The impact of Pu speciation on distribution coefficients in Mayak soil.

PubMed

Skipperud, L; Oughton, D; Salbu, B

2000-08-10

To assess the long-term consequences when radionuclides are released into the environment, information on the source term, transport and transformation processes, interaction with soils (KD) and biological uptake (CF) is needed. Among the artificial radionuclides released to the environment by nuclear activities, the transuranium elements are a major concern, due to very long half-lives and their accumulation in bone as well as high radiotoxicity. Plutonium has been produced in greater quantity than other transuranic elements, however, environmental assessments are complicated by the complex environmental behaviour. Physico-chemical forms of Pu will determine the interactions with soils and, thus, the degree to which soils can act as a sink or a potential diffuse source of contaminants. In the present work, dynamic tracer experiments have been performed where different Pu-species are added to a 'Mayak soil-rainwater system' to obtain information on KD values. After a defined contact time, the samples where then sequentially extracted and results are used in a dynamic box model to estimate interaction and fixation rates. The interaction of all Pu-species with soils seems to be rapid and follows a two-step reaction. Up to contact times of a few weeks, the KD for Pu(III,IV) (730 +/- 240 l/kg) is approximately one order of magnitude higher than for Pu(V,VI) (90 +/- 20 l/kg) and Pu(III,IV)-organic (40-60 l/kg). After 3 months contact time, the KD in only the two organic-bound Pu-species were significantly lower. This shows that the initial association with the soil is dependent on the Pu-species in the rainwater. After only 1 h of contact, between 33 and 40% of the plutonium was strongly bound to the soil components, i.e. only extractable with strong HNO3. The extraction of soil-bound Pu followed a similar pattern for all the original species, suggesting that the next step of Pu interaction mechanism with soil was rather independent of the original species. For both the Pu(V,VI) and Pu-organic species, the rainwater-desorption extract gave consistently higher KD values than that calculated from the rainwater-sorption data; whereas for Pu(III,IV), desorption KD values were more similar to sorption KD values. This supports the suggestion that the observed difference in Pu adsorption to soils reflects Pu-speciation in the water soluble phase, and that actual soil-Pu interactions are rather independent of the original speciation. Modelling of the extraction data show a different in association rate for the different Pu species, where the Pu(III,IV) has the fastest association rate as expected.

Quantification of Protein-Ligand Interactions by Laser Electrospray Mass Spectrometry

NASA Astrophysics Data System (ADS)

Archer, Jieutonne J.; Karki, Santosh; Shi, Fengjian; Sistani, Habiballah; Levis, Robert J.

2018-04-01

Laser electrospray mass spectrometry (LEMS) measurement of the dissociation constant (Kd) for hen egg white lysozyme (HEWL) and N,N',N″-triacetylchitotriose (NAG3) revealed an apparent Kd value of 313.2 ± 25.9 μM for the ligand titration method. Similar measurements for N,N',N″,N″'-tetraacetylchitotetraose (NAG4) revealed an apparent Kd of 249.3 ± 13.6 μM. An electrospray ionization mass spectrometry (ESI-MS) experiment determined a Kd value of 9.8 ± 0.6 μM. In a second LEMS approach, a calibrated measurement was used to determine a Kd value of 6.8 ± 1.5 μM for NAG3. The capture efficiency of LEMS was measured to be 3.6 ± 1.8% and is defined as the fraction of LEMS sample detected after merging with the ESI plume. When the dilution is factored into the ligand titration measurement, the adjusted Kd value was 11.3 μM for NAG3 and 9.0 μM for NAG4. The calibration method for measuring Kd developed in this study can be applied to solutions containing unknown analyte concentrations. [Figure not available: see fulltext.

Distribution coefficients (Kd's) for use in risk assessment models of the Kara Sea.

PubMed

Carroll, J; Boisson, F; Teyssie, J L; King, S E; Krosshavn, M; Carroll, M L; Fowler, S W; Povinec, P P; Baxter, M S

1999-07-01

As a prerequisite for most evaluations of radionuclide transport pathways in marine systems, it is necessary to obtain basic information on the sorption potential of contaminants onto particulate matter. Kd values for use in modeling radionuclide dispersion in the Kara Sea have been determined as part of several international programs addressing the problem of radioactive debris residing in Arctic Seas. Field and laboratory Kd experiments were conducted for the following radionuclides associated with nuclear waste: americium, europium, plutonium, cobalt, cesium and strontium. Emphasis has been placed on two regions in the Kara Sea: (i) the Novaya Zemlya Trough (NZT) and (ii) the mixing zones of the Ob and Yenisey Rivers (RMZ). Short-term batch Kd experiments were performed at-sea on ambient water column samples and on samples prepared both at-sea and in the laboratory by mixing filtered bottom water with small amounts of surficial bottom sediments (particle concentrations in samples = 1-30 mg/l). Within both regions, Kd values for individual radionuclides vary over two to three orders of magnitude. The relative particle affinities for radionuclides in the two regions are americium approximately equal to europium > plutonium > cobalt > cesium > strontium. The values determined in this study agree with minimum values given in the IAEA Technical Report [IAEA, 1985. Sediment Kd's and Concentration Factors for Radionuclides in the Marine Environment. Technical Report No. 247. International Atomic Energy Agency, Vienna.]. Given the importance of Kd's in assessments of critical transport pathways for radionuclide contaminants, we recommend that Kd ranges of values for specific elements rather than single mean values be incorporated into model simulations of radionuclide dispersion.

New best estimates for radionuclide solid-liquid distribution coefficients in soils. Part 2: naturally occurring radionuclides.

PubMed

Vandenhove, H; Gil-García, C; Rigol, A; Vidal, M

2009-09-01

Predicting the transfer of radionuclides in the environment for normal release, accidental, disposal or remediation scenarios in order to assess exposure requires the availability of an important number of generic parameter values. One of the key parameters in environmental assessment is the solid liquid distribution coefficient, K(d), which is used to predict radionuclide-soil interaction and subsequent radionuclide transport in the soil column. This article presents a review of K(d) values for uranium, radium, lead, polonium and thorium based on an extensive literature survey, including recent publications. The K(d) estimates were presented per soil groups defined by their texture and organic matter content (Sand, Loam, Clay and Organic), although the texture class seemed not to significantly affect K(d). Where relevant, other K(d) classification systems are proposed and correlations with soil parameters are highlighted. The K(d) values obtained in this compilation are compared with earlier review data.

The importance of organic matter distribution and extract soil:solution ratio on the desorption of heavy metals from soils.

PubMed

Yin, Yujun; Impellitteri, Christopher A; You, Sun-Jae; Allen, Herbert E

2002-03-15

The lability (mobility and bioavailability) of metals varies significantly with soil properties for similar total soil metal concentrations. We studied desorption of Cu, Ni and Zn, from 15 diverse, unamended soils. These studies included evaluation of the effects of soil:solution extraction ratio and the roles of soil properties on metal desorption. Dcsorption was examined for each metal by computing distribution coefficients (Kd) for each metal in each soil where Kd = [M]soil/[M]solution, Results from soil:solution ratio studies demonstrated that Kd values for the metals tended to increase with increasing soil:solution ratio. This result also held true for distribution of soil organic matter (SOM). Because the soil:solution ratio has a significant effect on measured metal distributions, we selected a high soil:solution ratio to more closely approach natural soil conditions. Copper showed strong affinity to operationally defined dissolved organic matter (DOM). In this study, DOM was operationally defined based on the total organic carbon (TOC) content in 0.45-microm or 0.22-microm filtrates of the extracts. The Kd of Cu correlated linearly (r2 = 0.91) with the Kd of organic matter (Kd-om) where the Kd-om is equal to SOM as measured by Walkley-Black wet combustion and converted to total carbon (TC) by a factor of 0.59. These values representing solid phase TC were then divided by soluble organic carbon as measured by TOC analysis (DOM). The conversion factor of 0.59 was employed in order to construct Kd-om values based on solid phase carbon and solution phase carbon. SOM plays a significant role in the fate of Cu in soil systems. Soil-solution distribution of Ni and Zn, as well as the activity of free Cu2+, were closely related to SOM, but not to DOM. Kd values for Ni, Zn and free Cu2+ in a particular soil were divided by the SOM content in the same soil. This normalization of the Kd values for Ni, Zn, and free Cu2+ to the SOM content resulted in significant improvements in the linear relationships between non-normalized Kd values and soil pH. The semi-empirical normalized regression equations can be used to predict the solubility of Ni and Zn and the activity of free Cu2+ as a function of pH.

King-Devick Test reference values and associations with balance measures in high school American football players.

PubMed

Alsalaheen, B; Haines, J; Yorke, A; Diebold, J

2016-02-01

The King-Devick test appears to be a promising tool in screening for concussions. However, limited evidence exists on the baseline associations between the K-D test and age and baseline screening tools used after concussion. Additionally, there are no published reference values for the K-D test in high school football players. The K-D test, the Balance Error Scoring System, and the Limits of Stability (LOS) test were administered to 157 high school football players. Additionally, a subsample of 62 participants completed the test twice to examine the reliability of K-D test. There was no relationship between the K-D test and the BESS, or the reaction time and directional control of LOS test. Students aged between 16 and 18 years demonstrated faster K-D test performance compared to students between 13 and 15 years of age. However, there was no association between K-D test and history of concussion. The reliability of the K-D test was (ICC2,1 = 0.89), and the minimal detectable change was 6.10 s. Normative reference values for high school football players are presented in this study. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.

PubMed

Jaggi, Preeti; Mejias, Asuncion; Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C; Tremoulet, Adriana H; Jordan-Villegas, Alejandro; Chaussabel, Damien; Texter, Karen; Pascual, Virginia; Ramilo, Octavio

2018-01-01

Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease

PubMed Central

Xu, Zhaohui; Yin, Han; Moore-Clingenpeel, Melissa; Smith, Bennett; Burns, Jane C.; Tremoulet, Adriana H.; Jordan-Villegas, Alejandro; Chaussabel, Damien; Texter, Karen; Pascual, Virginia; Ramilo, Octavio

2018-01-01

Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG. PMID:29813106

A review of the distribution coefficients of trace elements in soils: influence of sorption system, element characteristics, and soil colloidal properties.

PubMed

Shaheen, Sabry M; Tsadilas, Christos D; Rinklebe, Jörg

2013-12-01

Knowledge about the behavior and reactions of separate soil components with trace elements (TEs) and their distribution coefficients (Kds) in soils is a key issue in assessing the mobility and retention of TEs. Thus, the fate of TEs and the toxic risk they pose depend crucially on their Kd in soil. This article reviews the Kd of TEs in soils as affected by the sorption system, element characteristics, and soil colloidal properties. The sorption mechanism, determining factors, favorable conditions, and competitive ions on the sorption and Kd of TEs are also discussed here. This review demonstrates that the Kd value of TEs does not only depend on inorganic and organic soil constituents, but also on the nature and characteristics of the elements involved as well as on their competition for sorption sites. The Kd value of TEs is mainly affected by individual or competitive sorption systems. Generally, the sorption in competitive systems is lower than in mono-metal sorption systems. More strongly sorbed elements, such as Pb and Cu, are less affected by competition than mobile elements, such as Cd, Ni, and Zn. The sorption preference exhibited by soils for elements over others may be due to: (i) the hydrolysis constant, (ii) the atomic weight, (iii) the ionic radius, and subsequently the hydrated radius, and (iv) its Misono softness value. Moreover, element concentrations in the test solution mainly affect the Kd values. Mostly, values of Kd decrease as the concentration of the included cation increases in the test solution. Additionally, the Kd of TEs is controlled by the sorption characteristics of soils, such as pH, clay minerals, soil organic matter, Fe and Mn oxides, and calcium carbonate. However, more research is required to verify the practical utilization of studying Kd of TEs in soils as a reliable indicator for assessing the remediation process of toxic metals in soils and waters. © 2013 Elsevier B.V. All rights reserved.

Sorption and desorption of carbamazepine, naproxen and triclosan in a soil irrigated with raw wastewater: estimation of the sorption parameters by considering the initial mass of the compounds in the soil.

PubMed

Durán-Álvarez, Juan C; Prado-Pano, Blanca; Jiménez-Cisneros, Blanca

2012-06-01

In conventional sorption studies, the prior presence of contaminants in the soil is not considered when estimating the sorption parameters because this is only a transient state. However, this parameter should be considered in order to avoid the under/overestimation of the soil sorption capacity. In this study, the sorption of naproxen, carbamazepine and triclosan was determined in a wastewater irrigated soil, considering the initial mass of the compounds. Batch sorption-desorption tests were carried out at two soil depths (0-10 cm and 30-40 cm), using either 10 mM CaCl(2) solution or untreated wastewater as the liquid phase. Data were satisfactorily fitted to the initial mass model. For the two soils, release of naproxen and carbamazepine was observed when the CaCl(2) solution was used, but not in the soil/wastewater system. The compounds' release was higher in the topsoil than in the 30-40 cm soil. Sorption coefficients (K(d)) for CaCl(2) solution tests showed that in the topsoil, triclosan (64.9 L kg(-1)) is sorbed to a higher extent than carbamazepine and naproxen (5.81 and 2.39 L kg(-1), respectively). In the 30-40 cm soil, carbamazepine and naproxen K(d) values (11.4 and 4.41 L kg(-1), respectively) were higher than those obtained for the topsoil, while the triclosan K(d) value was significantly lower than in the topsoil (19.2 L kg(-1)). Differences in K(d) values were found when comparing the results obtained for the two liquid phases. Sorption of naproxen and carbamazepine was reversible for both soils, while sorption of triclosan was found to be irreversible. This study shows the sorption behavior of three pharmaceuticals in a wastewater irrigated soil, as well as the importance of considering the initial mass of target pollutants in the estimation of their sorption parameters. Copyright © 2012 Elsevier Ltd. All rights reserved.

Carotid Intima-Media Thickness and Lipid Profile in Children With Kawasaki Disease: A Single-Center Follow-up Study After a Mean Duration of 6.9 Years.

PubMed

Gopalan, Kavitha; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar; Attri, Savita Verma

2018-03-13

Kawasaki disease (KD) has a predilection to involve coronary arteries, leading to several long-term cardiovascular sequelae. Apart from coronary artery abnormalities, children with KD are also prone to develop premature atherosclerosis, endothelial dysfunction, and lipid abnormalities. Some of these complications may occur even in children who have received appropriate treatment with intravenous immunoglobulin in the acute phase. In 2009, we had studied carotid intima-media thickness (cIMT) and lipid profile in 27 children with KD at least 1 year after the acute episode. In the present study, we have followed up the same cohort of 27 children at least 5 years after the acute episode of KD. We measured the cIMT, a surrogate marker for premature atherosclerosis, and fasting lipid profile in the cohort and compared the results with values obtained in our previous study. There was significantly higher mean cIMT in children with KD as compared with control subjects. However, there was no significant difference in cIMT among children in the cohort at 1 and 5 years of follow-up. Abnormal lipid profile was seen in 7 of 27 children in the present study, 5 of whom also had had lipid abnormality at 1-year follow-up. This suggests that lipid abnormalities in KD may be long lasting. Children with KD need careful long-term follow-up even when they do not have overt and persistent coronary artery abnormalities. It is possible that consequences of KD in childhood may impact health status of young adults several years later.

Usefulness of Age-Stratified N-Terminal Prohormone of Brain Natriuretic Peptide for Diagnosing Kawasaki Disease

PubMed Central

Lee, Sang Hoon; Yoon, Somy; Hong, Seunghee; Yang, Eun Mi; Eom, Gwang Hyeon

2017-01-01

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited Chonnam National University Hospital between December 2007 and March 2016. The KD groups consisted of 214 patients with complete KD and 129 patients with incomplete KD. The control group included 62 children with simple febrile illness but without heart disease. Laboratory data including NT-proBNP level were evaluated. Each group was divided into subgroups according to patient age (<6 months, 6–12 months, 12–24 months, and >24 months), and different cutoff values of NT-proBNP were calculated. The cutoff values of NT-proBNP used to diagnose total KD and incomplete KD were 762 and 762 pg/mL (<6 months), 310 and 310 pg/mL (6–12 months), 326 and 326 pg/mL (12–24 months), and 208 and 137 pg/mL (>24 months), respectively. In conclusion, age-stratified NT-proBNP is a useful biomarker for the differential diagnosis of KD in patients with a simple febrile illness. PMID:29358841

Uranium partition coefficients (Kd) in forest surface soil reveal long equilibrium times and vary by site and soil size fraction.

PubMed

Whicker, Jeffrey J; Pinder, John E; Ibrahim, Shawki A; Stone, James M; Breshears, David D; Baker, Kristine N

2007-07-01

The environmental mobility of newly deposited radionuclides in surface soil is driven by complex biogeochemical relationships, which have significant impacts on transport pathways. The partition coefficient (Kd) is useful for characterizing the soil-solution exchange kinetics and is an important factor for predicting relative amounts of a radionuclide transported to groundwater compared to that remaining on soil surfaces and thus available for transport through erosion processes. Measurements of Kd for 238U are particularly useful because of the extensive use of 238U in military applications and associated testing, such as done at Los Alamos National Laboratory (LANL). Site-specific measurements of Kd for 238U are needed because Kd is highly dependent on local soil conditions and also on the fine soil fraction because 238U concentrates onto smaller soil particles, such as clays and soil organic material, which are most susceptible to wind erosion and contribute to inhalation exposure in off-site populations. We measured Kd for uranium in soils from two neighboring semiarid forest sites at LANL using a U.S. Environmental Protection Agency (EPA)-based protocol for both whole soil and the fine soil fraction (diameters<45 microm). The 7-d Kd values, which are those specified in the EPA protocol, ranged from 276-508 mL g-1 for whole soil and from 615-2249 mL g-1 for the fine soil fraction. Unexpectedly, the 30-d Kd values, measured to test for soil-solution exchange equilibrium, were more than two times the 7-d values. Rates of adsorption of 238U to soil from solution were derived using a 2-component (FAST and SLOW) exponential model. We found significant differences in Kd values among LANL sampling sites, between whole and fine soils, and between 7-d and 30-d Kd measurements. The significant variation in soil-solution exchange kinetics among the soils and soil sizes promotes the use of site-specific data for estimates of environmental transport rates and suggests possible differences in desorption rates from soil to solution (e.g., into groundwater or lung fluid). We also explore potential relationships between wind erosion, soil characteristics, and Kd values. Combined, our results highlight the need for a better mechanistic understanding of soil-solution partitioning kinetics for accurate risk assessment.

Kd Values for Agricultural and Surface Soils for Use in Hanford Site Farm, Residential, and River Shoreline Scenarios

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

Serne, R. Jeffrey

This report provides best estimate Kd values and a minimum and maximum range of Kd values to be used for agricultural soils and Columbia River bank sediments that exist today or would exist in the future when portions of the Hanford Site are released for farming, residential, and recreational use after the U. S. Department of Energy (DOE) completes clean up of defense waste on the site. The Kd values should be used to determine the fate and transport rates of contaminants and their availability for plant and animal uptake in selected non-groundwater scenarios included in Hanford Site environmental impactmore » statements, risk assessments and specific facility performance assessments. This report describes scenarios such as a small farm where drilling of a well inadvertently goes through buried waste and brings waste to the surface, allowing the tailings to become available for direct human exposure or incorporation into garden crops and farm animals used for food by the farm family. The Kd values recommended in this report can also be used to calculate sediment-water partitioning factors used to predict plant and animal uptake from interaction with the contaminated soil.« less

Clinical association between Kikuchi׳s disease and systemic lupus erythematosus: A systematic literature review.

PubMed

Sopeña, Bernardo; Rivera, Alberto; Chamorro, Antonio; Freire, Mayka; Alende, Vanessa; Seco, Elena; González-Gay, Miguel A; González-Quintela, Arturo

2017-08-01

To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE). We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients. The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio = 5.0); mean age at diagnosis was 34 years (range: 14-56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis. While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

K-Means Algorithm Performance Analysis With Determining The Value Of Starting Centroid With Random And KD-Tree Method

NASA Astrophysics Data System (ADS)

Sirait, Kamson; Tulus; Budhiarti Nababan, Erna

2017-12-01

Clustering methods that have high accuracy and time efficiency are necessary for the filtering process. One method that has been known and applied in clustering is K-Means Clustering. In its application, the determination of the begining value of the cluster center greatly affects the results of the K-Means algorithm. This research discusses the results of K-Means Clustering with starting centroid determination with a random and KD-Tree method. The initial determination of random centroid on the data set of 1000 student academic data to classify the potentially dropout has a sse value of 952972 for the quality variable and 232.48 for the GPA, whereas the initial centroid determination by KD-Tree has a sse value of 504302 for the quality variable and 214,37 for the GPA variable. The smaller sse values indicate that the result of K-Means Clustering with initial KD-Tree centroid selection have better accuracy than K-Means Clustering method with random initial centorid selection.

Measurement of density and affinity for dopamine D2 receptors by a single positron emission tomography scan with multiple injections of [11C]raclopride

PubMed Central

Ikoma, Yoko; Watabe, Hiroshi; Hayashi, Takuya; Miyake, Yoshinori; Teramoto, Noboru; Minato, Kotaro; Iida, Hidehiro

2010-01-01

Positron emission tomography (PET) with [11C]raclopride has been used to investigate the density (Bmax) and affinity (Kd) of dopamine D2 receptors related to several neurological and psychiatric disorders. However, in assessing the Bmax and Kd, multiple PET scans are necessary under variable specific activities of administered [11C]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the Bmax and Kd values from a single PET scan with three sequential injections of [11C]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of Bmax and Kd estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of Bmax and Kd, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the Bmax and Kd of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [11C]raclopride. Estimated Bmax and Kd values of D2 receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values. PMID:19904285

Influence of soil biochar aging on sorption of the herbicides MCPA, nicosulfuron, terbuthylazine, indaziflam, and fluoroethyldiaminotriazine.

PubMed

Trigo, Carmen; Spokas, Kurt A; Cox, Lucia; Koskinen, William C

2014-11-12

Sorption of four herbicides and a metabolite of indaziflam on a fresh macadamia nut biochar and biochars aged one or two years in soil was characterized. On fresh biochar, the sorption was terbuthylazine (Kd = 595) > indaziflam (Kd = 162) > MCPA (Kd = 7.5) > fluoroethyldiaminotriazine (Kd = 0.26) and nicosulfuron (Kd = 0). Biochar surface area increased with aging attributed to the loss of a surface film. This was also manifested in a decline in water extractable organic carbon with aging. Correspondingly, an increase in the aromaticity was observed. The higher surface area and porosity in aged biochar increased sorption of indaziflam (KdBC-2yr = 237) and fluoroethyldiaminotriazine (KdBC-1yr = 1.2 and KdBC-2yr = 3.0), but interestingly decreased sorption of terbuthylazine (KdBC-1yr = 312 and KdBC-2yr = 221) and MCPA (KdBC-1yr = 2 and KdBC-2yr = 2). These results will facilitate development of biochars for specific remediation purposes.

Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver.

PubMed

Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

2015-12-05

Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LFD). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% down-regulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.

PubMed

Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M; Pissios, Pavlos; Flier, Jeffrey S; Cantley, Lewis C; Locasale, Jason W; Maratos-Flier, Eleftheria

2015-10-01

Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice. Copyright © 2015. Published by Elsevier B.V.

Sociodemographic profile of children with Kawasaki disease in North India.

PubMed

Prakash, Jeya; Singh, Surjit; Gupta, Anju; Bharti, Bhavneet; Bhalla, A K

2016-03-01

Kawasaki disease (KD) is now the commonest cause of acquired heart disease in children in developed countries. KD occurs all over the world, including developing countries. The present study steps out to explore our hypothesis, driven by clinical observation over the last 18 years, whether children with KD in North India are of a higher socioeconomic status than children with other rheumatologic diseases. One hundred consecutive children with KD, registered in Pediatric Rheumatology Clinic before January 2011, were enrolled as cases. Children with other rheumatologic diseases were taken as controls. Assessment of socioeconomic status was done by administering the Aggarwal scale. Data were collected through interview. Statistical analysis was done using SPSS package version 16. On univariate analysis, male sex, higher educational status of parents, urban residence, immunization status being complete, and higher scores on Aggarwal scale were found to be significantly associated with KD. On multivariate analysis, only male sex and urban residence were found to be significantly associated with KD (p < 0.001). Families of children with KD tend to have a better sociodemographic profile when compared with other pediatric rheumatologic disorders in North India. These results, however, need to be replicated in a multicentric study for any firm conclusions to be drawn.

Thrombospondin-2 predicts response to treatment with intravenous immunoglobulin in children with Kawasaki disease.

PubMed

Yang, Shuai; Song, Ruixia; Li, Xiaohui; Zhang, Ting; Fu, Jin; Cui, Xiaodai

2018-01-01

To investigate the predictive value of thrombospondin-2 (TSP-2) in assessing the response to intravenous immunoglobulin (IVIG) in children with acute Kawasaki disease (KD). This was a cohort study with controls. 71 children with KD were recruited as the case group, including IVIG non-responder (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile children (n=30) were used as control groups. ELISA was used to measure plasma TSP-2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally distributed data. Predictive value was evaluated through the receiver operating characteristic (ROC) curve. Compared with the control groups, the plasma TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28) vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2 level in the IVIG non-responder was significantly higher than the responder group (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the specificity was 64.81%. The plasma TSP-2 level was elevated in acute KD and it might be a novel predictor for IVIG resistance, which could help guide clinicians to choose individualised initial therapeutic regimens.

Europium-labeled epidermal growth factor and neurotensin: novel probes for receptor-binding studies.

PubMed

Mazor, Ohad; Hillairet de Boisferon, Marc; Lombet, Alain; Gruaz-Guyon, Anne; Gayer, Batya; Skrzydelsky, Delphine; Kohen, Fortune; Forgez, Patricia; Scherz, Avigdor; Rostene, William; Salomon, Yoram

2002-02-01

We investigated the possibility of labeling two biologically active peptides, epidermal growth factor (EGF) and neurotensin (NT), with europium (Eu)-diethylenetriaminepentaacetic acid. More specifically, we tested them as probes in studying receptor binding using time-resolved fluorescence of Eu3+. The relatively simple synthesis yields ligands with acceptable binding characteristics similar to isotopically labeled derivatives. The binding affinity (Kd) of labeled Eu-EGF to human A431 epidermal carcinoid cells was 3.6 +/- 1.2 nM, similar to the reported Kd values of EGF, whereas the Kd of Eu-NT to human HT29 colon cancer cells (7.4 +/- 0.5 nM) or to Chinese hamster ovary (CHO) cells transfected with the high-affinity NT receptor (CHO-NT1) were about 10-fold higher than the Kd values of NT. The bioactivity of the Eu-labeled EGF as determined by stimulation of cultured murine D1 hematopoietic cell proliferation was nearly the same as that obtained with native EGF. The maximal stimulation of Ca2+ influx with NT and Eu-NT in CHO-NT1 cells was similar, but the respective K0.5 values were 20 pM and 1 nM, corresponding to differences in the binding affinities previously described. The results of these studies indicate that Eu labeling of peptide hormones and growth factor molecules ranging from 10(3) to 10(5) Da can be conveniently accomplished. Importantly, the Eu-labeled products are stable for approximately 2 years and are completely safe for laboratory use compared to the biohazardous radioligands. Thus, Eu-labeled peptides present an attractive alternative for commonly used radiolabeled ligands in biological studies in general and in receptor assays in particular.

Rainfall Lysimeter Evaluation of Leachability and Surface Transport of Heavy Metals From Six Soils With and Without Phosphate Amendment

DTIC Science & Technology

2005-09-01

found no significant change in concentration (+ 5 percent) occurring between 72 and 96 hr. The aqueous metal/ soil solution was then centrifuged and...environment. Soils with high Kd values strongly adsorb the lead onto the soil particles and slow the rate of migration of the lead in the soil solution . A...small Kd suggests faster migration rates and more rapid migration with the soil solution . Comparison of the Kd values obtained shows a large

Determination of the distribution coefficient (log Kd) of oxytetracycline, tylosin A, olaquindox and metronidazole in manure.

PubMed

Loke, Marie-Louise; Tjørnelund, Jette; Halling-Sørensen, Bent

2002-07-01

Olaquindox (log Kow = -2.3) and metronidazole (log Kow = -0.1) both have low tendencies to sorp to particles in manure. This corresponds with the negative log Kow values of these antibiotics. Tylosin (log Kow = 1.63) and oxytetracycline (log Kow = -1.12) sorp relatively strongly to the manure particles and have log Kd values between 1.5 and 2.0. The tendency to bind to manure was ranked after increasing binding as follows: metronidazole < olaquindox < tylosin A and oxytetracycline. This order of ranking is consistent with results of sorption in soil. Our experiments illustrate that for some antibacterial agents estimation of the partitioning coefficients, Kd, cannot be made from Kow and f(oc) alone. Sorption of oxytetracycline to manure is much higher than expected from the negative log Kow value of the compound. It is believed that sorption of oxytetracycline to manure is influenced by ionic binding to divalent metal ions as such Mg2+ and Ca2+ as well as other charged compounds in the matrix. Binding of oxytetracycline to soil is stronger than the binding to manure. This is most likely due to the strong mineral related metal complexes formed between soil, metal ion and oxytetracycline. These complexes are not known to exist in manure. The relatively strong sorption of tylosin A to manure corresponds with data found for soil sorption of tylosin. Tylosin has a log Kow value of 2.5, thus it is not surprising that this drug binds strongly to manure.

The King-Devick (K-D) test and concussion diagnosis in semi-professional rugby union players.

PubMed

Molloy, John H; Murphy, Ian; Gissane, Conor

2017-08-01

To determine the utility of the King-Devick (K-D) test in identifying sports-related concussion in semi-professional rugby players. Descriptive cohort study. 176 male players were recruited from a semi-professional rugby union competition in New Zealand (NZ). Baseline K-D scores were obtained in the pre-season. Post-match K-D and Pitch Side Concussion Assessment Version 2 (PSCA2) scores were obtained in those with suspected concussion. Post-match K-D scores were also administered to selected control players. 19 concussions in 18 players were analysed. In addition, 33 controls were used for analysis. A positive K-D test was identified in 53% of players with concussion post-match. Conversely, a positive test was identified in 33% of controls. The sensitivity and specificity of the K-D test was calculated as 53% and 69% respectively. The positive predictive value and negative predictive value was 48% and 73% respectively. The PSCA2 correctly identified 74% of concussions. The K-D test identified 3 cases not identified by the PSCA2. When the PSCA2 and K-D were combined, 89% of concussions were correctly identified. The K-D test does not appear to be effective if used as a stand-alone test for the diagnosis of concussion. However, if used alongside current side-line cognitive and balance tests, it may assist in more accurately diagnosing sports-related concussion. Further research should look to utilise the K-D test in in-match protocols to establish if this improves the diagnostic accuracy of in-match protocols for sports-related concussion. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Diffuse attenuation coefficient for downwelling irradiance at 490 nm and its spectral characteristics in the Black Sea upper layer: modeling, in situ measurements and ocean color data

NASA Astrophysics Data System (ADS)

Suslin, V. V.; Slabakova, V. K.; Churilova, T. Ya.

2017-11-01

Vertical diffuse attenuation coefficient, Kd(490), is one of the key parameter required for water quality modeling, hydrodynamic and biological processes in the sea. We showed that standard level-2 product of Kd(490) was underestimated in comparison with Kd(490) values simulated by the regional model during the diatom bloom in the Black Sea. Using data of SeaWiFS, MERIS and MODIS color scanners, a regional relationship between the model value of Kd(490) and the ratio of remote sensing reflectances has been obtained. Based on the bulgarian argo-bio-buoy dataset, the relationship between the attenuation coefficient of photosynthetically active radiation and attenuation coefficient at a wavelength of 490 nm is obtained. The simplified model, below as the S-model, of the diffuse attenuation coefficient spectrum for downwelling irradiance in the Black Sea upper layer is described. As a consequence of the S-model, the link between the depth of the euphotic zone and Kd(490) has been obtained. It is shown that the Kd(490) values, retrieved from ocean color data with using the regional link and from argo-bio-buoy measurements at depths between 6-20 m, are close to each other.

Extraction chromatographic separations of tantalum and tungsten from hafnium and complex matrix constituents

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

Snow, Mathew S.; Finck, Martha R.; Carney, Kevin P.

2017-02-01

Ta, Hf, and W analyses from complex matrices (including environmental samples) require high purification of these analytes from each other and major/trace matrix constituents, however, current state-of-the-art Ta/Hf/W separations rely on traditional anion exchange approaches that suffer from relatively similar distribution coefficient (Kd) values for these analytes. This work reports assessment of three commercially available extraction chromatographic resins (TEVA, TRU, and UTEVA) for Ta/Hf/W separations. Batch contact studies show differences in Ta/W,Hf Kd values of up to 106, representing an improvement of a factor of 100 and 300 in Ta/Hf and Ta/W Kd values (respectively) over AG1x4 resin. Variations inmore » the Kd values as a function of HCl concentration for TRU resin show that this resin is well suited for Ta/Hf/W separations, with Ta/Hf, Ta/W, and W/Hf Kd value improvements of 10, 200, and 30 (respectively) over AG1x4 resin. Finally, analyses of digested soil samples (NIST 2710a) using TRU resin and tandem TEVA-TRU columns demonstrate the ability to achieve extremely high purification (>99%) of Ta and W from each other and Hf, as well as enabling very high purification of Ta and W from the major and trace elemental constituents present in soils, using a single chromatographic step.« less

Extraction chromatographic separations of tantalum and tungsten from hafnium and complex matrix constituents

DOE PAGES

Snow, Mathew S.; Finck, Martha R.; Carney, Kevin P.; ...

2017-01-08

Ta, Hf, and W analyses from complex matrices (including environmental samples) require high purification of these analytes from each other and major/trace matrix constituents, but, current state-of-the-art Ta/Hf/W separations rely on traditional anion exchange approaches that suffer from relatively similar distribution coefficient (Kd) values for these analytes. Our work reports assessment of three commercially available extraction chromatographic resins (TEVA, TRU, and UTEVA) for Ta/Hf/W separations. Batch contact studies show differences in Ta/W,Hf Kd values of up to 10 6, representing an improvement of a factor of 100 and 300 in Ta/Hf and Ta/W Kd values (respectively) over AG1x4 resin. Furthermore,more » variations in the Kd values as a function of HCl concentration for TRU resin show that this resin is well suited for Ta/Hf/W separations, with Ta/Hf, Ta/W, and W/Hf Kd value improvements of 10, 200, and 30 (respectively) over AG1x4 resin. Finally, analyses of digested soil samples (NIST 2710a) using TRU resin and tandem TEVA-TRU columns demonstrate the ability to achieve extremely high purification (>99%) of Ta and W from each other and Hf, as well as enabling very high purification of Ta and W from the major and trace elemental constituents present in soils, using a single chromatographic step.« less

Filamin A regulates the organization and remodeling of the pericellular collagen matrix.

