies among M. indicus pranii, M. intracellulare ATCC 13950, and M. tuberculosis H37Rv were significantly lower. A total of 4,153 (~79%) M. indicus pranii proteins and 4,093 (~79%) M. intracellulare ATCC 13950 proteins exhibited homology with the M. tuberculosis H37Rv proteome, while 3,301 (~82%) and 3,295 (~82%) M. tuberculosis H37Rv proteins showed homology with M. indicus pranii and M. intracellulare ATCC 13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP mycobacteria showed enzymatic plasticity between M. indicus pranii (NP) and M. intracellulare ATCC 13950 (OP), Mycobacterium avium 104 (OP), and M. tuberculosis H37Rv (TP). Mycobacterium tuberculosis seems to have acquired novel alternate pathways with possible roles in metabolism, host-pathogen interactions, virulence, and intracellular survival, and by implication some of these could be potential drug targets. The complete sequence analysis of Mycobacterium indicus pranii, a novel species of Mycobacterium shown earlier to have strong immunomodulatory properties and currently in use for the treatment of leprosy, places it evolutionarily at the point of transition to pathogenicity. With the purpose of establishing the importance of M. indicus pranii in providing insight into the virulence mechanism of tuberculous and nontuberculous mycobacteria, we carried out comparative genomic and proteomic analyses of 44 mycobacterial species representing nonpathogenic (NP), opportunistic (OP), and totally pathogenic (TP) mycobacteria. Our results clearly placed M. indicus pranii as an ancestor of the M. avium complex. Analyses of comparative metabolic pathways between M. indicus pranii (NP), M. tuberculosis (TP), and M. intracellulare (OP) pointed to the presence of novel alternative pathways in M. tuberculosis with implications for pathogenesis and survival in the human host and identification of new drug targets. Copyright © 2014 Rahman et al.

Occurrence of phosphorus, iron, aluminum, silica, and calcium in a eutrophic lake during algae bloom sedimentation.

PubMed

Li, Guolian; Xie, Fazhi; Zhang, Jin; Wang, Jingrou; Yang, Ying; Sun, Ruoru

2016-09-01

Phosphorus (P) in a water body is mainly controlled by the interaction between surface sediment and the overlying water column after the complete control of external pollution. Significant enhancement of P in a water body would cause eutrophication of lakes. Thus, a better understanding is needed of the occurrences of P between the sediment and water column in eutrophic lakes. Here, we measured total phosphorus (TP) and major elements (Fe, Al, Ca, Mn, Si) in the water column, and total nitrogen, organic matter, TP and major oxides (Fe 2 O 3 , Al 2 O 3 , CaO, SiO 2 ) in surface sediment of Chaohu Lake, a continuously eutrophic lake. The results showed that the rank of TP levels was western lake > eastern lake > southern lake. There were significantly positive correlations between TP (including water TP and sedimentary TP) and Fe, Al, Mn, while the correlation coefficients between water TP and sedimentary TP were -0.43, -0.41 and 0.18 for the western, eastern and southern lake respectively. The negative and significant correlations of water TP and sedimentary TP may indicate that the risk of sedimentary P release was great in the western and eastern lake during algae bloom sedimentation, while the southern lake showed weak P exchange between the sediment and water column.

Influence of the Indian monsoon and the subtropical jet on climate change on the Tibetan Plateau since the late Pleistocene

NASA Astrophysics Data System (ADS)

Hou, Juzhi; D'Andrea, William J.; Wang, Mingda; He, Yue; Liang, Jie

2017-05-01

Precipitation atop the Tibetan Plateau (TP) is delivered by the Indian summer monsoon, the Asian summer monsoon, and weather systems associated with the subtropical westerly jet. Variations in the relative importance of the monsoon systems and the westerly jet are hypothesized to have occurred at decadal, millennial and glacial-interglacial scales. However, paleoclimate observations based on explicit climate proxies are still scarce, limiting our understanding of the mechanisms of Holocene climate variability on the Tibetan Plateau (TP). Here we present three independently dated compound specific hydrogen isotope records of sedimentary leaf waxes from lakes on the TP, Bangong Co, Lake Qinghai and Linggo Co. The leaf wax δD records reflect isotopes in precipitation, and we combine these observations with existing isotopic and hydrological data to investigate variations in the influence of the summer monsoon and the westerly jet on the moisture budget of the TP since the Late Pleistocene. δD values of precipitation at all three lakes were relatively positive during the Late Pleistocene indicating a weakened summer monsoon. During the early and mid-Holocene, δD values of precipitation at the three lakes were relatively negative, suggesting the importance of summer monsoon. During the middle to late Holocene, δD values at Bangong Co and Lake Qinghai gradually increased with superimposed episodes of short term of δD variability. However, at Linggo Co in the northern TP, periods of more positive δD values of precipitation correspond to wetter intervals inferred from lake level high stands, and likely reflect variations in moisture associated with the westerly jet. Thus, the δD records at Linggo Co imply the lesser importance of summer monsoon moisture in the hydrologic budget of the northern TP. Collectively, the hydrogen isotope records at these three lakes document millennial and centennial scale variations in the strength of the summer monsoon systems and concurrent changes in the westerly jet. Furthermore, millennial-scale fluctuations in the δD records at the three lakes during the middle to late Holocene suggest episodes of reduced summer monsoonal moisture delivery to these regions, and correspond with intervals of cool sea surface temperatures in the North Atlantic.

Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study

PubMed Central

Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

2016-01-01

Objective: Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. Methods: A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. Results: No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Conclusion: Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio. PMID:25868042

Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study.

PubMed

Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

2015-11-01

Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.

Beta-trace protein in ascites and pleural effusions: limits of CSF leakage detection.

PubMed

Dietzel, Joanna; Krebs, Alexander; Böttcher, Dominique; Sieb, Manuela; Glocker, Michael O; Lüdemann, Jan; Roser, Markus; Dressel, Alexander

2012-06-10

Rhino- and/or otoliquorrhea can be diagnosed by detecting beta-trace protein (β-TP) in nasal or ear secretions, as β-TP is found in high concentrations in cerebrospinal fluid (CSF) but not in serum. CSF fistulae following trauma or surgery can also occur at other anatomical sites, resulting in CSF leakage into the thoracic and abdominal cavities. By analogy, determination of ß-TP has also been used to diagnose CSF admixture in pleural effusions and ascites. However, no systematic study has yet evaluated the concentrations of β-TP in such fluids in the absence of CSF. To determine the validity of β-TP determination as a marker for the presence of CSF, we investigated β-TP concentrations in pleural effusions and ascites without CSF admixture. Patients from whom samples of ascites or pleural effusion and a paired plasma sample were available were investigated. One hundred sixty-four patients were prospectively recruited. ß-TP concentrations were determined by nephelometry. Mass spectrometric proteome analysis confirmed the presence of ß-TP in the samples. Median β-TP concentrations detected in ascites and pleural effusions (range, 0.014-26.5 mg/L, median 2.29 mg/L) exceeded the corresponding plasma concentrations 2.6-fold. According to cutoffs published to diagnose rhino- and otoliquorrhea, between 6.1% and 95.7% of the specimens would have been erroneously rated CSF-positive. Protein analysis confirmed the presence of β-TP in pleural effusion and ascites. Ascites and pleural effusion contain high concentrations of β-TP that exceed the levels in corresponding plasma. Therefore, β-TP is not a specific marker for the presence of CSF in these fluids.

Confocal raman microspectroscopy and imaging study of theraphthal in living cancer cells.

PubMed Central

Feofanov, A V; Grichine, A I; Shitova, L A; Karmakova, T A; Yakubovskaya, R I; Egret-Charlier, M; Vigny, P

2000-01-01

Binary systems combining a transition metal complex and ascorbate have been proposed recently for catalytic therapy of malignant tumors. The killing effect on tumor cells is achieved by production of free radicals in the course of accelerated oxidation of ascorbate by dioxygen in the presence of transition metal complexes. Further progress in the development of binary catalytic systems (BCSs) requires a special method for their investigation in cells and tissues, because neither component of BCSs fluoresces. Here a resonance Raman confocal spectral imaging (RR CSI) technique was introduced as a unique approach to monitor quantitatively the transition metal complexes within living cells. Intracellular accumulation, localization, and retention of theraphthal (TP), a catalyst of the advanced TP/ascorbate BCS, were investigated in A549 cells with the RR CSI technique. The cellular analysis was complemented with the detailed study of molecular interactions of TP in solution and environmental factors affecting the RR spectrum of TP. TP does not penetrate into membranes, it binds very weakly to DNA and RNA, but it readily forms complexes with proteins. Binding with Ca(2+) cations and decreasing pH below 6 induce aggregation of TP. By analyzing RR spectra recorded from every point within a TP-treated cell, three states of the agent were discriminated, namely, monomeric TP in polar environment, TP bound to proteins, and aggregated TP. Their cytoplasmic and nuclear distributions were mapped at different stages of uptake and efflux. By introducing organelle-selective fluorescent probes into drug-treated cells and measuring intracellular localization of both the probe and the drug, compartmentation of TP was revealed. Cell growth suppression by the TP/ascorbate system was measured, and probable molecular and organelle targets of radical damage were characterized. PMID:10620313

Assessment of future climate change impacts on nonpoint source pollution in snowmelt period for a cold area using SWAT.

PubMed

Wang, Yu; Bian, Jianmin; Zhao, Yongsheng; Tang, Jie; Jia, Zhuo

2018-02-05

The source area of Liao River is a typical cold region in northeastern China, which experiences serious problems with agricultural nonpoint source pollution (NPS), it is important to understand future climate change impacts on NPS in the watershed. This issue has been investigated by coupling semi distributed hydrological model (SWAT), statistical downscaling model (SDSM) and global circulation model (GCMs). The results show that annual average temperature would rise by 2.1 °C (1.3 °C) in the 2080 s under scenario RCP8.5 (RCP4.5), and annual precipitation would increase by 67 mm (33 mm). The change in winter temperature and precipitation is most significant with an increase by 0.23 °C/10a (0.17 °C/10a) and 1.94 mm/10a (2.78 mm/10a). The future streamflow, TN and TP loads would decrease by 19.05% (10.59%), 12.27% (8.81%) and 10.63% (6.11%), respectively. Monthly average streamflow, TN and TP loads would decrease from March to November, and increase from December to February. This is because the increased precipitation and temperature in winter, which made the spring snowpack melting earlier. These study indicate the trends of nonpoint source pollution during the snowmelt period under climate change conditions, accordingly adaptation measures will be necessary.

Compilation of NRL Publications on High Temperature Superconductivity.

DTIC Science & Technology

1987-01-01

Fig. 2. The upper critical field as a function of .R. Beasley: Phys. Rev 11(1979) 4545. temperature for Ial.8Sro.2Cu04 (left) and 10) A. Junod , A...commuication 10) T.P. Orlando. E.J. McNiff. Jr.. S. Foner. and M.R. Beasley: Fhys. Rev 9(1979) 4545.-,, 11) A. Junod . A. Bezinge. T. Graf. J.L. Jorda. J...of MRS meeting (Anaheim, i Uchida et al. Jpn. J. of Apph Phys. 26, L443 (1987). -s 1987; in press). 12. H. Junod et al. (preprint

Limits to TYMS and TP53 genes as predictive determinants for fluoropyrimidine sensitivity and further evidence for an RNA-based toxicity as a major influence

PubMed Central

Brody, Jonathan R.; Hucl, Tomas; Costantino, Christina L.; Eshleman, James; Gallmeier, Eike; Zhu, Heng; Heijden, Michael S. van der; Winter, Jordan M; Wikiewicz, Agnieszka K.; Yeo, Charles J.; Kern, Scott E.

2010-01-01

The major determinants of 5-flurouracil response would appear, based on accumulated literature, to be thymidylate synthase (TYMS, TS) expression levels, TS gene modifications, and TP53 status. We tested 5-fluorouracil sensitivity in yeast and human cancer cell models in which TS or TP53 alleles and expression were varied. Polymorphic TS tandem repeat status, TS expression levels reported, TS intragenic mutations, and TP53 status in outbred and experimental cancer cell lines did not predict 5-FU sensitivity or resistance. Novel observations included a dose-resistant persistence of unbound TS protein in many cancers and, upon 5-FU treatment of the colon cancer cell line, HCT116, evidence of allelic switching favoring transcripts of the mutant TS allele. The reported alleles having an intragenic mutation could not be causally associated with major degrees of 5-FU sensitivity. In yeast, TS protein was altered upon treatment with fluoro-deoxyuridine monophosphate, but 5-FU toxicity appeared largely to be RNA-based, being rescued by uridine rather than by thymidine. Cancer cell lines were also rescued from 5-FU toxicity with uridine rather than thymidine. Additionally, a TS (CDC21) knockout yeast strain, obviating any potential role for TS protein as a target, was hypersensitive to 5-FU. When denatured proteins from cancer cells treated with radio-labeled 5-FU were, labeled species with alternative molecular weights other than TS were visualized, providing further evidence for alternative 5-FU protein targets. These data emphasize that TS and TP53 status do not consistently explain the variance in responses of fluoropyrimidine-treated cancer cells, in part due to RNA-based toxicity. PMID:19155291

The Contribution of Thermally-Pulsing Asymptotic Giant Branch and Red Supergiant Starts to the Luminosities of the Magellanic Clouds at 1-24 micrometers

NASA Technical Reports Server (NTRS)

Melbourne, J.; Boyer, Martha L.