PubMed

Mezawa, Masaru; Pinto, Vanessa I; Kazembe, Mwayi P; Lee, Wilson S; McCulloch, Christopher A

2016-10-01

Extracellular matrix remodeling by cell adhesion-related processes is critical for proliferation and tissue homeostasis, but how adhesions and the cytoskeleton interact to organize the pericellular matrix (PCM) is not understood. We examined the role of the actin-binding protein, filamin A (FLNa), in pericellular collagen remodeling. Compared with wild-type (WT), mice with fibroblast-specific deletion of FLNa exhibited higher density but reduced organization of collagen fibers after increased loading of the periodontal ligament for 2 wk. In cultured fibroblasts, FLNa knockdown (KD) did not affect collagen mRNA, but after 24 h of culture, FLNa WT cells exhibited ∼2-fold higher cell-surface collagen KD cells and 13-fold higher levels of activated β1 integrins. In FLNa WT cells, there was 3-fold more colocalization of talin with pericellular cleaved collagen than in FLNa KD cells. MMP-9 mRNA and protein expression were >2-fold higher in FLNa KD cells than in WT cells. Cathepsin B, which is necessary for intracellular collagen digestion, was >3-fold higher in FLNa WT cells than in KD cells. FLNa WT cells exhibited 2-fold more collagen phagocytosis than KD cells, which involved the FLNa actin-binding domain. Evidently, FLNa regulates PCM remodeling through its effects on degradation pathways that affect the abundance and organization of collagen.-Mezawa, M., Pinto, V. I., Kazembe, M. P., Lee, W. S., McCulloch, C. A. Filamin A regulates the organization and remodeling of the pericellular collagen matrix. © FASEB.

Kawasaki Disease Increases the Incidence of Myopia.

PubMed

Kung, Yung-Jen; Wei, Chang-Ching; Chen, Liuh An; Chen, Jiin Yi; Chang, Ching-Yao; Lin, Chao-Jen; Lim, Yun-Ping; Tien, Peng-Tai; Chen, Hsuan-Ju; Huang, Yong-San; Lin, Hui-Ju; Wan, Lei

2017-01-01

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan's National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08-1.58; P < 0.01) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia.

Bioenergy residues as novel sorbents to clean up pesticide pollution

NASA Astrophysics Data System (ADS)

Mukherjee, Santanu

2016-04-01

Worldwide, water contamination from agricultural use of pesticides has received increasing attention within the last decades. In general, sources of pesticide water pollution are categorized into diffuse (stemming from treated fields) and point sources (stemming from farmyards and spillages). Research has demonstrated that 40 to 90% of surface water pesticide contamination is due to point source pollution. To reduce point pollution from farm yards, where the spray equipment is washed, biobed or biofilter systems are used to treat the washing water. The organic material usually used in these systems is often not environmentally sustainable (e.g. peat) and incorporated organic material such as straw leads to a highly heterogeneous water flow, with negative effects on the retention and degradation behavior of the pesticides. Therefore, the objective of this study was to assess the suitability of alternative materials based on bioenergy residues (biochar and digestate) for use in biofilters. To this aim the sorption-desorption potential of three contrasting pesticides (bentazone, boscalid, and pyrimethanil) on mixtures of soil with digestate and/or biochar were investigated in laboratory batch equilibrium experiments. The results indicate that the mixture of digestate and biochar increased pesticide sorption potential, whereby in all cases, the Kd des / Kf des values were lower than the Kd ads / Kf ads values indicating that the retention of the pesticides was weak. Thus, as Kf des were lower than the Kf ads values and H values were below 1, it can be concluded that the biomixtures presented negative desorption (higher hysteresis) in those cases. A higher Kd (>78 L kg-1), Kf (>400 μM1-1/nf L1/nfkg-1) and KL (>40 L kg-1) was obtained for all pesticides for the digestate and biochar based mixtures, which had a higher organic matter content. However, lower sorption of the pesticides was observed in blank soil compared to the other biomixtures, which was attributed to the lower organic carbon content of the blank soil. Our results showed that boscalid and pyrimethanil are highly sorbed to the mixture of digestate and biochar. SUVA254 values justified the aromatic character of digestate (5%) and biochar (5%) mixture which showed highest Koc values among all mixtures for all pesticides. This mixture was found to be the most promising substrate amongst the tested ones for a biobed setup and can be used as an effective and alternative adsorbent for removing pesticides, because of its higher adsorption capacity.

Effect of Time-Dependent Sorption on the Dissipation of Water-Extractable Pesticides in Soils.

PubMed

Motoki, Yutaka; Iwafune, Takashi; Seike, Nobuyasu; Inao, Keiya; Otani, Takashi

2016-06-08

The dissipation behavior of water-extractable pesticides in soils is important when assessing the phytoavailability of pesticides in soils. This process is less understood than pesticide extraction with organic solvents. To elucidate the dissipation behavior of water-extractable pesticides in soils, we conducted an incubation study using 27 pesticides and five Japanese soils. The rate of decrease of the level of pesticides in water extracts was faster in soils than that of total extracts (water extracts and acetone extracts). This suggests that time-dependent sorption contributed to the difference in the dissipation between the pesticides in water and total extracts from soils. Increased apparent sorption coefficients (Kd,app) with time were positively and significantly correlated with Kd,app values of a 0 day incubation [Kd,app(t0)]. This empirical relationship suggests that Kd,app(t0) values can predict the time-dependent increase in Kd,app and the dissipation of water-extractable pesticides in soils.

The Insecticide Susceptibility Status of Aedes aegypti (Diptera: Culicidae) in Farm and Nonfarm Sites of Lagos State, Nigeria

PubMed Central

Ayorinde, A.; Oboh, B.; Oduola, A.; Otubanjo, O.

2015-01-01

Nigeria is one of the malaria-endemic countries. In Lagos State, Nigeria, various malaria vector control programs including the use of chemical insecticides are currently being implemented. This study was designed to provide information on the susceptibility status of some nontargeted vectors such as Aedes aegypti. Adult Ae. aegypti mosquitoes from two farm sites and a nonfarm site were exposed to World Health Organization test papers impregnated with Deltamethrin (0.05%), Permethrin (0.75%), and DDT (4%) insecticides. The Knockdown time (KdT50 and KdT95) and percentage mortality after 24 h post exposure were determined. In all the exposed mosquito populations to permethrin, mortality rate > 98% (susceptibility) was recorded, whereas mortality rates < 95.8% (resistance) and > 98% (susceptibility) to deltamethrin were observed in the nonfarm site and farm sites mosquito populations, respectively. All the mosquito populations were resistant to DDT in 2 yr. The KdT50 of the populations to DDT increased (60.2–69.6) in one of the farm sites and the nonfarm site (68.9–199.96), while a decrease (243–63.4) in another farm site in 2 yr. Significant difference (P < 0.05) in KdT50 was recorded between the farm and nonfarm sites Ae. aegypti mosquitoes in the second year after exposure to deltamethrin and DDT. An increase in KdT95 after exposure to deltamethrin in the first year was recorded. Higher KdT values and lower mortality rates in Ae. aegypti populations in the nonfarm sites are indications there are existing factors selecting for insecticide resistance outside agricultural use of insecticides. PMID:26106087

A comparison of efficacy of six prediction models for intravenous immunoglobulin resistance in Kawasaki disease.

PubMed

Qian, Weiguo; Tang, Yunjia; Yan, Wenhua; Sun, Ling; Lv, Haitao

2018-03-09

Kawasaki disease (KD) is the most common pediatric vasculitis. Several models have been established to predict intravenous immunoglobulin (IVIG) resistance. The present study was aimed to evaluate the efficacy of prediction models using the medical data of KD patients. We collected the medical records of patients hospitalized in the Department of Cardiology in Children's Hospital of Soochow University with a diagnosis of KD from Jan 2015 to Dec 2016. IVIG resistance was defined as recrudescent or persistent fever ≥36 h after the end of their IVIG infusion. Patients with IVIG resistance tended to be younger, have higher occurrence of rash and changes of extremities. They had higher levels of c-reactive protein, aspartate aminotransferase, neutrophils proportion (N%), total bilirubin and lower level of albumin. Our prediction model had a sensitivity of 0.72 and a specificity of 0.75. Sensitivity of Kobayashi, Egami, Kawamura, Sano and Formosa were 0.72, 0.44, 0.48, 0.20, and 0.68, respectively. Specificity of these models were 0.62, 0.82, 0.66, 0.91, and 0.48, respectively. Our prediction model had a powerful predictive value in this area, followed by Kobayashi model while all the other prediction models had less excellent performances than ours.

Methods and Devices for Modifying Active Paths in a K-Delta-1-Sigma Modulator

NASA Technical Reports Server (NTRS)

Ardalan, Sasan (Inventor)

2017-01-01

The invention relates to an improved K-Delta-1-Sigma Modulators (KG1Ss) that achieve multi GHz sampling rates with 90 nm and 45 nm CMOS processes, and that provide the capability to balance performance with power in many applications. The improved KD1Ss activate all paths when high performance is needed (e.g. high bandwidth), and reduce the effective bandwidth by shutting down multiple paths when low performance is required. The improved KD1Ss can adjust the baseband filtering for lower bandwidth, and can provide large savings in power consumption while maintaining the communication link, which is a great advantage in space communications. The improved KD1Ss herein provides a receiver that adjusts to accommodate a higher rate when a packet is received at a low bandwidth, and at a initial lower rate, power is saved by turning off paths in the KD1S Analog to Digital Converter, and where when a higher rate is required, multiple paths are enabled in the KD1S to accommodate the higher band widths.

Carfilzomib-dexamethasone versus subcutaneous or intravenous bortezomib in relapsed or refractory multiple myeloma: secondary analysis of the phase 3 ENDEAVOR study.

PubMed

Goldschmidt, Hartmut; Moreau, Philippe; Ludwig, Heinz; Niesvizky, Ruben; Chng, Wee-Joo; Joshua, Douglas; Weisel, Katja; Spencer, Andrew; Orlowski, Robert Z; Feng, Shibao; Iskander, Karim S; Dimopoulos, Meletios A

2018-06-01

This is a secondary analysis of the phase 3 ENDEAVOR study comparing relapsed and/or refractory multiple myeloma (RRMM) patients receiving carfilzomib-dexamethasone (Kd) with those receiving subcutaneous (SC) bortezomib with dexamethasone (Vd) or intravenous (IV) Vd. Of Kd-treated patients, 356 Kd were pre-selected (by physician prior to randomization if to be randomized to Vd) for SC Vd (Kd [SC Vd]) and 108 for IV Vd (Kd [IV Vd], respectively. Of Vd-treated patients, 360 received SC Vd and 75 IV Vd. Kd (SC Vd) median PFS was not reached; SC Vd was 9.5 months. Median PFS for Kd (IV Vd) and IV Vd were 22.2 and 8.5 months, respectively. Median PFS was significantly longer and response rates were higher for Kd versus retreatment with bortezomib (SC or IV Vd) and in bortezomib naive patients. Overall, Kd was superior to Vd in RRMM regardless of route of bortezomib administration or prior bortezomib exposure.

Distribution of manganese between coexisting biotite and hornblende in plutonic rocks

USGS Publications Warehouse

Greenland, L.P.; Gottfried, D.; Tilling, R.I.

1968-01-01

The distribution of manganese between coexisting biotite and hornblende for 80 mineral pairs from igneous rocks of diverse provenance (including Southern California, Sierra Nevada, Boulder, and Boulder Creek batholiths and the Jemez Mountains volcanics) has been determined by neutron activation analysis. Data on the distribution ratio (Kd = Mnhornblende Mnbiotite) indicate that an equilibrium distribution of Mn is closely approached, though not completely attained, in most samples from plutonic environments. Comparison of Kd values of mineral pairs with bulk chemical composition of host rocks reveals no correlation. Because initial crystallization temperatures vary with rock composition, the lack of correlation of composition with Kd suggests that the equilibrium distribution of Mn between biotite and hornblende reflects exchange at subsolidus temperatures rather than initial crystallization temperatures. The highest Kd values are for volcanic rocks, in which rapid quenching prevents subsolidus redistribution of Mn. For sample pairs from the Southern California and Sierra Nevada batholiths there is a positive correlation of Kd with TiO2 content of biotite. Though the evidence is not compelling, Kd may also correlate with the rate of cooling and/or the presence or absence of sphene in the rock. ?? 1968.

Hounsfield unit values of retropharyngeal abscess-like lesions seen in Kawasaki disease.

PubMed

Sasaki, Toru; Miyata, Rie; Hatai, Yoshiho; Makita, Kohzoh; Tsunoda, Koichi

2014-04-01

Retropharyngeal abscess-like lesions are occasionally seen in computed tomography (CT) imaging of patients with Kawasaki disease (KD) and these patients often undergo unnecessary surgery. We could distinguish the lesions from true abscesses by measuring their Hounsfield unit values (HUs). To distinguish the retropharyngeal abscess-like lesions from true abscesses without any surgical procedure. We investigated six cases of KD showing such lesions on CTs, both with and without contrast enhancement (CE). We measured the HUs of those lesions and compared them with those of 10 true abscesses as controls. Abscess-like lesions of KD were well enhanced by CE, whereas abscesses showed virtually no enhancement. The mean HU in the six KD cases was 20.0 ± 4.65 (mean ± SD) on plain CTs and 35.6 ± 4.49 on contrast CTs. In abscesses, it was 30.3 ± 4.42 on plain CTs and 30.3 ± 3.57 on contrast CTs. The difference in HU values [(HU on contrast CT) - (HU on plain CT)] was defined as ΔHU. The mean ΔHU was 15.6 ± 5.36 in the six KD lesions and 0.0 ± 2.93 in abscesses, with statistical significance of p < 0.0001 by Student's t test. Thus, ΔHU value may potentially be a useful parameter for their distinction.

Atrioventricular depolarization differences identify coronary artery anomalies in Kawasaki disease.

PubMed

Cortez, Daniel; Sharma, Nandita; Jone, Pei-Ni

2017-03-01

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. Signal average electrocardiogram changes in patients during the acute phase of KD with coronary artery anomalies (CAA) include depolarization changes. We set out to determine if 12-lead-derived atrioventricular depolarization differences can identify CAA in patients with KD. A blinded, retrospective case-control study of patients with KD was performed. Deep Q waves, corrected QT-intervals (QTc), spatial QRS-T angles, T-wave vector magnitudes (RMS-T), and a novel parameter for assessment of atrioventricular depolarization difference (the spatial PR angle) and a two dimensional PR angle were assessed. Comparisons between groups were performed to test for significant differences. One hundred one patients with KD were evaluated, with 68 having CAA (67.3%, mean age 3.6 ± 3.0 years, 82.6% male), and 32 without CAA (31.7%, mean age 2.7 ± 3.2 years, 70.4% male). The spatial PR angle significantly discriminated KD patients with CAA from those without, 59.7° ± 31.1° versus 41.6° ± 11.5° (p < .001). A spatial PR angle cutoff value of 56.9° gave positive/negative predictive values and odds ratios of 93.8%, 43.5%, and 11.5% (95% confidence interval (CI) 2.6-52.2). The two dimensional PR angle either below 7° or above 92° gave positive/negative predictive values and odds ratios of 100.0%, 38.8%, and 21.1% (95% CI 1.2-362.8). No other parameters significantly differentiated the groups. Atrioventricular depolarization differences, measured by the spatial or two dimensional PR angle differentiate KD patients with CAA versus those without. © 2016 Wiley Periodicals, Inc.

Reassessment of carotid intima-media thickness by standard deviation score in children and adolescents after Kawasaki disease.

PubMed

Noto, Nobutaka; Kato, Masataka; Abe, Yuriko; Kamiyama, Hiroshi; Karasawa, Kensuke; Ayusawa, Mamoru; Takahashi, Shori

2015-01-01

Previous studies that used carotid ultrasound have been largely conflicting in regards to whether or not patients after Kawasaki disease (KD) have a greater carotid intima-media thickness (CIMT) than controls. To test the hypothesis that there are significant differences between the values of CIMT expressed as absolute values and standard deviation scores (SDS) in children and adolescents after KD and controls, we reviewed 12 published articles regarding CIMT on KD patients and controls. The mean ± SD of absolute CIMT (mm) in the KD patients and controls obtained from each article was transformed to SDS (CIMT-SDS) using age-specific reference values established by Jourdan et al. (J: n = 247) and our own data (N: n = 175), and the results among these 12 articles were compared between the two groups and the references for comparison of racial disparities. There were no significant differences in mean absolute CIMT and mean CIMT-SDS for J between KD patients and controls (0.46 ± 0.06 mm vs. 0.44 ± 0.04 mm, p = 0.133, and 1.80 ± 0.84 vs. 1.25 ± 0.12, p = 0.159, respectively). However, there were significant differences in mean CIMT-SDS for N between KD patients and controls (0.60 ± 0.71 vs. 0.01 ± 0.65, p = 0.042). When we assessed the nine articles on Asian subjects, the difference of CIMT-SDS between the two groups was invariably significant only for N (p = 0.015). Compared with the reference values, CIMT-SDS of controls was within the normal range at a rate of 41.6 % for J and 91.6 % for N. These results indicate that age- and race-specific reference values for CIMT are mandatory for performing accurate assessment of the vascular status in healthy children and adolescents, particularly in those after KD considered at increased long-term cardiovascular risk.

Improvement of Aptamer Affinity by Dimerization

PubMed Central

Hasegawa, Hijiri; Taira, Ken-ichi; Sode, Koji; Ikebukuro, Kazunori

2008-01-01

To increase the affinities of aptamers for their targets, we designed an aptamer dimer for thrombin and VEGF. This design is based on the avidity of the antibody, which enables the aptamer to connect easily since it is a single-strand nucleic acid. In this study, we connected a 15-mer thrombin-binding aptamer with a 29-mer thrombin-binding aptamer. Each aptamer recognizes a different part of the thrombin molecule, and the aptamer dimer has a Kd value which is 1/10 of that of the monomers from which it is composed. Also, the designed aptamer dimer has higher inhibitory activity than the reported (15-mer) thrombin-inhibiting aptamer. Additionally, we connected together two identical aptamers against vascular endothelial growth factor (VEGF165), which is a homodimeric protein. As in the case of the anti-thrombin aptamer, the dimeric anti-VEGF aptamer had a much lower Kd value than that of the monomer. This study demonstrated that the dimerization of aptamers effectively improves the affinities of those aptamers for their targets. PMID:27879754

Physical uniqueness of higher-order Korteweg-de Vries theory for continuously stratified fluids without background shear

NASA Astrophysics Data System (ADS)

Shimizu, Kenji

2017-10-01

The 2nd-order Korteweg-de Vries (KdV) equation and the Gardner (or extended KdV) equation are often used to investigate internal solitary waves, commonly observed in oceans and lakes. However, application of these KdV-type equations for continuously stratified fluids to geophysical problems is hindered by nonuniqueness of the higher-order coefficients and the associated correction functions to the wave fields. This study proposes to reduce arbitrariness of the higher-order KdV theory by considering its uniqueness in the following three physical senses: (i) consistency of the nonlinear higher-order coefficients and correction functions with the corresponding phase speeds, (ii) wavenumber-independence of the vertically integrated available potential energy, and (iii) its positive definiteness. The spectral (or generalized Fourier) approach based on vertical modes in the isopycnal coordinate is shown to enable an alternative derivation of the 2nd-order KdV equation, without encountering nonuniqueness. Comparison with previous theories shows that Parseval's theorem naturally yields a unique set of special conditions for (ii) and (iii). Hydrostatic fully nonlinear solutions, derived by combining the spectral approach and simple-wave analysis, reveal that both proposed and previous 2nd-order theories satisfy (i), provided that consistent definitions are used for the wave amplitude and the nonlinear correction. This condition reduces the arbitrariness when higher-order KdV-type theories are compared with observations or numerical simulations. The coefficients and correction functions that satisfy (i)-(iii) are given by explicit formulae to 2nd order and by algebraic recurrence relationships to arbitrary order for hydrostatic fully nonlinear and linear fully nonhydrostatic effects.

Can a systems biology approach unlock the mysteries of Kawasaki disease?

PubMed

Rowley, Anne H

2013-01-01

Kawasaki disease (KD) is a systemic inflammatory illness of childhood that particularly affects the coronary arteries. It can lead to coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data support an infectious cause, and the etiology remains unknown, but recent data support infection with a 'new' virus. Genetic factors influence KD susceptibility; the incidence is 10-fold higher in children of Asian when compared with Caucasian ethnicity. Recent research has identified genes affecting immune response that are associated with KD susceptibility and outcome. A re-examination of the pathologic features of KD has yielded a three process model of KD vasculopathy, providing a framework for understanding the KD arterial immune response and the damage it inflicts and for identifying new therapeutic targets for KD patients with coronary artery abnormalities. The researcher is faced with many challenges in determining the pathogenesis of KD. A systems biology approach incorporating genomics, proteomics, transcriptomics, and microbial bioinformatics analysis of high-throughput sequence data from KD tissues could provide the keys to unlocking the mysteries of this potentially fatal illness of childhood. Copyright © 2013 Wiley Periodicals, Inc.

The influence of the sorptive properties of organic soils on the migration rate of 137Cs.

PubMed

Chibowski, S; Zygmunt, J

2002-01-01

Using a compartment model, the migration rates of 137Cs were calculated for two types of organic soils: a low peat-muck soil and a black earth. The migration rates of 137Cs in the tested soils turned out to be significantly higher than in mineral types examined earlier and ranged from 0.6 to 12.3 cm/year. The partition coefficients (Kd) were also determined for samples with varying organic matter content (OM) that were taken from different layers of the studied soils. The experimental results indicate that there is a clear relationship between Kd values and OM. The investigation was widened by microcalorimetric measurements which confirmed that the adsorption of 137Cs on the organic soils is low.

Improved Accuracy of Low Affinity Protein-Ligand Equilibrium Dissociation Constants Directly Determined by Electrospray Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Jaquillard, Lucie; Saab, Fabienne; Schoentgen, Françoise; Cadene, Martine

2012-05-01

There is continued interest in the determination by ESI-MS of equilibrium dissociation constants (KD) that accurately reflect the affinity of a protein-ligand complex in solution. Issues in the measurement of KD are compounded in the case of low affinity complexes. Here we present a KD measurement method and corresponding mathematical model dealing with both gas-phase dissociation (GPD) and aggregation. To this end, a rational mathematical correction of GPD (fsat) is combined with the development of an experimental protocol to deal with gas-phase aggregation. A guide to apply the method to noncovalent protein-ligand systems according to their kinetic behavior is provided. The approach is validated by comparing the KD values determined by this method with in-solution KD literature values. The influence of the type of molecular interactions and instrumental setup on fsat is examined as a first step towards a fine dissection of factors affecting GPD. The method can be reliably applied to a wide array of low affinity systems without the need for a reference ligand or protein.

Effects of salinity and organic matter on the partitioning of perfluoroalkyl acid (PFAs) to clay particles.

PubMed

Jeon, Junho; Kannan, Kurunthachalam; Lim, Byung J; An, Kwang Guk; Kim, Sang Don

2011-06-01

The influence of salinity and organic matter on the distribution coefficient (K(d)) for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in a brackish water-clay system was studied. The distribution coefficients (K(d)) for PFAs onto inorganic clay surfaces increased with salinity, providing evidence for electrostatic interaction for the sorption of PFAs, whereas the relationship between K(d) and organic carbon content (f(oc)) suggested that hydrophobic interaction is the primary driving force for the sorption of PFAs onto organic matter. The organic carbon normalized adsorption coefficient (K(oc)) of PFAs can be slightly overestimated due to the electrostatic interaction within uncoated inorganic surfaces. In addition, the dissolved organic matter released from coated clay particles seemed to solvate PFA molecules in solution, which contributed to a decrease in K(d). A positive relationship between K(d) and salinity was apparent, but an empirical relationship for the 'salting-out' effect was not evident. The K(d) values of PFAs are relatively small compared with those reported for persistent organic pollutants. Thus, sorption may not be a significant route of mass transfer of PFAs from water columns in estuarine environments. However, enhancement of sorption of PFAs to particulate matter at high salinity values could evoke potential risks to benthic organisms in estuarine areas.

Sulfadimethoxine and sulfaguanidine: their sorption potential on natural soils.

PubMed

Białk-Bielińska, Anna; Maszkowska, Joanna; Mrozik, Wojciech; Bielawska, Agata; Kołodziejska, Marta; Palavinskas, Richard; Stepnowski, Piotr; Kumirska, Jolanta

2012-03-01

Sulfonamides (SAs) are one of the oldest groups of veterinary chemotherapeutic agents. As these compounds are not completely metabolized in animals, a high proportion of the native form is excreted in feces and urine. They are therefore released either directly to the environment in aquacultures and by grazing animals, or indirectly during the application of manure or slurry. Once released into the environment, SAs become distributed among various environmental compartments and may be transported to surface or ground waters. The physicochemical properties of SAs, dosage and nature of the matrix are the factors mainly responsible for their distribution in the natural environment. Although these rather polar compounds have been in use for over half a century, knowledge of their fate and behavior in soil ecosystems is still limited. Therefore, in this work we have determined the sorption potential of sulfadimethoxine and sulfaguanidine on various natural soils. The influence on sorption of external factors, such as ionic strength and pH, were also determined. The sorption coefficients (K(d)) obtained for the sulfonamides investigated were quite low (from 0.20 to 381.17 mL g(-1) for sulfadimethoxine and from 0.39 to 35.09 mL g(-1) for sulfaguanidine), which indicated that these substances are highly mobile and have the potential to run off into surface waters and/or infiltrate ground water. Moreover, the sorption of these pharmaceuticals was found to be influenced by OC, soil solution pH and ionic strength, with higher K(d) values for soils of higher OC and lower K(d) values with increasing pH and ionic strength. Copyright © 2011 Elsevier Ltd. All rights reserved.

Calcium-buffering effects of gluconate and nucleotides, as determined by a novel fluorimetric titration method.

PubMed

Woehler, Andrew; Lin, Kun-Han; Neher, Erwin

2014-11-15

Significantly more Ca(2+) influx is required for eliciting release of neurotransmitter during whole cell patch clamp recording in the Calyx of Held, when gluconate with 3 mm free ATP is used as pipette filling solution, as compared to a methanesulfonate-based solution with excess Mg(2+). This reduction in efficiency of Ca(2+) in eliciting release is due to low-affinity Ca(2+) binding of both gluconate and ATP(2-) anions. To study these effects we developed a simple fluorimeteric titration procedure, which reports the dissociation constant, KD, of a given Ca(2+) indicator dye, multiplied by 1 plus the sum of Ca(2+) binding ratios of any anions, which act as low-affinity Ca(2+) ligands. For solutions without Ca(2+) binding anions we find KD values for Fura2FF ranging from 11.5 ± 1.7 to 15.6 ± 7.47 μm depending on the dominant anion used. For Fura6F and KCl-based solutions we find KD = 17.8 ± 1.3 μm. For solutions with gluconate as the main anion and for solutions that contain nucleotides, such as ATP and GTP, we find much higher values for the product. Assuming that the KD of the indicator dye is equal to that of KCl-based solutions we calculate the summed Ca(2+) binding ratios and find a value of 3.55 for a solution containing 100 mm potassium gluconate and 4 mm ATP. Gluconate contributes a value of 1.75 to this number, while the contribution of ATP depends strongly on the presence of Mg(2+) and varies from 0.8 (with excess Mg(2+)) to 13.8 (in the presence of 3 mm free ATP). Methanesulfonate has negligible Ca(2+) binding capacity. These results explain the reduced efficiency of Ca(2+) influx in the presence of gluconate or nucleotides, as these anions are expected to intercept Ca(2+) ions at short distance. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Pedotransfer functions for isoproturon sorption on soils and vadose zone materials.

PubMed

Moeys, Julien; Bergheaud, Valérie; Coquet, Yves

2011-10-01

Sorption coefficients (the linear K(D) or the non-linear K(F) and N(F)) are critical parameters in models of pesticide transport to groundwater or surface water. In this work, a dataset of isoproturon sorption coefficients and corresponding soil properties (264 K(D) and 55 K(F)) was compiled, and pedotransfer functions were built for predicting isoproturon sorption in soils and vadose zone materials. These were benchmarked against various other prediction methods. The results show that the organic carbon content (OC) and pH are the two main soil properties influencing isoproturon K(D) . The pedotransfer function is K(D) = 1.7822 + 0.0162 OC(1.5) - 0.1958 pH (K(D) in L kg(-1) and OC in g kg(-1)). For low-OC soils (OC < 6.15 g kg(-1)), clay and pH are most influential. The pedotransfer function is then K(D) = 0.9980 + 0.0002 clay - 0.0990 pH (clay in g kg(-1)). Benchmarking K(D) estimations showed that functions calibrated on more specific subsets of the data perform better on these subsets than functions calibrated on larger subsets. Predicting isoproturon sorption in soils in unsampled locations should rely, whenever possible, and by order of preference, on (a) site- or soil-specific pedotransfer functions, (b) pedotransfer functions calibrated on a large dataset, (c) K(OC) values calculated on a large dataset or (d) K(OC) values taken from existing pesticide properties databases. Copyright © 2011 Society of Chemical Industry.

Pattern of subcutaneous fat during follow-up of a cohort of North Indian children with Kawasaki disease: a preliminary study.

PubMed

Suthar, Renu; Singh, Surjit; Bhalla, Anil Kumar; Attri, Savita Verma

2014-03-01

Kawasaki disease (KD) has been associated with abnormal lipid profiles. The latter, in turn, have been linked to changes in subcutaneous fat. In this comparative cross-sectional study we have quantified distribution of subcutaneous fat during follow-up of a cohort of North Indian children with KD. We compared 35 KD children (at least 2 years after disease) and 33 healthy controls. Study parameters included weight, height and skinfold thickness (SFT) over biceps, triceps, midaxillary, subscapular, medial calf and suprailiac areas. Waist and hip circumferences were also recorded. All parameters were measured four times at 6-monthly intervals using standardized techniques. Serum lipids were assayed in the study group. Study children were enrolled 3.7 ± 2.5 years after KD and mean age at enrolment was 8.26 ± 3.65 years. Suprailiac SFT measured higher in boys with KD (P ≤ 0.05). Biceps SFT was higher in the study group, but the difference was not significant. Other SFT were not affected. Waist and hip circumference was higher in the study group than controls (P ≤ 0.05). Waist/hip circumference ratio was not affected. Serum low-density lipoprotein cholesterol (LDL-C) and triglycerides were higher in the study group as compared to historical controls (95.60 ± 36.12 and 129.40 ± 64.62 mg/dL vs. 80.10 ± 2.20 and 91.1 ± 29.85; P ≤ 0.05). Total cholesterol and high-density lipoprotein cholesterol levels remained unaffected. Children with KD (especially boys) had increased subcutaneous fat deposition in the suprailiac region and waist, during follow-up. Serum LDL-C and triglycerides were elevated. KD children may have a tendency to develop central obesity. Further studies, with longer follow-up, would be necessary to show whether this has implications for development of coronary artery disease later in life. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid.

PubMed

Castro, Kamila; Baronio, Diego; Perry, Ingrid Schweigert; Riesgo, Rudimar Dos Santos; Gottfried, Carmem

2017-07-01

Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.

REVISED GUIDELINES FOR USING CELLULOSE DEGRADATION PRODUCT-IMPACTED KD VALUES FOR PERFORMANCE ASSESSMENTS AND COMPOSITE ANALYSES

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

Kaplan, D.

2012-05-14

Cellulosic materials include wood, paper, rags, and cardboard products. These materials are co-disposed with radiological waste at the Savannah River Site's (SRS) E-Area Low-Level Waste Facility (ELLWF). Cellulosic materials readily degrade in the environment to form cellulose degradation products (CDP) that will partition to the sediment or remain mobile in the groundwater. Savannah River National Lab (SRNL) has conducted studies to estimate the impact of CDP on radionuclide sorption to SRS sediments (Kd values). It was found that CDP impact on radionuclide sorption varies with radionuclide and CDP concentration. Furthermore, it was found that the amount of carbon (C) inmore » the system could increase or decrease Kd values with respect to the base case of when no CDP was added. Throughout the expected pH range of the ELLWF, a low concentration of CDP in the system would increase Kd values (because C would sorb to the sediment and provide more exchange sites for radionuclides to sorb), whereas greater concentrations of CDP ({ge}20 mg/L C) would decrease Kd values (because C would remain in solution and complex the radionuclide and not permit the radionuclide to sorb to the sediment). A review of >230 dissolved organic carbon (DOC) groundwater concentrations in the Old Radioactive Waste Burial Ground (ORWBG) at the SRS indicated that the average DOC concentration, a gross measure of CDP, was 5 mg/L C. At approximately this DOC concentration, the laboratory studies demonstrated that no anions (Tc, I, or Se) or cations (Ni, Sr, Ce, Eu, Zr, or Th) have decreased sorption in the presence of carbon (an analogue for CDP).« less

The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease

PubMed Central

Chang, Ling-Sai; Lo, Mao-Hung; Li, Sung-Chou; Yang, Ming-Yu; Hsieh, Kai-Sheng; Kuo, Ho-Chang

2017-01-01

Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA. We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation. PMID:27893416

Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.

PubMed

Zhang, Xiaoyu; Qin, Juliang; Zhao, Yihan; Shi, Jueping; Lan, Rong; Gan, Yunqiu; Ren, Hua; Zhu, Bing; Qian, Min; Du, Bing

2016-04-01

The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element-binding protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety and immunogenicity of a freeze-dried, Vero cell culture-derived, inactivated Japanese encephalitis vaccine (KD-287, ENCEVAC®) versus a mouse brain-derived inactivated Japanese encephalitis vaccine in children: a phase III, multicenter, double-blinded, randomized trial.

PubMed

Yun, Ki Wook; Lee, Hoan Jong; Kang, Jin Han; Eun, Byung Wook; Kim, Yae-Jean; Kim, Kyung-Hyo; Kim, Nam Hee; Hong, Young Jin; Kim, Dong Ho; Kim, Hwang Min; Cha, Sung-Ho

2015-01-08

Although mouse brain-derived, inactivated Japanese encephalitis vaccines (JE-MBs) have been successfully used for a long time, potential rare neurological complications have prompted the development of a Vero cell culture-derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC, in children. In this multicenter, double-blinded, randomized controlled trial, the study population consisted of 205 healthy Korean children aged 12-23 months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC twice at an interval of 2 weeks and then vaccinated once 12 months after the second vaccination. Neutralizing antibodies were measured by the plaque reduction neutralization test using the homologous and heterologous, as a post hoc analysis, challenge virus strains. The three-dose regimen of KD-287 showed a comparable safety profile with JEV-GCC except higher incidence of fever after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the neutralizing antibody, which were the primary endpoints, at 4 weeks after the third vaccination (95% CI: -1.00, 3.10 for the SCR difference and 10.8, 17.6 for the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the KD-287 group than in the JEV-GCC group after the second vaccination and before and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively, p < 0.001 in all). GMTs were higher in the KD-287 group in the heterologous analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p < 0.001 in all). This study suggests that the KD-287, a JE-VC is as safe as and may be more effective than the licensed MB-derived vaccine. KD-287 could thus be useful as a second-generation vaccine and substitute for the current JE-MB vaccine in Korean children. ClinicalTrials.gov: NCT01150942.

Enhanced biodegradation of mixed PAHs by mutated naphthalene 1,2-dioxygenase encoded by Pseudomonas putida strain KD6 isolated from petroleum refinery waste.

PubMed

Dutta, Kunal; Shityakov, Sergey; Das, Prangya P; Ghosh, Chandradipa

2017-12-01

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutant that are given top priority to maintain water and soil quality to the most amenable standard. Biodegradation of PAHs by bacteria is the convenient option for decontamination on site or off site. The aim of the present study was to isolate and identify naturally occurring bacteria having mixed PAHs biodegradation ability. The newly isolated Pseudomonas putida strain KD6 was found to efficiently degrade 97.729% of 1500 mg L -1 mixed PAHs within 12 days in carbon-deficient minimal medium (CSM). The half-life ( t 1/2 ) and degradation rate constant ( k ) were estimated to be 3.2 and 0.2165 days, respectively. The first-order kinetic parameters in soil by strain KD6 had shown efficient biodegradation potency with the higher concentration of total PAHs (1500 mg kg -1 soil), t 1/2  = 10.44 days -1 . However, the biodegradation by un-inoculated control soil was found slower ( t 1/2  = 140 days -1 ) than the soil inoculated with P. putida strain KD6. The enzyme kinetic constants are also in agreement with chemical data obtained from the HPLC analysis. In addition, the sequence analysis and molecular docking studies showed that the strain KD6 encodes a mutant version of naphthalene 1,2-dioxygenase which have better Benzpyrene binding energy (-9.90 kcal mol -1 ) than wild type (-8.18 kcal mol -1 ) enzyme (chain A, 1NDO), respectively, with 0.00 and 0.08 RMSD values. The mutated naphthalene 1,2-dioxygenase nah Ac has six altered amino acid residues near to the ligand binding site. The strain KD6 could be a good bioresource for in situ or ex situ biodegradation of polycyclic aromatic hydrocarbon.

UNDERSTANDING VARIATION IN PARTITION COEFFICIENT KD, VALUES, VOLUME III: AMERICIUM, ARSENIC, CURIUM, IODINE, NEPTUNIUM, RADIUM, AND TECHNETIUM

EPA Science Inventory

This report describes the conceptualization, measurement, and use of the partition (or distribution) coefficient, Kd, parameter, and the geochemical aqueous solution and sorbent properties that are most important in controlling adsorption/retardation behavior of selected contamin...

The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

PubMed Central

Kephart, Wesley C.; Pledge, Coree D.; Roberson, Paul A.; Mumford, Petey W.; Romero, Matthew A.; Mobley, Christopher B.; Young, Kaelin C.; Lowery, Ryan P.; Wilson, Jacob M.; Huggins, Kevin W.; Roberts, Michael D.

2018-01-01

Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD) on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio) were divided into a control group (CTL; n = 5) and a KD group (n = 7). KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA) and ultrasound, resting energy expenditure (REE), blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB) levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053). DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068), and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065). Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048). Between-group changes in REE, one-repetition maximum (1-RM) back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest that adopting a ketogenic diet causes marked reductions in whole-body adiposity while not impacting performance measures in recreationally-trained CrossFit trainees. Whether decrements in dual-leg muscle mass and vastus lateralis thickness in KD participants were due to fluid shifts remain unresolved, and increased LDL-C in these individuals warrants further investigation.

Ambient air pollution, temperature and kawasaki disease in Shanghai, China.

PubMed

Lin, Zhijing; Meng, Xia; Chen, Renjie; Huang, Guoying; Ma, Xiaojing; Chen, Jingjing; Huang, Min; Huang, Meirong; Gui, Yonghao; Chu, Chen; Liu, Fang; Kan, Haidong

2017-11-01

Kawasaki disease (KD) is a kind of pediatric vasculitis of unknown etiology which mainly affects the development of coronary artery aneurysms. Few studies have explored the potential environmental risk factors on KD incidence. We performed a time-series analysis to investigate the associations between air pollution and temperature and KD in Shanghai, China. We collected daily-hospitalized KD patients that were admitted in major pediatric specialty hospitals located in the urban areas of Shanghai from 2001 to 2010. The over-dispersed generalized additive model was used to estimate the effects of air pollutants on KD incidence on each day. Then, this model was combined with a distributed lag non-linear model to estimate the cumulative effects of temperature over a week. There were positive but statistically insignificant associations between three major air pollutants and KD incidence. The association between daily mean temperature and KD was generally J-shaped with higher risks on hot days. The cumulative relative risk of KD at extreme hot temperature (99th percentile, 32.4 °C) over a week was 1.91 [95% confidence interval (CI): 1.13, 3.23], compared with the referent temperature (10.0 °C). This study suggested that a short-term exposure to high temperature may significantly increase the incidence of KD, and the evidence linking air pollution and KD incidence was limited. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased Kawasaki Disease Incidence Associated With Higher Precipitation and Lower Temperatures, Japan, 1991-2004.

PubMed

Abrams, Joseph Y; Blase, Jennifer L; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2018-06-01

Kawasaki disease (KD) is an acute febrile vasculitis, which primarily affects children. The etiology of KD is unknown; while certain characteristics of the disease suggest an infectious origin, genetic or environmental factors may also be important. Seasonal patterns of KD incidence are well documented, but it is unclear whether these patterns are caused by changes in climate or by other unknown seasonal effects. The relationship between KD incidence and deviations from expected temperature and precipitation were analyzed using KD incidence data from Japanese nationwide epidemiologic surveys (1991-2004) and climate data from 136 weather stations of the Japan Meteorological Agency. Seven separate Poisson-distributed generalized linear regression models were run to examine the effects of temperature and precipitation on KD incidence in the same month as KD onset and the previous 1, 2, 3, 4, 5 and 6 months, controlling for geography as well as seasonal and long-term trends in KD incidence. KD incidence was negatively associated with temperature in the previous 2, 3, 4 and 5 months and positively associated with precipitation in the previous 1 and 2 months. The model that best predicted variations in KD incidence used climate data from the previous 2 months. An increase in total monthly precipitation by 100 mm was associated with increased KD incidence (rate ratio [RR] 1.012, 95% confidence interval [CI]: 1.005-1.019), and an increase of monthly mean temperature by 1°C was associated with decreased KD incidence (RR 0.984, 95% CI: 0.978-0.990). KD incidence was significantly affected by temperature and precipitation in previous months independent of other unknown seasonal factors. Climate data from the previous 2 months best predicted the variations in KD incidence. Although fairly minor, the effect of temperature and precipitation independent of season may provide additional clues to the etiology of KD.

Use of thermodynamic sorption models to derive radionuclide Kd values for performance assessment: Selected results and recommendations of the NEA sorption project

USGS Publications Warehouse

Ochs, M.; Davis, J.A.; Olin, M.; Payne, T.E.; Tweed, C.J.; Askarieh, M.M.; Altmann, S.

2006-01-01

For the safe final disposal and/or long-term storage of radioactive wastes, deep or near-surface underground repositories are being considered world-wide. A central safety feature is the prevention, or sufficient retardation, of radionuclide (RN) migration to the biosphere. To this end, radionuclide sorption is one of the most important processes. Decreasing the uncertainty in radionuclide sorption may contribute significantly to reducing the overall uncertainty of a performance assessment (PA). For PA, sorption is typically characterised by distribution coefficients (Kd values). The conditional nature of Kd requires different estimates of this parameter for each set of geochemical conditions of potential relevance in a RN's migration pathway. As it is not feasible to measure sorption for every set of conditions, the derivation of Kd for PA must rely on data derived from representative model systems. As a result, uncertainty in Kd is largely caused by the need to derive values for conditions not explicitly addressed in experiments. The recently concluded NEA Sorption Project [1] showed that thermodynamic sorption models (TSMs) are uniquely suited to derive K d as a function of conditions, because they allow a direct coupling of sorption with variable solution chemistry and mineralogy in a thermodynamic framework. The results of the project enable assessment of the suitability of various TSM approaches for PA-relevant applications as well as of the potential and limitations of TSMs to model RN sorption in complex systems. ?? by Oldenbourg Wissenschaftsverlag.

Sorption of Perfluorinated Compounds onto different types of sewage sludge and assessment of its importance during wastewater treatment.

PubMed

Arvaniti, Olga S; Andersen, Henrik R; Thomaidis, Nikolaos S; Stasinakis, Athanasios S

2014-09-01

The distribution coefficient (Kd) and the organic carbon distribution coefficient (KOC) were determined for four Perfluorinated Compounds (PFCs) to three different types of sludge taken from a conventional Sewage Treatment Plant (STP). Batch experiments were performed in six different environmental relevant concentrations (200ngL(-1)to 5μgL(-1)) containing 1gL(-1) sludge. Kd values ranged from 330 to 6015, 329 to 17432 and 162 to 11770Lkg(-1) for primary, secondary and digested sludge, respectively. The effects of solution's pH, ionic strength and cation types on PFCs sorption were also evaluated. Sorption capacities of PFCs significantly decreased with increased pH values from 6 to 8. Furthermore, the divalent cation (Ca(2+)) enhanced PFCs sorption to a higher degree in comparison with the monovalent cation (Na(+)) at the same ionic strength. The obtained Kd values were applied to estimate the sorbed fractions of each PFC in different stages of a typical STP and to calculate their removal through treated wastewater and sludge. In primary settling tank, the predicted sorbed fractions ranged from 3% for Perfluorooctanoic Acid (PFOA) to 55% for Perfluoroundecanoic acid (PFUdA), while in activated sludge tank and anaerobic digester sorption was more than 50% for all target compounds. Almost 86% of initial PFOA load is expected to be detected in treated wastewater; while Perfluorodecanoic acid (PFDA), PFUdA and Perfluorooctanesulfonate (PFOS) can be significantly removed (>49%) via sorption to primary and excess secondary sludge. In anaerobic digester, the major part (>76%) of target PFCs is expected to be sorbed to sludge, while almost 3% of initial PFOA load will be detected in sludge leachates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness of mineral soil to adsorb the natural occurring radioactive material (norm), uranium and thorium

NASA Astrophysics Data System (ADS)

Amir, Muhammad Nur Iman; Ismail, Nurul Izzatiafifi; Wood, Ab. Khalik; Saat, Ahmad; Hamzah, Zaini

2015-04-01

A study has been performed on U-soil and Th-soil adsorption of three types of soil collected from Selangor State of Malaysia which are Saujana Putra, Bukit Changgang and Jenderam Hilir. In this study, natural radionuclide (U and Th) soil adsorption based on batch experiments with various initial concentrations of the radionuclide elements were carried out. Parameters that were set constant include pH at 5;amount of soil used was 5 g each, contact time was 24 hour and different initial concentration for each solution of U and Th which is 5 mg/L, 10 mg/L, 15 mg/L, 20 mg/L, 25 mg/L and 40 mg/L were used. The Kd values for each type of soil were determined in this batch experiments which was based on US-EPA method, in order to estimate adsorption capacity of the soil.The Kd values of Th found higher than Kd values of U for all of the soil samples, and the highest was found on the soil collected from Bukit Changgang. The soil clay content was one of factors to influence the adsorption of both U and Th from dilute initial solution. The U-soil and Th-soil adsorption process for all the soil samples studied are generally obeying unimolecular layer Langmuir isotherm model. From Langmuir isotherm, the maximum adsorption capacity for U was 0.393mg/g and for Th was 1.53 mg/g for the soil that was taken from Bukit Changgang. From the study, it suggested that the soil from Bukit Changgang applicable as potential enhanced barrier for site disposing waste containing U and Th.

Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: laboratory photolysis, biodegradation, and sorption experiments.

PubMed

Yamamoto, Hiroshi; Nakamura, Yudai; Moriguchi, Shigemi; Nakamura, Yuki; Honda, Yuta; Tamura, Ikumi; Hirata, Yoshiko; Hayashi, Akihide; Sekizawa, Jun

2009-02-01

We selected eight pharmaceuticals with relatively high potential ecological risk and high consumption-namely, acetaminophen, atenolol, carbamazepine, ibuprofen, ifenprodil, indomethacin, mefenamic acid, and propranolol-and conducted laboratory experiments to examine the persistence and partitioning of these compounds in the aquatic environment. In the results of batch sunlight photolysis experiments, three out of eight pharmaceuticals-propranolol, indomethacin, and ifenprodil-were relatively easily photodegraded (i.e., half-life<24h), whereas the other five pharmaceuticals were relatively stable against sunlight. The results of batch biodegradation experiments using river water suggested relatively slow biodegradation (i.e., half-life>24h) for all eight pharmaceuticals, but the rate constant was dependent on sampling site and time. Batch sorption experiments were also conducted to determine the sorption coefficients to river sediments and a model soil sample. The determined coefficients (K(d) values) were much higher for three amines (atenolol, ifenprodil, and propranolol) than for neutral compounds or carboxylic acids; the K(d) values of the amines were comparable to those of a four-ring polycyclic aromatic hydrocarbon (PAH) pyrene. The coefficients were also higher for sediment/soil with higher organic content, and the organic carbon-based sorption coefficient (logK(oc)) showed a poor linear correlation with the octanol-water distribution coefficient (logD(ow)) at neutral pH. These results suggest other sorption mechanisms-such as electrochemical affinity, in addition to hydrophobic interaction-play an important role in sorption to sediment/soil at neutral pH.

Progesterone receptors in the female lower urinary tract

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

Batra, S.C.; Iosif, C.S.

1987-11-01

When female estrogenized rabbits were injected i.v. with /sup 3/H-progesterone, the tritium concentration determined after one hour was about two to three times higher in urethra, urinary bladder and vagina than in the heart. High affinity progesterone receptors (KD = 1-2 nM) could be demonstrated in both cytoplasmic and nuclear fractions prepared from estrogenized rabbit urethra, bladder and vagina. The cytosolic receptor concentration in both urethra and bladder was about half of that in the vagina. The concentration of nuclear receptors in urethra was not significantly different from that in the vagina, but in the bladder the concentration was onlymore » about one fourth of that in the vagina or urethra. The mean KD of cytosolic receptors from bladder was significantly higher than the corresponding values in urethra and vagina. Progesterone binding sites in the bladder had a broader hormonal specificity than those in the urethra or vagina. The present demonstration of specific progesterone receptors in the female urethra might provide a possible link between estrogen progesterone interaction and the appearance of urinary incontinence during pregnancy in women.« less

Development of a Water Clarity Index for the Southeastern U.S. As a Climate Indicator

NASA Astrophysics Data System (ADS)

Sheridan, S. C.; Hu, C.; Lee, C. C.; Barnes, B.; Pirhalla, D.; Ransi, V.; Shein, K. A.

2014-12-01

A common index of water quality is water clarity, which can be estimated by measuring the diffuse attenuation coefficient for downwelling irradiance (Kd). Kd estimates the availability of light to marine organisms at various depths. Marine habitats, including such species as coral and seagrass, can be negatively affected by extreme episodes of sediment suspension, where water clarity is reduced and little light penetrates. Evidence of increased stress on coastal ecosystems exists, partially due to climate change, yet a systematic analysis of extreme events and trends is difficult due to limited data. To address this concern, we have developed as a potential climate indicator a Kd-Index for nine regions along the US coast of the Gulf of Mexico, in which Kd values have been standardized over time and space to allow for a more holistic assessment of climate drivers and their trends. Variability in the Kd-Index is then assessed with regard to occurrences of surface weather types (using the Spatial Synoptic Classification), a synoptic climatology of mean sea-level-pressure patterns across the region, along with heavy precipitation events. Kd can be estimated from MODIS and SeaWiFS observations from 1997 to date; an earlier period of satellite observations from 1978-86 is also available. A non-linear autoregressive neural network model with external input (NARX) is used to develop the historical relationship between Kd-Index and atmospheric conditions, and then this model is used to simulate a full time series from 1948 to 2013. The modeled data set is strongly correlated with observations, with correlations above 0.8 for many regions. Hit rates of extreme Kd-Index values - those which would most likely be associated with a negative environmental impact - exceed 70% in some regions. Across the full data set, long term trends vary slightly across regions but are generally small. Trends in extreme events appear to be more consistently increasing across the domain.

From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

PubMed

Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S

2016-11-01

Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Assessing antibiotic sorption in soil: a literature review and new case studies on sulfonamides and macrolides

PubMed Central

2014-01-01

The increased use of veterinary antibiotics in modern agriculture for therapeutic uses and growth promotion has raised concern regarding the environmental impacts of antibiotic residues in soil and water. The mobility and transport of antibiotics in the environment depends on their sorption behavior, which is typically predicted by extrapolating from an experimentally determined soil-water distribution coefficient (Kd). Accurate determination of Kd values is important in order to better predict the environmental fate of antibiotics. In this paper, we examine different analytical approaches in assessing Kd of two major classes of veterinary antibiotics (sulfonamides and macrolides) and compare the existing literature data with experimental data obtained in our laboratory. While environmental parameters such as soil pH and organic matter content are the most significant factors that affect the sorption of antibiotics in soil, it is important to consider the concentrations used, the analytical method employed, and the transformations that can occur when determining Kd values. Application of solid phase extraction and liquid chromatography/mass spectrometry can facilitate accurate determination of Kd at environmentally relevant concentrations. Because the bioavailability of antibiotics in soil depends on their sorption behavior, it is important to examine current practices in assessing their mobility in soil. PMID:24438473

The King-Devick (K-D) test of rapid eye movements: a bedside correlate of disability and quality of life in MS.

PubMed

Moster, Stephen; Wilson, James A; Galetta, Steven L; Balcer, Laura J

2014-08-15

We investigated the King-Devick (K-D) test of rapid number naming as a visual performance measure in a cohort of patients with multiple sclerosis (MS). In this cross-sectional study, 81 patients with MS and 20 disease-free controls from an ongoing study of visual outcomes underwent K-D testing. A test of rapid number naming, K-D requires saccadic eye movements as well as intact vision, attention and concentration. To perform the K-D test, participants are asked to read numbers aloud as quickly as possible from three test cards; the sum of the three test card times in seconds constitutes the summary score. High-contrast visual acuity (VA), low-contrast letter acuity (1.25% and 2.5% levels), retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), MS Functional Composite (MSFC) and vision-specific quality of life (QOL) measures (25-Item NEI Visual Functioning Questionnaire [NEI-VFQ-25] and 10-Item Neuro-Ophthalmic Supplement) were also assessed. K-D time scores in the MS cohort (total time to read the three test cards) were significantly higher (worse) compared to those for disease-free controls (P=0.003, linear regression, accounting for age). Within the MS cohort, higher K-D scores were associated with worse scores for the NEI-VFQ-25 composite (P<0.001), 10-Item Neuro-Ophthalmic Supplement (P<0.001), binocular low-contrast acuity (2.5%, 1.25%, P<0.001, and high-contrast VA (P=0.003). Monocular low-contrast vision scores (P=0.001-0.009) and RNFL thickness (P=0.001) were also reduced in eyes of patients with worse K-D scores (GEE models accounting for age and within-patient, inter-eye correlations). Patients with a history of optic neuritis (ON) had increased (worse) K-D scores. Patients who classified their work disability status as disabled (receiving disability pension) did worse on K-D testing compared to those working full-time (P=0.001, accounting for age). The K-D test, a <2 minute bedside test of rapid number naming, is associated with visual dysfunction, neurologic impairment, and reduced vision-specific QOL in patients with MS. Scores reflect work disability as well as structural changes as measured by OCT imaging. History of ON and abnormal binocular acuities were associated with worse K-D scores, suggesting that abnormalities detected by K-D may go along with afferent dysfunction in MS patients. A brief test that requires saccadic eye movements, K-D should be considered for future MS trials as a rapid visual performance measure. Copyright © 2014 Elsevier B.V. All rights reserved.

Cardiac Complications, Earlier Treatment, and Initial Disease Severity in Kawasaki Disease.

PubMed

Abrams, Joseph Y; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

2017-09-01

To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible. Published by Elsevier Inc.

Glucocorticoid sensitivity and proinflammatory cytokines pattern in pemphigus.

PubMed

Chriguer, Rosangela Soares; Roselino, Ana Maria; de Castro, Margaret

2012-08-01

Glucocorticoids (GC) represent the main treatment for pemphigus; however, some patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus patients and 41 controls by the number of binding sites [B(max) (fmol/mg protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as well as by the pattern of cytokine by DEX-mediated inhibition of concanavalin-A (Con-A)-stimulated PBMC proliferation. The Kd (15.7 ± 2.8 vs.8.1 ± 1.3) and Bmax (6.5 ± 0.9 vs. 3.9 ± 0.3) were higher in pemphigus than controls (p = 0.002). Considering the values above the 95th percentile of normal group as a cut-off (K(d) > 24.9 nM and B(max) > 8.1 fmol/mg protein), elevated K(d) and B(max) were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p = 0.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p < 0.001) in both pemphigus and control groups. IL-6 and TNFα (pg/mL) basal production were higher in patients than controls. There was an increment of these cytokines after Con-A stimulation, and they were inhibited by DEX (p = 0.002) in controls and remained elevated in pemphigus (p < 0.02). Patients and controls showed no difference in basal and stimulated production of IL-8 and IL-10. There is an alteration on GC sensitivity in pemphigus patients and a higher production of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory cytokines might be involved in the mechanism of GC resistance and/or in its maintenance.

Effective therapy with infliximab for clinically mild encephalitis/encephalopathy with a reversible splenial lesion in an infant with Kawasaki disease.

PubMed

Kurokawa, Yoshie; Masuda, Hiroshi; Kobayashi, Tohru; Ono, Hiroshi; Kato, Hitoshi; Imadome, Ken-Ichi; Abe, Jun; Abe, Yuichi; Ito, Shuichi; Ishiguro, Akira

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis in infants. In KD, encephalopathy is rarely (0.1%) associated, however, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has previously been reported in some pediatric patients. Here, we report on a 2-year-old girl who had KD complicated with MERS. The patient experienced generalized clonic convulsion and prolonged consciousness disturbance with fever for 2 days. Her head MRI showed a high signal intensity lesion in the splenium of the corpus callosum in diffusion-weighted images, and low apparent diffusion coefficient (ADC) values on day 3. An electroencephalogram showed high voltage slow waves on the occipital and parietal head. On the same day, it was confirmed that the patient showed all the main symptoms of KD. Based on these findings, we diagnosed her with MERS-complicated KD. Even though she was treated with immunoglobulin (total 4 g/kg) and pulsed-dose methylprednisolone, her fever and consciousness disturbance continued, and blood tests showed that inflammation markers remained high. We then treated the patient with infliximab on day 9, and within a few hours of the treatment her fever dropped and all symptoms of KD and consciousness disturbance disappeared. No recurrence of KD or other complications of KD occurred, and she was discharged on day 23. We propose that infliximab is an effective optional treatment for immunoglobulin/glucocorticoid-resistant KD with MERS. To clarify this possibility, further case accumulation is warranted.

High Pressure Germination of Bacillus subtilis Spores with Alterations in Levels and Types of Germination Proteins

DTIC Science & Technology

2014-01-01

a rapidly growing non thermal food processing technology that ensures the safety of meat, fruit juice and seafood products, extends product shelf...spore germination with nutrient germinants are the sum of values for germination via the GerA GR with L valine and the GerB plus GerK GRs with AGFK...gerKD had no significant effect on mHP germination (Fig. 1d). Complementation of a gerKD strain by introduction of a wild type gerKD gene plus its own

Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

PubMed Central

Kimura, Yayoi; Yanagimachi, Masakatsu; Ino, Yoko; Aketagawa, Mao; Matsuo, Michie; Okayama, Akiko; Shimizu, Hiroyuki; Oba, Kunihiro; Morioka, Ichiro; Imagawa, Tomoyuki; Kaneko, Tetsuji; Yokota, Shumpei; Hirano, Hisashi; Mori, Masaaki

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features. PMID:28262744

Benzene and MTBE Sorption in Fine Grain Sediments

NASA Astrophysics Data System (ADS)

Leal-Bautista, R. M.; Lenczewski, M. E.

2003-12-01

The practice of adding methyl tert-butyl ether (MTBE) to gasoline started in the late 1970s and increased dramatically in the 1990s. MTBE first was added as a substitute for tetra-ethyl lead then later as a fuel oxygenate. Although the use of MTBE has resulted in significant reduction in air pollution, it has become a significant groundwater contaminant due to its high solubility in water, high environmental mobility, and low potential for biodegradation. A recent report (1999-2001) by the Metropolitan Water District of Southern California in collaboration with United State Geological Survey and the Oregon Health and Science University found that MTBE was the second most frequent detected volatile organic compound in groundwater. In Illinois, MTBE has been found in 26 of the 1,800 public water supplies. MTBE has also been blended in Mexico into two types of gasoline sold in the country by the state oil company (PEMEX) but is not monitored in groundwater at this time. Early research on MTBE considered it unable to adsorb to soils and sediments, however, by increasing the organic matter and decreasing the size of the grains (silts or clays) this may increase sorption. The objective of this study is to determine if fine grained materials have the potential for sorption of MTBE due to its high specific surface area (10-700 m 2/g) and potentially high organic matter (0.5-3.8%). The experiment consisted of sorption isotherms to glacial tills from DeKalb, Illinois and lacustrine clays from Chalco, Mexico. Experiments were performed with various concentrations of MTBE and benzene (10, 50, 100, 500 and 1000 ug/L) at 10° C and 25° C. Results showed a range of values for the distribution coefficient (Kd, linear model). At 10° C the Kd value for MTBE was 0.187 mL/g for lacustrine clay while the glacial loess had a value of 0.009 mL/g. The highest Kd values with MTBE were 0.2859 mL/g for organic rich lacustrine clays and 0.014 mL/g for glacial loess at 25° C. The highest values with benzene were 0.323 mL/g for organic rich lacustrine clays and 0.119 mL/g for glacial loess at 10° C. At 25° C the organic rich lacustrine clays the Kd value was 0.332 mL/g, while Kd value for glacial loess was 0.114 mL/g. Sands with no organic matter (Ottawa sand) had a value of < 0.001 mL/g for both temperatures 25° C and 10° C and both organic compounds. The retardation factor (R) for MTBE was 1.559 at 10° C and 1.855 at 25° C for lacustrine clays; while the glacial tills R was 1.058 at 10° C and 1.095 at 25° C. The retardation factor for benzene was 1.967 at 10° C and 1.996 at 25° C for lacustrine clays; while the glacial tills R was 1.039 at 10° C and 1.037 at 25° C. These results indicate higher retardation values than previously determined for a clayey sand; therefore show that sorption can occur in fine grain materials especially with high organic matter. This study contributes to the understanding of the sorption of MTBE and improves the knowledge to implement the optimal remediation method for sites contaminated by MTBE.

Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.

PubMed

Galetta, Kristin M; Chapman, Kimberly R; Essis, Maritza D; Alosco, Michael L; Gillard, Danielle; Steinberg, Eric; Dixon, Diane; Martin, Brett; Chaisson, Christine E; Kowall, Neil W; Tripodis, Yorghos; Balcer, Laura J; Stern, Robert A

2017-01-01

The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.

Mantle temperatures, and tests of experimentally calibrated olivine-melt equilibria

NASA Astrophysics Data System (ADS)

Putirka, K. D.

2005-12-01

Because the ratio Mgol/Mgliq (Kd(Mg)) is sensitive to T, olivine-liquid Kd's have long been used as geothermometers, and more recently, maximum Fo contents from volcanic rocks have been used to estimate mantle potential temperatures. Such estimates by Putirka (2005, G3) indicate higher mantle equilibration temperatures at Hawaii, compared to temperatures derived from earlier calibrations. Several published models were thus tested for their ability to reproduce T for 862 experimental data. The Putirka (2005) models did not include P corrections, which are added here: lnKd(Mg)=-1.88 + 30.85P(GPa)/T(C) - 0.04[H2O]liq + 0.068[Na2O+K2O]liq + 3629.7/T(C) + 0.0087[SiO2]liq - 0.015[CaO]liq lnKd(Fe)= -2.92 - 0.05[H2O]liq + 0.0264[Na2O+K2O]liq + 2976.13/T(C) + 0.01847[SiO2]liq + 0.0171[Al2O3]liq - 0.039[CaO]liq + 33.17P(GPa)/T(C) In these expressions, Kd(Mg) and Kd(Fe) are the partition coefficients for Mg and Fe between olivine and liquid, expressed as cation fractions; compositional corrections are in weight percent. The models are calibrated from 785 experimental data (P = 0.0001-15.5 GPa; 1213-2353 K). In the tests, the expressions of Beattie (1993) performed exceptionally well for dry systems with MgOliq < 17 wt. %, with a standard error of estimate of 35 K, compared to an SEE of 59 K for Ford et al. (1983) and an SEE of 51 K for the inversion of the Kd(Mg) model above. Recalibration of the Beattie (1993) model over this composition range thus appears unnecessary. But Beattie (1993), Ford et al. (1983), and other models overestimate T for hydrous systems, and for compositions with MgOliq > 17 wt. %; new models are therefore needed. Over the greater compositional range, model 1 above can be inverted to yield T with a SEE of 56 K, and an average mean (systematic) error of +3 K for 856 experimental data; this compares to a systematic error of -26 K for Beattie (1993) and -36 K for Ford et al. (1983). For use in equation (1) of Putirka (2005), the models above are also more precise at both low and high MgO, and hydrous and non-hydrous systems compared to Beattie (1993) and Ford et al. (1983). Herzberg (pers. comm.) has modeled olivine-melt pairs for Hawaii and MOR's, which are in accord with Putirka (2005); these pairs are used to test for the effects of systematic model error on estimates of mantle temperatures. The Beattie (1993) and Ford (1983) models appear to predict too low a value for T (by 100-150 K), given comparisons of lnKd(Mg) v. 1/T(K) for experimental data, and the very low values for Kd(Mg) observed at Hawaii. The new calibrations indicate mantle equilibration temperatures of 1855 K at Hawaii and 1608 K at MOR's, in agreement with calculations by Putirka (2005). Excess temperatures at Hawaii thus likely exceed 200 K, as suggested by dynamic model predictions (Sleep, 1990; Schilling, 1991) for a thermal plume origin for the Hawaiian Islands and other hot spots.

Estimation of bioavailability of metals from drilling mud barite.

PubMed

Neff, Jerry M

2008-04-01

Drilling mud and associated drill cuttings are the largest volume wastes associated with drilling of oil and gas wells and often are discharged to the ocean from offshore drilling platforms. Barite (BaSO4) often is added as a weighting agent to drilling muds to counteract pressure in the geologic formations being drilled, preventing a blowout. Some commercial drilling mud barites contain elevated (compared to marine sediments) concentrations of several metals. The metals, if bioavailable, may harm the local marine ecosystem. The bioavailable fraction of metals is the fraction that dissolves from the nearly insoluble, solid barite into seawater or sediment porewater. Barite-seawater and barite-porewater distribution coefficients (Kd) were calculated for determining the predicted environmental concentration (PEC; the bioavailable fraction) of metals from drilling mud barite in the water column and sediments, respectively. Values for Kdbarite-seawater and Kdbarite-porewater were calculated for barium, cadmium, chromium, copper, mercury, lead, and zinc in different grades of barite. Log Kdbarite-seawater values were higher (solubility was lower) for metals in the produced water plume than log Kdbarite-porewater values for metals in sediments. The most soluble metals were cadmium and zinc and the least soluble were mercury and copper. Log Kd values can be used with data on concentrations of metals in barite and of barite in the drilling mud-cuttings plume and in bottom sediments to calculate PECseawater and PECsediment.

Clinical characteristics and serum N-terminal pro-brain natriuretic peptide as a diagnostic marker of Kawasaki disease in infants younger than 3 months of age.

PubMed

Bae, Hyun Kyung; Lee, Do Kyung; Kwon, Jung Hyun; Kim, Hae Soon; Sohn, Sejung; Hong, Young Mi

2014-08-01

The incidence of Kawasaki disease (KD) is rare in young infants (less than 3 months of age), who present with only a few symptoms that fulfill the clinical diagnostic criteria. The diagnosis for KD can therefore be delayed, leading to a high risk of cardiac complications. We examined the clinical characteristics and measured the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of these patients for assessing its value in the early detection of KD. We retrospectively reviewed the data of young infants diagnosed with KD from 2004 to 2012. The control group included 20 hospitalized febrile patients. Laboratory data, including NT-proBNP were obtained for each patient in both groups. Incomplete KD was observed in 21/24 patients (87.5%). The mean fever duration on admission was 1.36±1.0 days in the KD group. Common symptoms included erythema at the site of Bacille Calmette-Guerin inoculation (70.8%), skin rash (50.0%), changes of oropharyngeal mucosa (29.1%), and cervical lymphadenopathy (20.8%). The mean number of major diagnostic criteria fulfilled was 2.8±1.4. Five KD patients (20.8%) had only one symptom matching these criteria. The incidence of coronary artery complications was 12.5%. The mean serum NT-proBNP level in the acute phase, in the KD and control groups, were 4,159±3,714 pg/mL and 957±902 pg/mL, respectively, which decreased significantly in the convalescent phase. Incomplete KD was observed in 87.5% patients. Serum NT-proBNP might be a valuable biomarker for the early detection of KD in febrile infants aged <3 months.

Kawasaki disease and ENSO-driven wind circulation

NASA Astrophysics Data System (ADS)

Ballester, Joan; Burns, Jane C.; Cayan, Dan; Nakamura, Yosikazu; Uehara, Ritei; Rodó, Xavier

2013-05-01

disease (KD) is the most common cause of acquired heart disease in children worldwide. Recently, a climatological study suggested that KD may be triggered by a windborne agent traveling across the north Pacific through the westerly wind flow prevailing at midlatitudes. Here we use KD records to describe the association between enhanced disease activity on opposite sides of the basin and different phases of the El Niño-Southern Oscillation (ENSO) phenomenon, via the linkage to these tropospheric winds. Results show that years with higher-than-normal KD cases in Japan preferentially occur during either El Niño Modoki or La Niña conditions, while in San Diego during the mature phase of El Niño or La Niña events. Given that ENSO offers a degree of predictability at lead times of 6 months, these modulations suggest that seasonal predictions of KD could be used to alert clinicians to periods of increased disease activity.

Isomer-Specific Binding Affinity of Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) to Serum Proteins.

PubMed

Beesoon, Sanjay; Martin, Jonathan W

2015-05-05

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are among the most prominent contaminants in human serum, and these were historically manufactured as technical mixtures of linear and branched isomers. The isomers display unique pharmacokinetics in humans and in animal models, but molecular mechanisms underlying isomer-specific PFOS and PFOA disposition have not previously been studied. Here, ultrafiltration devices were used to examine (i) the dissociation constants (Kd) of individual PFOS and PFOA isomers with human serum albumin (HSA) and (ii) relative binding affinity of isomers in technical mixtures spiked to whole calf serum and human serum. Measurement of HSA Kd's demonstrated that linear PFOS (Kd=8(±4)×10(-8) M) was much more tightly bound than branched PFOS isomers (Kd range from 8(±1)×10(-5) M to 4(±2)×10(-4) M). Similarly, linear PFOA (Kd=1(±0.9)×10(-4) M) was more strongly bound to HSA compared to branched PFOA isomers (Kd range from 4(±2)×10(-4) M to 3(±2)×10(-4) M). The higher binding affinities of linear PFOS and PFOA to total serum protein were confirmed when both calf serum and human serum were spiked with technical mixtures. Overall, these data provide a mechanistic explanation for the longer biological half-life of PFOS in humans, compared to PFOA, and for the higher transplacental transfer efficiencies and renal clearance of branched PFOS and PFOA isomers, compared to the respective linear isomer.

Methods for Estimating Adsorbed Uranium(VI) and Distribution Coefficients of Contaminated Sediments

USGS Publications Warehouse

Kohler, M.; Curtis, G.P.; Meece, D.E.; Davis, J.A.

2004-01-01

Assessing the quantity of U(VI) that participates in sorption/desorption processes in a contaminated aquifer is an important task when investigating U migration behavior. U-contaminated aquifer sediments were obtained from 16 different locations at a former U mill tailings site at Naturita, CO (U.S.A.) and were extracted with an artificial groundwater, a high pH sodium bicarbonate solution, hydroxylamine hydrochloride solution, and concentrated nitric acid. With an isotopic exchange method, both a KD value for the specific experimental conditions as well as the total exchangeable mass of U(VI) was determined. Except for one sample, KD values determined by isotopic exchange with U-contaminated sediments that were in equilibrium with atmospheric CO2 agreed within a factor of 2 with KD values predicted from a nonelectrostatic surface complexation model (NEM) developed from U(VI) adsorption experiments with uncontaminated sediments. The labile fraction of U(VI) and U extracted by the bicarbonate solution were highly correlated (r2 = 0.997), with a slope of 0.96 ?? 0.01. The proximity of the slope to one suggests that both methods likely access the same reservoir of U(VI) associated with the sediments. The results indicate that the bicarbonate extraction method is useful for estimating the mass of labile U(VI) in sediments that do not contain U(IV). In-situ KD values calculated from the measured labile U(VI) and the dissolved U(VI) in the Naturita alluvial aquifer agreed within a factor of 3 with in-situ K D values predicted with the NEM and groundwater chemistry at each well.