2013-01-01

We present the near-through mid-infrared flux contribution of thermally-pulsing asymptotic giant branch (TP-AGB) and massive red supergiant (RSG) stars to the luminosities of the Large and Small Magellanic Clouds (LMC and SMC, respectively). Combined, the peak contribution from these cool evolved stars occurs at approx 3 - 4 micron, where they produce 32% of the SMC light, and 25% of the LMC flux. The TP-AGB star contribution also peaks at approx 3 - 4 micron and amounts to 21% in both galaxies. The contribution from RSG stars peaks at shorter wavelengths, 2.2 micron, where they provide 11% of the SMC flux, and 7% for the LMC. Both TP-AGB and RSG stars are short lived, and thus potentially impose a large stochastic scatter on the near-IR derived mass-to-light (M/L) ratios of galaxies at rest-frame 1 - 4 micron. To minimize their impact on stellar mass estimates, one can use the M/L ratio at shorter wavelengths (e.g., at 0.8 - 1 micron). At longer wavelengths (much > 8 micron), emission from dust in the interstellar medium dominates the flux. In the LMC, which shows strong polycyclic aromatic hydrocarbon (PAH) emission at 8 micron, TP-AGB and RSG contribute less than 4% of the 8 micron flux. However, 19% of the SMC 8 micron flux is from evolved stars, nearly half of which is produced by the rarest, dustiest, carbon-rich TP-AGB stars. Thus, star formation rates of galaxies, based on an 8 micron flux (e.g., observed-frame 24 micron at z = 2), may be biased modestly high, especially for galaxies with little PAH emission.

Biochemical Characterization of the Active Anti-Hepatitis C Virus Metabolites of 2,6-Diaminopurine Ribonucleoside Prodrug Compared to Sofosbuvir and BMS-986094

PubMed Central

Ehteshami, Maryam; Tao, Sijia; Ozturk, Tugba; Zhou, Longhu; Cho, Jong Hyun; Zhang, Hongwang; Amiralaei, Sheida; Shelton, Jadd R.; Lu, Xiao; Khalil, Ahmed; Domaoal, Robert A.; Stanton, Richard A.; Suesserman, Justin E.; Lin, Biing; Lee, Sam S.; Amblard, Franck; Whitaker, Tony; Coats, Steven J.

2016-01-01

Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on β-d-2′-C-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhibitor of HCV. DAPN-PD1 is metabolized intracellularly into two distinct bioactive nucleoside triphosphate (TP) analogs. The first metabolite, 2′-C-methyl-GTP, is a well-characterized inhibitor of NS5B polymerase, whereas the second metabolite, 2′-C-methyl-DAPN-TP, behaves as an adenosine base analog. In vitro assays suggest that both metabolites are inhibitors of NS5B-mediated RNA polymerization. Additional factors, such as rNAI-TP incorporation efficiencies, intracellular rNAI-TP levels, and competition with natural ribonucleotides, were examined in order to further characterize the potential role of each nucleotide metabolite in vivo. Finally, we found that although both 2′-C-methyl-GTP and 2′-C-methyl-DAPN-TP were weak substrates for human mitochondrial RNA (mtRNA) polymerase (POLRMT) in vitro, DAPN-PD1 did not cause off-target inhibition of mtRNA transcription in Huh-7 cells. In contrast, administration of BMS-986094, which also generates 2′-C-methyl-GTP and previously has been associated with toxicity in humans, caused detectable inhibition of mtRNA transcription. Metabolism of BMS-986094 in Huh-7 cells leads to 87-fold higher levels of intracellular 2′-C-methyl-GTP than DAPN-PD1. Collectively, our data characterize DAPN-PD1 as a novel and potent antiviral agent that combines the delivery of two active metabolites. PMID:27216050

Increased expression of matrix metalloproteinases mediates thromboxane A2-induced invasion in lung cancer cells.

PubMed

Li, Xiuling; Tai, Hsin-Hsiung

2012-07-01

Thromboxane A(2) receptor (TP) has been shown to play an important role in multiple aspects of cancer development including regulation of tumor growth, survival and metastasis. Here we report that TP mediates cancer cell invasion by inducing expression of matrix metalloproteinases (MMPs). TP agonist, I-BOP, significantly elevated MMP-1, MMP-3, MMP-9 and MMP-10 mRNA levels in A549 human lung adenocarcinoma cells overexpressing TPα or TPβ. The secretion of MMP-1 and MMP-9 in conditioned media was determined using Western blot analysis and zymographic assay. Signaling pathways of I-BOP-induced MMP-1 expression were examined in further detail as a model system for MMPs induction. Signaling molecules involved in I-BOP-induced MMP-1 expression were identified by using specific inhibitors including small interfering (si)-RNAs of signaling molecules and promoter reporter assay. The results indicate that I-BOP-induced MMP-1 expression is mediated by protein kinase C (PKC), extracellular signal-regulated kinase (ERK)-activator protein-1(AP-1) and ERK-CCAAT/enhancer-binding protein β (C/EBPβ) pathways. I-BOP-induced cellular invasiveness of A549 cells expressing TPα or TPβ was determined by invasion assay. GM6001, a general inhibitor of MMPs, decreased basal and I-BOP-induced cell invasion. Knockdown of MMP-1 and MMP-9 by their respective siRNA partially reduced I-BOP-stimulated cell invasion suggesting that other MMPs induced by I-BOP were also involved. Our studies establish the relationship between TP and MMPs in cancer cell invasion and suggest that the thromboxane A(2) (TXA(2))-TP signaling is a potential therapeutic target for cancer invasion and metastasis.

Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer

PubMed Central

2012-01-01

Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5). Conclusions Our data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer. PMID:22420423

Low Temperature Deposition of Diamond Films for Optical Coatings

DTIC Science & Technology

1989-10-18

Optical Materials, " Infrared Opfical Materials VI, Solomon Musikant , Editor, Proc. SPIE 929, p. 65 (1988). 14. M.S. Wong, R. Meilunas, T.P. Ong and...of the grinding. The small arrow indicates the materials transferred from the steel bearing. So0 600 ’-400 200- At 00 n 0 20 40 60 So t (min) r.m.s

Trieu Mai | NREL

Science.gov Websites

Energy Laboratory. NREL/TP-6A20-52409-1. Brinkman, G., P. Denholm, E. Drury, E. Ela, T. Mai, R. Margolis . Brinkman, E. Drury, M. Mowers, and C. Turchi. 2012. Potential Role of Concentrating Solar Power in Enabling

Correlation between the shear-speed structure and thickness of the mantle transition zone

NASA Astrophysics Data System (ADS)

Lebedev, Sergei; Chevrot, Sébastien; van der Hilst, R. D.

2003-04-01

The 410 and 660 km seismic discontinuities that bound the mantle transition zone (TZ) are attributed to phase transformations in olivine structure. This implies that variations in TZ thickness ( HTZ) should correlate with those in TZ temperature. Pertinent seismic evidence has so far been ambiguous, however. We measure converted-wave ( Pd s) differential times tdiff= tP660 s- tP410 s in SE Asia and Australia and compare them with S-velocity ( βTZ) estimates from regional tomographic models. Both tdiff and βTZ vary on a scale of a few hundred kilometers. Inferred variations in HTZ are up to ±30 km over length scales larger than 500 km, implying ±200 K thermal heterogeneity if the effect of composition can be neglected. tdiff and βTZ correlate strongly; the linear dependence of HTZ on the average temperature within the TZ is consistent with olivine Clapeyron slopes. We also show that this relationship holds on a global-scale as well, provided that the scalelengths and uncertainties of the variations in tdiff and βTZ are taken into account. These results confirm that the transformations in olivine structure give rise to the 410 and 660 km discontinuities globally.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension.

PubMed

Demir, Mehmet; Uyan, Umut

2014-01-01

Non-dipper hypertension is associated with increased cardiovascular morbidity and mortality. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension. This study included 80 hypertensive patients. Hypertensive patients were divided into two groups: 50 dipper patients (29 male, mean age 51.5 ± 8 years) and 30 non-dipper patients (17 male, mean age 50.6 ± 5.4 years). Tp-e interval and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in non-dipper patients compared to the dippers (39.4 ± 11.5 versus 27.3 ± 7.5 ms and 37.5 ± 9.5 versus 29.2 ± 6.5 ms, p = 0.001 and p = 0.01, respectively). Tp-e interval and Tp-e/QT ratio were also significantly higher in non-dipper patients (97.5 ± 11.2 versus 84.2 ± 8.3 ms and 0.23 ± 0.02 versus 0.17 ± 0.02, all p value <0.001). Our study revealed that QTd, Tp-e interval and Tp-e/QT ratio are prolonged in patients with non-dipper hypertension.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis.

PubMed

Acar, Gu Rkan; Akkoyun, Murat; Nacar, Alper Bugra; Dirnak, Imran; Yıldırım Çetin, Gözde; Nur Yıldırım, Makbule; Zencir, Cemil; Karaman, Kayıhan; Cetin, Mustafa; Sayarlıoğlu, Mehmet

2014-01-01

Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using the Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis (RA), and to assess the relation with inflammation. Ninety-six patients (72 females, 24 males; mean age 43.8±11.8 years) with RA and 50 controls (35 females, 15 males; mean age 44.2±11.1 years) were included. From the 12-lead electrocardiogram, Tp-e interval and Tp-e/QT ratio were measured. Blood samples were taken for erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP). These parameters were compared between groups. The relationship between ventricular repolarization and inflammation was assessed by Pearson correlation coefficients. Tp-e interval and Tp-e/QT ratio were increased in RA patients compared to the controls (72.6±8.2 vs 66.4±8.5 ms, 0.20±0.02 vs 0.18±0.02; p<0.001 and p<0.001, respectively). The Tp-e interval was significantly correlated with CRP, ESR, and disease activity score (DAS-28) (r=0.56, p<0.001, r=0.57, p<0.001, and r=0.29, p=0.02, respectively). The Tp-e/QT ratio was also correlated with CRP, ESR, and DAS-28 score (r=0.43, p<0.001, r=0.53, p<0.001, and r=0.25, p=0.03, respectively). In RA patients, the increased frequency of ventricular arrhythmias may be explained by increased indexes of ventricular repolarization and their relationship with inflammation.

TP53 Germline Variations Influence the Predisposition and Prognosis of B-Cell Acute Lymphoblastic Leukemia in Children

PubMed Central

Qian, Maoxiang; Cao, Xueyuan; Devidas, Meenakshi; Yang, Wenjian; Cheng, Cheng; Dai, Yunfeng; Carroll, Andrew; Heerema, Nyla A.; Zhang, Hui; Moriyama, Takaya; Gastier-Foster, Julie M.; Xu, Heng; Raetz, Elizabeth; Larsen, Eric; Winick, Naomi; Bowman, W. Paul; Martin, Paul L.; Mardis, Elaine R.; Fulton, Robert; Zambetti, Gerard; Borowitz, Michael; Wood, Brent; Nichols, Kim E.; Carroll, William L.; Pui, Ching-Hon; Mullighan, Charles G.; Evans, William E.; Hunger, Stephen P.; Relling, Mary V.; Loh, Mignon L.

2018-01-01

Purpose Germline TP53 variation is the genetic basis of Li-Fraumeni syndrome, a highly penetrant cancer predisposition condition. Recent reports of germline TP53 variants in childhood hypodiploid acute lymphoblastic leukemia (ALL) suggest that this type of leukemia is another manifestation of Li-Fraumeni syndrome; however, the pattern, prevalence, and clinical relevance of TP53 variants in childhood ALL remain unknown. Patients and Methods Targeted sequencing of TP53 coding regions was performed in 3,801 children from the Children’s Oncology Group frontline ALL clinical trials, AALL0232 and P9900. TP53 variant pathogenicity was evaluated according to experimentally determined transcriptional activity, in silico prediction of damaging effects, and prevalence in non-ALL control populations. TP53 variants were analyzed for their association with ALL presenting features and treatment outcomes. Results We identified 49 unique nonsilent rare TP53 coding variants in 77 (2.0%) of 3,801 patients sequenced, of which 22 variants were classified as pathogenic. TP53 pathogenic variants were significantly over-represented in ALL compared with non-ALL controls (odds ratio, 5.2; P < .001). Children with TP53 pathogenic variants were significantly older at ALL diagnosis (median age, 15.5 years v 7.3 years; P < .001) and were more likely to have hypodiploid ALL (65.4% v 1.2%; P < .001). Carrying germline TP53 pathogenic variants was associated with inferior event-free survival and overall survival (hazard ratio, 4.2 and 3.9; P < .001 and .001, respectively). In particular, children with TP53 pathogenic variants were at a dramatically higher risk of second cancers than those without pathogenic variants, with 5-year cumulative incidence of 25.1% and 0.7% (P < .001), respectively. Conclusion Loss-of-function germline TP53 variants predispose children to ALL and to adverse treatment outcomes with ALL therapy, particularly the risk of second malignant neoplasms. PMID:29300620

Involvement of Cot/Tp12 in bone loss during periodontitis.

PubMed

Ohnishi, T; Okamoto, A; Kakimoto, K; Bandow, K; Chiba, N; Matsuguchi, T

2010-02-01

Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.

Biosignal-based relaxation evaluation of head-care robot.

PubMed

Ando, Takeshi; Takeda, Maki; Maruyama, Tomomi; Susuki, Yuto; Hirose, Toshinori; Fujioka, Soichiro; Mizuno, Osamu; Yamada, Kenji; Ohno, Yuko; Yukio, Honda

2013-01-01

Such popular head care procedures as shampooing and scalp massages provide physical and mental relaxation. However, they place a big burden such as chapped hands on beauticians and other practitioners. Based on our robot hand technology, we have been developing a head care robot. In this paper, we quantitatively evaluated its relaxation effect using the following biosignals: accelerated plethymography (SDNN, HF/TP, LF/HF), heart rate (HR), blood pressure, salivary amylase (sAA) and peripheral skin temperature (PST). We compared the relaxation of our developed head care robot with the head care provided by nurses. In our experimental result with 54 subjects, the activity of the autonomic nerve system changed before and after head care procedures performed by both a human nurse and our proposed robot. Especially, in the proposed robot, we confirmed significant differences with the procedure performed by our proposed head care robot in five indexes: HF/TP, LF/HF, HR, sAA, and PST. The activity of the sympathetic nerve system decreased, because the values of its indexes significantly decreased: LF/HF, HR, and sAA. On the other hand, the activity of the parasympathetic nerve system increased, because of the increase of its indexes value: HF/TP and PST. Our developed head care robot provided satisfactory relaxation in just five minutes of use.

Treponema pallidum western blot: comparison with the FTA-ABS test as a confirmatory test for syphilis.

PubMed

Backhouse, J L; Nesteroff, S I

2001-01-01

We developed a Treponema pallidum Western blot and compared the results with Treponema pallidum particle agglutination (TPPA) and fluorescent treponemal antibody absorption (FTA-ABS) tests. The Western blot was deemed reactive if the serum reacted with at least three major antigenic bands (TpN47, TpN44.5, TpN17, TpN15). The sensitivities of the Western blot, TPPA and FTA-ABS, were all 100% and the specificities of the Western blot, TPPA and FTA-ABS were 100%, 100% and 94.5% respectively. In 52 problem sera, reactive in only one treponemal test, the agreement between the Western blot and TPPA (61.5%) was significantly better than between Western blot and FTA-ABS (38.5%). The individual sensitivities and specificities of TpN47, TpN44.5, TpN17, TpN15 were 100%, 100%, 96%, 100% and 20%, 96%, 100%, 100% respectively. We conclude that the Western blot is a useful additional confirmatory test or alternative to the FTA-ABS and that a more sensitive and specific criterion for the Western blot would be reactivity with TpN15 and two of the three other major antigens.

Evaluation of a fully automated treponemal test and comparison with conventional VDRL and FTA-ABS tests.

PubMed

Park, Yongjung; Park, Younhee; Joo, Shin Young; Park, Myoung Hee; Kim, Hyon-Suk

2011-11-01

We evaluated analytic performances of an automated treponemal test and compared this test with the Venereal Disease Research Laboratory test (VDRL) and fluorescent treponemal antibody absorption test (FTA-ABS). Precision performance of the Architect Syphilis TP assay (TP; Abbott Japan, Tokyo, Japan) was assessed, and 150 serum samples were assayed with the TP before and after heat inactivation to estimate the effect of heat inactivation. A total of 616 specimens were tested with the FTA-ABS and TP, and 400 were examined with the VDRL. The TP showed good precision performance with total imprecision of less than a 10% coefficient of variation. An excellent linear relationship between results before and after heat inactivation was observed (R(2) = 0.9961). The FTA-ABS and TP agreed well with a κ coefficient of 0.981. The concordance rate between the FTA-ABS and TP was the highest (99.0%), followed by the rates between FTA-ABS and VDRL (85.0%) and between TP and VDRL (83.8%). The automated TP assay may be adequate for screening for syphilis in a large volume of samples and can be an alternative to FTA-ABS.

Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

PubMed Central

van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

2013-01-01

Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

Dose-response characteristics of Clematis triterpenoid saponins and clematichinenoside AR in rheumatoid arthritis rats by liquid chromatography/mass spectrometry-based serum and urine metabolomics.

PubMed

Li, Rui; Guo, Lin-Xiu; Li, Yi; Chang, Wen-Qi; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

2017-03-20

Clematidis Radix et Rhizoma is a traditional Chinese medicine widely used for treating arthritic disease. Clematis triterpenoid saponins (TS) and clematichinenoside AR (C-AR) have been considered to be responsible for its antiarthritic effects. However, the underling mechanism is still unclear because of their low bioavailability. To address of this issue, metabolomics tools were performed to determine metabolic variations associated with rheumatoid arthritis (RA) and responses to Clematis TS, C-AR and positive drug (Triptolide, TP) treatments. This metabolomics investigation of RA was conducted in collagen-induced arthritis (CIA) rats. Liquid chromatography/mass spectrometry and multivariate statistical tools were used to identify the alteration of serum and urine metabolites associated with RA and responses to drug treatment. As a result, 45 potential metabolites associated with RA were identified. After treatment, a total of 24 biomarkers were regulated to normal like levels. Among these, PC(18:0/20:4), 9,11-octadecadienoic acid, arachidonic acid, 1-methyladenosine, valine, hippuric acid and pantothenic acid etc, were reversed in Clematis TS and C-AR groups. Tetrahydrocortisol was regulated to normal levels in Clematis TS and TP groups, while 3,7,12-trihydroxycholan-24-oic acid was regulated in C-AR and TP groups. Biomarkers like citric acid, p-cresol glucuronide, creatinine, cortolone were reversed in TP group. Copyright © 2016 Elsevier B.V. All rights reserved.

Sediment pollution characteristics and in situ control in a deep drinking water reservoir.

PubMed

Zhou, Zizhen; Huang, Tinglin; Li, Yang; Ma, Weixing; Zhou, Shilei; Long, Shenghai

2017-02-01

Sediment pollution characteristics, in situ sediment release potential, and in situ inhibition of sediment release were investigated in a drinking water reservoir. Results showed that organic carbon (OC), total nitrogen (TN), and total phosphorus (TP) in sediments increased from the reservoir mouth to the main reservoir. Fraction analysis indicated that nitrogen in ion exchangeable form and NaOH-extractable P (Fe/Al-P) accounted for 43% and 26% of TN and TP in sediments of the main reservoir. The Risk Assessment Code for metal elements showed that Fe and Mn posed high to very high risk. The results of the in situ reactor experiment in the main reservoir showed the same trends as those observed in the natural state of the reservoir in 2011 and 2012; the maximum concentrations of total OC, TN, TP, Fe, and Mn reached 4.42mg/L, 3.33mg/L, 0.22mg/L, 2.56mg/L, and 0.61mg/L, respectively. An in situ sediment release inhibition technology, the water-lifting aerator, was utilized in the reservoir. The results of operating the water-lifting aerator indicated that sediment release was successfully inhibited and that OC, TN, TP, Fe, and Mn in surface sediment could be reduced by 13.25%, 15.23%, 14.10%, 5.32%, and 3.94%, respectively. Copyright © 2016. Published by Elsevier B.V.

Evaluation of the AnnAGNPS Model for Predicting Runoff and Nutrient Export in a Typical Small Watershed in the Hilly Region of Taihu Lake

PubMed Central

Luo, Chuan; Li, Zhaofu; Li, Hengpeng; Chen, Xiaomin

2015-01-01

The application of hydrological and water quality models is an efficient approach to better understand the processes of environmental deterioration. This study evaluated the ability of the Annualized Agricultural Non-Point Source (AnnAGNPS) model to predict runoff, total nitrogen (TN) and total phosphorus (TP) loading in a typical small watershed of a hilly region near Taihu Lake, China. Runoff was calibrated and validated at both an annual and monthly scale, and parameter sensitivity analysis was performed for TN and TP before the two water quality components were calibrated. The results showed that the model satisfactorily simulated runoff at annual and monthly scales, both during calibration and validation processes. Additionally, results of parameter sensitivity analysis showed that the parameters Fertilizer rate, Fertilizer organic, Canopy cover and Fertilizer inorganic were more sensitive to TN output. In terms of TP, the parameters Residue mass ratio, Fertilizer rate, Fertilizer inorganic and Canopy cover were the most sensitive. Based on these sensitive parameters, calibration was performed. TN loading produced satisfactory results for both the calibration and validation processes, whereas the performance of TP loading was slightly poor. The simulation results showed that AnnAGNPS has the potential to be used as a valuable tool for the planning and management of watersheds. PMID:26364642

High-frequency monitoring reveals nutrient sources and transport processes in an agriculture-dominated lowland water system

NASA Astrophysics Data System (ADS)

van der Grift, Bas; Broers, Hans Peter; Berendrecht, Wilbert; Rozemeijer, Joachim; Osté, Leonard; Griffioen, Jasper

2016-05-01

Many agriculture-dominated lowland water systems worldwide suffer from eutrophication caused by high nutrient loads. Insight in the hydrochemical functioning of embanked polder catchments is highly relevant for improving the water quality in such areas or for reducing export loads to downstream water bodies. This paper introduces new insights in nutrient sources and transport processes in a polder in the Netherlands situated below sea level using high-frequency monitoring technology at the outlet, where the water is pumped into a higher situated lake, combined with a low-frequency water quality monitoring programme at six locations within the drainage area. Seasonal trends and short-scale temporal dynamics in concentrations indicated that the NO3 concentration at the pumping station originated from N loss from agricultural lands. The NO3 loads appear as losses via tube drains after intensive rainfall events during the winter months due to preferential flow through the cracked clay soil. Transfer function-noise modelling of hourly NO3 concentrations reveals that a large part of the dynamics in NO3 concentrations during the winter months can be related to rainfall. The total phosphorus (TP) concentration and turbidity almost doubled during operation of the pumping station, which points to resuspension of particulate P from channel bed sediments induced by changes in water flow due to pumping. Rainfall events that caused peaks in NO3 concentrations did not results in TP concentration peaks. The rainfall induced and NO3 enriched quick interflow, may also be enriched in TP but retention of TP due to sedimentation of particulate P then results in the absence of rainfall induced TP concentration peaks. Increased TP concentrations associated with run-off events is only observed during a rainfall event at the end of a freeze-thaw cycle. All these observations suggest that the P retention potential of polder water systems is primarily due to the artificial pumping regime that buffers high flows. As the TP concentration is affected by operation of the pumping station, timing of sampling relative to the operating hours of the pumping station should be accounted for when calculating P export loads, determining trends in water quality, or when judging water quality status of polder water systems.

Redox interplay of oxo-thio-tungsten centers with sulfur-donor co-ligands.

PubMed

Thomas, Simon; Eagle, Aston A; Sproules, Stephen A; Hill, Jason P; White, Jonathan M; Tiekink, Edward R T; George, Graham N; Young, Charles G

2003-09-22

The oxo-thio-W(VI) complexes TpWOS(S(2)PR(2)-S) and TpWOS(pyS-S) (Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate, R = OEt, Ph; pyS = pyridine-2-thiolate) have been prepared and characterized by microanalytical, spectroscopic, and structural techniques. Crystals of the 1,2-dichloroethane hemisolvate of TpWOS(S(2)PPh(2)-S) belong to the triclinic space group Ponemacr; with a = 10.732(6) A, b = 16.91(1) A, c = 10.021(4) A, alpha = 104.40(4) degrees, beta = 107.52(3) degrees, gamma = 96.09(5) degrees, V = 1647(1) A(3) for Z = 2. The complex exhibits a distorted octahedral structure featuring a facial tridentate Tp ligand and mutually cis terminal oxo (W-O(1) = 1.712(7) A), terminal thio (W-S(1) = 2.162(3) A), and monodentate dithiophosphinate ligands. X-ray absorption and extended X-ray absorption fine structure results support a related oxo-thio formulation for TpWOS(pyS-S). The complexes are reduced to the corresponding oxo-thio-W(V) anions, [TpWOS(S(2)PR(2)-S)](-) and [TpWOS(pyS-S)](-), which exhibit highly anisotropic EPR spectra. They are oxidized to form the EPR-active (dithio)oxo-W(V) cations, [TpWO(S(3)PR(2)-S,S')](+) and [TpWO(pyS(2)-N,S)](+) (pyS(2) = pyridine-2-dithio). Green [TpWO(pyS(2)-N,S)]BF(4), formed in the reaction of TpWOS(pyS) and NOBF(4), has been isolated and spectroscopically and structurally characterized. Crystals of [TpWO(pyS(2)-N,S)]BF(4) belong to the monoclinic space group Cc with a = 16.007(5) A, b = 14.091(4) A, c = 13.608(4) A, beta = 124.525(4) degrees, V = 2528.8(13) A(3) for Z = 4. The cation exhibits a distorted octahedral structure featuring facial tridentate Tp, terminal oxo (W-O(1) = 1.632(12) A), and bidentate pyridine-2-dithio-N,S (W-S(1) = 2.317(7) A, S(1)-S(2) = 2.037(9) A) ligands. The structures and redox behavior of the complexes are compared and contrasted with those of the related molybdenum complexes, TpMo(VI)OS(S(2)PR(2)-S) and TpMo(IV)O(pyS(2)-N,S) (Hill, J. P.; Laughlin, L. J.; Gable, R. W.; Young, C. G. Inorg. Chem. 1996, 35, 3447).