Seasonality of Kawasaki Disease: A Global Perspective

PubMed Central

Burns, Jane C.; Herzog, Lauren; Fabri, Olivia; Tremoulet, Adriana H.; Rodó, Xavier; Uehara, Ritei; Burgner, David; Bainto, Emelia; Pierce, David; Tyree, Mary; Cayan, Daniel

2013-01-01

Background Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Methods Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. Results A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Conclusion Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics. PMID:24058585

Seasonality of Kawasaki disease: a global perspective.

PubMed

Burns, Jane C; Herzog, Lauren; Fabri, Olivia; Tremoulet, Adriana H; Rodó, Xavier; Uehara, Ritei; Burgner, David; Bainto, Emelia; Pierce, David; Tyree, Mary; Cayan, Daniel

2013-01-01

Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.

Hemodynamic Based Coronary Artery Aneurysm Thrombosis Risk Stratification in Kawasaki Disease Patients

NASA Astrophysics Data System (ADS)

Grande Gutierrez, Noelia; Mathew, M.; McCrindle, B.; Kahn, A.; Burns, J.; Marsden, A.

2017-11-01

Coronary artery aneurysms (CAA) as a result of Kawasaki Disease (KD) put patients at risk for thrombosis and myocardial infarction. Current AHA guidelines recommend CAA diameter >8 mm or Z-score >10 as the criterion for initiating systemic anticoagulation. Our hypothesis is that hemodynamic data derived from computational blood flow simulations is a better predictor of thrombosis than aneurysm diameter alone. Patient-specific coronary models were constructed from CMRI for a cohort of 10 KD patients (5 confirmed thrombosis cases) and simulations with fluid structure interaction were performed using the stabilized finite element Navier-Stokes solver available in SimVascular. We used a closed-loop lumped parameter network (LPN) to model the heart and vascular boundary conditions coupled numerically to the flow solver. An automated parameter estimation method was used to match LPN values to clinical data for each patient. Hemodynamic data analysis resulted in low correlation between Wall Shear Stress (WSS)/ Particle Residence Time (PRT) and CAA diameter but demonstrates the positive correlation between hemodynamics and adverse patient outcomes. Our results suggest that quantifying WSS and PRT should enable identification of regions at higher risk of thrombosis. We propose a quantitative method to non-invasively assess the abnormal flow in CAA following KD that could potentially improve clinical decision-making regarding anticoagulation therapy.

Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

PubMed

Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

2017-12-01

We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and <$150,000/QALY up to an 85% discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

[Changes in molecular forms of sex hormone binding globulin during menstrual cycle and menopause].

PubMed

Fonseca, M E; Masón, M; Ochoa, R; Hernández-V, M; Zárate, A

1996-11-01

Sex hormone binding globulin (SHBG) is a glycoprotein that transports mainly androgens and estrogens regulating the amount of free and bound hormone which in turn plays a role in the metabolic balance. It is also known that estrogens increase the hepatic production of SHBG which circulates in various molecular forms containing different amounts of sialic acid as the main component of carbohydrates. In the present work we studied physiological variations of molecular forms of SHBG during the normal menstrual cycle and the menopause. During the follicular phase the form 54 KD was the predominant variant, in the periovulatory period was isomers 90 KD, and during the luteal phase corresponded to both 54 and 90 KD. In the menopause dimeric form of 90 KD corresponded to the major proportion and was present a higher molecular forms of 115-135 KD. Following estrogen therapy the chromatographic profile changed as to that observed during the menstrual cycle. Important changes in the proportion of sialic acid were observed in each of the phases of menstrual cycle and following estrogen replacement. And increase in the amount of sialic acid corresponded to higher estrogen concentrations. It is concluded that SHBG concentrations varies during the menstrual cycle according the estrogen levels which in addition regulates the proportion of molecular forms and sialic acid containt.

Resistance to intravenous immunoglobulin in children with Kawasaki disease

PubMed Central

Tremoulet, Adriana H.; Best, Brookie M.; Song, Sungchan; Wang, Susan; Corinaldesi, Elena; Eichenfield, Julia R.; Martin, Danielle D.; Newburger, Jane W.; Burns, Jane C.

2008-01-01

Objectives To explore the increased incidence of intravenous immunoglobulin (IVIG) resistance among San Diego County Kawasaki disease (KD) patients in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD. Study design We performed a retrospective review of patients with KD treated within 10 days of fever onset. Using multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. Results In 2006, 38.3 % of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher % bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase (GGT). They also had lower platelet counts and age-adjusted hemoglobin (zHgb) concentrations and were more likely to have aneurysms (p=0.0008). A scoring system developed to predict IVIG-resistant patients using illness day, % bands, GGT, and zHgb, had a sensitivity of 73.3% and specificity of 61.9%. Conclusions An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population. PMID:18571548

Levels of intra- and extracellular heat shock protein 60 in Kawasaki disease patients treated with intravenous immunoglobulin.

PubMed

Yin Ji, Xu; Kang, Mi-Ran; Choi, Jong-Sung; Jeon, Hak-Soo; Han, Heon-Seok; Kim, Ji-Yoon; Son, Bo-Ra; Lee, Young-Min; Hahn, Youn-Soo

2007-09-01

Immune reactivity to autologous heat shock protein 60 (HSP60) has been reported to be associated with a favorable prognosis in autoimmune diseases. To provide a clue for the possible role of HSP60 in Kawasaki disease (KD), we investigated the levels of intra- and extracellular HSP60 in the course of KD. In KD patients, autologous HSP60 was abundantly expressed in CD11c(+) cells during the acute phase and subsequently decreased during the subacute phase. Most of HSP60-expressing CD11c(+) cells observed in the acute phase was composed of CD11c(low) cells instead of CD11c(high) cells, which were dominant in the subacute phase. In contrast, circulating HSP60 levels were higher in the subacute phase than those in the acute phase, reflecting higher level of HSP60 exposure to the immune system of patients during recovery. These changes in the levels of intra- and extracellular HSP60 were not observed in patients with other febrile diseases. The observed features of HSP60 expression in patients with KD are in favor of a role for autologous HSP60 as a regulator for control of inflammation, rather than a proinflammatory mediator in KD.

Soil pH on mobility of imazaquin in oxisols with positive balance of charges.

PubMed

Regitano, Jussara B; da Rocha, Wadson S D; Alleoni, Luís R F

2005-05-18

The influence of soil pH on the leaching potential of the ionizable herbicide imazaquin was assessed on the profile of two highly weathered soils having a net positive charge in the B horizon, in contrast to a soil having a net negative charge in the whole profile, using packed soil column experiments. Imazaquin leached to a large extent and faster at Kd values lower than 1.0 L kg(-1), a much more lenient limit than usually proposed for pesticides in the literature (Kd < 5.0 L kg(-1)). The amount of imazaquin leached increased with soil pH. As the soil pH increased, the percentage of imazaquin in the anionic forms, the negative surface potential of the soils, as well as imazaquin water solubility also increased, thus reducing sorption because of repulsive electrostatic forces (hydrophilic interactions). For all surface samples (0-0.2 m), imazaquin did not leach at soil pH values lower than pKa (3.8) and more than 80% of the applied amount was leached at pH values higher than 5.5. For subsurface samples from the acric soils, imazaquin only began to leach at soil pH values > zero point of salt effects (ZPSE > 5.7). In conclusion, the use of surface K(oc) values to predict the amount of imazaquin leached within soil profiles having a positive balance of charges may greatly overestimate its actual leaching potential.

Genetic variants of CD209 associated with Kawasaki disease susceptibility.

PubMed

Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

2014-01-01

Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.

Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility

PubMed Central

Kuo, Ho-Chang; Huang, Ying-Hsien; Chien, Shu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Chang, Wei-Chiao

2014-01-01

Background Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. Methods A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Results Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. Conclusion CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness. PMID:25148534

Characterization of T cell repertoire changes in acute Kawasaki disease

PubMed Central

1993-01-01

Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease. PMID:8094737

How To Functionalize Ceramics by Perfluoroalkylsilanes for Membrane Separation Process? Properties and Application of Hydrophobized Ceramic Membranes.

PubMed

Kujawa, Joanna; Cerneaux, Sophie; Kujawski, Wojciech; Bryjak, Marek; Kujawski, Jan

2016-03-23

The combination of microscopic (atomic force microscopy and scanning electron microscopy) and goniometric (static and dynamic measurements) techniques, and surface characterization (surface free energy determination, critical surface tension, liquid entry pressure, hydraulic permeability) was implemented to discuss the influence of perfluoroalkylsilanes structure and grafting time on the physicochemistry of the created hydrophobic surfaces on the titania ceramic membranes of 5 kD and 300 kD. The impact of molecular structure of perfluoroalkylsilanes modifiers (possessing from 6 to 12 carbon atoms in the fluorinated part of the alkyl chain) and the time of the functionalization process in the range of 5 to 35 h was studied. Based on the scanning electron microscopy with energy-dispersive X-ray spectroscopy, it was found that the localization of grafting molecules depends on the membrane pore size (5 kD or 300 kD). In the case of 5 kD titania membranes, modifiers are attached mainly on the surface and only partially inside the membrane pores, whereas, for 300 kD membranes, the perfluoroalkylsilanes molecules are present within the whole porous structure of the membranes. The application of 4 various types of PFAS molecules enabled for interesting observations and remarks. It was explained how to obtain ceramic membrane surfaces with controlled material (contact angle, roughness, contact angle hysteresis) and separation properties. Highly hydrophobic surfaces with low values of contact angle hysteresis and low roughness were obtained. These surfaces possessed also low values of critical surface tension, which means that surfaces are highly resistant to wetting. This finding is crucial in membrane applicability in separation processes. The obtained and characterized hydrophobic membranes were subsequently applied in air-gap membrane distillation processes. All membranes were very efficient in MD processes, showing good transport and selective properties (∼99% of NaCl salt rejection). Depending on the membrane pore size and used modifiers, the permeate flux was in the range of 0.5-4.5 kg·m(-2)·h(-1) and 0.3-4.2 kg·m(-2)·h(-1) for 5 kD and 300 kD membranes, respectively.

Super-high-affinity binding site for [3H]diazepam in the presence of Co2+, Ni2+, Cu2+, or Zn2+.

PubMed

Mizuno, S; Ogawa, N; Mori, A

1982-12-01

Chloride salts of Li+, Na+, K+, Mg2+, Ca2+, Cr3+, Mn2+, Fe2+, and Fe3+ had no effect on [3H]diazepam binding. Chloride salts of Co2+, Ni2+, Cu2+, and Zn2+ increased [3H]diazepam binding by 34 to 68% in a concentration-dependent fashion. Since these divalent cations potentiated the GABA-enhanced [3H]diazepam binding and the effect of each divalent cation was nearly additive with GABA, these cations probably act at a site different from the GABA recognition site in the benzodiazepine-receptor complex. Scatchard plots of [3H]diazepam binding without an effective divalent cation showed a single class of binding, with a Kd value of 5.3 nM. In the presence of 1 mM Co2+, Ni2+, Cu2+, or Zn2+, two distinct binding sites were evident with apparent Kd values of 1.0 nM and 5.7 nM. The higher-affinity binding was not detected in the absence of an effective divalent cation and is probably a novel, super-high-affinity binding site.

Two-dimensional interaction of a shear flow with a free surface in a stratified fluid and its solitary-wave solutions via mathematical methods

NASA Astrophysics Data System (ADS)

Seadawy, Aly R.

2017-12-01

In this study, we presented the problem formulations of models for internal solitary waves in a stratified shear flow with a free surface. The nonlinear higher order of extended KdV equations for the free surface displacement is generated. We derived the coefficients of the nonlinear higher-order extended KdV equation in terms of integrals of the modal function for the linear long-wave theory. The wave amplitude potential and the fluid pressure of the extended KdV equation in the form of solitary-wave solutions are deduced. We discussed and analyzed the stability of the obtained solutions and the movement role of the waves by making graphs of the exact solutions.

A Neural Network Model for K(λ) Retrieval and Application to Global Kpar Monitoring.

PubMed

Chen, Jun; Zhu, Yuanli; Wu, Yongsheng; Cui, Tingwei; Ishizaka, Joji; Ju, Yongtao

2015-01-01

Accurate estimation of diffuse attenuation coefficients in the visible wavelengths Kd(λ) from remotely sensed data is particularly challenging in global oceanic and coastal waters. The objectives of the present study are to evaluate the applicability of a semi-analytical Kd(λ) retrieval model (SAKM) and Jamet's neural network model (JNNM), and then develop a new neural network Kd(λ) retrieval model (NNKM). Based on the comparison of Kd(λ) predicted by these models with in situ measurements taken from the global oceanic and coastal waters, all of the NNKM, SAKM, and JNNM models work well in Kd(λ) retrievals, but the NNKM model works more stable and accurate than both SAKM and JNNM models. The near-infrared band-based and shortwave infrared band-based combined model is used to remove the atmospheric effects on MODIS data. The Kd(λ) data was determined from the atmospheric corrected MODIS data using the NNKM, JNNM, and SAKM models. The results show that the NNKM model produces <30% uncertainty in deriving Kd(λ) from global oceanic and coastal waters, which is 4.88-17.18% more accurate than SAKM and JNNM models. Furthermore, we employ an empirical approach to calculate Kpar from the NNKM model-derived diffuse attenuation coefficient at visible bands (443, 488, 555, and 667 nm). The results show that our model presents a satisfactory performance in deriving Kpar from the global oceanic and coastal waters with 20.2% uncertainty. The Kpar are quantified from MODIS data atmospheric correction using our model. Comparing with field measurements, our model produces ~31.0% uncertainty in deriving Kpar from Bohai Sea. Finally, the applicability of our model for general oceanographic studies is briefly illuminated by applying it to climatological monthly mean remote sensing reflectance for time ranging from July, 2002- July 2014 at the global scale. The results indicate that the high Kd(λ) and Kpar values are usually found around the coastal zones in the high latitude regions, while low Kd(λ) and Kpar values are usually found in the open oceans around the low-latitude regions. These results could improve our knowledge about the light field under waters at either the global or basin scales, and be potentially used into general circulation models to estimate the heat flux between atmosphere and ocean.

Phosphate fertilizer impacts on glyphosate sorption by soil.

PubMed

Munira, Sirajum; Farenhorst, Annemieke; Flaten, Don; Grant, Cynthia

2016-06-01

This research examined the impact of field-aged phosphate and cadmium (Cd) concentrations, and fresh phosphate co-applications, on glyphosate sorption by soil. Soil samples were collected in 2013 from research plots that had received, from 2002 to 2009, annual applications of mono ammonium phosphate (MAP) at 20, 40 and 80 kg P ha(-1) and from products containing 0.4, 70 or 210 mg Cd kg(-1) as an impurity. A series of batch equilibrium experiments were carried out to quantify the glyphosate sorption distribution constant, Kd. Extractable Cd concentrations in soil had no significant effect on glyphosate sorption. Glyphosate Kd values significantly decreased with increasing Olsen-P concentrations in soil, regardless of the pH conditions studied. Experiments repeated with a commercially available glyphosate formulation showed statistically similar results as the experiments performed with analytical-grade glyphosate. Co-applications of MAP with glyphosate also reduced the available sorption sites to retain glyphosate, but less so when soils already contain large amounts of phosphate. Glyphosate Kd values in soils ranged from 173 to 939 L kg(-1) under very strong to strongly acidic condition but the Kd was always <100 L kg(-1) under moderately acidic to slightly alkaline conditions. The highest Olsen-P concentrations in soil reduced Kd values by 25-44% relative to control soils suggesting that, under moderately acidic to slightly alkaline conditions, glyphosate may become mobile by water in soils with high phosphate levels. Otherwise, glyphosate residues in agricultural soils are more likely to be transported off-site by wind and water-eroded sediments than by leaching or runoff. Copyright © 2016 Elsevier Ltd. All rights reserved.

Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation.

PubMed

Chwiej, J; Patulska, A; Skoczen, A; Matusiak, K; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

2017-07-01

In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2). KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals. Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region. Copyright © 2017 Elsevier GmbH. All rights reserved.

Involvement of serotonin system in bullimia

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

Marazziti, D.; Macchi, E.; Rotondo, A.

1988-01-01

Platelet /sup 3/H-imipramine binding was investigated in 8 patients affected by bulimia according to DSM III criteria, and in 7 health volunteers. The Bmax /+ -/SD (fmol/mg protein) was 356 /+ -/ 53 in patients, and 1144 /+ -/ 134 in controls. The Kd /+ -/ SD (nM) was 1.35 /+ -/ 0.44 in patients, and 1.90 /+ -/ 0.72 in controls. There was a significant difference in Bmax values in the two groups, whereas no significant difference was observed in Kd values. This study suggests the possible involvement of the indoleamine system in bullimia.

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

Anderson, G.F.; Marks, B.H.

This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing (/sup 125/I)iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results weremore » compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population.« less

Results of a prospective clinical study on the diagnostic performance of standard magnetic resonance imaging in comparison to a combination of 3T MRI and additional CT imaging in Kienböck's disease.

PubMed

Stahl, Stephane; Hentschel, Pascal; Ketelsen, Dominik; Grosse, Ulrich; Held, Manuel; Wahler, Theodora; Syha, Roland; Schaller, Hans-Eberhard; Nikolaou, Konstantin; Grözinger, Gerd

2017-05-01

This prospective clinical study examined standard wrist magnetic resonance imaging (MRI) examinations and the incremental value of computed tomography (CT) in the diagnosis of Kienböck's disease (KD) with regard to reliability and precision in the different diagnostic steps during diagnostic work-up. Sixty-four consecutive patients referred between January 2009 and January 2014 with positive initial suspicion of KD according to external standard wrist MRI were prospectively included (step one). Institutional review board approval was obtained. Clinical examination by two handsurgeons were followed by wrist radiographs (step two), ultrathin-section CT, and 3T contrast-enhanced MRI (step three). Final diagnosis was established in a consensus conference involving all examiners and all examinations results available from step three. In 12/64 patients, initial suspicion was discarded at step two and in 34/64 patients, the initial suspicion of KD was finally discarded at step three. The final external MRI positive predictive value was 47%. The most common differential diagnoses at step three were intraosseous cysts (n=15), lunate pseudarthrosis (n=13), and ulnar impaction syndrome (n=5). A correlation between radiograph-based diagnoses (step two) with final diagnosis (step three) showed that initial suspicion of stage I KD had the lowest sensitivity for correct diagnosis (2/11). Technical factors associated with a false positive external MRI KD diagnosis were not found. Standard wrist MRI should be complemented with thin-section CT, and interdisciplinary interpretation of images and clinical data, to increase diagnostic accuracy in patients with suspected KD. Copyright © 2017. Published by Elsevier B.V.

Predicting sorption of pharmaceuticals and personal care products onto soil and digested sludge using artificial neural networks.

PubMed

Barron, Leon; Havel, Josef; Purcell, Martha; Szpak, Michal; Kelleher, Brian; Paull, Brett

2009-04-01

A comprehensive analytical investigation of the sorption behaviour of a large selection of over-the-counter, prescribed pharmaceuticals and illicit drugs to agricultural soils and freeze-dried digested sludges is presented. Batch sorption experiments were carried out to identify which compounds could potentially concentrate in soils as a result of biosolid enrichment. Analysis of aqueous samples was carried out directly using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For solids analysis, combined pressurised liquid extraction and solid phase extraction methods were used prior to LC-MS/MS. Solid-water distribution coefficients (K(d)) were calculated based on slopes of sorption isotherms over a defined concentration range. Molecular descriptors such as log P, pK(a), molar refractivity, aromatic ratio, hydrophilic factor and topological surface area were collected for all solutes and, along with generated K(d) data, were incorporated as a training set within a developed artificial neural network to predict K(d) for all solutes within both sample types. Therefore, this work represents a novel approach using combined and cross-validated analytical and computational techniques to confidently study sorption modes within the environment. The logarithm plots of predicted versus experimentally determined K(d) are presented which showed excellent correlation (R(2) > 0.88), highlighting that artificial neural networks could be used as a predictive tool for this application. To evaluate the developed model, it was used to predict K(d) for meclofenamic acid, mefenamic acid, ibuprofen and furosemide and subsequently compared to experimentally determined values in soil. Ratios of experimental/predicted K(d) values were found to be 1.00, 1.00, 1.75 and 1.65, respectively.

Mycobacterium leprae antigens involved in human immune responses. I. Identification of four antigens by monoclonal antibodies

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

Britton, W.J.; Hellqvist, L.; Basten, A.

1985-12-01

Four distinct antigens were identified in soluble sonicates of Mycobacterium leprae by using a panel of 11 monoclonal antibodies. Cross-reactivity studies with other mycobacterial species were conducted by using ELISA and immunoblot assays, and demonstrated that determinants on two of the antigens were present in many mycobacteria, whereas the other two were limited in distribution. Competitive inhibition experiments with radiolabeled monoclonal antibodies showed cross-inhibition between antibodies identifying two of the four antigenicbands. These two bands, of M/sub tau/ 4.5 to 6 KD and 30 to 40 KD, were resistant to protease treatment after immunoblotting. In contrast the two other bandsmore » of 16 and 70 KD were protease-sensitive. Although all four bands reacted with some human lepromatous leprosy sera in immunoblots, the 4.5 to 6 KD and 30 to 40 KD bands were most prominent. Lepromatous leprosy sera also inhibited the binding of radiolabeled monoclonal antibodies to each of the four antigens, with the mean titer causing 50% inhibition being higher for antibodies reacting with the 4.5 to 6 KD and 30 to 40 KD bands. These findings indicated that all four antigens were involved in the human B cell response to M. leprae.« less

Comparative Analysis of the 15.5kD Box C/D snoRNP Core Protein in the Primitive Eukaryote Giardia lamblia Reveals Unique Structural and Functional Features

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

Biswas, Shyamasri; Buhrman, Greg; Gagnon, Keith

2012-07-11

Box C/D ribonucleoproteins (RNP) guide the 2'-O-methylation of targeted nucleotides in archaeal and eukaryotic rRNAs. The archaeal L7Ae and eukaryotic 15.5kD box C/D RNP core protein homologues initiate RNP assembly by recognizing kink-turn (K-turn) motifs. The crystal structure of the 15.5kD core protein from the primitive eukaryote Giardia lamblia is described here to a resolution of 1.8 {angstrom}. The Giardia 15.5kD protein exhibits the typical {alpha}-{beta}-{alpha} sandwich fold exhibited by both archaeal L7Ae and eukaryotic 15.5kD proteins. Characteristic of eukaryotic homologues, the Giardia 15.5kD protein binds the K-turn motif but not the variant K-loop motif. The highly conserved residues ofmore » loop 9, critical for RNA binding, also exhibit conformations similar to those of the human 15.5kD protein when bound to the K-turn motif. However, comparative sequence analysis indicated a distinct evolutionary position between Archaea and Eukarya. Indeed, assessment of the Giardia 15.5kD protein in denaturing experiments demonstrated an intermediate stability in protein structure when compared with that of the eukaryotic mouse 15.5kD and archaeal Methanocaldococcus jannaschii L7Ae proteins. Most notable was the ability of the Giardia 15.5kD protein to assemble in vitro a catalytically active chimeric box C/D RNP utilizing the archaeal M. jannaschii Nop56/58 and fibrillarin core proteins. In contrast, a catalytically competent chimeric RNP could not be assembled using the mouse 15.5kD protein. Collectively, these analyses suggest that the G. lamblia 15.5kD protein occupies a unique position in the evolution of this box C/D RNP core protein retaining structural and functional features characteristic of both archaeal L7Ae and higher eukaryotic 15.5kD homologues.« less

Calcium affecting protein expression in longan under simulated acid rain stress.

PubMed

Pan, Tengfei; Li, Yongyu; Ma, Cuilan; Qiu, Dongliang

2015-08-01

Longan (Dimocarpus longana Lour. cv. Wulongling) of uniform one-aged seedlings grown in pots were selected to study specific proteins expressed in leaves under simulated acid rain (SiAR) stress and exogenous Ca(2+) regulation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results showed that there was a protein band specifically expressed under SiAR of pH 2.5 stress for 15 days with its molecular weight of about 23 kD. A 17 kD protein band specifically expressed after SiAR stress 5 days. Compared with pH 2.5, the pH 3.5 of SiAR made a less influence to protein expression. Two-dimensional electrophoresis (2-DE) results showed that six new specific proteins including C4 (20.2 kD pI 6.0), F (24 kD pI 6.35), B3 (22.3 kD pI 6.35), B4 (23.5 kD pI 6.5), C5 (21.8 kD pI 5.6), and C6 (20.2 kD pI 5.6) specifically expressed. C4 always expressed during SiAR stress. F expressed under the stress of pH 2.5 for 15 days and expressed in all pH SiAR stress for 20 days. The expression of proteins including B3, C5, and C6 was related to pH value and stress intensity of SiAR. The expression of B4 resulted from synergistic effects of SiAR and Ca. The expression of G1 (Mr 19.3 kD, pI 4.5), G2 (Mr 17.8 kD, pI 4.65), G3 (Mr 16.6 kD, pI 4.6), and G4 (Mr 14.7 kD, pI 4.4) enhanced under the treatment of 5 mM ethylene glycol tetraacetic acid (EGTA) and 2 mM chlorpromazine (CPZ). These proteins showed antagonistic effects and might be relative to the Ca-calmodulin (Ca-CaM) system of longan in response to SiAR stress.

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease.

PubMed

Kuo, Ho-Chang; Wong, Henry Sung-Ching; Chang, Wei-Pin; Chen, Ben-Kuen; Wu, Mei-Shin; Yang, Kuender D; Hsieh, Kai-Sheng; Hsu, Yu-Wen; Liu, Shih-Feng; Liu, Xiao; Chang, Wei-Chiao

2017-10-01

Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have persistent fever after IVIG treatment and are defined as IVIG resistant. To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P value 4.518×10 - 03 and 8.224×10 - 10 , respectively). This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG. © 2017 The Authors.

Estimating the sorption of pharmaceuticals based on their pharmacological distribution.

PubMed

Williams, Mike; Ong, Poh L; Williams, Desmond B; Kookana, Rai S

2009-12-01

Pharmaceuticals released into aquatic systems are expected to sorb to sediments to varying degrees. Their sorption is likely to influence their fate and, ultimately, the risk they pose to aquatic organisms. This has led to the European Medicines Agency requiring an assessment of affinity to solids, using batch sorption methods, for the environmental risk assessment (ERA) of new human medicines. However, a large body of data is generated before pharmaceuticals are released onto the market, including their extent of distribution throughout the human body, measured by the volume of distribution (VD). In the present study, batch sorption experiments were undertaken using 12 different soils and sediments to determine whether VD was a good indicator of experimental Kd values for 21 pharmaceuticals. The r2 values obtained from the regressions ranged from 0.39 to 0.76 (with a median value of 0.5) and all regressions were found to be significant. The use of this more comprehensive set of soils and sediments was consistent with previous studies comparing VD and Kd, despite the Kd values of the selected pharmaceuticals varying greatly between soils. The relationship between Kd and VD was greatly improved when zwitterionic antibiotics and carbamazepine were not included, possibly due to complex sorption or pharmacokinetic behavior. There are likely to be a number of factors affecting the sorption of pharmaceuticals that cannot be explained by VD. However, further work may elucidate how these factors can be accounted for, enabling VD to be effectively used to facilitate the ERA of human pharmaceuticals with already available information.

Incidence, epidemiology and clinical features of Kawasaki disease in Catalonia, Spain.

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estíbaliz; Calzada-Hernandez, Joan

2016-01-01

To assess the incidence, epidemiology and clinical features of Kawasaki disease (KD) in Catalonia (northeast region of Spain). This was an observational population-based study including all Paediatric Units in Catalonia, under both public and private management. Retrospective data retrieval was performed for 10 years (2004-2013). A 12-month (March 2013 to March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. Data from 399 patients over the 10-year study period was analysed, revealing that 233 (58.4%) had complete KD, 159 (39.8) incomplete KD and 7 (1.7%) were considered atypical KD. Mean annual incidence was 3.5/105 children <14 years old (yo) and 8/105 children <5 yo (mean age 37±33 months, range 1.3-191.3). KD was more frequent in boys (59.6%, p<0.001) and in rural areas (p<0.001). Patients with IVIG non-responsiveness, need of a 2(nd) IVIG dose, delay of treatment >10(th) day of illness, ages <1 yo and >8 yo and the presence of sterile piuria, aseptic meningitis, abdominal pain and uveitis at diagnosis were found to have higher risk of coronary aneurisms (CAA) (p<0.05). This is the first population-based study on the epidemiology of KD in the western Mediterranean area. Incidence, clinical features and treatment plans in our cohort are similar to those described in other European studies.

Quality and Quantity of Sorghum Hydroponic Fodder from Different Varieties and Harvest Time

NASA Astrophysics Data System (ADS)

Chrisdiana, R.

2018-02-01

This experiment was designed to compare different varieties and harvest time of sorghum hydroponic fodder based on nutrient content and biomass production. Experimental design for fodder productivity was completely randomized design with 2 x 3 factorial, i.e., sorghum varieties (KD 4 and Super-1) and time of harvesting the sorghum hydroponic fodder (8,12 and 16 d). Total biomass and DM production, were affected significantly (p<0.05) on harvest time. Total biomass and nutrient content were increased in longer harvest time. The nutrient content were increased with decreasing total value of DM. Super-1 varieties produce larger biomass and nutrient content higher than KD4 (p<0.05). Based on sorghum hidroponic fodder quality and quantity, sorghum hidroponic fodder with Super-1 varieties harvested at 12 d had a good quality of fodder and it can be alternative of technology providing quality forage and land saving with a short time planting period and continous production.

Characterization, Recovery Opportunities, and Valuation of Metals in Municipal Sludges from U.S. Wastewater Treatment Plants Nationwide.

PubMed

Westerhoff, Paul; Lee, Sungyun; Yang, Yu; Gordon, Gwyneth W; Hristovski, Kiril; Halden, Rolf U; Herckes, Pierre

2015-08-18

U.S. sewage sludges were analyzed for 58 regulated and nonregulated elements by ICP-MS and electron microscopy to explore opportunities for removal and recovery. Sludge/water distribution coefficients (KD, L/kg dry weight) spanned 5 orders of magnitude, indicating significant metal accumulation in biosolids. Rare-earth elements and minor metals (Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) detected in sludges showed enrichment factors (EFs) near unity, suggesting dust or soils as likely dominant sources. In contrast, most platinum group elements (i.e., Ru, Rh, Pd, Pt) showed high EF and KD values, indicating anthropogenic sources. Numerous metallic and metal oxide colloids (<100-500 nm diameter) were detected; the morphology of abundant aggregates of primary particles measuring <100 nm provided clues to their origin. For a community of 1 million people, metals in biosolids were valued at up to US$13 million annually. A model incorporating a parameter (KD × EF × $Value) to capture the relative potential for economic value from biosolids revealed the identity of the 13 most lucrative elements (Ag, Cu, Au, P, Fe, Pd, Mn, Zn, Ir, Al, Cd, Ti, Ga, and Cr) with a combined value of US $280/ton of sludge.

Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment

PubMed Central

Battula, V. Lokesh; Chen, Ye; Cabreira, Maria da Graca; Ruvolo, Vivian; Wang, Zhiqiang; Ma, Wencai; Konoplev, Sergej; Shpall, Elizabeth; Lyons, Karen; Strunk, Dirk; Bueso-Ramos, Carlos; Davis, Richard Eric; Konopleva, Marina

2013-01-01

Mesenchymal stromal cells (MSCs) are a major component of the leukemia bone marrow (BM) microenvironment. Connective tissue growth factor (CTGF) is highly expressed in MSCs, but its role in the BM stroma is unknown. Therefore, we knocked down (KD) CTGF expression in human BM-derived MSCs by CTGF short hairpin RNA. CTGF KD MSCs exhibited fivefold lower proliferation compared with control MSCs and had markedly fewer S-phase cells. CTGF KD MSCs differentiated into adipocytes at a sixfold higher rate than controls in vitro and in vivo. To study the effect of CTGF on engraftment of leukemia cells into BM, an in vivo model of humanized extramedullary BM (EXM-BM) was developed in NOD/SCID/IL-2rgnull mice. Transplanted Nalm-6 or Molm-13 human leukemia cells engrafted at a threefold higher rate in adipocyte-rich CTGF KD MSC-derived EXM-BM than in control EXM-BM. Leptin was found to be highly expressed in CTGF KD EXM-BM and in BM samples of patients with acute myeloid and acute lymphoblastic leukemia, whereas it was not expressed in normal controls. Given the established role of the leptin receptor in leukemia cells, the data suggest an important role of CTGF in MSC differentiation into adipocytes and of leptin in homing and progression of leukemia. PMID:23741006

Prevalence of acute kidney injury in intensive care units: the "COrte de prevalencia de disFunción RenAl y DEpuración en críticos" point-prevalence multicenter study.

PubMed

Herrera-Gutiérrez, Manuel E; Seller-Pérez, Gemma; Sánchez-Izquierdo-Riera, José A; Maynar-Moliner, Javier

2013-10-01

This study aimed to measure the point prevalence of kidney dysfunction (KD) in the intensive care setting. A point-prevalence, single-day, prospective study was conducted. Of 919 patients present in 42 Intensive care units (ICUs) for 2 specific days (September 2009 and March 2010), 832 cases were included. Mild KD was defined as a measured creatinine clearance of 90 to 60 mL min(-1) 1.73 m(-2), and severe KD was defined as a creatinine clearance less than 60 mL min(-1) 1.73 m(-2). Prevalence of mild KD was 15.9/100 patients/d (13.5-18.5), and severe KD was 42.4/100 patients/d (39.1-45.8). We considered as having a low probability of experiencing KD those patients without chronic kidney disease, acute kidney injury network stage 0, and a serum creatinine less than 1.2 mg/dL, but among them (557 patients), 18.1% (15.2%-21.6%) had mild KD and 24.2% (20.9%-28%) had severe KD. ICU mortality was 10.6% (7.81%-14.4%) for patients without dysfunction, 16.6% (11.2%-24%) for patients with mild KD, and 29.7% (25.2%-34.7%; P<.001) for patients with severe KD, with a relative risk for severe KD vs no KD of 2.54 (1.90-3.40). In 54.3% patients, at least 1 renal insult was reported. One nephrotoxic drug was administered to 34.4% and 2 or more to 14.9% patients, with a lower frequency among those with chronic kidney disease (30.6% vs 50.8%; P<.05). Each day of study, more that half of the patients admitted to the ICU showed some derangement in kidney function. More than 25% of patients not fulfilling the KD criteria by serum creatinine or acute kidney injury network showed, in fact, a severe KD, and this finding was associated with higher mortality. More than 50% of the patients admitted to the ICU were subjected to at least 1 renal insult. Copyright © 2013 Elsevier Inc. All rights reserved.

Surface complexation modeling of americium sorption onto volcanic tuff.