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

PubMed

Xie, Fang-Yun; Zou, Guo-Rong; Hu, Wei-Han; Qi, Shu-Nan; Peng, Miao; Li, Ji-Shi

2009-03-01

Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC. Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions. The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05). The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.

Prophylaxis of venous thromboembolism in elderly patients with multimorbidity.

PubMed

Marcucci, Maura; Iorio, Alfonso; Nobili, Alessandro; Tettamanti, Mauro; Pasina, Luca; Djade, Codjo Djignefa; Marengoni, Alessandra; Salerno, Francesco; Corrao, Salvatore; Mannucci, Pier Mannuccio

2013-09-01

Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. We analyze data on elderly patients with multimorbidities admitted in the year 2010 to the Italian internal medicine wards participating in the REPOSI registry to investigate the rate of TP during the hospital stay, and analyze the factors that are related to its prescription. Multivariate logistic regression, area under the ROC curve and CART analysis were performed to look for independent predictors of TP prescription. Association between TP and VTE, bleeding and death in hospital and during the 3-month post-discharge follow-up were explored by logistic regression and propensity score analysis. Among the 1,380 patients enrolled, 171 (15.2 %) were on TP during the hospital stay (162 on low molecular weight heparins, 9 on fondaparinux). The disability Barthel index was the main independent predictor of TP prescription. Rate of fatal and non-fatal VTE and bleeding during and after hospitalization did not differ between TP and non-TP patients. In-hospital and post-discharge mortality was significantly higher in patients on TP, that however was not an independent predictor of mortality. Among elderly medical patients there was a relatively low rate of TP, that was more frequently prescribed to patients with a higher degree of disability and who had an overall higher mortality.

Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor.

PubMed

Terada, Kazuki; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kobayashi, Yutaka; Tajika, Kenji; Gomi, Seiji; Kurosawa, Saiko; Miyadera, Keiki; Tokura, Taichiro; Omori, Ikuko; Marumo, Atushi; Fujiwara, Yusuke; Yui, Shunsuke; Ryotokuji, Takeshi; Osaki, Yoshiki; Arai, Kunihito; Kitano, Tomoaki; Kosaka, Fumiko; Wakita, Satoshi; Tamai, Hayato; Fukuda, Takahiro; Inokuchi, Koiti

2018-01-01

TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%). TP53 gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion with TP53 gene mutation on the opposite allele. Multivariate analysis demonstrated that TP53 gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor in FLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search for TP53 gene mutation is therefore very important.

TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters.

PubMed

Xu, Yinfeng; Wan, Wei; Shou, Xin; Huang, Rui; You, Zhiyuan; Shou, Yanhong; Wang, Lingling; Zhou, Tianhua; Liu, Wei

2016-07-02

Cells control their metabolism through modulating the anabolic and catabolic pathways. TP53INP2/DOR (tumor protein p53 inducible nuclear protein 2), participates in cell catabolism by serving as a promoter of autophagy. Here we uncover a novel function of TP53INP2 in protein synthesis, a major biosynthetic and energy-consuming anabolic process. TP53INP2 localizes to the nucleolus through its nucleolar localization signal (NoLS) located at the C-terminal domain. Chromatin immunoprecipitation (ChIP) assays detected an association of TP53INP2 with the ribosomal DNA (rDNA), when exclusion of TP53INP2 from the nucleolus repressed rDNA promoter activity and the production of ribosomal RNA (rRNA) and proteins. The removal of TP53INP2 also impaired the association of the POLR1/RNA polymerase I preinitiation complex (PIC) with rDNA. Further, TP53INP2 interacts directly with POLR1 PIC, and is required for the assembly of the complex. These data indicate that TP53INP2 promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus, suggesting a dual role of TP53INP2 in cell metabolism, assisting anabolism on the nucleolus, and stimulating catabolism off the nucleolus.

Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.

PubMed

Bertheau, Philippe; Turpin, Elisabeth; Rickman, David S; Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-03-01

In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.

The Fate of Sulfur during Decompression Melting of Peridotite and Crystallization of Basalts - Implications for Sulfur Geochemistry of MORB and the Earth's Upper Mantle

NASA Astrophysics Data System (ADS)

Ding, S.; Dasgupta, R.

2014-12-01

Magmatism in mid-ocean ridges is the main pathway of sulfur (S) from the Earth's mantle to the surficial reservoir. MORB is generally considered sulfide saturated due to the positive correlation between S and FeOT concentration (e.g., [1]). However, most MORBs are differentiated, and both S content and sulfur concentration at sulfide saturation (SCSS) change with P, T, and magma composition (e.g., [2]). Therefore, it remains uncertain, from the MORB chemistry alone, whether mantle melts parental to MORB are sulfide saturated. In this study, we modeled the behavior of S during isentropic partial melting of a fertile peridotite using pMELTS [3] and an SCSS parameterization [4]. Our results show that during decompression melting, at a fixed mantle potential temperature, TP (e.g., 1300 °C), SCSS of aggregate melt first slightly increases then decreases at shallower depth with total variation <200 ppm. However, an increase of TP results in a significant increase of SCSS of primitive melts. Our model shows that at 15% melting (F), sulfide in the residue is exhausted for a mantle with <200 ppm S. The resulted sulfide-undersaturated partial melts contain <1000 ppm S and are 4-6 times enriched in Cu compared to the source. In order to compare our modeled results directly to the differentiated basalts, isobaric crystallization calculation was performed on 5, 10, and 15% aggregate melts. SCSS changes along liquid line of descent with a decrease in T and increase in FeOT. Comparison of S contents between the model results and MORB glasses [5] reveals that many MORBs derive from sulfide undersaturated melts. Further, for a TP of 1300-1350 °C and F of 10-15 wt.%, reproduction of self-consistent S, and Cu budget of many MORB glasses requires that S of their mantle source be ~25-200 ppm. We will discuss the interplay of TP, average F, and the conditions of differentiation to bracket the S geochemistry of MORB and MORB source mantle and develop similar systematics for OIBs and OIB source. References: [1] Le Roux et al. (2006) EPSL, 251, 209-231. [2] Baker and Moritti (2011) Rev. in Mineral. Geochem, 73, 167-213. [3] Ghiorso et al. (2002) Geochem. Geophy. Geosy. 3, 5. [4] Li and Ripley (2009) Econ. Geol. 104, 405-412. [5] Jenner and O'Neill (2012) Geochem. Geophy. Geosy. 13, 1.

Estimating Air Temperature over the Tibetan Plateau Using MODIS Data

NASA Astrophysics Data System (ADS)

Huang, Fangfang; Ma, Weiqiang; Ma, Yaoming; Li, Maoshan; Hu, Zeyong

2016-04-01

Time series of MODIS land surface temperature (LST) data and normalized difference vegetation index (NDVI) data, combined with digital elevation model (DEM) and meterological data for 2001-2012, were used to estimate and map the spatial distribution of monthly mean air temperature over the Tibatan Plateau (TP). Time series and regression analysis of monthly mean land surface temperature (Ts) and air temperature (Ta) were both conducted by ordinary liner regression (OLR) and geographical weighted regression (GWR) methods. Analysis showed that GWR method had much better result (Adjusted R2 > 0.79, root mean square error (RMSE) is between 0.51° C and 1.12° C) for estimating Ta than OLR method. The GWR model, with MODIS LST, NDVI and altitude as independent variables, was used to estimate Ta over the Tibetan Plateau. All GWR models in each month were tested by F-test with significant level of α=0.01 and the regression coefficients were all tested by T-test with significant level of α=0.01. This illustrated that Ts, NDVI and altitude play an important role on estimating Ta over the Tibetan Plateau. Finally, the major conclusions are as follows: (1) GWR method has higher accuracy for estimating Ta than OLR (Adjusted R2=0.40˜0.78, RMSE=1.60˜4.38° C), and the Ta control precision can be up to 1.12° C. (2) Over the Northern TP, the range of Ta variation in January is -29.28 ˜ -5.0° C, and that in July is -0.53 ˜ 14.0° C. Ta in summer half year (from May to October) is between -15.92 ˜ 14.0° C. From October on, 0° C isothermal level is gradually declining from the altitude of 4˜5 kilometers, and hits the bottom with altitude of 3200 meters in December, and Ta is all under 0° C in January. 10° C isothermal level gradually starts rising from the altitude of 3200 meters from May, and reaches the highest level with altitude of 4˜5 kilometers in July. In addition, Ta in south slope of the Tanggula Mountains is obviously higher than that in the north slope. Ta in east of Qinghai-Tibet Railway is higher than that in the west, and Ta shows an increasing tendency from northwest to southeast. (3) Over the Northern TP, the variation range of the difference between surface and air temperature (DT) in January is -6.52˜6.0° C, and that in July is -6.32˜6.0° C. DT in summer half year (from May to October) is between -6.34˜8.0° C, and DT along Qinghai-Tibet Railway is greater than that in the east and west areas of Qinghai-Tibet Railway. However, except of the southeastern area of the Northern TP, where DT is under 0° C, DT values in other areas are all more than 0° C in winter half year. In summer half year, the altitude of the area lower than 0° C rises to 4˜5 kilometers, and DT in south of the Tanggula Mountains is between -2.0° C and 0° C.

Study of variability of permittivity and its mapping over lunar surface and subsurface using multisensors datasets

NASA Astrophysics Data System (ADS)

Calla, O. P. N.; Mathur, Shubhra; Gadri, Kishan Lal; Jangid, Monika

2016-12-01

In the present paper, permittivity maps of equatorial lunar surface are generated using brightness temperature (TB) data obtained from Microwave Radiometer (MRM) of Chang'e-1 and physical temperature (TP) data obtained from Diviner of Lunar Reconnaissance Orbiter (LRO). Here, permittivity mapping is not carried out above 60° latitudes towards the lunar poles due to large anomaly in the physical temperature obtained from the Diviner. Microwave frequencies, which are used to generate these maps are 3 GHz, 7.8 GHz, 19.35 GHz and 37 GHz. Permittivity values are simulated using TB values at these four frequencies. Here, weighted average of physical temperature obtained from Diviner are used to compute permittivity at each microwave frequencies. Longer wavelengths of microwave signals give information of more deeper layers of the lunar surface as compared to smaller wavelength. Initially, microwave emissivity is estimated using TB values from MRM and physical temperature (TP) from Diviner. From estimated emissivity the real part of permittivity (ε), is calculated using Fresnel equations. The permittivity maps of equatorial lunar surface is generated. The simulated permittivity values are normalized with respect to density for easy comparison of simulated permittivity values with the permittivity values of Apollo samples as well as with the permittivity values of Terrestrial Analogue of Lunar Soil (TALS) JSC-1A. Lower value of dielectric constant (ε‧) indicates that the corresponding lunar surface is smooth and doesn't have rough rocky terrain. Thus a future lunar astronaut can use these data to decide proper landing site for future lunar missions. The results of this paper will serve as input to future exploration of lunar surface.

A modified MOD16 algorithm to estimate evapotranspiration over alpine meadow on the Tibetan Plateau, China

NASA Astrophysics Data System (ADS)

Chang, Yaping; Qin, Dahe; Ding, Yongjian; Zhao, Qiudong; Zhang, Shiqiang

2018-06-01

The long-term change of evapotranspiration (ET) is crucial for managing water resources in areas with extreme climates, such as the Tibetan Plateau (TP). This study proposed a modified algorithm for estimating ET based on the MOD16 algorithm on a global scale over alpine meadow on the TP in China. Wind speed and vegetation height were integrated to estimate aerodynamic resistance, while the temperature and moisture constraints for stomatal conductance were revised based on the technique proposed by Fisher et al. (2008). Moreover, Fisher's method for soil evaporation was adopted to reduce the uncertainty in soil evaporation estimation. Five representative alpine meadow sites on the TP were selected to investigate the performance of the modified algorithm. Comparisons were made between the ET observed using the Eddy Covariance (EC) and estimated using both the original and modified algorithms. The results revealed that the modified algorithm performed better than the original MOD16 algorithm with the coefficient of determination (R2) increasing from 0.26 to 0.68, and root mean square error (RMSE) decreasing from 1.56 to 0.78 mm d-1. The modified algorithm performed slightly better with a higher R2 (0.70) and lower RMSE (0.61 mm d-1) for after-precipitation days than for non-precipitation days at Suli site. Contrarily, better results were obtained for non-precipitation days than for after-precipitation days at Arou, Tanggula, and Hulugou sites, indicating that the modified algorithm may be more suitable for estimating ET for non-precipitation days with higher accuracy than for after-precipitation days, which had large observation errors. The comparisons between the modified algorithm and two mainstream methods suggested that the modified algorithm could produce high accuracy ET over the alpine meadow sites on the TP.

Vertical eddy diffusivity as a control parameter in the tropical Pacific

NASA Astrophysics Data System (ADS)

Martinez Avellaneda, N.; Cornuelle, B.

2011-12-01

Ocean models suffer from errors in the treatment of turbulent sub-grid-scale motions responsible for mixing and energy dissipation. Unrealistic small-scale physics in models can have large-scale consequences, such as biases in the upper ocean temperature, a symptom of poorly-simulated upwelling, currents and air-sea interactions. This is of special importance in the tropical Pacific Ocean (TP), which is home to energetic air-sea interactions that affect global climate. It has been shown in a number of studies that the simulated ENSO variability is highly dependent on the state of the ocean (e.g.: background mixing). Moreover, the magnitude of the vertical numerical diffusion is of primary importance in properly reproducing the Pacific equatorial thermocline. This work is part of a NASA-funded project to estimate the space- and time-varying ocean mixing coefficients in an eddy-permitting (1/3dgr) model of the TP to obtain an improved estimate of its time-varying circulation and its underlying dynamics. While an estimation procedure for the TP (26dgr S - 30dgr N) in underway using the MIT general circulation model, complementary adjoint-based sensitivity studies have been carried out for the starting ocean state from Forget (2010). This analysis aids the interpretation of the estimated mixing coefficients and possible error compensation. The focus of the sensitivity tests is the Equatorial Undercurrent and sub-thermocline jets (i.e., Tsuchiya Jets), which have been thought to have strong dependence on vertical diffusivity and should provide checks on the estimated mixing parameters. In order to build intuition for the vertical diffusivity adjoint results in the TP, adjoint and forward perturbed simulations were carried out for an idealized sharp thermocline in a rectangular domain.

Relative importance of phosphorus, invasive mussels and climate for patterns in chlorophyll a and primary production in Lakes Michigan and Huron

USGS Publications Warehouse

Warner, David M.; Lesht, Barry M.

2015-01-01

1. Lakes Michigan and Huron, which are undergoing oligotrophication after reduction of phosphorus loading, invasion by dreissenid mussels and variation in climate, provide an opportunity to conduct large-scale evaluation of the relative importance of these changes for lake productivity. We used remote sensing, field data and an information-theoretic approach to identify factors that showed statistical relationships with observed changes in chlorophyll a (chla) and primary production (PP). 2. Spring phosphorus (TP), annual mean chla and PP have all declined significantly in both lakes since the late 1990s. Additionally, monthly mean values of chla have decreased in many but not all months, indicating altered seasonal patterns. The most striking change has been the decrease in chla concentration during the spring bloom. 3. Mean chlorophyll a concentration was 17% higher in Lake Michigan than in Lake Huron, and total production for 2008 in Lake Michigan (9.5 tg year 1 ) was 10% greater than in Lake Huron (7.8 tg year 1 ), even though Lake Michigan is slightly smaller (by 3%) than Lake Huron. Differences between the lakes in the early 1970s evidently persisted to 2008. 4. Invasive mussels influenced temporal trends in spring chla and annual primary production. However, TP had a greater effect on chla and primary production than did the mussels, and TP varied independently from them. Two climatic variables (precipitation and air temperature in the basins) influenced annual chla and annual PP, while the extent of ice cover influenced TP but not chla or primary production. Our results demonstrate that observed temporal patterns in chla and PP are the result of complex interactions of P, climate and invasive mussels.

Radiation Pressure Forces, the Anomalous Acceleration, and Center of Mass Motion for the TOPEX/POSEIDON Spacecraft

NASA Technical Reports Server (NTRS)

Kubitschek, Daniel G.; Born, George H.

2000-01-01

Shortly after launch of the TOPEX/POSEIDON (T/P) spacecraft (s/c), the Precision Orbit Determination (POD) Team at NASA's Goddard Space Flight Center (GSFC) and the Center for Space Research at the University of Texas, discovered residual along-track accelerations, which were unexpected. Here, we describe the analysis of radiation pressure forces acting on the T/P s/c for the purpose of understanding and providing an explanation for the anomalous accelerations. The radiation forces acting on the T/P solar army, which experiences warping due to temperature gradients between the front and back surfaces, are analyzed and the resulting along-track accelerations are determined. Characteristics similar to those of the anomalous acceleration are seen. This analysis led to the development of a new radiation form model, which includes solar array warping and a solar array deployment deflection of as large as 2 deg. As a result of this new model estimates of the empirical along-track acceleration are reduced in magnitude when compared to the GSFC tuned macromodel and are less dependent upon beta(prime), the location of the Sun relative to the orbit plane. If these results we believed to reflect the actual orientation of the T/P solar array then motion of the solar array must influence the location of the s/c center of mass. Preliminary estimates indicate that the center of mass can vary by as much as 3 cm in the radial component of the s/c's position due to rotation of the deflected, warped solar array panel .The altimeter measurements rely upon accurate knowledge of the center of mass location relative to the s/c frame of reference. Any radial motion of the center of mass directly affects the altimeter measurements.

Effects of lattice deformation on magnetic properties of electron-doped La0.8Hf0.2MnO3 thin films

NASA Astrophysics Data System (ADS)

Wu, Z. P.; Jiang, Y. C.; Gao, J.

2013-05-01

The lattice deformation effects on electric and magnetic properties of electron-doped La0.8Hf0.2MnO3 (LHMO) thin films have been systematically investigated. LHMO films with various thicknesses (15 nm, 40 nm, and 80 nm) were grown on (001) SrTiO3 and (001) LaAlO3 substrates, which induces in-plane tensile and compressive biaxial stress, respectively. The metal-insulator phase transition temperature (TP) and magnetoresistance (MR) effect show a strong dependence on film thickness. TP increases with a decrease in thickness and is enhanced as the lattice strain rises, regardless of whether it is tensile or compressive. The maximum MR ratio is suppressed by reduction of the film thickness. These anomalous phenomena may be attributed to the competition between the strain induced modification of the Mn-O bond length and the eg orbital stability.

An Overview of Climatic Elements

NASA Technical Reports Server (NTRS)

Crutcher, H. L.; Johnson, D. L.

2007-01-01

This Technical Publication (TP) addresses some climatic elements with emphasis on atmospheric composition, including gas radiative characteristics. Solar radiation is discussed with considerable information on the mathematical and statistical formulae. On a worldwide basis, temperature and precipitation for the globe are discussed along with interaction in drought. Also included is the simultaneous interaction with winds, humidity, and solar radiation. Volcanology gets minimum treatment. The oceans and seas are treated in chart form along with the interrelationship of oceanic currents and El Nino and La Nina, and ENSO phenomena. Upper air circulations are discussed. Various cloud formations up to 85-95 km altitude are described. Information on tornadoes and hurricanes is also included. One section is devoted to the climate physical-chemical elements. A short discussion is given on the importance for the quality of data and/or information in descriptions of the climate. This TP presents only an overview or survey of these and other various climatic elements.

Understanding and improving the low optical emission of InGaAs quantum wells grown on oxidized patterned (001) silicon substrate

NASA Astrophysics Data System (ADS)

Roque, J.; Haas, B.; David, S.; Rochat, N.; Bernier, N.; Rouvière, J. L.; Salem, B.; Gergaud, P.; Moeyaert, J.; Martin, M.; Bertin, F.; Baron, T.

2018-05-01

In 0.3 Ga 0.7 As quantum wells (QW) embedded in AlGaAs barriers and grown on oxidized patterned (001) silicon substrates by metalorganic chemical vapor deposition using the aspect ratio trapping method are studied. An appropriate method combining cathodoluminescence and high resolution scanning transmission electron microscopy characterization is performed to spatially correlate the optical and structural properties of the QW. A triple period (TP) ordering along the ⟨111⟩ direction induced by the temperature decrease during the growth to favor indium incorporation and aligned along the oxidized patterns is observed in the QW. Local ordering affects the band gap and contributes to the decrease of the optical emission efficiency. Using thermal annealing, we were able to remove the TP ordering and improve the QW optical emission by two orders of magnitude.

Convolutional Neural Networks as Feature Extractors for Data Scarce Visual Searches

DTIC Science & Technology

2016-09-01

50 Figure C.16 TP for the Ferrari Logo (layer=FC7). . . . . . . . . . . . . . . . 50 Figure C.17 TP for the Kia Logo (layer=FC6...51 Figure C.18 TP for the Kia Logo (layer=FC7). . . . . . . . . . . . . . . . . . 51 Figure C.19 TP for the Liege Logo (layer=FC6...represent results for test samples from the Ferrari class for k=1, k=3, and k=5. 50 Figure C.17. TP for the Kia Logo (layer=FC6). The x-axis represents

Seasonal variations of nitrogen and phosphorus retention in an agricultural drainage river in East China.

PubMed

Chen, Dingjiang; Lu, Jun; Wang, Hailong; Shen, Yena; Kimberley, Mark O

2010-02-01

Riverine retention decreases loads of nitrogen (N) and phosphorus (P) in running water. It is an important process in nutrient cycling in watersheds. However, temporal riverine nutrient retention capacity varies due to changes in hydrological, ecological, and nutrient inputs into the watershed. Quantitative information of seasonal riverine N and P retention is critical for developing strategies to combat diffuse source pollution and eutrophication in riverine and coastal systems. This study examined seasonal variation of riverine total N (TN) and total P (TP) retention in the ChangLe River, an agricultural drainage river in east China. Water quality, hydrological parameters, and hydrophyte coverage were monitored along the ChangLe River monthly during 2004-2006. Nutrient export loads (including chemical fertilizer, livestock, and domestic sources) entering the river from the catchment area were computed using an export coefficient model based on estimated nutrient sources. Riverine TN and TP retention loads (RNRL and RPRL) were estimated using mass balance calculations. Temporal variations in riverine nutrient retention were analyzed statistically. Estimated annual riverine retention loads ranged from 1,538 to 2,127 t year(-1) for RNRL and from 79.4 to 90.4 t year(-1) for RPRL. Monthly retention loads varied from 6.4 to 300.8 t month(-1) for RNRL and from 1.4 to 15.3 t month(-1) for RPRL. Both RNRL and RPRL increased with river flow, water temperature, hydrophyte coverage, monthly sunshine hours, and total TN and TP inputs. Dissolved oxygen concentration and the pH level of the river water decreased with RNRL and RPRL. Riverine nutrient retention ratios (retention as a percentage of total input) were only related to hydrophyte coverage and monthly sunshine hours. Monthly variations in RNRL and RPRL were functions of TN and TP loads. Riverine nutrient retention capacity varied with environmental conditions. Annual RNRL and RPRL accounted for 30.3-48.3% and 52.5-71.2%, respectively, of total input TN and TP loads in the ChangLe River. Monthly riverine retention ratios were 3.5-88.7% for TN and 20.5-92.6% for TP. Hydrophyte growth and coverage on the river bed is the main cause for seasonal variation in riverine nutrient retention capacity. The total input TN and TP loads were the best indicators of RNRL and RPRL, respectively. High riverine nutrient retention capacity during summer due to hydrophytic growth is favorable to the avoidance of algal bloom in both river systems and coastal water in southeast China. Policies should be developed to strictly control nutrient applications on agricultural lands. Strategies for promoting hydrophyte growth in rivers are desirable for water quality management.

Thymidine Phosphorylase is Angiogenic and Promotes Tumor Growth

NASA Astrophysics Data System (ADS)

Moghaddam, Amir; Zhang, Hua-Tang; Fan, Tai-Ping D.; Hu, De-En; Lees, Vivien C.; Turley, Helen; Fox, Stephen B.; Gatter, Kevin C.; Harris, Adrian L.; Bicknell, Roy

1995-02-01

Platelet-derived endothelial cell growth factor was previously identified as the sole angiogenic activity present in platelets; it is now known to be thymidine phosphorylase (TP). The effect of TP on [methyl-^3H]thymidine uptake does not arise from de novo DNA synthesis and the molecule is not a growth factor. Despite this, TP is strongly angiogenic in a rat sponge and freeze-injured skin graft model. Neutralizing antibodies and site-directed mutagenesis confirmed that the enzyme activity of TP is a condition for its angiogenic activity. The level of TP was found to be elevated in human breast tumors compared to normal breast tissue (P < 0.001). Overexpression of TP in MCF-7 breast carcinoma cells had no effect on growth in vitro but markedly enhanced tumor growth in vivo. These data and the correlation of expression in tumors with malignancy identify TP as a target for antitumor strategies.

A time to be stressed? Time perspectives and cortisol dynamics among healthy adults.

PubMed

Olivera-Figueroa, Lening A; Juster, Robert-Paul; Morin-Major, Julie Katia; Marin, Marie-France; Lupien, Sonia J

2015-10-01

Perceptions of past, present, and future events may be related to stress pathophysiology. We assessed whether Time Perspective (TP) is associated with cortisol dynamics among healthy adults (N=61, Ages=18-35, M=22.9, SD=4.1) exposed to the Trier Social Stress Test (TSST). TP was measured according to two profiles: maladaptive Deviation from Balanced TP (DBTP) and adaptive Deviation from Negative TP (DNTP). Eight salivary cortisol samples were analyzed using area under the curve with respect to ground (AUCg) and to increase (AUCi). Statistic analyses involved partial correlations controlling for depressive symptoms. Results for both sexes showed that higher DBTP scores were associated with lower cortisol AUCg scores, while higher DNTP scores were associated with higher cortisol AUCg scores. These novel findings suggest that maladaptive TP profiles influence hypocortisolism, whereas adaptive TP profiles influence hypercortisolism. Thus, TP profiles may impact conditions characterized by altered cortisol concentrations. Published by Elsevier B.V.