PubMed

Ding, M; Kelkar, S; Meijer, A

2014-10-01

Results of a surface complexation model (SCM) for americium sorption on volcanic rocks (devitrified and zeolitic tuff) are presented. The model was developed using PHREEQC and based on laboratory data for americium sorption on quartz. Available data for sorption of americium on quartz as a function of pH in dilute groundwater can be modeled with two surface reactions involving an americium sulfate and an americium carbonate complex. It was assumed in applying the model to volcanic rocks from Yucca Mountain, that the surface properties of volcanic rocks can be represented by a quartz surface. Using groundwaters compositionally representative of Yucca Mountain, americium sorption distribution coefficient (Kd, L/Kg) values were calculated as function of pH. These Kd values are close to the experimentally determined Kd values for americium sorption on volcanic rocks, decreasing with increasing pH in the pH range from 7 to 9. The surface complexation constants, derived in this study, allow prediction of sorption of americium in a natural complex system, taking into account the inherent uncertainty associated with geochemical conditions that occur along transport pathways. Published by Elsevier Ltd.

Energy invariant for shallow-water waves and the Korteweg-de Vries equation: Doubts about the invariance of energy

NASA Astrophysics Data System (ADS)

Karczewska, Anna; Rozmej, Piotr; Infeld, Eryk

2015-11-01

It is well known that the Korteweg-de Vries (KdV) equation has an infinite set of conserved quantities. The first three are often considered to represent mass, momentum, and energy. Here we try to answer the question of how this comes about and also how these KdV quantities relate to those of the Euler shallow-water equations. Here Luke's Lagrangian is helpful. We also consider higher-order extensions of KdV. Though in general not integrable, in some sense they are almost so within the accuracy of the expansion.

Identification of natural rubber and characterization of rubber biosynthetic activity in fig tree.

PubMed

Kang, H; Kang, M Y; Han, K H

2000-07-01

Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea as part of a survey of rubber producing plants. Fourier transform infrared and (13)C nuclear magnetic resonance analysis of samples prepared by successive extraction with acetone and benzene confirmed that the benzene-soluble residues are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was 0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that the molecular size of the natural rubber from fig tree is about 190 kD. Similar to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray), rubber biosynthesis in fig tree is tightly associated with rubber particles. The rubber transferase in rubber particles exhibited a higher affinity for farnesyl pyrophosphate than for isopentenyl pyrophosphate, with apparent K(m) values of 2.8 and 228 microM, respectively. Examination of latex serum from fig tree by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins of 25 and 48 kD in size, and several proteins with molecular mass below 20 and above 100 kD. Partial N-terminal amino acid sequencing and immunochemical analyses revealed that the 25- and 48-kD proteins were novel and not related to any other suggested rubber transferases. The effect of EDTA and Mg(2+) ion on in vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent metal ion present in the latex serum is an important factor in determining the different rubber biosynthetic activities in fig tree and rubber tree.

Identification of Natural Rubber and Characterization of Rubber Biosynthetic Activity in Fig Tree1

PubMed Central

Kang, Hunseung; Kang, Min Young; Han, Kyung-Hwan

2000-01-01

Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea as part of a survey of rubber producing plants. Fourier transform infrared and 13C nuclear magnetic resonance analysis of samples prepared by successive extraction with acetone and benzene confirmed that the benzene-soluble residues are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was 0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that the molecular size of the natural rubber from fig tree is about 190 kD. Similar to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray), rubber biosynthesis in fig tree is tightly associated with rubber particles. The rubber transferase in rubber particles exhibited a higher affinity for farnesyl pyrophosphate than for isopentenyl pyrophosphate, with apparent Km values of 2.8 and 228 μm, respectively. Examination of latex serum from fig tree by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins of 25 and 48 kD in size, and several proteins with molecular mass below 20 and above 100 kD. Partial N-terminal amino acid sequencing and immunochemical analyses revealed that the 25- and 48-kD proteins were novel and not related to any other suggested rubber transferases. The effect of EDTA and Mg2+ ion on in vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent metal ion present in the latex serum is an important factor in determining the different rubber biosynthetic activities in fig tree and rubber tree. PMID:10889262

Purification and biochemical characterization of ionically unbound polyphenol oxidase from Musa paradisiaca leaf.

PubMed

Diwakar, Sanjeev Kumar; Mishra, Sarad Kumar

2011-01-01

An ionically unbound and thermostable polyphenol oxidase (PPO) was extracted from the leaf of Musa paradisiaca. The enzyme was purified 2.54-fold with a total yield of 9.5% by ammonium sulfate precipitation followed by Sephadex G-100 gel filtration chromatography. The purified enzyme exhibited a clear single band on native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS) PAGE. It was found to be monomeric protein with molecular mass of about 40 kD. The zymographic study using crude extract as enzyme source showed a very clear band around 40 kD and a faint band at around 15 kD, which might be isozymes. The enzyme was optimally active at pH 7.0 and 50°C temperature. The enzyme was active in wide range of pH (4.0-9.0) and temperature (30-90°C). From the thermal inactivation studies in the range 60-75°C, the half-life (t(1/2)) values of the enzyme ranged from 17 to 77 min. The inactivation energy (Ea) value of PPO was estimated to be 91.3 kJ mol(-1). It showed higher specificity with catechol (K(m) = 8 mM) as compared to 4-methylcatechol (K(m) = 10 mM). Among metal ions and reagents tested, Cu(2+), Fe(2+), Hg(2+), Mn(2+), Ni(2+), protocatechuic acid, and ferrulic acid enhanced the enzyme activity, while K(+), Na(+), Co(2+), kojic acid, ascorbic acid, ethylenediamine tetraacetic acid (EDTA), sodium azide, β-mercaptoethanol, and L-cysteine inhibited the activity of the enzyme.

Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

PubMed

Rubini, Alessandro; Bosco, Gerardo; Lodi, Alessandra; Cenci, Lorenzo; Parmagnani, Andrea; Grimaldi, Keith; Zhongjin, Yang; Paoli, Antonio

2015-12-01

The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients

PubMed Central

Huang, Ying-Hsien; Kuo, Ho-Chang; Huang, Fu-Chen; Yu, Hong-Ren; Hsieh, Kai-Sheng; Yang, Ya-Ling; Sheen, Jiunn-Ming; Li, Sung-Chou; Kuo, Hsing-Chun

2016-01-01

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD’s acute inflammatory phase. PMID:27187366

Design of chimeric peptide ligands to galanin receptors and substance P receptors.

PubMed

Langel, U; Land, T; Bartfai, T

1992-06-01

Several chimeric peptides were synthesized and found to be high-affinity ligands for both galanin and substance P receptors in membranes from the rat hypothalamus. The peptide galantide, composed of the N-terminal part of galanin and C-terminal part of substance P (SP), galanin-(1-12)-Pro-SP-(5-11) amide, which is the first galanin antagonist to be reported, recognizes two classes of galanin binding sites (KD(1) less than 0.1 nM and KD(2) approximately 6 nM) in the rat hypothalamus, while it appears to bind to a single population of SP receptors (KD approximately 40 nM). The chimeric peptide has higher affinity towards galanin receptors than the endogenous peptide galanin-(1-29) (KD approximately 1 nM) or its N-terminal fragment galanin-(1-13) (KD approximately 1 microM), which constitutes the N-terminus of the chimeric peptide. Galantide has also higher affinity for the SP receptors than the C-terminal SP fragment-(4-11) amide (KD = 0.4 microM), which constitutes its C-terminal portion. Substitution of amino acid residues, which is of importance for recognition of galanin by galanin receptors, such as [Trp2], in the galanin portion of the chimeric peptide or substitution of ([Phe7] or [Met11]-amide) in the SP portion of chimeric peptide both cause significant loss in affinity of the analogs of galantide for both the galanin- and the SP-receptors. These results suggest that the high affinity of the chimeric peptide, galantide, may in part be accounted for by simultaneous recognition/binding to both receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Petrogenetic evolution of the Mesoproterozoic garnet-bearing granitoids of Dumka, Eastern India: Implication of garnet and biotite composition

NASA Astrophysics Data System (ADS)

Roy, P.; Goswami, B.; Ghosal, A.; Nanda, J.; Basak, A.; Bhattacharyya, C.

2017-12-01

Garnet is a petrologically significant accessory mineral of igneous rocks. Granite, tonalite, charnoenderbite and enderbite are prominent facies of 1450 Ma old Dumka Granitoids, Jharkhand district, India. Interestingly all the facies of Dumka granitoids contain good amount of garnet and biotite. Sphene, magnetite, ilmenite, zircon, monazite, allanite and rare hornblende present as accessory minerals. The garnets are mainly solid solutions between almandine, pyrope and grossular. Garnets contain 70.5-75.8 mol% of the almandine, 12.8-17.5 mol% of pyrope, 8-11 mol% of grossular and 0.6-2.9 mol% of spessartine. Composition of garnets fit well in the compositional range of igneous garnets suggested by Miller and Stoddard (1981). High MgO and CaO contents together with very low MnO of these garnets suggest that these have been crystallized from granitoid magma under high pressure in the lower crust. No compositional zoning is found in the analyzed garnets. Biotites of the granitoids are rich in Mg [Mg/(Fe+Mg) ratio > 0.4]. Biotites plot in Abdel-Rahman's (1994) field for biotites of calc-alkaline granites. The matrix biotites in these granitoids have higher Ti content than biotites coexist with garnets. Biotites coexisting with garnet are richer in Mg/Fe ratio than matrix biotites. Mg/Fe distribution coefficients between garnet core and matrix biotite (KD= (Mg/Fe)grt/(Mg/Fe)bt) for the Dumka enderbite and tonalite are 0.275 to 0.280 while for the granites the KD varies from 0.189 to 0.264. These KD values are higher than the values obtained from high-grade metamorphic rocks and are consistent with the values of igneous granitoids as shown by Lyons and Morse (1970). Absence of zoning in magmatic garnets in Dumka Granitoids indicate that these have crystallized above 700 °C, whereas absence of "spessartine bell-shaped profile" of the garnets of present study refute their metamorphic origin or that these crystallized below 700 °C (Dahlquist et al., 2007). Geothermobaric calculations reveal an initial crystallization temperature of 850°C and a pressure of 7.0-8.0 kbar, indicating that the parental magma was emplaced at lower crustal depths ( 25 km). Our studies reveal that garnets of Dumka Granitoids formed by direct crystallization from calc-alkaline magma in equilibrium with solid phases such as biotite.

A method for estimating the diffuse attenuation coefficient (KdPAR)from paired temperature sensors

USGS Publications Warehouse

Read, Jordan S.; Rose, Kevin C.; Winslow, Luke A.; Read, Emily K.

2015-01-01

A new method for estimating the diffuse attenuation coefficient for photosynthetically active radiation (KdPAR) from paired temperature sensors was derived. We show that during cases where the attenuation of penetrating shortwave solar radiation is the dominant source of temperature changes, time series measurements of water temperatures at multiple depths (z1 and z2) are related to one another by a linear scaling factor (a). KdPAR can then be estimated by the simple equation KdPAR ln(a)/(z2/z1). A suggested workflow is presented that outlines procedures for calculating KdPAR according to this paired temperature sensor (PTS) method. This method is best suited for conditions when radiative temperature gains are large relative to physical noise. These conditions occur frequently on water bodies with low wind and/or high KdPARs but can be used for other types of lakes during time periods of low wind and/or where spatially redundant measurements of temperatures are available. The optimal vertical placement of temperature sensors according to a priori knowledge of KdPAR is also described. This information can be used to inform the design of future sensor deployments using the PTS method or for campaigns where characterizing sub-daily changes in temperatures is important. The PTS method provides a novel method to characterize light attenuation in aquatic ecosystems without expensive radiometric equipment or the user subjectivity inherent in Secchi depth measurements. This method also can enable the estimation of KdPAR at higher frequencies than many manual monitoring programs allow.

Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study

PubMed Central

Huang, Li-Min; Huang, Fu-Yuan; Chiu, Nan-Chang; Chen, Ming-Ren; Chi, Hsin; Lee, Yann-Jinn; Chang, Li-Ching; Liu, Yi-Min; Wang, Hsiang-Hua; Chen, Chien-Hsiun; Chen, Yuan-Tsong; Wu, Jer-Yuarn

2011-01-01

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD. PMID:21326860

Identification of dehydrin-like proteins responsive to chilling in floral buds of blueberry (Vaccinium, section Cyanococcus).

PubMed

Muthalif, M M; Rowland, L J

1994-04-01

The level of three major polypeptides of 65, 60, and 14 kD increased in response to chilling unit accumulation in floral buds of a woody perennial, blueberry (Vaccinium, section Cynaococcus). The level of the polypeptides increased most dramatically within 300 h of chilling and decreased to the prechilling level with the initiation of budbreak. Cold-hardiness levels were assessed for dormant buds of Vaccinium corymbosum and Vaccinium ashei after different chilling treatments until the resumption of growth. These levels coincided with the level of the chilling-responsive polypeptides. Like some other previously described cold-induced proteins in annual plants, the level of the chilling-induced polypeptides also increased in leaves in response to cold treatment; the chilling-induced polypeptides were heat stable, resisting aggregation after incubation at 95 degrees C for 15 min. By fractionating bud proteins first by isoelectric point (pI) and then by molecular mass, the pI values of the 65- and 60-kD polypeptides were found to be 7.5 to 8.0 and the pI value of the 14-kD polypeptide was judged to be 8.5. Purification of the 65- and 60-kD polypeptides, followed by digestion with endoproteinase Lys-C and sequencing of selected fragments, revealed similarities in amino acid composition between the 65- and 60-kD polypeptides and dehydrins. Indeed, antiserum to the lysine-rich consensus sequence EKKGIMDKIKEKLPG of dehydrin proteins cross-reacted to all three of the major chilling-responsive polypeptides of blueberry, identifying these as dehydrins or dehydrin-like proteins.

Identification of dehydrin-like proteins responsive to chilling in floral buds of blueberry (Vaccinium, section Cyanococcus).

PubMed Central

Muthalif, M M; Rowland, L J

1994-01-01

The level of three major polypeptides of 65, 60, and 14 kD increased in response to chilling unit accumulation in floral buds of a woody perennial, blueberry (Vaccinium, section Cynaococcus). The level of the polypeptides increased most dramatically within 300 h of chilling and decreased to the prechilling level with the initiation of budbreak. Cold-hardiness levels were assessed for dormant buds of Vaccinium corymbosum and Vaccinium ashei after different chilling treatments until the resumption of growth. These levels coincided with the level of the chilling-responsive polypeptides. Like some other previously described cold-induced proteins in annual plants, the level of the chilling-induced polypeptides also increased in leaves in response to cold treatment; the chilling-induced polypeptides were heat stable, resisting aggregation after incubation at 95 degrees C for 15 min. By fractionating bud proteins first by isoelectric point (pI) and then by molecular mass, the pI values of the 65- and 60-kD polypeptides were found to be 7.5 to 8.0 and the pI value of the 14-kD polypeptide was judged to be 8.5. Purification of the 65- and 60-kD polypeptides, followed by digestion with endoproteinase Lys-C and sequencing of selected fragments, revealed similarities in amino acid composition between the 65- and 60-kD polypeptides and dehydrins. Indeed, antiserum to the lysine-rich consensus sequence EKKGIMDKIKEKLPG of dehydrin proteins cross-reacted to all three of the major chilling-responsive polypeptides of blueberry, identifying these as dehydrins or dehydrin-like proteins. PMID:8016270

Diffusion of Eu(III) in compacted bentonite-effect of pH, solution concentration and humic acid.

PubMed

Wang, Xiangke; Chen, Yixue; Wu, Yican

2004-06-01

The effect of pH, Eu(III) solution concentration and humic acid on the diffusion of Eu(III) in compacted bentonite (rho(b) = 1000 +/- 30 kg/m(3)) was studied with "in-diffusion" method at an ionic strength of 0.1M NaClO(4). The results (K(d) values from the first slice and theoretical calculation, apparent and effective diffusion coefficients) derived from the new capillary method are in good agreement with the literature data under similar conditions, and fit the Fick's second law very well. The results suggest that the diffusion of Eu(III) is dependent on pH values and independent on solution concentration in our experimental conditions. Humic acid forms precipitation/complexation with Eu(III) at the surface of compacted bentonite and thus deduces the diffusion/transport of Eu(III) in compacted bentonite. The K(d) values in compacted bentonite are in most cases lower than those in powdered bentonite obtained from batch experiments. The difference between the K(d) values from powdered and compacted bentonite is a strong function of the bulk density of the bentonite. The results suggest that the content of interlaminary space plays a very important role to the diffusion, sorption and migration of Eu(III) in compacted bentonite.

Classification of Dark Modified KdV Equation

NASA Astrophysics Data System (ADS)

Xiong, Na; Lou, Sen-Yue; Li, Biao; Chen, Yong

2017-07-01

The dark Korteweg-de Vries (KdV) systems are defined and classified by Kupershmidt sixteen years ago. However, there is no other classifications for other kinds of nonlinear systems. In this paper, a complete scalar classification for dark modified KdV (MKdV) systems is obtained by requiring the existence of higher order differential polynomial symmetries. Different to the nine classes of the dark KdV case, there exist twelve independent classes of the dark MKdV equations. Furthermore, for the every class of dark MKdV system, there is a free parameter. Only for a fixed parameter, the dark MKdV can be related to dark KdV via suitable Miura transformation. The recursion operators of two classes of dark MKdV systems are also given. Supported by the Global Change Research Program of China under Grant No. 2015Cb953904, National Natural Science Foundation of China under Grant Nos. 11675054, 11435005, 11175092, and 11205092 and Shanghai Knowledge Service Platform for Trustworthy Internet of Things (No. ZF1213) and K. C. Wong Magna Fund in Ningbo University

Radiometry from Bio-Argo Floats: a New Strategy to Validate Ocean Color Products at the Global Scale.

NASA Astrophysics Data System (ADS)

Organelli, E.; Claustre, H.; Serra, R.; Bricaud, A.; Schmechtig, C.; D'Ortenzio, F.; Poteau, A.; Mangin, A.; Leymarie, E.; Obolensky, G.; Prieur, L. M.; Dall'Olmo, G.; Xing, X.

2016-02-01

Thanks to a new generation of Bio-Argo floats equipped with sensors for PAR (Photosynthetically Available Irradiance) and downward irradiance measurements at selected wavelengths (i.e., 380, 412 and 490 nm), the number of radiometric measurements has been dramatically increasing and data are available for diverse open ocean systems, including winter periods with harsh seas when ships can hardly sample. More than 6500 radiometric profiles have so far been acquired around solar noon in the upper 250 m of the ocean. These radiometric profiles, acquired simultaneously to other key biogeochemical and bio-optical variables (chlorophyll a, CDOM, light backscattering), represent a fruitful data source for validation of Ocean Color (OC) products. Two different strategies can be implemented: direct validation of satellite OC products and identification of regions characterized by bio-optical anomalies. Diffuse attenuation coefficients (Kd) derived from these profiles, after a specifically developed quality control, are used for these purposes.A good agreement is observed between satellite-derived Kd values at 490 nm and their Bio-Argo counterparts. However, satellite overestimates low in situ Kd values found in very clear waters (e.g., Atlantic and Pacific Sub-Tropical Gyres). The analysis of the spectral Kd variability in the surface ocean shows the potential of Bio-Argo floats in identifying those regions with optical properties departing from global bio-optical relationships. Divergences of the ratio between Kd values at 380 nm and those at 490 nm from global bio-optical models are observed in areas such as the Mediterranean Sea and the North Atlantic in winter. This might cause difficulties in retrieving biogeochemical parameters from satellite data. Hence, delineation of "anomalous" regions by Bio-Argo floats represents a useful strategy for planning dedicated cruises, setting mooring buoys or using CAL/VAL floats in order to improve Ocean Color applications.

Quantitative Comparison of Human Parainfluenza Virus Hemagglutinin-Neuraminidase Receptor Binding and Receptor Cleavage

PubMed Central

Tappert, Mary M.; Porterfield, J. Zachary; Mehta-D'Souza, Padmaja; Gulati, Shelly

2013-01-01

The human parainfluenza virus (hPIV) hemagglutinin-neuraminidase (HN) protein binds (H) oligosaccharide receptors that contain N-acetylneuraminic acid (Neu5Ac) and cleaves (N) Neu5Ac from these oligosaccharides. In order to determine if one of HN′s two functions is predominant, we measured the affinity of H for its ligands by a solid-phase binding assay with two glycoprotein substrates and by surface plasmon resonance with three monovalent glycans. We compared the dissociation constant (Kd) values from these experiments with previously determined Michaelis-Menten constants (Kms) for the enzyme activity. We found that glycoprotein substrates and monovalent glycans containing Neu5Acα2-3Galβ1-4GlcNAc bind HN with Kd values in the 10 to 100 μM range. Km values for HN were previously determined to be on the order of 1 mM (M. M. Tappert, D. F. Smith, and G. M. Air, J. Virol. 85:12146–12159, 2011). A Km value greater than the Kd value indicates that cleavage occurs faster than the dissociation of binding and will dominate under N-permissive conditions. We propose, therefore, that HN is a neuraminidase that can hold its substrate long enough to act as a binding protein. The N activity can therefore regulate binding by reducing virus-receptor interactions when the concentration of receptor is high. PMID:23740997

Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice.

PubMed

Yamamoto, Kenta; Wang, Yunyue; Jiang, Wenxia; Liu, Xiangyu; Dubois, Richard L; Lin, Chyuan-Sheng; Ludwig, Thomas; Bakkenist, Christopher J; Zha, Shan

2012-08-06

Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients and mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic DNA repair defects. In this paper, we report that mice carrying homozygous kinase-dead mutations in Atm (Atm(KD/KD)) died during early embryonic development. Atm(KD/-) cells exhibited proliferation defects and genomic instability, especially chromatid breaks, at levels higher than Atm(-/-) cells. Despite this increased genomic instability, Atm(KD/-) lymphocytes progressed through variable, diversity, and joining recombination and immunoglobulin class switch recombination, two events requiring nonhomologous end joining, at levels comparable to Atm(-/-) lymphocytes. Together, these results reveal an essential function of ATM during embryogenesis and an important function of catalytically inactive ATM protein in DNA repair.

Modulation of thyroid hormone receptors by non-thyroidal stimuli

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

ErkenBrack, D.E.; Clemons, G.K.

1988-01-01

The ability of non-thyroidal stimuli to affect the binding affinity and capacity of solubilized nuclear receptors for thyroid hormones was studied in a normal homeostatic system (erythropoiesis) and a pathobiologic one (lung-ozone interaction). No significant effects on affinity were found, as Kd control values for receptors derived from rat bone marrow averaged 57 (+/- 28) pM while experimental (hypoxic) values averaged 89 (+/- 55) pM. Kd control values in rat lung were found to average 142 (+/- 22) pM while average values derived from experimental protocols with ozone and methimazole were 267 (+/- 44) pM and 161 (+/- 35) pMmore » respectively. Finally, Kd control values for receptors derived from cultured MEL cells averaged 19 (+/- 2.6) pM while experimental values during exposure to DMSO or IGF1 were 23 (+/- 3.6) pM and 26 (+/- 11) pM respectively. In contrast, binding capacity (expressed as fmoles of hormone bound per unit protein of solubilized receptor) was markedly perturbed in several tissues by various agents: ozone effects on lung were shown by an average control value of 3.3 (+/- 0.4) as opposed to an experimental average of 28 (+/- 1.9); and hypoxia effects on erythroid tissue were displayed by an average control value of 0.7 (+/- 0.07) as opposed to the experimental figure of 1.8 (+/- 0.03). In cultured MEL cells, binding capacity was seen to be increased from control values of 388 (+/- 15) sites/cell to 1243 (+/- 142) sites/cell after DMSO exposure and 2002 (+/- 10) sites/cell after IGF1 exposure. Parallel experiments done with receptors derived from rat liver yielded values similar to those reported by other investigators and were unaffected by the experimental agents.« less

Sorption of radioiodide in an acidic, nutrient-poor boreal bog: insights into the microbial impact.

PubMed

Lusa, M; Bomberg, M; Aromaa, H; Knuutinen, J; Lehto, J

2015-05-01

Batch sorption experiments were conducted to evaluate the sorption behaviour of iodide and the microbial impact on iodide sorption in the surface moss, subsurface peat, gyttja, and clay layers of a nutrient-poor boreal bog. The batch distribution coefficient (Kd) values of iodide decreased as a function of sampling depth. The highest Kd values, 4800 L/Kg dry weight (DW) (geometric mean), were observed in the fresh surface moss and the lowest in the bottom clay (geometric mean 90 mL/g DW). In the surface moss, peat and gyttja layers, which have a high organic matter content (on average 97%), maximum sorption was observed at a pH between ∼ 4 and 5 and in the clay layer at pH 2. The Kd values were significantly lower in sterilized samples, being 20-fold lower than the values found for the unsterilized samples. In addition, the recolonization of sterilized samples with a microbial population from the fresh samples restored the sorption capacity of surface moss, peat and gyttja samples, indicating that the decrease in the sorption was due to the destruction of microbes and supporting the hypothesis that microbes are necessary for the incorporation of iodide into the organic matter. Anoxic conditions reduced the sorption of iodide in fresh, untreated samples, similarly to the effect of sterilization, which supports the hypothesis that iodide is oxidized into I2/HIO before incorporation into the organic matter. Furthermore, the Kd values positively correlated with peroxidase activity in surface moss, subsurface peat and gyttja layers at +20 °C, and with the bacterial cell counts obtained from plate count agar at +4 °C. Our results demonstrate the importance of viable microbes for the sorption of iodide in the bog environment, having a high organic matter content and a low pH. Copyright © 2015 Elsevier Ltd. All rights reserved.

Whole genome sequencing of an African American family highlights toll like receptor 6 variants in Kawasaki disease susceptibility.

PubMed

Kim, Jihoon; Shimizu, Chisato; Kingsmore, Stephen F; Veeraraghavan, Narayanan; Levy, Eric; Ribeiro Dos Santos, Andre M; Yang, Hai; Flatley, Jay; Hoang, Long Truong; Hibberd, Martin L; Tremoulet, Adriana H; Harismendy, Olivier; Ohno-Machado, Lucila; Burns, Jane C

2017-01-01

Kawasaki disease (KD) is the most common acquired pediatric heart disease. We analyzed Whole Genome Sequences (WGS) from a 6-member African American family in which KD affected two of four children. We sought rare, potentially causative genotypes by sequentially applying the following WGS filters: sequence quality scores, inheritance model (recessive homozygous and compound heterozygous), predicted deleteriousness, allele frequency, genes in KD-associated pathways or with significant associations in published KD genome-wide association studies (GWAS), and with differential expression in KD blood transcriptomes. Biologically plausible genotypes were identified in twelve variants in six genes in the two affected children. The affected siblings were compound heterozygous for the rare variants p.Leu194Pro and p.Arg247Lys in Toll-like receptor 6 (TLR6), which affect TLR6 signaling. The affected children were also homozygous for three common, linked (r2 = 1) intronic single nucleotide variants (SNVs) in TLR6 (rs56245262, rs56083757 and rs7669329), that have previously shown association with KD in cohorts of European descent. Using transcriptome data from pre-treatment whole blood of KD subjects (n = 146), expression quantitative trait loci (eQTL) analyses were performed. Subjects homozygous for the intronic risk allele (A allele of TLR6 rs56245262) had differential expression of Interleukin-6 (IL-6) as a function of genotype (p = 0.0007) and a higher erythrocyte sedimentation rate at diagnosis. TLR6 plays an important role in pathogen-associated molecular pattern recognition, and sequence variations may affect binding affinities that in turn influence KD susceptibility. This integrative genomic approach illustrates how the analysis of WGS in multiplex families with a complex genetic disease allows examination of both the common disease-common variant and common disease-rare variant hypotheses.

The King-Devick test as a determinant of head trauma and concussion in boxers and MMA fighters.

PubMed

Galetta, K M; Barrett, J; Allen, M; Madda, F; Delicata, D; Tennant, A T; Branas, C C; Maguire, M G; Messner, L V; Devick, S; Galetta, S L; Balcer, L J

2011-04-26

Sports-related concussion has received increasing attention as a cause of short- and long-term neurologic symptoms among athletes. The King-Devick (K-D) test is based on measurement of the speed of rapid number naming (reading aloud single-digit numbers from 3 test cards), and captures impairment of eye movements, attention, language, and other correlates of suboptimal brain function. We investigated the K-D test as a potential rapid sideline screening for concussion in a cohort of boxers and mixed martial arts fighters. The K-D test was administered prefight and postfight. The Military Acute Concussion Evaluation (MACE) was administered as a more comprehensive but longer test for concussion. Differences in postfight K-D scores and changes in scores from prefight to postfight were compared for athletes with head trauma during the fight vs those without. Postfight K-D scores (n = 39 participants) were significantly higher (worse) for those with head trauma during the match (59.1 ± 7.4 vs 41.0 ± 6.7 seconds, p < 0.0001, Wilcoxon rank sum test). Those with loss of consciousness showed the greatest worsening from prefight to postfight. Worse postfight K-D scores (r(s) = -0.79, p = 0.0001) and greater worsening of scores (r(s) = 0.90, p < 0.0001) correlated well with postfight MACE scores. Worsening of K-D scores by ≥5 seconds was a distinguishing characteristic noted only among participants with head trauma. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.97 [95% confidence interval 0.90-1.0]). The K-D test is an accurate and reliable method for identifying athletes with head trauma, and is a strong candidate rapid sideline screening test for concussion.

The King-Devick test as a determinant of head trauma and concussion in boxers and MMA fighters

PubMed Central

Galetta, K.M.; Barrett, J.; Allen, M.; Madda, F.; Delicata, D.; Tennant, A.T.; Branas, C.C.; Maguire, M.G.; Messner, L.V.; Devick, S.; Galetta, S.L.

2011-01-01

Objective: Sports-related concussion has received increasing attention as a cause of short- and long-term neurologic symptoms among athletes. The King-Devick (K-D) test is based on measurement of the speed of rapid number naming (reading aloud single-digit numbers from 3 test cards), and captures impairment of eye movements, attention, language, and other correlates of suboptimal brain function. We investigated the K-D test as a potential rapid sideline screening for concussion in a cohort of boxers and mixed martial arts fighters. Methods: The K-D test was administered prefight and postfight. The Military Acute Concussion Evaluation (MACE) was administered as a more comprehensive but longer test for concussion. Differences in postfight K-D scores and changes in scores from prefight to postfight were compared for athletes with head trauma during the fight vs those without. Results: Postfight K-D scores (n = 39 participants) were significantly higher (worse) for those with head trauma during the match (59.1 ± 7.4 vs 41.0 ± 6.7 seconds, p < 0.0001, Wilcoxon rank sum test). Those with loss of consciousness showed the greatest worsening from prefight to postfight. Worse postfight K-D scores (rs = −0.79, p = 0.0001) and greater worsening of scores (rs = 0.90, p < 0.0001) correlated well with postfight MACE scores. Worsening of K-D scores by ≥5 seconds was a distinguishing characteristic noted only among participants with head trauma. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.97 [95% confidence interval 0.90–1.0]). Conclusions: The K-D test is an accurate and reliable method for identifying athletes with head trauma, and is a strong candidate rapid sideline screening test for concussion. PMID:21288984

Laboratory Biomarkers to Facilitate Differential Diagnosis between Measles and Kawasaki Disease in a Pediatric Emergency Room: A Retrospective Study.

PubMed

Buonsenso, Danilo; Macchiarulo, Giulia; Supino, Maria Chiara; La Penna, Francesco; Scateni, Simona; Marchesi, Alessandra; Reale, Antonino; Boccuzzi, Elena

2018-01-01

This retrospective study was conducted to analyze clinical and laboratoristic parameters to individuate specific differences and facilitate differential diagnosis between Measles and Kawasaki Disease (KD) at first evaluation in an emergency room. We found similar clinical features as duration of fever and number of KD criteria (p > 0.5) but significant differences in white blood cell count, neutrophils, CRP and LDH levels (p < 0.001). LDH value ≥ 800 mg/dl had sensibility of 89% and specificity of 90% for Measles while CRP ≥ 3 mg/dl had sensibility 89% and specificity of 85% for KD. The combined use of CRP, LDH and AST showed accuracy of 86.67%.

A systematic review of the etiopathogenesis of Kienböck's disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration.

PubMed

Stahl, Stéphane; Stahl, Adelana Santos; Meisner, Christoph; Rahmanian-Schwarz, Afshin; Schaller, Hans-Eberhard; Lotter, Oliver

2012-11-21

We systematically reviewed etiological factors of Kienböck's disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck's disease (KD) in the European Listing of Occupational Diseases. We searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria. A total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration. A systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand-arm vibration is a risk factor for KD.

Predicting both passive intestinal absorption and the dissociation constant toward albumin using the PAMPA technique.

PubMed

Bujard, Alban; Sol, Marine; Carrupt, Pierre-Alain; Martel, Sophie

2014-10-15

The parallel artificial membrane permeability assay (PAMPA) is a high-throughput screening (HTS) method that is widely used to predict in vivo passive permeability through biological barriers, such as the skin, the blood brain barrier (BBB) and the gastrointestinal tract (GIT). The PAMPA technique has also been used to predict the dissociation constant (Kd) between a compound and human serum albumin (HSA) while disregarding passive permeability. Furthermore, the assay is based on the use of two separate 5-point kinetic experiments, which increases the analysis time. In the present study, we adapted the hexadecane membrane (HDM)-PAMPA assay to both predict passive gastrointestinal absorption via the permeability coefficient logPe value and determine the Kd. Two assays were performed: one in the presence and one in the absence of HSA in the acceptor compartment. In the absence of HSA, logPe values were determined after a 4-h incubation time, as originally described, but the dimethylsulfoxide (DMSO) percentage and pH were altered to be compatible with the protein. In parallel, a second PAMPA assay was performed in the presence of HSA during a 16-h incubation period. By adding HSA, a variation in the amount of compound crossing the membrane was observed compared to the permeability measured in the absence of HSA. The concentration of compound reaching the acceptor compartment in each case was used to determine both parameters (logPe and logKd) using numerical simulations, which highlighted the originality of this method because these calculations required only two endpoint measurements instead of a complete kinetic study. It should be noted that the amount of compound that reaches the acceptor compartment in the presence of HSA is modulated by complex dissociation in the receptor compartment. Only compounds that are moderately bound to albumin (-3

New insight into pesticide partition coefficient Kd for modelling pesticide fluvial transport: application to an agricultural catchment in south-western France.

PubMed

Boithias, Laurie; Sauvage, Sabine; Merlina, Georges; Jean, Séverine; Probst, Jean-Luc; Sánchez Pérez, José Miguel

2014-03-01

Pesticides applied on crops are leached with rainfall to groundwater and surface water. They threat the aquatic environment and may render water unfit for human consumption. Pesticide partitioning is one of the pesticide fate processes in the environment that should be properly formalised in pesticide fate models. Based on the analysis of 7 pesticide molecules (alachlor, atrazine, atrazine's transformation product deethylatrazine or DEA, isoproturon, tebuconazole and trifluralin) sampled from July 2009 to October 2010 at the outlet of the river Save (south-western France), the objectives of this study were (1) to check which of the environmental factors (discharge, pH, concentrations of total suspended matter (TSM), dissolved organic carbon (DOC) and particulate organic carbon (POC) could control the pesticide sorption dynamic, and (2) to establish a relationship between environmental factors, the partition coefficient Kd and the octanol/water distribution coefficient Kow. The comparison of physico-chemical parameters values during low flow and high flow shows that discharge, TSM and POC are the factors most likely controlling the pesticide sorption processes in the Save river network, especially for lower values of TSM (below 13mgL(-1)). We therefore express Kd depending on the widely literature-related variable Kow and on the commonly simulated variable TSM concentration. The equation can be implemented in any model describing the fluvial transport and fate of pesticides in both dissolved and sorbed phases, thus, Kd becomes a variable in time and space. The Kd calculation method can be applied to a wide range of catchments and organic contaminants. Copyright © 2013 Elsevier Ltd. All rights reserved.