SRT Evaluation of AIRS Version-6.02 and Version-6.02 AIRS Only (6.02 AO) Products

NASA Technical Reports Server (NTRS)

Susskind, Joel; Iredell, Lena; Molnar, Gyula; Blaisdell, John

2012-01-01

Version-6 contains a number of significant improvements over Version-5. This report compares Version-6 products resulting from the advances listed below to those from Version-5. 1. Improved methodology to determine skin temperature (T(sub s)) and spectral emissivity (Epsilon(sub v)). 2. Use of Neural-net start-up state. 3. Improvements which decrease the spurious negative Version-5 trend in tropospheric temperatures. 4. Improved QC methodology. Version-6 uses separate QC thresholds optimized for Data Assimilation (QC=0) and Climate applications (QC=0,1) respectively. 5. Channel-by-channel clear-column radiances R-hat(sub tau) QC flags. 6. Improved cloud parameter retrieval algorithm. 7. Improved OLR RTA. Our evaluation compared V6.02 and V6.02 AIRS Only (V6.02 AO) Quality Controlled products with those of Version-5.0. In particular we evaluated surface skin temperature T(sub s), surface spectral emissivity Epsilon(sub v), temperature profile T(p), water vapor profile q(p), OLR, OLR(sub CLR), effective cloud fraction alpha-Epsilon, and cloud cleared radiances R-hat(sub tau) . We conducted two types of evaluations. The first compared results on 7 focus days to collocated ECMWF truth. The seven focus days are: September 6, 2002; January 25, 2003; September 29, 2004; August 5, 2005; February 24, 2007; August 10, 2007; and May 30, 2010. In these evaluations, we show results for T(sub s), Epsilon(sub v), T(p), and q(p) in terms of yields, and RMS differences and biases with regard to ECMWF. We also show yield trends as well as bias trends of these quantities relative to ECMWF truth. We also show yields and accuracy of channel by channel QC d values of R-hat(sub tau) for V6.02 and V6.02 AO. Version-5 did not contain channel by channel QC d values of R-hat(sub tau). In the second type of evaluation, we compared V6.03 monthly mean Level-3 products to those of Version-5.0, for four different months: January, April, July, and October; in 3 different years 2003, 2007, and 2011. In particular, we compared V6.03 and V5.0 trends of T(p), q(p), alpha-Epsilon, OLR, and OLR(sub CLR) computed based on results for these 12 time periods

The prevalence of transpancreatic common hepatic artery and coexisting variant anatomy.

PubMed

Ishigami, Kousei; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Yoshizumi, Tomoharu; Harimoto, Norifumi; Ohtsuka, Takao; Nakata, Kohei; Honda, Hiroshi

2018-05-01

We studied the prevalence of the transpancreatic common hepatic artery (tp-CHA) and coexisting variant anatomy. The study group comprised 788 consecutive liver transplant donor candidates who had undergone thin-section multidetector-row computed tomography (MDCT) studies to investigate vascular anatomy. Multiplanar reformatted (MPR) images obtained from the arterial phase were retrospectively reviewed to assess the presence/absence of the tp-CHA. Five cases of tp-CHA with pancreaticobiliary tumors were also included in an investigation of the presence/absence of variant hepatic arteries, celiac stenosis, and circumportal pancreas. Three of the 788 (0.38%) donor candidates had a tp-CHA. Overall, eight tp-CHA cases were assessed for coexisting variant anatomy. Seven of these eight cases had a hepatomesenteric trunk, six had celiac stenosis, and two had a circumportal pancreas. The prevalence of the tp-CHA was 0.38% (approx. one in 260 in normal populations). A tp-CHA can commonly be associated with a hepatomesenteric trunk and celiac stenosis. A circumportal pancreas can also coexist with a tp-CHA. Clin. Anat. 31:598-604, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Association between Washing Residue on the Feet and Tinea Pedis in Diabetic Patients

PubMed Central

Takehara, Kimie; Amemiya, Ayumi; Mugita, Yuko; Tsunemi, Yuichiro; Seko, Yoko; Ohashi, Yumiko; Ueki, Kohjiro; Kadowaki, Takashi; Nagase, Takashi; Ikeda, Mari; Sanada, Hiromi

2015-01-01

Tinea pedis (TP) may lead to the development of foot ulcers in diabetic patients; thus, its prevention in diabetic patients is important. TP occurs after dermatophytes on the skin scales of TP patients attach to the feet. Therefore, it is necessary to remove the scales and dermatophytes, and this can be performed using various methods, including foot washing. This study aimed to objectively examine the association between the presence of TP and foot-washing habits. We included 33 diabetic patients, and, of these, 17 had TP. The presence of washing residue on the feet was determined by applying a fluorescent cream to the participants' feet, and images of the feet were captured under ultraviolet light before and after foot washing. Our results showed that diabetic patients with TP had higher levels of washing residue on their feet than those without TP. The importance of washing feet to prevent TP needs to be emphasized through educational programs for diabetic patients. Furthermore, the development of an effective foot-washing technique is essential. PMID:25793125

Metabolic fate of fenetylline in rat and man.

PubMed

Yoshimura, H; Yoshimitsu, T; Yamada, H; Koga, N; Oguri, K

1988-08-01

1. Metabolic fate of 7-[2-(alpha-methylphenylethylamino)ethyl]theophylline hydrochloride (fenetylline) was investigated in male Sprague-Dawley rats and three male volunteers. 2. Six metabolites were identified in the rat urine as amphetamine(AP), p-hydroxy-AP, acetylaminoethyl-theophylline(TP), aminoethyl-TP, hydroxyethyl-TP and carboxymethyl-TP by comparison of their spectral properties and h.p.l.c. and g.l.c. characteristics with those of authentic samples. All these metabolites was also detected in the urine of humans receiving fenetylline. 3. Quantification of these metabolites using h.p.l.c. and g.l.c. showed that carboxymethyl-TP, p-hydroxy-AP and acetylaminoethyl-TP were the major metabolites in 0-24 h rat urine at 13.7%, 11.2% and 9.3% of dose, respectively. In men, carboxymethyl-TP(39-43% dose) and AP(23-33% dose) were the major metabolites in 0-48 h urine. 4. These results suggest that fenetylline metabolism proceeds via oxidative cleavage at two different sites to produce aminoethyl-TP and AP, respectively. The pathway producing AP predominates, in both man and rat, but is more predominant in the former.

An ecophysiological background for biogeographic patterns of two island lizards?

NASA Astrophysics Data System (ADS)

Carretero, Miguel A.; Lopes, Evandro P.; Vasconcelos, Raquel

2016-12-01

Distributions of sedentary ectotherms are dependent on temperature and humidity due to their low homeostatic and dispersal abilities. Lizards are strongly conditioned by temperature, but hydric environment may be also important, at least in arid environments. Biotic interactions may also play a role in range patterns, but they are of minor importance in islands where native species monopolize well-delimited niche spaces. On the arid island of São Vicente (Cabo Verde), two endemic lizards display different spatial patterns. While the gecko Tarentola substituta is widely distributed across the island, the skink Chioninia stangeri is restricted to the NE, which is cooler, more humid, and vegetated. We hypothesized that this is due to differences in the fundamental niche, specifically in ecophysiology. We predict that C. stangeri should select for lower temperatures and lose more water by evaporation than T. substituta. We submitted adults of each species to standard experiments to assess preferred body temperatures (Tp) and evaporative water loss (EWL) rates, and examined the variation between species and through time using repeated-measures AN(C)OVAs. Results only partially supported our expectations. Contrary to the prediction, skinks attained higher Tp than geckos but in the long term showed a trend for higher EWL as predicted. Thus, while ecophysiology certainly contributes to functional interpretation of species distributions, it needs to be combined with other evidence such as habitat use and evolutionary history. These findings will be useful to perform mechanistic models to better understand the impact of climate change and habitat disturbance on these endemic species.

TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants

PubMed Central

Sulak, Michael; Fong, Lindsey; Mika, Katelyn; Chigurupati, Sravanthi; Yon, Lisa; Mongan, Nigel P; Emes, Richard D; Lynch, Vincent J

2016-01-01

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore, we show that several of the TP53 retrogenes (TP53RTGs) are transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans. DOI: http://dx.doi.org/10.7554/eLife.11994.001 PMID:27642012

Phosphatidylcholine transfer protein interacts with thioesterase superfamily member 2 to attenuate insulin signaling.

PubMed

Ersoy, Baran A; Tarun, Akansha; D'Aquino, Katharine; Hancer, Nancy J; Ukomadu, Chinweike; White, Morris F; Michel, Thomas; Manning, Brendan D; Cohen, David E

2013-07-30

Phosphatidylcholine transfer protein (PC-TP) is a phospholipid-binding protein that is enriched in liver and that interacts with thioesterase superfamily member 2 (THEM2). Mice lacking either protein exhibit improved hepatic glucose homeostasis and are resistant to diet-induced diabetes. Insulin receptor substrate 2 (IRS2) and mammalian target of rapamycin complex 1 (mTORC1) are key effectors of insulin signaling, which is attenuated in diabetes. We found that PC-TP inhibited IRS2, as evidenced by insulin-independent IRS2 activation after knockdown, genetic ablation, or chemical inhibition of PC-TP. In addition, IRS2 was activated after knockdown of THEM2, providing support for a role for the interaction of PC-TP with THEM2 in suppressing insulin signaling. Additionally, we showed that PC-TP bound to tuberous sclerosis complex 2 (TSC2) and stabilized the components of the TSC1-TSC2 complex, which functions to inhibit mTORC1. Preventing phosphatidylcholine from binding to PC-TP disrupted interactions of PC-TP with THEM2 and TSC2, and disruption of the PC-TP-THEM2 complex was associated with increased activation of both IRS2 and mTORC1. In livers of mice with genetic ablation of PC-TP or that had been treated with a PC-TP inhibitor, steady-state amounts of IRS2 were increased, whereas those of TSC2 were decreased. These findings reveal a phospholipid-dependent mechanism that suppresses insulin signaling downstream of its receptor.

Long noncoding RNA TP73-AS1 promotes non-small cell lung cancer progression by competitively sponging miR-449a/EZH2.

PubMed

Zhang, Lin; Fang, Fengqi; He, Xin

2018-08-01

Long noncoding RNAs (lncRNAs) are a type of noncoding RNA transcript that are characterized by lack of protein-coding capacity. The vital role of lncRNAs in non-small cell lung cancer (NSCLC) is attracting increasingly more attention. In the present study, we investigate the role of lncRNA antisense RNA of the TP73 gene (TP73-AS1) in NSCLC carcinogenesis. The results demonstrate that TP73-AS1 is markedly upregulated in NSCLC tissues, and functional experiments revealed that TP73-AS1 is significantly increased in NSCLC tissue and cell lines, indicating a possible oncogenic role. In loss-of-function assays, the knockdown of TP73-AS1 inhibited NSCLC cell proliferation, tumor growth and cycle progression in vivo and in vitro. Bioinformatic tools predicted that miR-449a both targeted the 3'-UTR of TP73-AS1 and EZH2, which was confirmed using luciferase reporter assay and AGO2-dependent RNA immunoprecipitate (RIP). TP73-AS1 and miR-449a were in the same RNA-induced silencing complex (RISC). In summary, the results indicate an explicit oncogenic role of TP73-AS1 in the NSCLC tumorigenesis, suggesting a TP73-AS1-miR-449a-EZH2 axis and providing new insight for NSCLC tumorigenesis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status

PubMed Central

Kubesova, B; Pavlova, S; Malcikova, J; Kabathova, J; Radova, L; Tom, N; Tichy, B; Plevova, K; Kantorova, B; Fiedorova, K; Slavikova, M; Bystry, V; Kissova, J; Gisslinger, B; Gisslinger, H; Penka, M; Mayer, J; Kralovics, R; Pospisilova, S; Doubek, M

2018-01-01

The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2–16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression. PMID:28744014

Effect of Vanadium and Tea Polyphenols on Intestinal Morphology, Microflora and Short-Chain Fatty Acid Profile of Laying Hens.

PubMed

Yuan, Z H; Wang, J P; Zhang, K Y; Ding, X M; Bai, S P; Zeng, Q F; Xuan, Y; Su, Z W

2016-12-01

Vanadium (V) is a trace element which can induce dysfunction of gastro-intestine and egg quality deterioration of laying hens. This study was conducted to determine the effect of tea polyphenols (TP) on intestinal morphology, microflora, and short-chain fatty acid (SCFA) profile of laying hens fed vanadium containing diets. A total of 120 Lohman laying hens (67-week-old) were randomly divided into 4 groups with 6 replicates and 5 birds each for a 35-day feeding trial. The dietary treatments were as follows: (1) control (CON), fed a basal diet; (2) vanadium treatment (V10), CON +10 mg V/kg; (3) TP treatment 1 (TP1): V10 + 600 mg TP/kg; (4) TP treatment 2 (TP2): V10 + 1000 mg TP/kg. Fed 10 mg V/kg diets to laying hens did not affect the cecum flora diversity index (H), degree of homogeneity (EH), and richness (S), but hens fed TP2 diet decreased the H, EH, and S (P < 0.05). The cecum butyrate acid concentration was lower in V10 treatment and higher in TP2 treatment (P < 0.05). Addition of 10 mg/kg V resulted in an increased (P < 0.01) duodenal cell apoptosis rate, and 1000 mg/kg TP supplementation overcame (P < 0.01) this reduction effect induced by vanadium. The results indicated that supplementation of 10 mg/kg vanadium increased duodenal cell apoptosis and reduced cecum butyrate acid content. Addition of 1000 mg/kg TP increased the SCFA production to affect cecum flora ecology and protected the duodenal cell from excess apoptosis caused by vanadium.

Quantitative identification of moisture sources over the Tibetan Plateau and the relationship between thermal forcing and moisture transport

NASA Astrophysics Data System (ADS)

Pan, Chen; Zhu, Bin; Gao, Jinhui; Kang, Hanqing; Zhu, Tong

2018-02-01

Despite the importance of the Tibetan Plateau (TP) to the surrounding water cycle, the moisture sources of the TP remain uncertain. In this study, the moisture sources of the TP are quantitatively identified based on a 33-year simulation with a horizontal resolution of 1.9° × 2.5° using the Community Atmosphere Model version 5.1 (CAM5.1), in which atmospheric water tracer technology is incorporated. Results demonstrate that the major moisture sources differ over the southern TP (STP) and northern TP (NTP). During the winter, Africa, the TP, and India are the dominant source regions, contributing nearly half of the water vapour over the STP. During the summer, the tropical Indian Ocean (TIO) supplies 28.5 ± 3.6% of the water vapour over the STP and becomes the dominant source region. The dominant moisture source regions of the water vapour over the NTP are Africa (19.0 ± 2.8%) during the winter and the TP (25.8 ± 2.4%) during the summer. The overall relative contribution of each source region to the precipitation is similar to the contribution to the water vapour over the TP. Like most models, CAM5.1 generally overestimates the precipitation over the TP, yielding uncertainty in the absolute contributions to the precipitation. Composite analyses exhibit significant variations in the TIO-supplied moisture transport and precipitation over the STP during the summer alongside anomalous TP heating. This relationship between moisture transport from the TIO and the TP heating primarily involves the dynamic change in the TIO-supplied moisture flux, which further controls the variation in the TIO-contributed precipitation over the STP.

Neural correlates of auditory recognition memory in the primate dorsal temporal pole

PubMed Central

Ng, Chi-Wing; Plakke, Bethany

2013-01-01

Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects. PMID:24198324

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

PubMed Central

Haricharan, Svasti; Brown, Powel

2015-01-01

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30–50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types. PMID:26063617

TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

PubMed

Haricharan, Svasti; Brown, Powel

2015-06-23

Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual regulators of autophagy and transcription.

PubMed

Sancho, Ana; Duran, Jordi; García-España, Antonio; Mauvezin, Caroline; Alemu, Endalkachew A; Lamark, Trond; Macias, Maria J; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U; Palacín, Manuel; Johansen, Terje; Zorzano, Antonio

2012-01-01

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28-42; region 2, 66-112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription.

DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription

PubMed Central

Sancho, Ana; Duran, Jordi; García-España, Antonio; Mauvezin, Caroline; Alemu, Endalkachew A.; Lamark, Trond; Macias, Maria J.; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U.; Palacín, Manuel; Johansen, Terje; Zorzano, Antonio

2012-01-01

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription. PMID:22470510

Autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

PubMed

Xie, Xiaolei; Le, Li; Fan, Yanxin; Lv, Lin; Zhang, Junjie

2012-07-01

Mitoribosome in mammalian cells is responsible for synthesis of 13 mtDNA-encoded proteins, which are integral parts of four mitochondrial respiratory chain complexes (I, III, IV and V). ERAL1 is a nuclear-encoded GTPase important for the formation of the 28S small mitoribosomal subunit. Here, we demonstrate that knockdown of ERAL1 by RNA interference inhibits mitochondrial protein synthesis and promotes reactive oxygen species (ROS) generation, leading to autophagic vacuolization in HeLa cells. Cells that lack ERAL1 expression showed a significant conversion of LC3-I to LC3-II and an enhanced accumulation of autophagic vacuoles carrying the LC3 marker, all of which were blocked by the autophagy inhibitor 3-MA as well as by the ROS scavenger NAC. Inhibition of mitochondrial protein synthesis either by ERAL1 siRNA or chloramphenicol (CAP), a specific inhibitor of mitoribosomes, induced autophagy in HTC-116 TP53 (+/+) cells, but not in HTC-116 TP53 (-/-) cells, indicating that tumor protein 53 (TP53) is essential for the autophagy induction. The ROS elevation resulting from mitochondrial protein synthesis inhibition induced TP53 expression at transcriptional levels by enhancing TP53 promoter activity, and increased TP53 protein stability by suppressing TP53 ubiquitination through MAPK14/p38 MAPK-mediated TP53 phosphorylation. Upregulation of TP53 and its downstream target gene DRAM1, but not CDKN1A/p21, was required for the autophagy induction in ERAL1 siRNA or CAP-treated cells. Altogether, these data indicate that autophagy is induced through the ROS-TP53-DRAM1 pathway in response to mitochondrial protein synthesis inhibition.

Climate Change Impacts on Rivers and Implications for Electricity Generation in the United States

NASA Astrophysics Data System (ADS)

Miara, A.; Vorosmarty, C. J.; Macknick, J.; Corsi, F.; Cohen, S. M.; Tidwell, V. C.; Newmark, R. L.; Prousevitch, A.

2015-12-01

The contemporary power sector in the United States is heavily reliant on water resources to provide cooling water for thermoelectric generation. Efficient thermoelectric plant operations require large volumes of water at sufficiently cool temperatures for their cooling process. The total amount of water that is withdrawn or consumed for cooling and any potential declines in efficiencies are determined by the sector's fuel mix and cooling technologies. As such, the impact of climate change, and the extent of impact, on the power sector is shaped by the choice of electricity generation technologies that will be built over the coming decades. In this study, we model potential changes in river discharge and temperature in the contiguous US under a set of climate scenarios to year 2050 using the Water Balance Model-Thermoelectric Power and Thermal Pollution Model (WBM-TP2M). Together, these models quantify, in high-resolution (3-min), river temperatures, discharge and power plant efficiency losses associated with changes in available cooling water that incorporates climate, hydrology, river network dynamics and multi-plant impacts, on both single power plant and regional scales. Results are used to assess the aptness and vulnerability of contemporary and alternative electricity generation pathways to changes in climate and water availability for cooling purposes, and the concomitant impacts on power plant operating efficiencies. We assess the potential impacts by comparing six regions (Northeast, Southeast, Midwest, Great Plains, Southwest, Northwest as in the National Climate Assessment (2014)) across the US. These experiments allow us to assess tradeoffs among electricity-water-climate to provide useful insight for decision-makers managing regional power production and aquatic environments.

Synthesis, structure and reactivity of a terminal magnesium fluoride compound, [TpBut,Me]MgF: hydrogen bonding, halogen bonding and C-F bond formation.

PubMed

Rauch, Michael; Ruccolo, Serge; Mester, John Paul; Rong, Yi; Parkin, Gerard

2016-01-01

The bulky tris(3- tert -butyl-5-pyrazolyl)hydroborato ligand, [Tp Bu t ,Me ], has been employed to obtain the first structurally characterized example of a molecular magnesium compound that features a terminal fluoride ligand, namely [Tp Bu t ,Me ]MgF, via the reaction of [Tp Bu t ,Me ]MgMe with Me 3 SnF. The chloride, bromide and iodide complexes, [Tp Bu t ,Me ]MgX (X = Cl, Br, I), can also be obtained by an analogous method using Me 3 SnX. The molecular structures of the complete series of halide derivatives, [Tp Bu t ,Me ]MgX (X = F, Cl, Br, I) have been determined by X-ray diffraction. In each case, the Mg-X bond lengths are shorter than the sum of the covalent radii, thereby indicating that there is a significant ionic component to the bonding, in agreement with density functional theory calculations. The fluoride ligand of [Tp Bu t ,Me ]MgF undergoes halide exchange with Me 3 SiX (X = Cl, Br, I) to afford [Tp Bu t ,Me ]MgX and Me 3 SiF. The other halide derivatives [Tp Bu t ,Me ]MgX undergo similar exchange reactions, but the thermodynamic driving forces are much smaller than those involving fluoride transfer, a manifestation of the often discussed silaphilicity of fluorine. In accord with the highly polarized Mg-F bond, the fluoride ligand of [Tp Bu t ,Me ]MgF is capable of serving as a hydrogen bond and halogen bond acceptor, such that it forms adducts with indole and C 6 F 5 I. [Tp Bu t ,Me ]MgF also reacts with Ph 3 CCl to afford Ph 3 CF, thereby demonstrating that [Tp Bu t ,Me ]MgF may be used to form C-F bonds.

Erosion-protecting effect of oral-care products available on the Swiss market. A pilot study

PubMed

Wasser, Gregor; João-Souza, Samira H; Lussi, Adrian; Carvalho, Thiago S

2018-03-28

The present study sought to test oral-care products available on the Swiss market, such as toothpastes and gels, with respect to the protection of enamel against erosive tooth wear. A total of 56 enamel specimens were divided into 7 groups (n = 8): F-TP = Migros Budget Anti-Caries Toothpaste (Negative Control); F+Sn3500-TP = Elmex Erosion Protection Toothpaste (Positive Control); F-TP + F+Oligopep-Gel = Migros Budget Anti-Caries Toothpaste + Emofluor Protect Gel Professional; F+Sn3120-Gel = Emofluor Gel Intensive Care; F+Oligopep-TP = Candida Protect Professional Toothpaste; F+Sn1260-TP = Emoform-F Protect Toothpaste; and F+Sn3440-TP = Sensodyne Repair & Protect Toothpaste. The specimens were incubated in artificial saliva for 30 min and then brushed in a toothbrushing machine (10 s brushing; total 2 min exposure to the product). After the toothbrush abrasion, the specimens were rinsed, dried and submitted to an erosive challenge (2 min; 1% citric acid; pH 3.6). This sequence was repeated 4 times, and the total enamel surface loss was calculated using indentation measurements before and after the brushing period. All groups presented progressive surface loss throughout the experiment; after 4 cycles, total surface loss values ranged from 0.11 µm (F+Sn3120-Gel) to 0.89 µm (F+Sn1260-TP). Regarding the total surface loss values (median; interquartile range), F-TP (0.54; 0.42–0.59) presented no significant differences compared to any of the other groups. F+Sn3500-TP (0.33; 0.30–0.40), F-TP + F+Oligopep-Gel (0.34; 0.29–0.42) and F+Sn3120-Gel (0.11; 0.09–0.15) presented lower surface loss than F+Oligopep-TP (0.75; 0.59–0.98), F+Sn1260-TP (0.89; 0.68–1.13) and F+Sn3440-TP (0.69; 0.66–0.78). Conclusion: Although some of the oral-care products containing stannous ions or oligopeptide-104 presented numerically lower SL values, they did not present significantly better protection than a regular fluoride toothpaste. The gels showed a general trend of better enamel protection against ETW.

Insights into wild-type and mutant p53 functions provided by genetically engineered mice.

PubMed

Donehower, Lawrence A

2014-06-01

Recent whole-exome sequencing studies of numerous human cancers have now conclusively shown that the TP53 tumor-suppressor gene is the most frequently mutated gene in human cancers. Despite extensive studies of the TP53 gene and its encoded protein (p53), our understanding of how TP53 mutations contribute to cancer initiation and progression remain incomplete. Genetically engineered mice with germline or inducible Trp53 somatic mutations have provided important insights into the mechanisms by which different types of p53 mutation influence cancer development. Trp53 germline mutations that alter specific p53 structural domains or posttranslation modification sites have benefitted our understanding of wild-type p53 functions in a whole organism context. Moreover, genetic approaches to reestablish functional wild-type p53 to p53-deficient tissues and tumors have increased our understanding of the therapeutic potential of restoring functional p53 signaling to cancers. This review outlines many of the key insights provided by the various categories of Trp53 mutant mice that have been generated by multiple genetic engineering approaches. © 2014 WILEY PERIODICALS, INC.

Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

PubMed Central

Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-01-01

Background In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. Methods and Findings In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m2 epirubicin and 1,200 mg/m2 cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. Conclusions This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin–cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features. PMID:17388661

Crystal Properties and Radiation Effects in Solid Molecular Hydrogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozioiziemski, B

2000-09-01

The crystal lattice structure, growth shapes and helium generated by beta-decay of solid deuterium-tritium (D-T) mixtures have been studied. Understanding of these D-T properties is important for predicting and optimizing the target design of the National Ignition Facility (NIF). Raman spectroscopy showed the D-T crystal structure is hexagonal close packed, common to the non-tritiated isotopes. The isotopic mixtures of both tritiated and non-tritiated species broadens the rotational transitions, especially of the lighter species in the mixture. The vibrational frequencies of each isotope is shifted to higher energy in the mixture than the pure components. The J = 1-0 population decreasesmore » exponentially with a 1/e time constant which rapidly increases above 10.5 K for both D{sub 2} and T{sub 2} in D-T. The conversion rate is nearly constant from 5 K to 10 K for both D{sub 2} and T{sub 2} at 7.1 hours and 2.1 hours, respectively. The smoothing of D-T layers by beta decay heating is limited by the crystal surface energy. Deuterium and hydrogen-deuteride crystals were grown at a number of temperatures below the triple point to determine the surface energy and roughening transition. Several distinct crystal shapes were observed on a number of different substrates. The a facet roughens between 0.9 T{sub TP} and T{sub TP}, while the c facet persists up to the melting temperature. This is very different from the behavior of the other rare gas crystals which grow completely rounded above 0.8 T{sub TP}. Helium bubbles formed as a product of the beta decay were observed using optical microscopy and the diffusion of smaller bubbles measured with dynamic light scattering. Bubble diffusion coefficients as high as 2.0 x 10{sup -16} m{sup 2}/s were measured for 10-50 nm bubbles. The bubbles move in response to a thermal gradient, with speeds between 1 {micro}m/hour and 100 {micro}m/hour for thermal gradients and temperatures appropriate to NIF targets.« less

Tp-Te interval predicts heart rate reduction after fingolimod administration in patients with multiple sclerosis.

PubMed

Tocci, Giuliano; Giuliani, Manuela; Canichella, Flaminia; Timpano, Jacopo; Presta, Vivianne; Francia, Pietro; Musumeci, Maria Beatrice; Fubelli, Federica; Pozzilli, Carlo; Volpe, Massimo; Ferrucci, Andrea

2016-10-15

FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod. We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration. At these time intervals, conventional and new ECG indexes for cardiac damage, including Tp-Te interval, were measured. Univariate and multivariate analyses were performed to test the outcome of HR reduction more than median difference between baseline and final observations. 69 outpatients with MS (46 males, age 35.1±9.4years, BP 119.0±12.7/73.0±9.3mmHg, HR 73.5±11.4bpm) were included. No relevant adverse reactions were reported. Fingolimod induced progressive systolic (P=0.024) and diastolic (P<0.001) BP, as well as HR (P<0.001) reductions compared to baseline. Prolonged PQ (150.4±19.5 vs. 157.0±19.5ms; P<0.001), QT (374.9±27.0 vs. 400.0±25.8ms; P<0.001), Tp-Te (1.8±0.3 vs. 1.9±0.3mm; P=0.021), and reduced QTc (414.4±24.4 vs. 404.5±24.5ms; P<0.001) intervals were also recorded at final observation. Baseline HR, QT and Tp-Te intervals provided prognostic information at univariate analysis, although Tp-Te interval resulted the best independent predictor for HR reduction at multivariate analysis [0.057 (0.005-0.660); P=0.022]. This study firstly demonstrates that prolonged Tp-Te interval may identify those MS patients treated with fingolimod at higher risk of having significant, asymptomatic HR reduction during clinical observation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Copper-induced ammonia N-H functionalization.

PubMed

Álvarez, María; Álvarez, Eleuterio; Fructos, Manuel R; Urbano, Juan; Pérez, Pedro J

2016-10-07

The activation of ammonia has been achieved with the aid of the Tp(Ms)Cu core (Tp(Ms) = hydrotris(3-mesityl-pyrazolyl)borate). Complexes of the general composition Tp(Ms)Cu(amine) (1-4) including the ammonia adduct Tp(Ms)Cu(NH3) (1) have been synthesized and fully spectroscopical- and structurally characterized. Coordinated ammonia in 1 has been reacted with Ph3CPF6 yielding Tp(Ms)Cu(NH2CPh3) (5) as a result of N-H cleavage and N-C bond formation. In a parallel manner the catalytic functionalization of ammonia with ethyl diazoacetate leading to glycinate derivatives has been developed with Tp(Ms)Cu(THF) as the catalyst, in the first example of this transformation with ammonia and a copper-based system.

Calf and colostrum management practices on New Zealand dairy farms and their associations with concentrations of total protein in calf serum.

PubMed

Cuttance, E L; Mason, W A; Laven, R A; Denholm, K S; Yang, D

2018-05-01

To gather information on management practices and farmer attitudes to management of cows and calves during the immediate post-partum period on dairy farms in New Zealand, and to assess these practices for associations with concentrations of total protein (TP) in serum of calves 1-8 days-old. Between July and September 2015 blood samples were collected from calves aged between 24 hours and 7 days, from dairy farms (n=105) in nine areas in New Zealand, on three occasions throughout the calving period. Concentrations of TP were determined in all serum samples. At each visit technicians collected 1 L of the pooled colostrum that was intended for feeding to newborn calves that day. These samples were assessed for Brix, coliform and total bacterial counts. After the last sampling visit, the calf rearer or farm manager were asked to complete a questionnaire describing calf and colostrum management practices on the farm. Potential farm-level variables associated with concentrations of TP in serum of sampled calves were identified using univariable and multivariable linear mixed models. Mean concentration of TP in serum of calves across all farms was 59.8 (95% CI=59.4-60.2) g/L, and was associated with region and herd size in the final multivariable model. Concentrations of TP were lower in calves from farms in Otago (56.2 (95% CI=53.4-58.9) g/L) and Southland (56.9 (95% CI=54.1-59.7) g/L) compared to calves on farms in the Far North (62.6 (95% CI=59.8-65.3) g/L), and were lower in calves from farms with a herd size >600 (58.3 (95% CI=56.7-59.8) g/L) than ≤600 (61.3 (95% CI=60.1-62.5) g/L) cows. After accounting for fixed effects, farm accounted for only 8.4% of the unexplained variation. There was no association between any of the measures of colostrum quality and concentrations of TP in serum (p>0.2). Very few herd-level variables were associated with concentrations of TP in serum. Risk factors that have been shown to be of importance in previous studies outside New Zealand were not identified as important in the current study. It is possible that, in the situation where calves are kept at pasture with their dams for prolonged periods, variables which influence how well a cow can feed its calf in the first 12-24 hours have a larger influence on concentrations of TP in serum than the collection and management of calves once they reach the rearing shed.

Ligand Noninnocence in Iron Corroles: Insights from Optical and X-ray Absorption Spectroscopies and Electrochemical Redox Potentials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganguly, Sumit; Giles, Logan J.; Thomas, Kolle E.

Two new series of iron meso-tris(para-X-phenyl)corrole (TpXPC) complexes, Fe[TpXPC]Ph and Fe[TpXPC]Tol, in which X=CF 3, H, Me, and OMe, and Tol=p-methylphenyl (p-tolyl), have been synthesized, allowing a multitechnique electronic–structural comparison with the corresponding FeCl, FeNO, and Fe 2(μ-O) TpXPC derivatives. Optical spectroscopy revealed that the Soret maxima of the FePh and FeTol series are insensitive to the phenyl para substituent, consistent with the presumed innocence of the corrole ligand in these compounds. Accordingly, we may be increasingly confident in the ability of the substituent effect criterion to serve as a probe of corrole noninnocence. Furthermore, four complexes—Fe[TPC]Cl, Fe[TPC](NO), {Fe[TPC]} 2O,more » and Fe[TPC]Ph—were selected for a detailed XANES investigation of the question of ligand noninnocence. The intensity-weighted average energy (IWAE) positions were found to exhibit rather modest variations (0.8 eV over the series of corroles). The integrated Fe-K pre-edge intensities, on the other hand, vary considerably, with a 2.5 fold increase for Fe[TPC]Ph relative to Fe[TPC]Cl and Fe[TPC](NO). Given the approximately C 4v local symmetry of the Fe in all the complexes, the large increase in intensity for Fe[TPC]Ph may be attributed to a higher number of 3d holes, consistent with an expected Fe IV-like description, in contrast to Fe[TPC]Cl and Fe[TPC](NO), in which the Fe is thought to be Fe III-like. In conclusion, these results afford strong validation of XANES as a probe of ligand noninnocence in metallocorroles. Electrochemical redox potentials, on the other hand, were found not to afford a simple probe of ligand noninnocence in Fe corroles.« less

Ligand Noninnocence in Iron Corroles: Insights from Optical and X-ray Absorption Spectroscopies and Electrochemical Redox Potentials

DOE PAGES

Ganguly, Sumit; Giles, Logan J.; Thomas, Kolle E.; ...

2017-10-06

Two new series of iron meso-tris(para-X-phenyl)corrole (TpXPC) complexes, Fe[TpXPC]Ph and Fe[TpXPC]Tol, in which X=CF 3, H, Me, and OMe, and Tol=p-methylphenyl (p-tolyl), have been synthesized, allowing a multitechnique electronic–structural comparison with the corresponding FeCl, FeNO, and Fe 2(μ-O) TpXPC derivatives. Optical spectroscopy revealed that the Soret maxima of the FePh and FeTol series are insensitive to the phenyl para substituent, consistent with the presumed innocence of the corrole ligand in these compounds. Accordingly, we may be increasingly confident in the ability of the substituent effect criterion to serve as a probe of corrole noninnocence. Furthermore, four complexes—Fe[TPC]Cl, Fe[TPC](NO), {Fe[TPC]} 2O,more » and Fe[TPC]Ph—were selected for a detailed XANES investigation of the question of ligand noninnocence. The intensity-weighted average energy (IWAE) positions were found to exhibit rather modest variations (0.8 eV over the series of corroles). The integrated Fe-K pre-edge intensities, on the other hand, vary considerably, with a 2.5 fold increase for Fe[TPC]Ph relative to Fe[TPC]Cl and Fe[TPC](NO). Given the approximately C 4v local symmetry of the Fe in all the complexes, the large increase in intensity for Fe[TPC]Ph may be attributed to a higher number of 3d holes, consistent with an expected Fe IV-like description, in contrast to Fe[TPC]Cl and Fe[TPC](NO), in which the Fe is thought to be Fe III-like. In conclusion, these results afford strong validation of XANES as a probe of ligand noninnocence in metallocorroles. Electrochemical redox potentials, on the other hand, were found not to afford a simple probe of ligand noninnocence in Fe corroles.« less

The p53 Isoform Δ133p53β Promotes Cancer Stem Cell Potential

PubMed Central

Arsic, Nikola; Gadea, Gilles; Lagerqvist, E. Louise; Busson, Muriel; Cahuzac, Nathalie; Brock, Carsten; Hollande, Frederic; Gire, Veronique; Pannequin, Julie; Roux, Pierre

2015-01-01

Summary Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Δ133p53β, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. Δ133p53β stimulated the expression of the key pluripotency factors SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells, aggressiveness was coupled with enhanced CSC potential and Δ133p53β expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were positively regulated by Δ133p53β in these cells. Finally, treatment of MCF-7 cells with etoposide, a cytotoxic anti-cancer drug, increased CSC formation and SOX2, OCT3/4, and NANOG expression via Δ133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that Δ133p53β supports CSC potential. Moreover, they indicate that the TP53 gene, which is considered a major tumor suppressor gene, also acts as an oncogene via the Δ133p53β isoform. PMID:25754205

Spontaneous and radiation-induced genomic instability in human cell lines differing in cellular TP53 status.

PubMed

Moore, Stephen R; Ritter, Linda E; Gibbons, Catherine F; Grosovsky, Andrew J

2005-10-01

Structural chromosomal rearrangements are commonly observed in tumor karyotypes and in radiation-induced genomic instability. Here we report the effects of TP53 deficiency on karyotypic stability before and after irradiation using related cells and clones differing in cellular TP53 status. The parental cell line, TK6, is a TP53 wild-type human B-lymphoblastoid line with a highly stable karyotype. In the two TK6 derivatives used here, TP53 has been inactivated by biochemical means (expression of HPV16 E6; TK6-5E) or genetic means (allelic inactivation; NH32). Biochemical inactivation of TP53 (TK6-5E) had little effect on the spontaneous karyotype, whereas allelic inactivation of TP53 (NH32) resulted in a modest increase in spontaneous karyotypic instability. After 2 Gy gamma irradiation, the number of unstable clones derived from TP53-deficient cells was significantly elevated compared to the TP53 wild-type counterpart. Extensively destabilized clones were common after irradiation in the set of clones derived from NH32 cells, and one was observed in the set of TK6-5E clones; however, they were never observed in TK6-derived clones. In two of the irradiated NH32 clones, whole chromosomes or chromosome bands were preferentially involved in alterations. These results suggest that genomic instability may differ both quantitatively and qualitatively as a consequence of altered TP53 expression. Some of the results showing repeated and preferential chromosome involvement in aberrations support a model in which instability may be driven by cis mechanisms.

Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P-gp In Vitro.

PubMed

Li, Zhihua; Yan, Miao; Cao, Lingjuan; Fang, Pingfei; Guo, Zhaohui; Hou, Zhenyan; Zhang, Bikui

2017-07-01

Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process. An ultra performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) analytical method was established to determine the intracellular concentration of TP. In order to study the role of efflux transporters of P-gp and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results showed that GA could enhance the elimination of TP and reduce the TP accumulation in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration of TP; in addition, GA co-incubation with verapamil significantly increased the TP cellular concentration compared with the control group. In conclusion, GA could reduce the accumulation of TP in HK-2 cells, which was related to P-gp. This is probably one of the mechanisms that TP combined with GA to detoxify its toxicity. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.