A solid-phase extraction method for rapidly determining the adsorption coefficient of pharmaceuticals in sewage sludge.

PubMed

Berthod, Laurence; Roberts, Gary; Whitley, David C; Sharpe, Alan; Mills, Graham A

2014-12-15

The partitioning of pharmaceuticals in the environment can be assessed by measuring their adsorption coefficients (Kd) between aqueous and solid phases. Measuring this coefficient in sewage sludge gives an indication of their partitioning behaviour in a wastewater treatment plant and hence contributes to an understanding of their subsequent fate. The regulatory approved method for measuring Kd in sewage sludge is the US Environmental Protection Agency's Office of Prevention, Pesticides and Toxic Substances (OPPTS) guideline 835.1110, which is labour intensive and time consuming. We describe an alternative method for measuring the Kd of pharmaceuticals in sewage sludge using a modified solid-phase extraction (SPE) technique. SPE cartridges were packed at different sludge/PTFE ratios (0.4, 6.0, 24.0 and 40.0% w/w sludge) and eluted with phosphate buffer at pH 7.4. The approach was tested initially using three pharmaceuticals (clofibric acid, diclofenac and oxytetracycline) that covered a range of Kd values. Subsequently, the sorption behaviour of ten further pharmaceuticals with varying physico-chemical properties was evaluated. Results from the SPE method were comparable to those of the OPPTS test, with a correlation coefficient of 0.93 between the two approaches. SPE cartridges packed with sludge and PTFE were stable for up to one year; use within one month reduced variability in measurements (to a maximum of 0.6 log units). The SPE method is low-cost, easy to use and enables the rapid measurement of Kd values for a large number of chemicals. It can be used as an alternative to the more laborious full OPPTS test in environmental fate studies and risk assessments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A solid-phase extraction method for rapidly determining the adsorption coefficient of pharmaceuticals in sewage sludge

PubMed Central

Berthod, Laurence; Roberts, Gary; Whitley, David C.; Sharpe, Alan; Mills, Graham A.

2014-01-01

The partitioning of pharmaceuticals in the environment can be assessed by measuring their adsorption coefficients (Kd) between aqueous and solid phases. Measuring this coefficient in sewage sludge gives an indication of their partitioning behaviour in a wastewater treatment plant and hence contributes to an understanding of their subsequent fate. The regulatory approved method for measuring Kd in sewage sludge is the US Environmental Protection Agency's Office of Prevention, Pesticides and Toxic Substances (OPPTS) guideline 835.1110, which is labour intensive and time consuming. We describe an alternative method for measuring the Kd of pharmaceuticals in sewage sludge using a modified solid-phase extraction (SPE) technique. SPE cartridges were packed at different sludge/PTFE ratios (0.4, 6.0, 24.0 and 40.0% w/w sludge) and eluted with phosphate buffer at pH 7.4. The approach was tested initially using three pharmaceuticals (clofibric acid, diclofenac and oxytetracycline) that covered a range of Kd values. Subsequently, the sorption behaviour of ten further pharmaceuticals with varying physico-chemical properties was evaluated. Results from the SPE method were comparable to those of the OPPTS test, with a correlation coefficient of 0.93 between the two approaches. SPE cartridges packed with sludge and PTFE were stable for up to one year; use within one month reduced variability in measurements (to a maximum of 0.6 log units). The SPE method is low-cost, easy to use and enables the rapid measurement of Kd values for a large number of chemicals. It can be used as an alternative to the more laborious full OPPTS test in environmental fate studies and risk assessments. PMID:25299795

Tungsten Transport Protein A (WtpA) in Pyrococcus furiosus: the First Member of a New Class of Tungstate and Molybdate Transporters

PubMed Central

Bevers, Loes E.; Hagedoorn, Peter-Leon; Krijger, Gerard C.; Hagen, Wilfred R.

2006-01-01

A novel tungstate and molybdate binding protein has been discovered from the hyperthermophilic archaeon Pyrococcus furiosus. This tungstate transport protein A (WtpA) is part of a new ABC transporter system selective for tungstate and molybdate. WtpA has very low sequence similarity with the earlier-characterized transport proteins ModA for molybdate and TupA for tungstate. Its structural gene is present in the genome of numerous archaea and some bacteria. The identification of this new tungstate and molybdate binding protein clarifies the mechanism of tungstate and molybdate transport in organisms that lack the known uptake systems associated with the ModA and TupA proteins, like many archaea. The periplasmic protein of this ABC transporter, WtpA (PF0080), was cloned and expressed in Escherichia coli. Using isothermal titration calorimetry, WtpA was observed to bind tungstate (dissociation constant [KD] of 17 ± 7 pM) and molybdate (KD of 11 ± 5 nM) with a stoichiometry of 1.0 mol oxoanion per mole of protein. These low KD values indicate that WtpA has a higher affinity for tungstate than do ModA and TupA and an affinity for molybdate similar to that of ModA. A displacement titration of molybdate-saturated WtpA with tungstate showed that the tungstate effectively replaced the molybdate in the binding site of the protein. PMID:16952940

Temperature-dependent sorption of naphthalene, phenanthrene, and pyrene to low organic carbon aquifer sediments

USGS Publications Warehouse

Piatt, Joseph J.; Backhus, Debera A.; Capel, Paul D.; Eisenreich, Steven J.

1996-01-01

Sorption experiments were conducted with naphthalene, phenanthrene, and pyrene on low organic carbon sediments at 4 and 26 °C using batch and column techniques. Experimental controls ensured the absence of biologic and photolytic activity and colloid-free solution supernatants. Equilibrium distribution coefficients (Kd) increased 1.1−1.6 times with a decrease in temperature of 22 °C. Fraction instantaneous sorption (F) values did not change significantly with a decrease in temperature of 22 °C. Desorption rate constants (k2) decreased 1.2−2.6 times with a decrease in temperature of 22 °C. Times to equilibrium were at least 40 h. The magnitude of observed Kd and k2 values and the effect of temperature on Kd (e.g., low enthalpy of sorption) are consistent with sorbate partitioning between the aqueous phase and small amounts of organic matter (foc = 0.02%) on the sediments. The temperature dependence of Kd and k2 may be small as compared to the effects of heterogeneities in field-scale aquifer systems. Thus, thermal gradients may not be of major importance in most saturated subsurface regimes when predicting solute transport. However, aquifer remediation pump-and-treat times could be decreased because increased temperature decreases both retardation and tailing.

The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

PubMed

Güzel, Orkide; Yılmaz, Unsal; Uysal, Utku; Arslan, Nur

2016-03-01

Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

Cholera Toxin Inhibitors Studied with High-Performance Liquid Affinity Chromatography: A Robust Method to Evaluate Receptor–Ligand Interactions

PubMed Central

Bergström, Maria; Liu, Shuang; Kiick, Kristi L.; Ohlson, Sten

2009-01-01

Anti-adhesion drugs may be an alternative to antibiotics to control infection of micro-organisms. The well-characterized interaction between cholera toxin and the cellular glycolipid GM1 makes it an attractive model for inhibition studies in general. In this report, we demonstrate a high-performance liquid affinity chromatography approach called weak affinity chromatography to evaluate cholera toxin inhibitors. The cholera toxin B-subunit was covalently coupled to porous silica and a (weak) affinity column was produced. The KD values of galactose and meta-nitrophenyl α-D-galactoside were determined with weak affinity chromatography to be 52 and 1 mM, respectively, which agree well with IC50 values previously reported. To increase inhibition potency multivalent inhibitors have been developed and the interaction with multivalent glycopolypeptides was also evaluated. The affinity of these compounds was found to correlate with the galactoside content but KD values were not obtained because of the inhomogeneous response and slow off-rate from multivalent interactions. Despite the limitations in obtaining direct KD values of the multivalent galactopolypeptides, weak affinity chromatography represents an additional and valuable tool in the evaluation of monovalent as well as multivalent cholera toxin inhibitors. It offers multiple advantages, such as a low sample consumption, high reproducibility and short analysis time, which are often not observed in other methods of analysis. PMID:19152642

Korteweg-deVries-Burgers (KdVB) equation in a five component cometary plasma with kappa described electrons and ions

NASA Astrophysics Data System (ADS)

Michael, Manesh; Willington, Neethu T.; Jayakumar, Neethu; Sebastian, Sijo; Sreekala, G.; Venugopal, Chandu

2016-12-01

We investigate the existence of ion-acoustic shock waves in a five component cometary plasma consisting of positively and negatively charged oxygen ions, kappa described hydrogen ions, hot solar electrons, and slightly colder cometary electrons. The KdVB equation has been derived for the system, and its solution plotted for different kappa values, oxygen ion densities, as well as the temperature ratios for the ions. It is found that the amplitude of the shock wave decreases with increasing kappa values. The strength of the shock profile decreases with increasing temperatures of the positively charged oxygen ions and densities of negatively charged oxygen ions.

Hemodynamic simulations in coronary aneurysms of children with Kawasaki disease

NASA Astrophysics Data System (ADS)

Sengupta, Dibyendu; Burns, Jane; Marsden, Alison

2009-11-01

Kawasaki disease (KD) is a serious pediatric illness affecting the cardiovascular system. One of the most serious complications of KD, occurring in about 25% of untreated cases, is the formation of large aneurysms in the coronary arteries, which put patients at risk for myocardial infarction. In this project we performed patient specific computational simulations of blood flow in aneurysmal left and right coronary arteries of a KD patient to gain an understanding about their hemodynamics. Models were constructed from CT data using custom software. Typical pulsatile flow waveforms were applied at the model inlets, while resistance and RCR lumped models were applied and compared at the outlets. Simulated pressure waveforms compared well with typical physiologic data. High wall shear stress values are found in the narrow region at the base of the aneurysm and low shear values occur in regions of recirculation. A Lagrangian approach has been adopted to perform particle tracking and compute particle residence time in the recirculation. Our long-term goal will be to develop links between hemodynamics and the risk for thrombus formation in order to assist in clinical decision-making.

Improved Algorithms for Accurate Retrieval of UV - Visible Diffuse Attenuation Coefficients in Optically Complex, Inshore Waters

NASA Technical Reports Server (NTRS)

Cao, Fang; Fichot, Cedric G.; Hooker, Stanford B.; Miller, William L.

2014-01-01

Photochemical processes driven by high-energy ultraviolet radiation (UVR) in inshore, estuarine, and coastal waters play an important role in global bio geochemical cycles and biological systems. A key to modeling photochemical processes in these optically complex waters is an accurate description of the vertical distribution of UVR in the water column which can be obtained using the diffuse attenuation coefficients of down welling irradiance (Kd()). The Sea UV Sea UVc algorithms (Fichot et al., 2008) can accurately retrieve Kd ( 320, 340, 380,412, 443 and 490 nm) in oceanic and coastal waters using multispectral remote sensing reflectances (Rrs(), Sea WiFS bands). However, SeaUVSeaUVc algorithms are currently not optimized for use in optically complex, inshore waters, where they tend to severely underestimate Kd(). Here, a new training data set of optical properties collected in optically complex, inshore waters was used to re-parameterize the published SeaUVSeaUVc algorithms, resulting in improved Kd() retrievals for turbid, estuarine waters. Although the updated SeaUVSeaUVc algorithms perform best in optically complex waters, the published SeaUVSeaUVc models still perform well in most coastal and oceanic waters. Therefore, we propose a composite set of SeaUVSeaUVc algorithms, optimized for Kd() retrieval in almost all marine systems, ranging from oceanic to inshore waters. The composite algorithm set can retrieve Kd from ocean color with good accuracy across this wide range of water types (e.g., within 13 mean relative error for Kd(340)). A validation step using three independent, in situ data sets indicates that the composite SeaUVSeaUVc can generate accurate Kd values from 320 490 nm using satellite imagery on a global scale. Taking advantage of the inherent benefits of our statistical methods, we pooled the validation data with the training set, obtaining an optimized composite model for estimating Kd() in UV wavelengths for almost all marine waters. This optimized composite set of SeaUVSeaUVc algorithms will provide the optical community with improved ability to quantify the role of solar UV radiation in photochemical and photobiological processes in the ocean.

Robust Means for Estimating Black Carbon-Water Sorption Coefficients of Organic Contaminants in Sediments

DTIC Science & Technology

2015-07-01

multiple lines of reasoning should be used to build confidence in what we believe is going on at any particular site. Hence, it will certainly be more...site depends on its Kd value (Fernandez et al., 2009). Consequently, we need to understand factors that go into the Kd sorption parameter in order...models of sorption to GAC (Kamlet et al. 1985, Luehrs et al. 1996, Poole and Poole 1997, Shih and Gschwend 2009) and multi-walled carbon nanotubes ( MWCNT

Principal component analysis of chemical shift perturbation data of a multiple-ligand-binding system for elucidation of respective binding mechanism.

PubMed

Konuma, Tsuyoshi; Lee, Young-Ho; Goto, Yuji; Sakurai, Kazumasa

2013-01-01

Chemical shift perturbations (CSPs) in NMR spectra provide useful information about the interaction of a protein with its ligands. However, in a multiple-ligand-binding system, determining quantitative parameters such as a dissociation constant (K(d) ) is difficult. Here, we used a method we named CS-PCA, a principal component analysis (PCA) of chemical shift (CS) data, to analyze the interaction between bovine β-lactoglobulin (βLG) and 1-anilinonaphthalene-8-sulfonate (ANS), which is a multiple-ligand-binding system. The CSP on the binding of ANS involved contributions from two distinct binding sites. PCA of the titration data successfully separated the CSP pattern into contributions from each site. Docking simulations based on the separated CSP patterns provided the structures of βLG-ANS complexes for each binding site. In addition, we determined the K(d) values as 3.42 × 10⁻⁴ M² and 2.51 × 10⁻³ M for Sites 1 and 2, respectively. In contrast, it was difficult to obtain reliable K(d) values for respective sites from the isothermal titration calorimetry experiments. Two ANS molecules were found to bind at Site 1 simultaneously, suggesting that the binding occurs cooperatively with a partial unfolding of the βLG structure. On the other hand, the binding of ANS to Site 2 was a simple attachment without a significant conformational change. From the present results, CS-PCA was confirmed to provide not only the positions and the K(d) values of binding sites but also information about the binding mechanism. Thus, it is anticipated to be a general method to investigate protein-ligand interactions. Copyright © 2012 Wiley Periodicals, Inc.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

PubMed

McNeal-Davidson, Ariane; Fournier, Anne; Spigelblatt, Linda; Saint-Cyr, Claire; Mir, Thomas S; Nir, Amiram; Dallaire, Frédéric; Cousineau, Jocelyne; Delvin, Edgard; Dahdah, Nagib

2012-10-01

The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Radioiodine sorption/desorption and speciation transformation by subsurface sediments from the Hanford Site.

PubMed

Xu, Chen; Kaplan, Daniel I; Zhang, Saijin; Athon, Matthew; Ho, Yi-Fang; Li, Hsiu-Ping; Yeager, Chris M; Schwehr, Kathleen A; Grandbois, Russell; Wellman, Dawn; Santschi, Peter H

2015-01-01

During the last few decades, considerable research efforts have been extended to identify more effective remediation treatment technologies to lower the (129)I concentrations to below federal drinking water standards at the Hanford Site (Richland, USA). Few studies have taken iodate into consideration, though recently iodate, instead of iodide, was identified as the major species in the groundwater of 200-West Area within the Hanford Site. The objective of this study was thus to quantify and understand aqueous radioiodine species transformations and uptake by three sediments collected from the semi-arid, carbonate-rich environment of the Hanford subsurface. All three sediments reduced iodate (IO3(-)) to iodide (I(-)), but the loamy-sand sediment reduced more IO3(-) (100% reduced within 7 days) than the two sand-textured sediments (∼20% reduced after 28 days). No dissolved organo-iodine species were observed in any of these studies. Iodate uptake Kd values ([Isolid]/[Iaq]; 0.8-7.6 L/kg) were consistently and appreciably greater than iodide Kd values (0-5.6 L/kg). Furthermore, desorption Kd values (11.9-29.8 L/kg) for both iodate and iodide were consistently and appreciably greater than uptake Kd values (0-7.6 L/kg). Major fractions of iodine associated with the sediments were unexpectedly strongly bound, such that only 0.4-6.6 % of the total sedimentary iodine could be exchanged from the surface with KCl solution, and 0-1.2% was associated with Fe or Mn oxides (weak NH2HCl/HNO3 extractable fraction). Iodine incorporated into calcite accounted for 2.9-39.4% of the total sedimentary iodine, whereas organic carbon (OC) is likely responsible for the residual iodine (57.1-90.6%) in sediments. The OC, even at low concentrations, appeared to be controlling iodine binding to the sediments, as it was found that the greater the OC concentrations in the sediments, the greater the values of uptake Kd, desorption Kd, and the greater residual iodine concentrations (non-exchangeable, non-calcite-incorporated and non-Mn, Fe-oxide associated). This finding is of particular interest because it suggests that even very low OC concentrations, <0.2%, may have an impact on iodine geochemistry. The findings that these sediments can readily reduce IO3(-), and that IO3(-) sorbs to a greater extent than I(-), sheds light into earlier unexplained Hanford field data that demonstrated increases in groundwater (127)I(-)/(127)IO3(-) ratios and a decrease groundwater (129)IO3(-) concentrations along a transect away from the point sources, where iodine was primarily introduced as IO3(-). While a majority of the radioiodine does not bind to these alkaline sediments, there is likely a second smaller iodine fraction in the Hanford subsurface that is strongly bound, presumably to the sediment OC (and carbonate) phases. This second fraction may have an impact on establishing remediation goals and performance assessment calculations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular recognition of live methicillin-resistant staphylococcus aureus cells using DNA aptamers

PubMed Central

Turek, Diane; Van Simaeys, Dimitri; Johnson, Judith; Ocsoy, Ismail; Tan, Weihong

2014-01-01

AIM To generate DNA-aptamers binding to Methicillin-resistant Staphylococcus aureus (MRSA). METHODS The Cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology was used to run the selection against MRSA bacteria and develop target-specific aptamers. MRSA bacteria were targeted while Enterococcus faecalis bacteria were used for counter selection during that process. Binding assays to determine the right aptamer candidates as well as binding assays on clinical samples were performed through flow cytometry and analyzed using the FlowJo software. The characterization of the aptamers was done by determination of their Kd values and determined by analysis of flow data at different aptamer concentration using SigmaPlot. Finally, the recognition of the complex Gold-nanoparticle-aptamer to the bacteria cells was observed using transmission electron microscopy (TEM). RESULTS During the cell-SELEX selection process, 17 rounds were necessary to generate enrichment of the pool. While the selection was run using fixed cells, it was shown that the binding of the pools with live cells was giving similar results. After sequencing and analysis of the two last pools, four sequences were identified to be aptamer candidates. The characterization of those aptamers showed that based on their Kd values, DTMRSA4 presented the best binding with a Kd value of 94.61 ± 18.82 nmol/L. A total of ten clinical samples of MRSA , S. aureus and Enterococcus faecalis were obtained to test those aptamers and determine their binding on a panel of samples. DTMRSA1 and DTMRSA3 showed the best results regarding their specificity to MRSA , DTMRSA1 being the most specific of all. Finally, those aptamers were coupled with gold-nanoparticle and their binding to MRSA cells was visualized through TEM showing that adduction of nanoparticles on the aptamers did not change their binding property. CONCLUSION A total of four aptamers that bind to MRSA were obtained with Kd values ranking from 94 to 200 nmol/L. PMID:25436184

The partition behavior of perfluorooctanesulfonate (PFOS) and perfluorooctanesulfonamide (FOSA) on microplastics.

PubMed

Wang, Fei; Shih, Kai Min; Li, Xiao Yan

2015-01-01

Microplastics have been recognized as transport vectors for heavy metals and organic pollutants to marine animals. Thus, the sorption behavior of contaminant on microplastic is crucial to their transport in marine system. In this study, the sorption behavior of PFOS and FOSA (two perfluorochemicals) on three kinds of microplastics (PE, PS, and PVC) are reported. The isotherm study showed that the sorption of PFOS and FOSA on microplastics is highly linear, and it indicated that partition by hydrophobic interaction is the predominant sorption mechanism. The Kd values of FOSA on three kinds of microplastics are all higher than those of PFOS, and the reason is attributed to their different functional groups. The Kd value of FOSA on three types of microplastics followed the order as: PE>PVC>PS. Such finding may indicate that the molecule composition and structure of microplastics play important roles in their sorption processes of organic pollutants. The PFOS sorption levels on PE and PS particles were increased with the increase of NaCl and CaCl2 concentrations, while the ion concentrations have no effect on FOSA sorption. The study on the pH effects on PFOS and FOSA sorption indicated FOSA could partition under various pH conditions on three types of microplastics while PFOS sorption on PE and PS were favored with lower pH. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monitoring of antifouling booster biocides in water and sediment from the port of Osaka, Japan.

PubMed

Harino, Hiroya; Mori, Yoshiaki; Yamaguchi, Yoshitaka; Shibata, Kiyoshi; Senda, Tetsuya

2005-04-01

Concentrations of booster antifouling compounds in the port of Osaka, Japan were assessed. Concentrations of Sea-Nine 211 (4,5-dichloro-2-n-octyl-3-isothiazolone), thiabendazole (2-(4-thiazolyl)-benzimidazole), IPBC (3-iodo-2-propynyl butylcarbamate), Diuron (3,4-dichlorophenyl-N, N-dimethylurea), Irgarol 1051 (2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine), and M1 (2-methylthio-4-t-butylamino-6-amino-s-triazine) in port water samples were in the range of <0.003-0.004 microg L(-1), <0.0008-0.020 microg L(-1), <0.0007-1.54 microg L(-1), <0.0008-0.267 microg L(-1), and <0.0019-0.167 microg L(-1), respectively. IPBC was not detected in the water samples, but the concentration of Diuron was higher than any previously reported. The concentrations of Sea-Nine 211, thiabendazole, Diuron, Irgarol 1051, and M1 in sediment samples were in the range of <0.04-2.4 microg kg(-1) dry, <0.08-1.2 microg kg(-1) dry, <0.64-1350 microg kg(-1) dry, <0.08-8.2 microg kg(-1) dry, and <0.18-2.9 microg kg(-1) dry, respectively. IPBC was again not detected. The levels of Sea-Nine 211, Diuron, and Irgarol 1051 in water and sediment samples were high in a poorly flushed mooring area for small and medium-hull vessels. Levels of Diuron and Irgarol 1051 were highest in summer. The concentration of Sea-Nine 211 in water increased between August and October 2002. Except for M1, increases in the levels of booster biocides in sediment were observed during the study period. The sediment-water partition (Kd) was calculated by dividing the concentrations in sediment by the concentrations in water. The Kd values for Sea-Nine 211, thiabendazole, Diuron, Irgarol 1051, and M1 were 690, 180, 2700, 300, and 870. The Kd value for these alternative compounds was lower than for TBT.

Determination of solid-liquid partition coefficients (Kd) for the herbicides isoproturon and trifluralin in five UK agricultural soils.

PubMed

Cooke, Cindy M; Shaw, George; Collins, Chris D

2004-12-01

Isoproturon and trifluralin are herbicides of contrasting chemical characters and modes of action. Standard batch sorption procedures were carried out to investigate the individual sorption behaviour of 14C-isoproturon and 14C-trifluralin in five agricultural soils (1.8-4.2% OC), and the soil solid-liquid partition coefficients (Kd values) were determined. Trifluralin exhibited strong partitioning to the soil solid phase (Kd range 106-294) and low desorption potential, thus should not pose a threat to sensitive waters via leaching, although particle erosion and preferential flow pathways may facilitate transport. For isoproturon, soil adsorption was low (Kd range 1.96-5.75) and desorption was high, suggesting a high leaching potential, consistent with isoproturon being the most frequently found pesticide in UK surface waters. Soil partitioning was directly related to soil organic carbon (OC) content. Accumulation isotherms were modelled using a dual-phase adsorption model to estimate adsorption and desorption rate coefficients. Associations between herbicides and soil humic substances were also shown using gel filtration chromatography.

Reported concussion incidence in youth community Rugby Union and parental assessment of post head injury cognitive recovery using the King-Devick test.

PubMed

Silver, David; Brown, Nicola; Gissane, Conor

2018-05-15

To assess the frequency of reported head injuries in youth community Rugby Union and determine whether the King-Devick (K-D) test could be used by parents as a means to chart cognitive recovery following head injury. A prospective cohort study of 489 junior players (U9-U18) conducted at a community level Rugby Union club over four seasons. All players undertook a baseline K-D test at the start of each season. Players identified with suspected concussion performed the K-D test post injury and results were compared to their most recent baseline assessment. Parent/Guardians of the player then oversaw repeated daily testing until baseline scores were surpassed. 49 players were sent for assessment after suspected head injury. 46 parents oversaw daily repeated K-D testing (93.8% engagement). The median reduction in K-D test performance speed post-injury from baseline was 7.32 s (IQR 2.46 - 7.98). A median of 5.1 days/tests were taken for players to surpass baseline performance. No correlation was found between initial post-injury test and cognitive recovery time. 38 head injuries were reported from match play with an incidence rate of 12.7 per 1000 match hours (95% CI 9.2-17.5). The K-D test is a practical tool for baseline, post injury and parentally supervised repeated testing within youth community Rugby Union. Incidence of reported head injuries following match play is higher than previously reported. Parental engagement was high. Post-Injury K-D test performance should not be used as a means to predict symptom recovery. Copyright © 2018 Elsevier B.V. All rights reserved.

FIBRILLIN4 Is Required for Plastoglobule Development and Stress Resistance in Apple and Arabidopsis1[W][OA

PubMed Central

Singh, Dharmendra K.; Maximova, Siela N.; Jensen, Philip J.; Lehman, Brian L.; Ngugi, Henry K.; McNellis, Timothy W.

2010-01-01

The fibrillins are a large family of chloroplast proteins that have been linked with stress tolerance and disease resistance. FIBRILLIN4 (FIB4) is found associated with the photosystem II light-harvesting complex, thylakoids, and plastoglobules, which are chloroplast compartments rich in lipophilic antioxidants. For this study, FIB4 expression was knocked down in apple (Malus 3 domestica) using RNA interference. Plastoglobule osmiophilicity was decreased in fib4 knockdown (fib4 KD) tree chloroplasts compared with the wild type, while total plastoglobule number was unchanged. Compared with the wild type, net photosynthetic CO2 fixation in fib4 KD trees was decreased at high light intensity but was increased at low light intensity. Furthermore, fib4 KD trees produced more anthocyanins than the wild type when transferred from low to high light intensity, indicating greater sensitivity to high light stress. Relative to the wild type, fib4 KD apples were more sensitive to methyl viologen and had higher superoxide levels during methyl viologen treatment. Arabidopsis (Arabidopsis thaliana) fib4 mutants and fib4 KD apples were more susceptible than their wild-type counterparts to the bacterial pathogens Pseudomonas syringae pathovar tomato and Erwinia amylovora, respectively, and were more sensitive to ozone-induced tissue damage. Following ozone stress, plastoglobule osmiophilicity decreased in wild-type apple and remained low in fib4 KD trees; total plastoglobule number increased in fib4 KD apples but not in the wild type. These results indicate that FIB4 is required for plastoglobule development and resistance to multiple stresses. This study suggests that FIB4 is involved in regulating plastoglobule content and that defective regulation of plastoglobule content leads to broad stress sensitivity and altered photosynthetic activity. PMID:20813909

Fibrogenic response of hepatic stellate cells in ovariectomised rats exposed to ketogenic diet.

PubMed

Bobowiec, R; Wojcik, M; Jaworska-Adamu, J; Tusinska, E

2013-02-01

The discrepancy about the role of estrogens in hepatic fibrogenesis and lack of studies addressed of ketogenic diet (KD) on hepatic stellate cells (HSC), prompted us to investigate the activity of HSC in control, KD- and thioacetamide (TAA)-administrated rats with different plasma concentration of estradiol (E2). HSC were isolated by the collagenase perfusion methods and separated by the Percoll gradient centrifugation. After the 4(th) and 8(th) day of incubation, lysates of HSC and the media were collected for further analysis. The HSC derived from KD-rats released remarkably more transforming growth factor (TGF)-β1 than cells obtained from animals fed with a standard diet. The ovariectomy of KD-rats markedly intensified the secretion of this fibrogenic cytokine on the 8(th) day of incubation (201.33 ±1 7.15 pg/ml). In HSC of rats exposed to E2, the TGF-β1 concentration did not exceed 157 ± 34.39 pg/ml. In respect to the collagen type I, the HSC obtained from ovariectomised KD-rats released an augmented amount of this ECM protein after the 8(th) day of culture (1.83 ± 0.14 U/ml). In the same time, higher quantities of ASMA appeared in the KD rats (1.41 ± 0.3 pg/mg protein). Exposition of rats to E2 did not markedly decrease the amount of ASMA. In summary, KD was able to induce morphological and functional changes in HSC, especially derived from rats deprived of ovarian estrogens. However, the preservation of E2 in ovariectomised rats didn't substantially alter the activation of HSC.

Long-term follow-up of saphenous vein, internal jugular vein, and knitted Dacron patches for carotid artery endarterectomy.

PubMed

Jacobowitz, G R; Kalish, J A; Lee, A M; Adelman, M A; Riles, T S; Landis, R

2001-05-01

To determine whether choice of material used for patch closure following carotid artery endarterectomy (CAE) influences rates of early or late restenosis, stroke, and death, 274 consecutive CAEs were retrospectively reviewed. Saphenous vein (SV) was used in 159 (58.0%) procedures; everted, double-thickness jugular vein (JV) was used in 25 (9.1%); and knitted Dacron (KD) was used in 90 (32.9%). Primary closure was not used in this series. There were four perioperative strokes: two (1.3%) in SV, one (4%) in JV, and one (1.1%) in KD (NS). Follow-up was obtained on 263 (96%) operated arteries (mean 41.5 months). Duplex scan results were available for 236 (89.7%) of these arteries (mean follow-up time 33.7 months). There were three (2%) late strokes in SV and two (2.2%) in KD (NS). In long-term follow-up, one patient (0.7%) in SV and two (2.4%) in KD developed > 80% stenosis (NS). One patient (0.7%) in SV, one (5.3%) in JV, and one (1.2%) in KD had total occlusion of the operated vessel (NS). Three procedures (2.2%) in SV, 1 (5.3%) in JV, and 7 (8.5%) in KD demonstrated moderate stenosis (50-79%) (NS). Three-year follow-up shows that choice of patch material does not affect early or late stroke rate, stroke-related death rate, rate of high-grade (> 80%) restenosis, or rate of total occlusion. There is a higher incidence of moderate stenosis in KD. Although our results and a review of the literature do not indicate that these patients are at increased risk for symptoms or progression of stenosis, they should be followed by duplex scanning to ensure that this is the case.

Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures.

PubMed

Ni, Hong; Zhao, Dong-Jing; Tian, Tian

2016-02-01

Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group. On P28, they were further randomly divided into the seizure group without ketogenic diet (RS+ND), seizure plus ketogenic diet (RS+KD), the control group without ketogenic diet (NS+ND), and the control plus ketogenic diet (NS+KD). Morris water maze test was performed during P37-P43. Then mossy fiber sprouting and the protein levels were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced RS+ND rats show a long-term lower amount of cPLA2 and LC3II/I, and higher amount of clusterin, Beclin-1, p62 and Cathepsin-E which are in parallel with hippocampal mossy fiber sprouting and cognitive deficits. Furthermore, chronic KD treatment (RS+KD) is effective in restoring these molecular, neuropathological and cognitive changes. The results imply that a lipid membrane peroxidation and autophagy-associated pathway is involved in the aberrant hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures, which might be a potential target of KD for the treatment of neonatal seizure-induced brain damage. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

PubMed

Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

2016-08-01

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. Copyright © 2016 the American Physiological Society.

The King-Devick test for sideline concussion screening in collegiate football.

PubMed

Leong, Danielle F; Balcer, Laura J; Galetta, Steven L; Evans, Greg; Gimre, Matthew; Watt, David

2015-01-01

Sports-related concussion has received increasing attention as a result of neurologic sequelae seen among athletes, highlighting the need for a validated, rapid screening tool. The King-Devick (K-D) test requires vision, eye movements, language function and attention in order to perform and has been proposed as a promising tool for assessment of concussion. We investigated the K-D test as a sideline screening tool in a collegiate cohort to determine the effect of concussion. Athletes (n=127, mean age 19.6±1.2 years) from the Wheaton College football and men's and women's basketball teams underwent baseline K-D testing at pre-season physicals for the 2012-2013 season. K-D testing was administered immediately on the sidelines for football players with suspected head injury during regular games and changes compared to baseline were determined. Post-season testing was also performed to compare non-concussed athletes' test performance. Concussed athletes (n=11) displayed sideline K-D scores that were significantly higher (worse) than baseline (36.5±5.6s vs. 31.3±4.5s, p<0.005, Wilcoxon signed-rank test). Post-season testing demonstrated improvement of scores and was consistent with known learning effects (35.1±5.2s vs. 34.4±5.0s, p<0.05, Wilcoxon signed-rank test). Test-retest reliability was analyzed between baseline and post-season administrations of the K-D test resulting in high levels of test-retest reliability (intraclass correlation coefficient (ICC)=0.95 [95% Confidence Interval 0.85-1.05]). The data show worsening of K-D test scores following concussion further supporting utility of the K-D test as an objective, reliable and effective sideline visual screening tool to help identify athletes with concussion. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

A systematic review of the etiopathogenesis of Kienböck's disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration

PubMed Central

2012-01-01

Background We systematically reviewed etiological factors of Kienböck’s disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck’s disease (KD) in the European Listing of Occupational Diseases. Methods We searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria. Results A total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration. Conclusions A systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand-arm vibration is a risk factor for KD. PMID:23171057

Adsorption characteristics of 210Pb, 210Po and 7Be onto micro-particle surfaces and the effects of macromolecular organic compounds

NASA Astrophysics Data System (ADS)

Yang, Weifeng; Guo, Laodong; Chuang, Chia-Ying; Schumann, Dorothea; Ayranov, Marin; Santschi, Peter H.

2013-04-01

210Po, 210Pb and Be isotopes (e.g. 7Be and 10Be) have long been used as proxies of particle/sediment dynamics, carbon cycling, and oceanographic investigations of coupled processes. However, adsorption characteristics and interactions between these nuclides and particle surfaces remain poorly understood. Laboratory studies have been conducted to examine the adsorption of 210Po, 210Pb and 7Be onto micro-particles, including marine suspended particulate matter, kaolinite, Al2O3, SiO2, CaCO3, Fe2O3, MnO2, and chitin in natural seawater (<1 kDa), and the role of macromolecular organic compounds (MOCs), including humic acids (HA), acid polysaccharides (APS) and proteins (BSA) in regulating the adsorption process. In the absence of MOCs, the partition coefficients (Kd, reported in log Kd) range from 3.02 to 5.19 for 210Po, from 3.22 to 6.29 for 210Pb, and from 3.57 to 4.65 for 7Be. Ferric and manganese oxides are the strongest sorbents of 210Po and 210Pb, comparing with SiO2 and CaCO3. In the presence of the protein BSA, both SiO2 and CaCO3 preferentially adsorb 210Po over 210Pb, whereas the opposite effect was observed in the presence of acid polysaccharides, indicating that proteins could enhance the adsorption of 210Po and acid polysaccharides enhance the adsorption of 210Pb. The log Kd values of both 210Po and 210Pb in the presence of MOCs become similar (log Kd at ˜4.0) for all lithogenic and biogenic particles, suggesting that their adsorption is likely controlled by specific natural organic compounds associated with particle surfaces. For 7Be, the highest and lowest log Kd value was measured, in general, on SiO2 and CaCO3, respectively, consistent with field observations. Nevertheless, the log Kd values of 7Be varied little between particle types regardless of the presence or absence of MOCs, suggesting that the adsorption of Be on particle surfaces is less affected by particle composition or MOCs. These results indicate that 7Be and 10Be could quantitatively track the bulk particles and their fluxes in marine environments while both 210Po and 210Pb could be quantitative proxies for the bulk organic carbon, although 210Po and 210Pb could be fractionated by specific organic compounds during their sorption or scavenging on particle surfaces.

Numerical simulation of KdV equation by finite difference method

NASA Astrophysics Data System (ADS)

Yokus, A.; Bulut, H.

2018-05-01

In this study, the numerical solutions to the KdV equation with dual power nonlinearity by using the finite difference method are obtained. Discretize equation is presented in the form of finite difference operators. The numerical solutions are secured via the analytical solution to the KdV equation with dual power nonlinearity which is present in the literature. Through the Fourier-Von Neumann technique and linear stable, we have seen that the FDM is stable. Accuracy of the method is analyzed via the L2 and L_{∞} norm errors. The numerical, exact approximations and absolute error are presented in tables. We compare the numerical solutions with the exact solutions and this comparison is supported with the graphic plots. Under the choice of suitable values of parameters, the 2D and 3D surfaces for the used analytical solution are plotted.

On the nonintegrability of equations for long- and short-wave interactions

NASA Astrophysics Data System (ADS)

Deconinck, Bernard; Upsal, Jeremy

2018-07-01

We examine the integrability of two models used for the interaction of long and short waves in dispersive media. One is more classical but arguably cannot be derived from the underlying water wave equations, while the other one was recently derived. We use the method of Zakharov and Schulman to attempt to construct conserved quantities for these systems at different orders in the magnitude of the solutions. The coupled KdV-NLS model is shown to be nonintegrable, due to the presence of fourth-order resonances. A coupled real KdV-complex KdV system is shown to suffer the same fate, except for three special choices of the coefficients, where higher-order calculations or a different approach are necessary to conclude integrability or the absence thereof.

Recurrent Kawasaki disease: USA and Japan.

PubMed

Maddox, Ryan A; Holman, Robert C; Uehara, Ritei; Callinan, Laura S; Guest, Jodie L; Schonberger, Lawrence B; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D

2015-12-01

Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Data from the USA and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance(1984-2008) and the 17th Japanese nationwide survey (2001-2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared with non-recurrent KD patients. Of the 5557 US KD patients <18 years of age during 1984-2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared with non-recurrent KD patients, KD patients [with recurrent KD] were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite i.v. immunoglobulin (IVIG) treatment. Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. © 2015 Japan Pediatric Society.

Recurrent Kawasaki disease, United States and Japan

PubMed Central

Maddox, Ryan A.; Holman, Robert C.; Uehara, Ritei; Callinan, Laura S.; Guest, Jodie L.; Schonberger, Lawrence B.; Nakamura, Yosikazu; Yashiro, Mayumi; Belay, Ermias D.

2015-01-01

Background Descriptive epidemiologic studies of recurrent and non-recurrent Kawasaki disease (KD) may identify other potentially important differences between these illnesses. Methods Data from the United States and Japan, the Centers for Disease Control and Prevention (CDC) national KD surveillance (1984–2008) and the 17th Japanese nationwide survey (2001–2002), respectively, were analyzed to examine recurrent KD patients <18 years of age meeting the CDC KD case or atypical KD case definition. These patients were compared to non-recurrent KD patients. Results Of the 5557 US KD patients <18 years of age during 1984–2008, 97 (1.7%) were identified as having had recurrent KD. Among the US Asian/Pacific Islander KD patients, 3.5% had recurrent KD, which was similar to the percentage identified among KD patients (3.5%) in the Japanese survey. Compared to non-recurrent KD patients, KD patients experiencing a recurrent KD episode were more likely to be older, fulfill the atypical KD case definition, and have coronary artery abnormalities (CAA) despite IVIG treatment. Conclusions Differences in the age, race, and frequency of CAA exist between recurrent and non-recurrent KD patients. The increased association of CAA with recurrent KD suggests that more aggressive treatment strategies in conjunction with IVIG may be indicated for the second episode of KD. PMID:26096590

Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children with Kawasaki Disease and Transient Coronary Abnormalities.

PubMed

Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar

2017-08-01

There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis and myocarditis in a subset of children with KD and transient coronary artery abnormalities is not significant.

Higher-Order Hamiltonian Model for Unidirectional Water Waves

NASA Astrophysics Data System (ADS)

Bona, J. L.; Carvajal, X.; Panthee, M.; Scialom, M.

2018-04-01

Formally second-order correct, mathematical descriptions of long-crested water waves propagating mainly in one direction are derived. These equations are analogous to the first-order approximations of KdV- or BBM-type. The advantage of these more complex equations is that their solutions corresponding to physically relevant initial perturbations of the rest state may be accurate on a much longer timescale. The initial value problem for the class of equations that emerges from our derivation is then considered. A local well-posedness theory is straightforwardly established by a contraction mapping argument. A subclass of these equations possess a special Hamiltonian structure that implies the local theory can be continued indefinitely.

Bio-optical characterization of offshore NW Mediterranean waters: CDOM contribution to the absorption budget and diffuse attenuation of downwelling irradiance

NASA Astrophysics Data System (ADS)

Pérez, Gonzalo L.; Galí, Martí; Royer, Sarah-Jeanne; Sarmento, Hugo; Gasol, Josep M.; Marrasé, Cèlia; Simó, Rafel

2016-08-01

We investigated the peculiar bio-optical characteristics of the Mediterranean Sea focusing on the spectral diffuse attenuation coefficient [Kd (λ)] and its relationship with chlorophyll a concentration (Chl a), complemented with measurements of light absorption by chromophoric dissolved organic matter (CDOM) and the optical properties of particulate material. The non-water absorption budget showed that CDOM was the largest contributor in the 300-600 nm range (>60% of the absorption at 443 nm in the euphotic layer), increasing to 80% within the first optical depth (FOD). This translated into CDOM accounting for >50% of KdBio (λ) (the irradiance attenuation coefficient caused by all non-water absorptions) between 320 and 555 nm and throughout both layers (FOD and euphotic). Indeed, we tested three Chl a-based bio-optical models and all three underestimated Kd (λ), evidencing the importance of CDOM beside Chl a to fully account for light attenuation. The Morel & Maritorena (2001) model (M&M 01) underestimated Kd (λ) in the UV and blue spectral regions within the FOD layer, showing lower differences with increasing wavelengths. The Morel et al. (2007a) model (BGS 07) also underestimated Kd (λ) in the FOD layer, yet it performed much better in the 380-555 nm range. In the euphotic layer, the Morel (1988) model (JGR 88) underestimated Kd (λ) showing higher differences at 412 and 443 nm and also performed better at higher wavelengths. Observed euphotic layer depths (Z1%) were 28 m shallower than those predicted with the M&M 01 empirical relationship, further highlighting the role of CDOM in the bio-optical peculiarity of Mediterranean Sea. In situ measurements of the CDOM index (Φ), an indicator of the deviation of the CDOM-Chl a average relationship for Case 1 waters, gave a mean of 5.9 in the FOD, consistent with simultaneous estimates from MODIS (4.8±0.4). The implications of the bio-optical anomaly for ecological and biogeochemical inferences in the Mediterranean Sea are discussed.

Organo-iodine formation in soils and aquifer sediments at ambient concentrations.

PubMed

Schwehr, K A; Santschi, P H; Kaplan, D J; Yeager, C M; Brinkmeyer, R

2009-10-01

One of the key risk drivers at radioactive waste disposal facilities is radioiodine, especially 129I. As iodine mobility varies greatly with iodine speciation, experiments with 129I-contaminated aquifer sediments from the Savannah River Site located in Aiken, SC, were carried out to test iodine interactions with soils and aquifer sediments. Using tracer 125I- and stable 127I- additions, it was shown that such interactions were highly dependent on I- concentrations added to sediment suspensions, contact time with the sediment, and organic carbon (OC) content, resulting in an empirical particle-water partition coefficient (Kd) that was an inverse power function of the added I- concentration. However, Kd values of organically bound 127I were 3 orders of magnitude higher than those determined after 1-2 weeks of tracer equilibration, approaching those of OC. Under ambient conditions, organo-iodine (OI) was a major fraction (67%) of the total iodine in the dissolved phase and by implication of the particulate phase. As the total concentration of amended I- increased, the fraction of detectable dissolved OI decreased. This trend, attributed to OC becoming the limiting factor in the aquifer sediment explains why at elevated I-concentrations OI is often not detected.

Facilitating primary care provider use in a patient-centered medical home intervention study for chronic hemodialysis patients.

PubMed

Chukwudozie, Ifeanyi Beverly; Fitzgibbon, Marian L; Schiffer, Linda; Berbaum, Michael; Gilmartin, Cheryl; David, Pyone; Ekpo, Eson; Fischer, Michael J; Porter, Anna C; Aziz-Bradley, Alana; Hynes, Denise M

2018-05-23

Patients with chronic kidney disease have a high disease burand may benefit from primary care services and care coord A medical home model with direct access to primary care services is one approach that may address this need, yet has not been examined. As a substudy of the Patient-Centered Outcomes Research Institute (PCORI) patient-centered medical home for kidney disease (PCMH-KD) health system intervention study, we examined the uptake of free primary care physician (PCP) services. The PCORI PCMH-KD study was an initial step toward integrating PCPs, a nurse coordinator, a pharmacist, and community health workers (CHWs) within the health care delivery team. Adult chronic hemodialysis (CHD) at two urban dialysis centers were enrolled in the intervention. We examined trends and factors associated with the use of the PCMH-KD PCP among two groups of patients based on their report of having a regular physician for at least six months (established-PCP) or not (no-PCP). Of the 173 enrolled patients, 91 (53%) patients had at least one visit with the PCMH-KD PCP. The rate of visits was higher in those in the no-PCP group compared with those in the established-PCP group (62% vs. 41%, respectively). Having more visits with the CHW was positively associated with having a visit with the PCMH-KD PCPs for both groups. Embedded CHWs within the care team played a role in facilithe uptake of PCMH-KD PCP. Lessons from this health system intervention can inform future approaches on the integration of PCPs and care coordination for CHD patients.

A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.

PubMed

Zhao, Zhong; Lange, Dale J; Voustianiouk, Andrei; MacGrogan, Donal; Ho, Lap; Suh, Jason; Humala, Nelson; Thiyagarajan, Meenakshisundaram; Wang, Jun; Pasinetti, Giulio M

2006-04-03

The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-beta-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.

The University Münster Model Surgery System for Orthognathic Surgery. Part II -- KD-MMS.

PubMed

Ehmer, Ulrike; Joos, Ulrich; Ziebura, Thomas; Flieger, Stefanie; Wiechmann, Dirk

2013-01-04

Model surgery is an integral part of the planning procedure in orthognathic surgery. Most concepts comprise cutting the dental cast off its socket. The standardized spacer plates of the KD-MMS provide for a non-destructive, reversible and reproducible means of maxillary and/or mandibular plaster cast separation. In the course of development of the system various articulator types were evaluated with regard to their capability to provide a means of realizing the concepts comprised of the KD-MMS. Special attention was dedicated to the ability to perform three-dimensional displacements without cutting of plaster casts. Various utilities were developed to facilitate maxillary displacement in accordance to the planning. Objectives of this development comprised the ability to implement the values established in the course of two-dimensional ceph planning. The system - KD-MMS comprises a set of hardware components as well as a defined procedure. Essential hardware components are red spacer and blue mounting plates. The blue mounting plates replace the standard yellow SAM mounting elements. The red spacers provide for a defined leeway of 8 mm for three-dimensional movements. The non-destructive approach of the KD-MMS makes it possible to conduct different model surgeries with the same plaster casts as well as to restore the initial, pre-surgical situation at any time. Thereby, surgical protocol generation and gnathologic splint construction are facilitated. The KD-MMS hardware components in conjunction with the defined procedures are capable of increasing efficiency and accuracy of model surgery and splint construction. In cases where different surgical approaches need to be evaluated in the course of model surgery, a significant reduction of chair time may be achieved.

Diagnostic potential of Western blot analysis of sera from dogs with leishmaniasis in endemic areas and significance of the pattern.

PubMed

Aisa, M J; Castillejo, S; Gallego, M; Fisa, R; Riera, M C; de Colmenares, M; Torras, S; Roura, X; Sentis, J; Portus, M

1998-02-01

Serum samples collected from 237 dogs in Catalonia (northeastern Spain) were screened by Western blot analysis to detect the presence of antibodies specific to different Leishmania infantum polypeptide fractions. Leishmaniasis was confirmed in 72 of these dogs by direct examination and/or culture. Another 165 animals from the Priorat region were studied periodically for 2-8 years between 1987 and 1995, giving a total of 565 determinations. A control group of 93 dogs from nonendemic areas was also studied. Sera from dogs with leishmaniasis recognized antigens with molecular weights ranging from 12 to 85 kD. The most sensitive antigens were those of 70, 65, 46, 30, 28, 14, and 12 kD, which were recognized by 75%, 75%, 78%, 75%, 81%, 79%, and 75%, respectively, of the sera from dogs with positive parasitologic examination results. Antigens of 70 and 65 kD were also recognized by two dogs from nonendemic areas. Antigens of 14 and 12 kD were the first to be recognized by sera of asymptomatic dogs with titers less than the cut-off value of the dot-ELISA that increased during the longitudinal study, and the presence of antibodies specific for these fractions was observed for up to six years before seroconversion observed by dot-ELISA. These antibodies were also the first to disappear in dogs in which the disease was self-limited. The study corroborates the high sensitivity and specificity of Western blots in the diagnosis of canine leishmaniasis when the bands of low molecular weight (less than 46 kD) are considered, and indicates that fractions of 14 and 12 kD are useful in detecting early forms of the disease.

Rotation-induced nonlinear wavepackets in internal waves

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

Whitfield, A. J., E-mail: ashley.whitfield.12@ucl.ac.uk; Johnson, E. R., E-mail: e.johnson@ucl.ac.uk

2014-05-15

The long time effect of weak rotation on an internal solitary wave is the decay into inertia-gravity waves and the eventual formation of a localised wavepacket. Here this initial value problem is considered within the context of the Ostrovsky, or the rotation-modified Korteweg-de Vries (KdV), equation and a numerical method for obtaining accurate wavepacket solutions is presented. The flow evolutions are described in the regimes of relatively-strong and relatively-weak rotational effects. When rotational effects are relatively strong a second-order soliton solution of the nonlinear Schrödinger equation accurately predicts the shape, and phase and group velocities of the numerically determined wavepackets.more » It is suggested that these solitons may form from a local Benjamin-Feir instability in the inertia-gravity wave-train radiated when a KdV solitary wave rapidly adjusts to the presence of strong rotation. When rotational effects are relatively weak the initial KdV solitary wave remains coherent longer, decaying only slowly due to weak radiation and modulational instability is no longer relevant. Wavepacket solutions in this regime appear to consist of a modulated KdV soliton wavetrain propagating on a slowly varying background of finite extent.« less

Molecularly imprinted polymers for RGD selective recognition and separation.

PubMed

Papaioannou, Emmanuel; Koutsas, Christos; Liakopoulou-Kyriakides, Maria

2009-03-01

Molecularly imprinted polymers that could recognize the tripeptide Arg-Gly-Asp have been produced with the use of two functional monomers and three different cross-linkers, respectively. Methacrylic acid and acrylamide were used as functional monomers and the role of the ethylene glycol dimethacrylate, trimethylpropane trimethacrylate and N,N'-methylene-bisacrylamide as crosslinking monomers, was investigated on their recognition capability. The % net rebinding and the imprinting factor values were obtained, giving for the methacrylic acid-trimethylpropane trimethacrylate polymer the highest values 12.3% and 2.44, respectively. In addition, this polymer presented lower dissociation constant (K(D)) value and the higher B (max)% of theoretical total binding sites than all the other polymers. Rebinding experiments with Lys-Gly-Asp, an analogue of Arg-Gly-Asp, and other different peptides, such as cholecystokinin C-terminal tri- and pentapeptide and gramicidin, further indicated the selectivity of methacrylic acid-trimethylpropane trimethacrylate copolymer for Arg-Gly-Asp giving specific selectivity factor values 1.27, 1.98, 1.31 and 1.67, respectively.

Kawasaki disease in Sicily: clinical description and markers of disease severity.

PubMed

Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando

2016-11-02

Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. We studied the clinical data of 70 KD Sicilian children (36 males: 51 %; 34 females: 49 %), analysed retrospectively, including: demographic and laboratory parameters; echocardiographic findings at diagnosis, at 2, 6 and 8 weeks, and at 1 year after the onset of the illness. Forty-seven had Typical KD, three Atypical KD and twenty Incomplete KD. Age at the disease onset ranged from 0.1 to 8.9 years. IVIG were administered 5 ± 2 days after the fever started. Defervescence occurred 39 ± 26 hours after the first IVIG infusion. Fifty-six patients (80 %) received 1 dose of IVIG (responders); 14 patients (20 %) had a resistant KD, with persistent fever after the first IVIG dose (non responders). Ten (14 %) non responders responded to the second dose, 4 (5 %) responded to three doses; one needed treatment with high doses of steroids and Infliximab. Cardiac involvement was documented in twenty-two cases (eighteen with transient dilatation/ectasia, fifteen with aneurysms). Pericardial effusion, documented in eleven, was associated with coronaritis and aneurysms, and was present earlier than coronary involvement in seven. Hypoalbuminemia, D-dimer pre-IVIG, gamma-GT pre-IVIG showed a statistically significant direct correlation with IVIG doses, highlighting the role of these parameters as predictor markers of refractory disease. The persistence of elevated CRP, AST, ALT levels, a persistent hyponatremia and hypoalbuminemia after IVIG therapy, also had a statistical significant correlation with IVIG doses. Non responders showed higher levels of D-dimer and gamma-GT pre-IVIG, persistent high levels of D-dimer, CRP, AST, ALT, hypoalbuminemia and hyponatremia after IVIG. This is the first study on KD in Sicily. We suggest some laboratory parameters as predictive criteria for resistant KD. Patients who show early pericarditis need careful surveillance for coronary lesions.

Peripheral markers of serotonergic and noradrenergic function in post-pubertal, caucasian males with autistic disorder.

PubMed

Croonenberghs, J; Delmeire, L; Verkerk, R; Lin, A H; Meskal, A; Neels, H; Van der Planken, M; Scharpe, S; Deboutte, D; Pison, G; Maes, M

2000-03-01

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study group of 13 male, post-pubertal, caucasian autistic patients (age 12-18 y; I.Q. > 55) and 13 matched volunteers. [3H]-paroxetine binding Kd values were significantly higher in patients with autism than in healthy volunteers. Plasma concentrations of tryptophan, the precursor of 5-HT, were significantly lower in autistic patients than in healthy volunteers. There were no significant differences between autistic and normal children in the serum concentrations of 5-HT, or the 24-hr urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA), adrenaline, noradrenaline, and dopamine. There were no significant differences in [3H]-rauwolscine binding Bmax or Kd values, or in the serum concentrations of tyrosine, the precursor of noradrenaline, between both study groups. There were highly significant positive correlations between age and 24-hr urinary excretion of 5-HIAA and serum tryptophan. The results suggest that: 1) serotonergic disturbances, such as defects in the 5-HT transporter system and lowered plasma tryptophan, may play a role in the pathophysiology of autism; 2) autism is not associated with alterations in the noradrenergic system; and 3) the metabolism of serotonin in humans undergoes significant changes between the ages of 12 and 18 years.

The King-Devick test was useful in management of concussion in amateur rugby union and rugby league in New Zealand.

PubMed

King, D; Gissane, C; Hume, P A; Flaws, M

2015-04-15

To use the King-Devick (K-D) test in senior amateur rugby union and rugby league players over a domestic competition season to see if it could identify witnessed and unwitnessed episodes of concussion that occurred from participation in competition matches over three years. A prospective observational cohort study was conducted on a club level senior amateur rugby union team (n=36 players in 2012 and 35 players in 2013) and a rugby league team (n=33 players in 2014) during competition seasons in New Zealand. All 104 players completed two trials 10min apart of the K-D at the beginning of their competition season. Concussions (witnessed or unwitnessed) were only recorded if they were formally diagnosed by a health practitioner. A total of 52 (8 witnessed; 44 unwitnessed) concussive events were identified over the duration of the study resulting in a concussion injury incidence of 44 (95% CI: 32 to 56) per 1000 match participation hours. There was a six-fold difference between witnessed and unwitnessed concussions recorded. There were observable learning effects observed between the first and the second K-D test baseline testing (50 vs. 45s; z=-8.81; p<0.001). For every 1 point reduction in each of the post-injury SAC components there was a corresponding increase (worsening) of K-D test times post-match for changes in orientation (2.9s), immediate memory (1.8s) concentration (2.8s), delayed recall (2.0s) and SAC total score (1.7s). The rate of undetected concussion was higher than detected concussions by using the K-D test routinely following matches. Worsening of the K-D test post-match was associated with reduction in components of the SAC. The appeal of the K-D test is in the rapid, easy manner of its administration and the reliable, objective results it provides to the administrator. The K-D test helped identify cognitive impairment in players without clinically observable symptoms. Copyright © 2015 Elsevier B.V. All rights reserved.

Sports Nutrition and Doping Factors in Synchronized Swimming: Parallel Analysis among Athletes and Coaches.

PubMed

Furjan Mandic, Gordana; Peric, Mia; Krzelj, Lucijana; Stankovic, Sladana; Zenic, Natasa

2013-01-01

Although nutrition and doping are important factors in sports, neither is often investigated in synchronized swimming (Synchro).This study aimed to define and compare Synchro athletes and their coaches on their knowledge of sports nutrition (KSN)and knowledge of doping (KD); and to study factors related to KSN and KD in each of these groups. Additionally, the KSNand KD questionnaires were evaluated for their reliability and validity. Altogether, 82 athletes (17.2 ± 1.92 years of age) and 28 coaches (30.8 ± 5.26 years of age) from Croatia and Serbia were included in the study, with a 99% response rate. The testand retest correlations were 0.94 and 0.90 for the KD and KSN,respectively. Subjects responded equally to 91% queries of the KD and 89% queries of the KSN. Although most of the coache sare highly educated, they declared self-education as the primary source of information about doping and sport-nutrition. Coaches scored higher than their athletes on both questionnaires which defined appropriate discriminative validity of the questionnaires. Variables such as age, sports experience and formal education are positively correlated to KSN and KD scores among athletes. The athletes who scored better on the KD are less prone to doping behavior in the future. These data reinforce the need for systematic educational programs on doping and sports nutrition in synchronized swimming. Special attention should be placed on younger athletes. Key PointsAlthough most of the synchro coaches are highly educated, self-education is declared as the primary source of information about doping and sportnutrition.The knowledge of doping and doping-health hazards are negatively related to potential doping behavior in the future among synchronized swimmersThe data reinforce the need for systematic educational programs on doping and sports nutrition in synchronized swimming.We advocate improving the knowledge of sports nutrition among older coaches and the knowledge of doping among younger coaches, while among athletes,younger swimmers should be targeted.

Sports Nutrition and Doping Factors in Synchronized Swimming: Parallel Analysis among Athletes and Coaches

PubMed Central

Furjan Mandic, Gordana; Peric, Mia; Krzelj, Lucijana; Stankovic, Sladana; Zenic, Natasa

2013-01-01

Although nutrition and doping are important factors in sports, neither is often investigated in synchronized swimming (Synchro).This study aimed to define and compare Synchro athletes and their coaches on their knowledge of sports nutrition (KSN)and knowledge of doping (KD); and to study factors related to KSN and KD in each of these groups. Additionally, the KSNand KD questionnaires were evaluated for their reliability and validity. Altogether, 82 athletes (17.2 ± 1.92 years of age) and 28 coaches (30.8 ± 5.26 years of age) from Croatia and Serbia were included in the study, with a 99% response rate. The testand retest correlations were 0.94 and 0.90 for the KD and KSN,respectively. Subjects responded equally to 91% queries of the KD and 89% queries of the KSN. Although most of the coache sare highly educated, they declared self-education as the primary source of information about doping and sport-nutrition. Coaches scored higher than their athletes on both questionnaires which defined appropriate discriminative validity of the questionnaires. Variables such as age, sports experience and formal education are positively correlated to KSN and KD scores among athletes. The athletes who scored better on the KD are less prone to doping behavior in the future. These data reinforce the need for systematic educational programs on doping and sports nutrition in synchronized swimming. Special attention should be placed on younger athletes. Key Points Although most of the synchro coaches are highly educated, self-education is declared as the primary source of information about doping and sportnutrition. The knowledge of doping and doping-health hazards are negatively related to potential doping behavior in the future among synchronized swimmers The data reinforce the need for systematic educational programs on doping and sports nutrition in synchronized swimming. We advocate improving the knowledge of sports nutrition among older coaches and the knowledge of doping among younger coaches, while among athletes,younger swimmers should be targeted PMID:24421736

Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature.

PubMed

Ud-Din, S; Bayat, A

2013-10-01

Keloid disease (KD) is a common, benign, dermal fibroproliferative growth of unknown aetiology. Lesions tend to grow over time; they often recur following therapy and do not regress spontaneously. KD causes considerable discomfort due to pain, pruritus and inflammation, and a significant psychosocial impact with reduced quality of life. It is unique to humans and occurrence is higher in individuals with dark, pigmented, ethnic skin. There is a strong familial heritability, with a high ethnic predisposition in individuals of African, Asian and Hispanic descent. High recurrence rates and unknown resolution rates present a major problem for both the patient and clinician. Many treatment modalities exist; however, there is no single advocated therapy. Therefore, the aim of this review was to explore the most current literature regarding the range of treatment options for KD and to offer a structured approach in the management of KD, based on evidence and experience, to aid clinicians in their current practice. A focused history involving careful evaluation of the patient's symptoms, signs, quality of life and psychosocial well-being should direct targeted therapy, complemented with regular follow-up and re-evaluation. Many treatment modalities, such as intralesional steroid injection, silicone gel application, cryotherapy, lasers, 5-fluorouracil and, relatively recently, photodynamic therapy, are currently being used in clinical practice for the management of KD. Combination therapies have also been shown to be beneficial. However, there is a lack of robust, randomized, level-one, evidence-controlled trials evaluating these treatment options. Management of KD in ethnic pigmented skin remains a clinical challenge. Thus, a strategic approach with structured assessment, targeted therapy and focus on prevention of recurrence is highly recommended. Quality evidence is essential in order to tailor treatment effectively for the ethnic patient presenting with KD. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Stability of Viscous St. Venant Roll Waves: From Onset to Infinite Froude Number Limit

NASA Astrophysics Data System (ADS)

Barker, Blake; Johnson, Mathew A.; Noble, Pascal; Rodrigues, L. Miguel; Zumbrun, Kevin

2017-02-01

We study the spectral stability of roll wave solutions of the viscous St. Venant equations modeling inclined shallow water flow, both at onset in the small Froude number or "weakly unstable" limit F→ 2^+ and for general values of the Froude number F, including the limit F→ +∞ . In the former, F→ 2^+, limit, the shallow water equations are formally approximated by a Korteweg-de Vries/Kuramoto-Sivashinsky (KdV-KS) equation that is a singular perturbation of the standard Korteweg-de Vries (KdV) equation modeling horizontal shallow water flow. Our main analytical result is to rigorously validate this formal limit, showing that stability as F→ 2^+ is equivalent to stability of the corresponding KdV-KS waves in the KdV limit. Together with recent results obtained for KdV-KS by Johnson-Noble-Rodrigues-Zumbrun and Barker, this gives not only the first rigorous verification of stability for any single viscous St. Venant roll wave, but a complete classification of stability in the weakly unstable limit. In the remainder of the paper, we investigate numerically and analytically the evolution of the stability diagram as Froude number increases to infinity. Notably, we find transition at around F=2.3 from weakly unstable to different, large- F behavior, with stability determined by simple power-law relations. The latter stability criteria are potentially useful in hydraulic engineering applications, for which typically 2.5≤ F≤ 6.0.

Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for presumed Kawasaki disease.

PubMed

Dong, Siwen; Bout-Tabaku, Sharon; Texter, Karen; Jaggi, Preeti

2015-05-01

To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Ad-/desorption behavior of Sulfadiazine on soil and soil components

NASA Astrophysics Data System (ADS)

Meng, N.; Lewandowski, H.; Kasteel, R.; Narres, H.-D.; Klumpp, E.; Vereecken, H.

2009-04-01

Sulfadiazine [4-amino-N-(2-pyrimidinyl)benzene sulfonamide, SDZ] belongs to the widely used antibacterial veterinary pharmaceuticals which reach the environment by the application of manure. Therefore the adsorption and desorption behavior of 14C labeled sulfadiazine was investigated with different inorganic soil components including Al2O3, goethite, illite and compared with air-dried topsoil. The batch sorption experiments with Al2O3and soil were performed in natural pH-values (8.2 and 7.5, negatively charged SDZ). Experiments with illite and goethite were done with pH-values of 4.2 and 6.8 (natural pH of illite and goethite, neutral and partly negatively charged SDZ) and also done in buffer solution about pH 8 for comparing the adsorption on all adsorbents in same pH range. The adsorption isotherms on all sorbents are strongly nonlinear and can be fitted well by the Freundlich equation. From the initial slope of the isotherm the partition coefficient Kd could be determined. The adsorption of SDZ on illite at pH 4.2 and on goethite at pH 6.8 has higher Kd-values than at pH 8, which demonstrates that the negative charge of SDZ obstructs the adsorption. The desorption isotherms show hysteresis effects for all adsorbents. The strong hysteresis was found for goethite and soil indicates strongly physical or chemical binding. On the other hand, the low hysteresis effect for Al2O3 and illite indicates the weak binding of the adsorbed SDZ. The properties of the inorganic matrix and especially the charges of the inorganic compounds in relation to the charge of SDZ are important parameters for the sorption process. The data could be described by modeling with different sorption rates and sites.

Results of the second national forest soil inventory in Germany - Interpretation of level and stock profiles for PCDD/F and PCB in terms of vegetation and humus type.

PubMed

Pandelova, Marchela; Henkelmann, Bernhard; Bussian, Bernd M; Schramm, Karl-Werner

2018-01-01

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) were detected in 86 humic topsoil layers and in a subset of 11 randomly selected top mineral forest soils at the depths of 0-5cm and 5-10cm collected from different federal states of Germany. The distribution of these persistent organic pollutants (POPs) in humic topsoils with respect to vegetation cover (coniferous vs. deciduous vs. mixed), total organic carbon (TOC), altitude and latitude data was investigated. There is cross correlation between the contents and TOC while the correlation with latitude indicates higher abundances of POPs in central Germany where there is high population density accompanied with industrial activities. The calculated stocks suggest that humus type (mor, mull, or moder) in conjunction with forest type can explain the relative POPs abundances in different soil layers. Generally, humic topsoils show highest contents of POPs compare to the two mineral soils with a ratio of 100:10:1. However, the stock humic layers of coniferous stands contribute about 50% to the total stock, whereas at deciduous stands the stock is mainly located in the upper mineral soil layer (0-5cm). The soil-water distribution coefficients (Kd) were calculated to estimate the potential translocation in the different soil types. The Kd values vary among the PCBs and PCDD/Fs congeners and are most variable for humic topsoils. There is pronounced chemical abundance in the top mineral soils with increasing Kd and this points to non-water bound transport processes for superlipophilic compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Higher-Order Nonlinear Effects on Wave Structures in a Multispecies Plasma with Nonisothermal Electrons

NASA Astrophysics Data System (ADS)

Gill, Tarsem Singh; Bala, Parveen; Kaur, Harvinder

2010-04-01

In the present investigation, we have studied ion-acoustic solitary waves in a plasma consisting of warm positive and negative ions and nonisothermal electron distribution. We have used reductive perturbation theory (RPT) and derived a dispersion relation which supports only two ion-acoustic modes, viz. slow and fast. The expression for phase velocities of these modes is observed to be a function of parameters like nonisothermality, charge and mass ratio, and relative temperature of ions. A modified Korteweg-de Vries (KdV) equation with a (1+1/2) nonlinearity, also known as Schamel-mKdV model, is derived. RPT is further extended to include the contribution of higher-order terms. The results of numerical computation for such contributions are shown in the form of graphs in different parameter regimes for both, slow and fast ion-acoustic solitary waves having several interesting features. For the departure from the isothermally distributed electrons, a generalized KdV equation is derived and solved. It is observed that both rarefactive and compressive solitons exist for the isothermal case. However, nonisothermality supports only the compressive type of solitons in the given parameter regime.

Characterization of WY 14,643 and its Complex with Aldose Reductase

PubMed Central

Sawaya, Michael R.; Verma, Malkhey; Balendiran, Vaishnavi; Rath, Nigam P.; Cascio, Duilio; Balendiran, Ganesaratnam K.

2016-01-01

The peroxisome proliferator, WY 14,643 exhibits a pure non-competitive inhibition pattern in the aldehyde reduction and in alcohol oxidation activities of human Aldose reductase (hAR). Fluorescence emission measurements of the equilibrium dissociation constants, Kd, of oxidized (hAR•NADP+) and reduced (hAR•NADPH) holoenzyme complexes display a 2-fold difference between them. Kd values for the dissociation of WY 14,643 from the oxidized (hAR•NADP+•WY 14,643) and reduced (hAR•NADPH•WY 14,643) ternary complexes are comparable to each other. The ternary complex structure of hAR•NADP+•WY 14,643 reveals the first structural evidence of a fibrate class drug binding to hAR. These observations demonstrate how fibrate molecules such as WY 14,643, besides being valued as agonists for PPAR, also inhibit hAR. PMID:27721416

U(VI) adsorption on aquifer sediments at the Hanford Site.

PubMed

Um, Wooyong; Serne, R Jeffrey; Brown, Christopher F; Last, George V

2007-08-15

Aquifer sediments collected via split-spoon sampling in two new groundwater wells in the 200-UP-1 operable unit at the Hanford Site were characterized and showed typical Ringold Unit E Formation properties dominated by gravel and sand. High iron-oxide content in Fe oxide/clay coatings caused the highest U(VI) adsorption as quantified by batch K(d) values, indicating iron oxides are the key solid adsorbent in the 200-UP-1 sediments that affect U(VI) fate and mobility. Even though U(VI) adsorption on the gravel-sized fraction of the sediments is considered to be negligible, careful characterization should be conducted to determine U(VI) adsorption on gravel, because of presence of Fe oxides coatings and diffusion-controlled adsorption into the gravel particles' interior surfaces. A linear adsorption isotherm was observed up to 10(-6) M (238 microg/L) of total U(VI) concentration in batch U(VI) adsorption tests with varying total U(VI) concentrations in spiked groundwater. U(VI) adsorption decreased with increasing concentrations of dissolved carbonate, because strong anionic aqueous uranium-carbonate complexes formed at high pH and high alkalinity conditions. Noticeable uranium desorption hysteresis was observed in a flow-through column experiment, suggesting that desorption K(d) values for aged uranium-contaminated sediments at the Hanford Site can be larger than adsorption K(d) values determined in short-term laboratory experiments and slow uranium release from contaminated sediments into the groundwater is expected.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease: An Observational Study.

PubMed

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise.Sixty-three KD patients were recruited as KD group 1 from children (aged 5-18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator.All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = -0.301; by Fuse, P = 0.014, Spearman rho = -0.309).Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to assess and monitor cardiovascular risk of KD patients. Max-Z of CA correlates with PRPP modest inversely and might be used as a follow-up indicator of CA reserve during exercise after acute stage of KD.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease

PubMed Central

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Abstract Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise. Sixty-three KD patients were recruited as KD group 1 from children (aged 5–18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator. All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = −0.301; by Fuse, P = 0.014, Spearman rho = −0.309). Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to assess and monitor cardiovascular risk of KD patients. Max-Z of CA correlates with PRPP modest inversely and might be used as a follow-up indicator of CA reserve during exercise after acute stage of KD. PMID:26765431

Binding affinities of NKG2D and CD94 to sialyl Lewis X-expressing N-glycans and heparin.

PubMed

Higai, Koji; Suzuki, Chiho; Imaizumi, Yuzo; Xin, Xin; Azuma, Yutaro; Matsumoto, Kojiro

2011-01-01

Lectin-like receptors natural killer group 2D (NKG2D) and CD94 on natural killer (NK) cells bind to α2,3-NeuAc-containing N-glycans and heparin/heparan sulfate (HS). Using recombinant glutathione S-transferase-fused extracellular lectin-like domains of NKG2D (rGST-NKG2Dlec) and CD94 (rGST-CD94lec), we evaluated their binding affinities (K(d)) to high sialyl Lewis X (sLeX)-expressing transferrin secreted by HepG2 cells (HepTf) and heparin-conjugated bovine serum albumin (Heparin-BSA), using quartz crystal microbalance (QCM) and enzyme immunoassay (EIA) microplate methods. K(d) values obtained by linear reciprocal plots revealed good coincidence between the two methods. K(d) values of rGST-NKG2Dlec obtained by QCM and EIA, respectively, were 1.19 and 1.11 µM for heparin-BSA >0.30 and 0.20 µM for HepTf, while those of rGST-CD94lec were 1.31 and 1.45 µM for HepTf >0.37 and 0.36 µM for heparin-BSA. These results suggested that these glycans can interact with NKG2D and CD94 to modulate NK cell-dependent cytotoxicity.

Attempt to model laboratory-scale diffusion and retardation data.

PubMed

Hölttä, P; Siitari-Kauppi, M; Hakanen, M; Tukiainen, V

2001-02-01

Different approaches for measuring the interaction between radionuclides and rock matrix are needed to test the compatibility of experimental retardation parameters and transport models used in assessing the safety of the underground repositories for the spent nuclear fuel. In this work, the retardation of sodium, calcium and strontium was studied on mica gneiss, unaltered, moderately altered and strongly altered tonalite using dynamic fracture column method. In-diffusion of calcium into rock cubes was determined to predict retardation in columns. In-diffusion of calcium into moderately and strongly altered tonalite was interpreted using a numerical code FTRANS. The code was able to interprete in-diffusion of weakly sorbing calcium into the saturated porous matrix. Elution curves of calcium for the moderately and strongly altered tonalite fracture columns were explained adequately using FTRANS code and parameters obtained from in-diffusion calculations. In this paper, mass distribution ratio values of sodium, calcium and strontium for intact rock are compared to values, previously obtained for crushed rock from batch and crushed rock column experiments. Kd values obtained from fracture column experiments were one order of magnitude lower than Kd values from batch experiments.

Investigations of the partitioning and residence times of Po-210 and Pb-210 in a riverine system in Southeast Michigan, USA.

PubMed

Mudbidre, R; Baskaran, M; Schweitzer, L

2014-12-01

Some of the daughter products in the (222)Rn-decay series, such as (210)Po and (210)Pb, have been widely used as tracers and chronometers in aqueous systems. We measured the concentrations of (210)Pb and (210)Po in the dissolved (≤0.5 μm), bulk (unfiltered) and particulate phases (≥1 μm) collected in the Clinton River in the Lake St. Clair watershed in Southeast Michigan in order to investigate their partitioning between particulate and dissolved phases. Activity measurements of the dissolved and particulate phases revealed that an average of 38% (range: 12-59%) and 33% (range: 12-66%) of the total (210)Pb and (210)Po, respectively, in the water column was found in the particulate phase. The activity of dissolved and total (210)Pb was higher than that of (210)Po because of the higher atmospheric depositional fluxes of (210)Pb compared to (210)Po. Although the calculated Kd values of (210)Pb and (210)Po were similar, there was an inverse relationship between the Kd and suspended particulate matter concentration, indicating the presence of a particle concentration effect and we attribute this observation to the presence of significant amounts of colloidal (210)Po and (210)Pb in the dissolved phase. The fractionation factors for Po and Pb were found to be less than 1 in most cases. The first-order box model calculation-based residence times with respect to scavenging varied from 2 to 25 days for (210)Pb and 19-78 days for (210)Po, indicating higher particle-reactivity of (210)Pb compared to (210)Po. Copyright © 2014 Elsevier Ltd. All rights reserved.

High Affinity Binding of Indium and Ruthenium Ions by Gastrins

PubMed Central

Baldwin, Graham S.; George, Graham N.; Pushie, M. Jake

2015-01-01

The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated forms of the hormone. Since gastrins act as growth factors in gastrointestinal cancers, and as peptides labelled with Ga and In isotopes are increasingly used for cancer diagnosis, the ability of gastrins to bind other metal ions was investigated systematically by absorption spectroscopy. The coordination structures of the complexes were characterized by extended X-ray absorption fine structure (EXAFS) spectroscopy. Changes in the absorption of gastrin in the presence of increasing concentrations of Ga3+ were fitted by a 2 site model with dissociation constants (Kd) of 3.3 x 10−7 and 1.1 x 10−6 M. Although the absorption of gastrin did not change upon the addition of In3+ ions, the changes in absorbance on Fe3+ ion binding in the presence of indium ions were fitted by a 2 site model with Kd values for In3+ of 6.5 x 10−15 and 1.7 x 10−7 M. Similar results were obtained with Ru3+ ions, although the Kd values for Ru3+ of 2.6 x 10−13 and 1.2 x 10−5 M were slightly larger than observed for In3+. The structures determined by EXAFS all had metal:gastrin stoichiometries of 2:1 but, while the metal ions in the Fe, Ga and In complexes were bridged by a carboxylate and an oxygen with a metal-metal separation of 3.0–3.3 Å, the Ru complex clearly demonstrated a short range Ru—Ru separation, which was significantly shorter, at 2.4 Å, indicative of a metal-metal bond. We conclude that gastrin selectively binds two In3+ or Ru3+ ions, and that the affinity of the first site for In3+ or Ru3+ ions is higher than for ferric ions. Some of the metal ion-gastrin complexes may be useful for cancer diagnosis and therapy. PMID:26457677

Rational Design, Synthesis, and Biological Evaluation of Third Generation α-Noscapine Analogues as Potent Tubulin Binding Anti-Cancer Agents

PubMed Central

Manchukonda, Naresh Kumar; Naik, Pradeep Kumar; Santoshi, Seneha; Lopus, Manu; Joseph, Silja; Sridhar, Balasubramanian; Kantevari, Srinivas

2013-01-01

Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol) than the parent compound, noscapine (-5.505 kCal/mol) and its existing derivatives (-5.563 to -6.412 kCal/mol). Free energy (ΔG bind) calculations based on the linear interaction energy (LIE) empirical equation utilizing Surface Generalized Born (SGB) continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol). Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol). The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl) noscapine (6f) binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM), which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM) and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM). All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents. PMID:24205049

The water-water cycle is essential for chloroplast protection in the absence of stress.

PubMed

Rizhsky, Ludmila; Liang, Hongjian; Mittler, Ron

2003-10-03

Maintaining electron flow through the photosynthetic apparatus, even in the absence of a sufficient amount of NADP+ as an electron acceptor, is essential for chloroplast protection from photooxidative stress. At least two different pathways are thought to participate in this process, i.e. cyclic electron flow and the water-water cycle. Although the function of the water-water cycle was inferred from a number of biochemical and physiological studies, genetic evidence for the function of this cycle is very limited. Here we show that knockdown Arabidopsis plants with suppressed expression of the key water-water cycle enzyme, thylakoid-attached copper/zinc superoxide dismutase (KD-SOD), are suppressed in their growth and development. Chloroplast size, chlorophyll content, and photosynthetic activity were also reduced in KD-SOD plants. Microarray analysis of KD-SOD plants, grown under controlled conditions, revealed changes in transcript expression consistent with an acclimation response to light stress. Although a number of transcripts involved in the defense of plants from oxidative stress were induced in KD-SOD plants, and seedlings of KD-SOD plants were more tolerant to oxidative stress, these mechanisms were unable to compensate for the suppression of the water-water cycle in mature leaves. Thus, the localization of copper/zinc superoxide dismutase at the vicinity of photosystem I may be essential for its function. Our studies provide genetic evidence for the importance of the water-water cycle in protecting the photosynthetic apparatus of higher plants from photooxidative damage.

[Changes in peripheral blood T helper 9 cells and interleukin-9 in children in the acute stage of Kawasaki disease].

PubMed

Sun, Rui-Li; Zhu, Shu-Xia; Zhang, Yan-Yan; Wu, Yi-Fei; Wang, Xing-Jian

2016-08-01

To investigate the changes in the expression levels of peripheral blood T helper 9 (Th9) cells and cytokine interleukin-9 (IL-9) in children in the acute stage of Kawasaki disease (KD) and their clinical significance. A total of 45 children in the acute stage of KD who were treated from April 2014 to July 2015 were enrolled, and the children were followed up in the recovery stage. Another 45 healthy children who underwent physical examination were enrolled as the control group. Flow cytometry was used to measure the percentage of peripheral blood Th9 cells, and ELISA was used to measure the serum level of IL-9. The children in the acute stage of KD showed a significantly higher percentage of Th9 cells and a significantly higher serum level of IL-9 compared with those in the recovery stage and the control group (P<0.05). The percentage of Th9 cells and serum level of IL-9 showed no significant differences between the children in the recovery stage and those in the control group (P>0.05). In the acute stage, the percentage of Th9 cells was positively correlated with the levels of IL-9, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), platelet count (PLT), and globulin (r=0.624, 0.324, 0.402, 0.382, 0.467, and 0.386 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.306, P<0.05). The serum level of IL-9 was positively correlated with the levels of CRP, PCT, ESR, PLT, and globulin (r=0.365, 0.456, 0.403, 0.423, and 0.453 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.343, P<0.05). The children in the acute stage of KD show significant increases in the percentage of peripheral Th9 cells and serum cytokine IL-9 level, which return to normal in the recovery stage. In the acute stage of KD, the expression levels of Th9 and IL-9 are closely correlated with laboratory markers. The results suggest that Th9 cells and IL-9 play important roles in the pathogenesis and outcome of KD.

Mutant prenyltransferase-like mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice

PubMed Central

Peng, Min; Jarett, Leonard; Meade, Ray; Madaio, Michael P.; Hancock, Wayne W.; George, Alfred L.; Neilson, Eric G.; Gasser, David L.

2008-01-01

Background Mice that are homozygous for the kidney disease (kd) mutation are apparently healthy for the first 8 weeks of life, but spontaneously develop a severe form of interstitial nephritis that progresses to end-stage renal disease (ESRD) by 4 to 8 months of age. By testing for linkage to microsatellite markers, we previously localized the kd gene to a YAC/BAC contig. Methods The sequence of the entire critical region was examined, and candidate genes were identified. These candidate genes were sequenced in both mutant (kd/kd) mice and normal controls. The phenotype was further characterized by immunohistochemistry and electron microscopy. Transgenic mice were constructed that carried the wild-type allele of the prime candidate gene, and this transgene was transferred to a kd/kd background by breeding. Results We have obtained evidence that kd is a mutant allele of a novel gene for a prenyltransferase-like mitochondrial protein (PLMP). This gene is alternatively spliced, with the larger gene product having one domain that resembles transprenyltransferase and another that is similar to geranylgeranyl pyrophosphate synthase. The smaller gene product includes only the first domain. An antiserum to PLMP localizes to mitochondria, and ultrastructural defects are present in the mitochondria of renal tubular epithelial cells, and to a lesser extent, hepatocytes and heart cells from kd/kd mice. In a line of kd/kd mice that carried the wild-type PLMP allele as a transgene, only 1 out of 13 animals expressed the disease by 120 days of age. Conclusion The kd allele codes for a novel protein that localizes to the mitochondria, and the kd/kd mouse has dysmorphic mitochondria in the renal tubular epithelial cells. This mouse is therefore a unique animal model for studying mechanisms that lead to tubulointerstitial nephritis. PMID:15200409

Ursodeoxycholic Acid Ameliorates Intrahepatic Cholestasis Independent of Biliary Bicarbonate Secretion in Vil2kd/kd Mice.

PubMed

Hatano, Ryo; Kawaguchi, Kotoku; Togashi, Fumitaka; Sugata, Masato; Masuda, Shizuka; Asano, Shinji

2017-01-01

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that possesses many pharmacological effects, including increasing bile flow, changing the hydrophobicity of the bile acid pool, and modulation of the immune response. UDCA has been approved for treating cholestatic liver disease, such as primary biliary cholangitis. However, several unanticipated severe side effects of UDCA are observed in cholestatic patients, and its pharmacological benefits remain controversial. We reported that ezrin-knockdown (Vil2 kd/kd ) mice exhibited severe hepatic injury because of a functional disorder in bile duct fluidity and alkalinity regulation, resembling human intrahepatic cholestatic disease. Here we used Vil2 kd/kd mice as a cholestatic model to investigate the pharmacological effects of UDCA. We investigated the effects of oral and parenteral administration of UDCA on Vil2 kd/kd mice. In Vil2 kd/kd mice, fed a 0.5% (w/w) UDCA diet for 3 weeks, hepatic injury was exacerbated, although oral administration of a lower dose of UDCA slightly improved hepatic function in Vil2 kd/kd mice. On the other hand, intraperitoneal administration of UDCA (50 mg/kg/d) ameliorated hepatic function and markedly reduced periductal fibrosis and cholangiocyte proliferation in Vil2 kd/kd mice although biliary pH and HCO 3 - concentration were not improved. The expression levels of inflammatory and profibrotic genes were also significantly decreased in these mice. Furthermore, UDCA prevented cholangiocytes from hydrophobic bile acid-induced cytotoxicity independent of extracellular pH in in vitro experiments. These results suggest that an appropriate dosage of UDCA can ameliorate the intrahepatic cholestasis in Vil2 kd/kd mice without changing the biliary bicarbonate secretion.

[Clinical analysis of 942 cases of Kawasaki disease].

PubMed

Zhang, Wei; Li, Qiu; Zhao, Xiao-dong; Tang, Xue-mei; Wang, Xiao-gang; Wang, Mo; Wu, Dao-qi; Ou, Qian; Yang, Xi-qiang

2006-05-01

The study was designed to investigate the clinical characteristics and the effects of therapeutic proposal on Kawasaki disease (KD). Clinical features, diagnosis and treatment for totally 942 patients with KD hospitalized during Jan, 2000 to Dec, 2004 were reviewed. Clinical features of typical and incomplete KD were compared. Also, influential factors for KD resistant to intravenous immune globulin (IVIG) therapy were analyzed. Five hundred and ten cases were followed up for analyzing the prognosis of coronary artery lesion (CAL). (1) 774 cases were diagnosed as typical KD, and 168 cases as incomplete KD. The incidence of infants with incomplete KD was higher than that of infants with typical KD (18.5% vs. 10.1%, P < 0.01). As compared with typical KD, the cases of incomplete KD had a long duration of fever before final diagnosis [(7.7 +/- 2.9) d vs. (7.0 +/- 2.4) d, P < 0.01], high hemoglobin level [Hb, (106.6 +/- 13.4) g/L vs. (103.5 +/- 12.3) g/L, P < 0.01], high hematocrit [Hct, (32.0 +/- 4.3)% vs. (31.0 +/- 4.0)%, P < 0.01], and high prevalence of CAL (23.8% vs. 16.8%, P < 0.05), respectively. The occurrence rate and emerging time of clinical manifestations in incomplete KD and in typical KD were presented, respectively: non-exudative conjunctivitis [occurrence rate, 64.9% vs. 93.5%; emerging time, (4.4 +/- 1.4) d vs. (4.0 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], erythema and cracking of lips [occurrence rate, 50.6% vs. 94.8%; emerging time, (4.9 +/- 1.4) d vs. (4.5 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], rash [occurrence rate, 35.1% vs. 87.7%; emerging time, (3.9 +/- 1.9) d vs. (3.4 +/- 1.7) d, respectively (P < 0.05 or P < 0.01)], erythema and edema of extremity [occurrence rate, 26.8% vs. 71.4%; emerging time, (6.7 +/- 1.5) d vs. (5.3 +/- 1.7) d, respectively (P < 0.01)], cervical lymphadenopathy [occurrence rate, 34.5% vs. 68.0%; emerging time, (4.3 +/- 2.5) d vs. (3.6 +/- 2.2) d, respectively (P < 0.05 or P < 0.01)], strawberry tongue [occurrence rate, 31.0% vs. 59.8%; emerging time, (5.6 +/- 2.2) d vs. (4.9 +/- 1.8) d, respectively (P < 0.05 or P < 0.01)], membranous desquamation of fingertips [occurrence rate, 34.5% vs. 56.3%; emerging time, (11.7 +/- 3.3) d vs. (10.3 +/- 2.7) d, respectively (P < 0.01)], and desquamation peri-anus [occurrence rate, 42.9% vs. 50.0%; emerging time, (6.7 +/- 2.7) d vs. (6.9 +/- 2.5) d, respectively (P > 0.05)]. Except for peri-anus desquamation, other clinical manifestations in incomplete KD were sporadical as compared to typical KD. (2) Six per cent (51/857) of cases were resistant to the IVIG therapy. As compared to the group responding to IVIG therapy, high prevalence of CAL (31.4% vs. 17.1%, P < 0.05), long fever duration [(10.6 +/- 3.9) d vs. (7.5 +/- 2.3) d, P < 0.01], low Hb level [(99.9 +/- 14.1) g/L vs. (104.3 +/- 12.4) g/L, P < 0.01], low Hct [(30.1 +/- 4.5)% vs. (31.2 +/- 4.0)%, P < 0.05], low platelet [PLT, (256.9 +/- 142.4) x 10(9)/L vs. (309.7 +/- 131.5) x 10(9)/L, P < 0.05], and low albumin level [ALB, (27.8 +/- 8.4) g/L vs. (33.5 +/- 6.7) g/L, P < 0.01] were found in the group resistant to IVIG therapy, respectively. (3) In patients who received IVIG 1 g/kg and 2 g/kg, the recovery rates from CAL were 83.1% and 89.7% (P > 0.05), respectively. The prevalence of CAL in those without CAL in acute and subacute stages was 0.9% and 3.5% (P > 0.05), respectively, during 2 year-follow-up period. (1) Infants appeared to have more chances to suffer from incomplete KD. Incomplete KD had high prevalence of CAL. The peri-anus desquamation might be an important clue for early diagnosis of incomplete KD. (2) In acute stage, the influential factors for KD resistance to IVIG therapy included prolonged fever, non-elevated PLT, and persistent decrease in Hb, Hct and ALB levels. (3) Children receiving IVIG 1 g/kg and 2 g/kg had the similar effects on recovery and prevention from CAL within the first two years after KD onset.

Role of the Excitability Brake Potassium Current IKD in Cold Allodynia Induced by Chronic Peripheral Nerve Injury.

PubMed

González, Alejandro; Ugarte, Gonzalo; Restrepo, Carlos; Herrera, Gaspar; Piña, Ricardo; Gómez-Sánchez, José Antonio; Pertusa, María; Orio, Patricio; Madrid, Rodolfo

2017-03-22

Cold allodynia is a common symptom of neuropathic and inflammatory pain following peripheral nerve injury. The mechanisms underlying this disabling sensory alteration are not entirely understood. In primary somatosensory neurons, cold sensitivity is mainly determined by a functional counterbalance between cold-activated TRPM8 channels and Shaker-like Kv1.1-1.2 channels underlying the excitability brake current I KD Here we studied the role of I KD in damage-triggered painful hypersensitivity to innocuous cold. We found that cold allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in mice, was related to both an increase in the proportion of cold-sensitive neurons (CSNs) in DRGs contributing to the sciatic nerve, and a decrease in their cold temperature threshold. I KD density was reduced in high-threshold CSNs from CCI mice compared with sham animals, with no differences in cold-induced TRPM8-dependent current density. The electrophysiological properties and neurochemical profile of CSNs revealed an increase of nociceptive-like phenotype among neurons from CCI animals compared with sham mice. These results were validated using a mathematical model of CSNs, including I KD and TRPM8, showing that a reduction in I KD current density shifts the thermal threshold to higher temperatures and that the reduction of this current induces cold sensitivity in former cold-insensitive neurons expressing low levels of TRPM8-like current. Together, our results suggest that cold allodynia is largely due to a functional downregulation of I KD in both high-threshold CSNs and in a subpopulation of polymodal nociceptors expressing TRPM8, providing a general molecular and neural mechanism for this sensory alteration. SIGNIFICANCE STATEMENT This paper unveils the critical role of the brake potassium current I KD in damage-triggered cold allodynia. Using a well-known form of nerve injury and combining behavioral analysis, calcium imaging, patch clamping, and pharmacological tools, validated by mathematical modeling, we determined that the functional expression of I KD is reduced in sensory neurons in response to peripheral nerve damage. This downregulation not only enhances cold sensitivity of high-threshold cold thermoreceptors signaling cold discomfort, but it also transforms a subpopulation of polymodal nociceptors signaling pain into neurons activated by mild temperature drops. Our results suggest that cold allodynia is linked to a reduction of I KD in both high-threshold cold thermoreceptors and nociceptors expressing TRPM8, providing a general model for this form of cold-induced pain. Copyright © 2017 the authors 0270-6474/17/373109-18$15.00/0.

Age- and weight-based differences in haemodialysis prescription and delivery in children, adolescents and young adults.

PubMed

Gotta, Verena; Marsenic, Olivera; Pfister, Marc

2018-04-18

Limited systematic data are available on prescription and dosing of haemodialysis (HD) in children and adolescents compared with adults. We aimed to characterize age- and weight-based differences in HD delivery in children, adolescents and young adults. This is a retrospective observational study including 1852 patients <30 years on chronic HD from childhood (53 903 HD sessions), receiving thrice weekly outpatient HD between 2004 and 2016 in the USA (6075 patient-years, of which 2535 were in patients aged 1-18 years; weight range 8.3-168 kg). Median individual prescriptions per year were calculated and overall 50% (IQR) and 90% distribution ranges over age and weight were derived. Repeated measurements analysis of variance assessed differences between age and weight groups. Prescriptions significantly differed among age and weight groups (P < 0.001). Lower weight patients (<75 kg) had higher (inter-quartile range, IQR) weight-normalized blood flow rate (highest in <25 kg: QB/kg = 6.5-9.1 mL/min/kg), urea dialytic clearance (KD/kg) and single pool Kt/V (spKt/V) (<25 kg: 1.43-1.78; 25-50 kg: 1.52-1.92; 50-75 kg: 1.43-1.74) than heavier patients (lowest in >100 kg: QB/kg = 3.1-4.0 mL/min/kg, spKt/V = 1.22-1.47, respectively). Adolescents had significantly lower QB/kg, KD/kg and spKt/V (1.34-1.71) compared with adults (1.45-1.79) and children <12 years (range of 25th percentiles: 1.37-1.44). Dialytic clearance derived from a mechanistic equation underpredicted KD in children but not in young adults. Significant growth retardation was observed, with the proportion of patients <3rd percentile (height for age) decreasing from 71% (1-2 years) to 15% (>18 years). Delivered HD treatment varies with age and weight and is more intensified in children aged <12 years, compared with adolescents and overweight young adults, who appear to be at highest risk of receiving suboptimal treatment. Still, delivery of target or higher spKt/V values did not result in appropriate growth in these children, questioning the value of spKt/V as a measure of HD adequacy in children. Provided ranges of outpatient HD prescription can help clinicians and researchers in personalizing and optimizing delivery of dialysis treatment.

Sorption of atrazine and ametryn by carbonatic and non-carbonatic soils of varied origin.

PubMed

Kasozi, G N; Nkedi-Kizza, P; Li, Y; Zimmerman, A R

2012-10-01

Sorption of two s-triazines, atrazine and ametryn, by carbonatic soils, Histosols, Spodosols and Oxisols was examined. Linear isotherms were observed and sorption coefficients (K(d)) of both compounds were significantly lower (α = 0.05) onto carbonatic soils compared to non-carbonatic soils. Furthermore, among carbonatic soil types, the marl-carbonatic soils had the lowest sorption affinities. K(d) and organic carbon content were highly correlated, suggesting predominant influence of organic carbon in the sorption of the s-triazine, except in Oxisols and Spodosols where variations suggest other factors. Upon removal of organic matter (OM) using sodium hypochlorite and hydrogen peroxide, the K(d) values were reduced by ~90%, indicating minimal contribution of mineral surfaces. Thus OM compositional differences likely explain the large variation in s-triazine sorption within and between soil orders. This study highlights the need to consider OM composition in addition to quantity when determining pesticide applications rates, particularly for carbonatic soils. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reversible watermarking for knowledge digest embedding and reliability control in medical images.

PubMed

Coatrieux, Gouenou; Le Guillou, Clara; Cauvin, Jean-Michel; Roux, Christian

2009-03-01

To improve medical image sharing in applications such as e-learning or remote diagnosis aid, we propose to make the image more usable by watermarking it with a digest of its associated knowledge. The aim of such a knowledge digest (KD) is for it to be used for retrieving similar images with either the same findings or differential diagnoses. It summarizes the symbolic descriptions of the image, the symbolic descriptions of the findings semiology, and the similarity rules that contribute to balancing the importance of previous descriptors when comparing images. Instead of modifying the image file format by adding some extra header information, watermarking is used to embed the KD in the pixel gray-level values of the corresponding images. When shared through open networks, watermarking also helps to convey reliability proofs (integrity and authenticity) of an image and its KD. The interest of these new image functionalities is illustrated in the updating of the distributed users' databases within the framework of an e-learning application demonstrator of endoscopic semiology.

Two-soliton interaction as an elementary act of soliton turbulence in integrable systems

NASA Astrophysics Data System (ADS)

Pelinovsky, E. N.; Shurgalina, E. G.; Sergeeva, A. V.; Talipova, T. G.; El, G. A.; Grimshaw, R. H. J.

2013-01-01

Two-soliton interactions play a definitive role in the formation of the structure of soliton turbulence in integrable systems. To quantify the contribution of these interactions to the dynamical and statistical characteristics of the nonlinear wave field of soliton turbulence we study properties of the spatial moments of the two-soliton solution of the Korteweg-de Vries (KdV) equation. While the first two moments are integrals of the KdV evolution, the 3rd and 4th moments undergo significant variations in the dominant interaction region, which could have strong effect on the values of the skewness and kurtosis in soliton turbulence.

Exact solutions to the time-fractional differential equations via local fractional derivatives

NASA Astrophysics Data System (ADS)

Guner, Ozkan; Bekir, Ahmet

2018-01-01

This article utilizes the local fractional derivative and the exp-function method to construct the exact solutions of nonlinear time-fractional differential equations (FDEs). For illustrating the validity of the method, it is applied to the time-fractional Camassa-Holm equation and the time-fractional-generalized fifth-order KdV equation. Moreover, the exact solutions are obtained for the equations which are formed by different parameter values related to the time-fractional-generalized fifth-order KdV equation. This method is an reliable and efficient mathematical tool for solving FDEs and it can be applied to other non-linear FDEs.

Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex

PubMed Central

2016-01-01

Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a KD of 124 nM, SMARCA2B and SMARCA4 with KD values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4. PMID:27119626

Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes.

PubMed

Doan, Son; Maehara, Cleo K; Chaparro, Juan D; Lu, Sisi; Liu, Ruiling; Graham, Amanda; Berry, Erika; Hsu, Chun-Nan; Kanegaye, John T; Lloyd, David D; Ohno-Machado, Lucila; Burns, Jane C; Tremoulet, Adriana H

2016-05-01

Delayed diagnosis of Kawasaki disease (KD) may lead to serious cardiac complications. We sought to create and test the performance of a natural language processing (NLP) tool, the KD-NLP, in the identification of emergency department (ED) patients for whom the diagnosis of KD should be considered. We developed an NLP tool that recognizes the KD diagnostic criteria based on standard clinical terms and medical word usage using 22 pediatric ED notes augmented by Unified Medical Language System vocabulary. With high suspicion for KD defined as fever and three or more KD clinical signs, KD-NLP was applied to 253 ED notes from children ultimately diagnosed with either KD or another febrile illness. We evaluated KD-NLP performance against ED notes manually reviewed by clinicians and compared the results to a simple keyword search. KD-NLP identified high-suspicion patients with a sensitivity of 93.6% and specificity of 77.5% compared to notes manually reviewed by clinicians. The tool outperformed a simple keyword search (sensitivity = 41.0%; specificity = 76.3%). KD-NLP showed comparable performance to clinician manual chart review for identification of pediatric ED patients with a high suspicion for KD. This tool could be incorporated into the ED electronic health record system to alert providers to consider the diagnosis of KD. KD-NLP could serve as a model for decision support for other conditions in the ED. © 2016 by the Society for Academic Emergency Medicine.

[Characteristics of cationic polymers PEI-CyD, PEI-PHPA, PEE-PHPA and PEI25kD in vitro and in vivo].

PubMed

Yao, Qi; Jin, Xue; Hu, Tian-nan; Wang, Qi-wen; Wang, Xun-shi; Hu, Qi-da; Xu, Sang; Zhou, Jun; Tang, Gu-ping

2012-11-01

To study the characteristics of cationic polymers polyethylenimine-β-cyclodextrin (PEI-CyD), polyethylenimine-poly-(3-hydroxypropyl)-aspartamide (PEI-PHPA), N,N-Dimethyldipropylenetriamine-Bis(3-aminopropyl)amine-aspartamide (PEE-PHPA) in vitro and in vivo. PEI-PHPA, PEI-CyD and PEE-PHPA were synthesized and the chemistry structure of PEI-PHPA, PEI-CyD and PEE-PHPA was confirmed by (1)H-NMR. The particle size and zeta potential of these polymers were measured, and capacity of plasmid DNA condensation was tested. The inhibition of COS-7, A549, HEK293 and C6 cells was measured by MTT assay. The transfection efficiency was determined in HEK293 cell lines. The toxicity, tissue distribution and transfection efficiency of cationic polymers were tested in vivo. When the N/P of polymers/DNA at 30, the particle sizes were close 250 nm and the zeta-potential were near 35 mv. They were able to condense DNA at N/P ratio < 5. The MTT assay showed that the IC(50) of PEE-PHPA was 21.5, 20.2, 7.30 and 37.1 μg/ml, and that of PEI25kD was 15.8, 18.3, 11.4 and 36.7 μg/ml in C6, COS-7, A549 and HEK293cell lines, respectively. The cell viability of PEI-CyD and PEI-PHPA in above cell lines was over 60%. They had high transfection efficiency in HEK293 cell lines. The LD(50) of PEI25Kd, PEI-CyD, PEI-PHPA and PEE-PHPA in vivo was 19.50, 100.4, 521.2 and 630.0, respectively by intraperitoneal (ip) injection. The contractions of these polymers were higher in kidney than in other organs and tissues.PEE-PHPA had slight effect on kidney and liver function. PEE and PEI25kD have higher transfection efficiency and higher toxicity; while PC and PHPA-PEI have lower toxicity and higher transfection efficiency to be used as non-viral gene vector.

Competitive adsorption/desorption of tetracycline, oxytetracycline and chlortetracycline on two acid soils: Stirred flow chamber experiments.

PubMed

Fernández-Calviño, David; Bermúdez-Couso, Alipio; Arias-Estévez, Manuel; Nóvoa-Muñoz, Juan Carlos; Fernández-Sanjurjo, Maria J; Álvarez-Rodríguez, Esperanza; Núñez-Delgado, Avelino

2015-09-01

The objective of this work was to study the competitive adsorption/desorption of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) on two acid soils. We used the stirred flow chamber technique to obtain experimental data on rapid kinetic processes affecting the retention/release of the antibiotics. Both adsorption and desorption were higher on soil 1 (which showed the highest carbon, clay and Al and Fe oxides content) than on soil 2. Moreover, hysteresis affected the adsorption/desorption processes. Experimental data were fitted to a pseudo-first order equation, resulting qamax (adsorption maximum) values that were higher for soil 1 than for soil 2, and indicating that CTC competed with TC more intensely than OTC in soil 1. Regarding soil 2, the values corresponding to the adsorption kinetics constants (ka) and desorption kinetics constants for fast sites (kd1), followed a trend inverse to qamax and qdmax respectively. In conclusion, competition affected adsorption/desorption kinetics for the three antibiotics assayed, and thus retention/release and subsequent transport processes in soil and water environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of WY 14,643 and its Complex with Aldose Reductase

DOE PAGES

Sawaya, Michael R.; Verma, Malkhey; Balendiran, Vaishnavi; ...

2016-10-10

The peroxisome proliferator, WY 14,643 exhibits a pure non-competitive inhibition pattern in the aldehyde reduction and in alcohol oxidation activities of human Aldose reductase (hAR). Fluorescence emission measurements of the equilibrium dissociation constants, Kd, of oxidized (hAR•NADP+) and reduced (hAR•NADPH) holoenzyme complexes display a 2-fold difference between them. Kd values for the dissociation of WY 14,643 from the oxidized (hAR•NADP+•WY 14,643) and reduced (hAR•NADPH•WY 14,643) ternary complexes are comparable to each other. The ternary complex structure of hAR•NADP+•WY 14,643 reveals the first structural evidence of a fibrate class drug binding to hAR. These observations demonstrate how fibrate molecules such asmore » WY 14,643, besides being valued as agonists for PPAR, also inhibit hAR.« less

Characterization of WY 14,643 and its Complex with Aldose Reductase

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

Sawaya, Michael R.; Verma, Malkhey; Balendiran, Vaishnavi

The peroxisome proliferator, WY 14,643 exhibits a pure non-competitive inhibition pattern in the aldehyde reduction and in alcohol oxidation activities of human Aldose reductase (hAR). Fluorescence emission measurements of the equilibrium dissociation constants, Kd, of oxidized (hAR•NADP+) and reduced (hAR•NADPH) holoenzyme complexes display a 2-fold difference between them. Kd values for the dissociation of WY 14,643 from the oxidized (hAR•NADP+•WY 14,643) and reduced (hAR•NADPH•WY 14,643) ternary complexes are comparable to each other. The ternary complex structure of hAR•NADP+•WY 14,643 reveals the first structural evidence of a fibrate class drug binding to hAR. These observations demonstrate how fibrate molecules such asmore » WY 14,643, besides being valued as agonists for PPAR, also inhibit hAR.« less

Sorption and stability of the polycyclic nitramine explosive CL-20 in soil.

PubMed

Balakrishnan, Vimal K; Monteil-Rivera, Fanny; Gautier, Mathieu A; Hawari, Jalal

2004-01-01

The polycyclic nitramine CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane) is being considered for use as a munition, but its environmental fate and impact are unknown. The present study consisted of two main elements. First, sorption-desorption data were measured with soils and minerals to evaluate the respective contributions of organic matter and minerals to CL-20 immobilization. Second, since CL-20 hydrolyzes at a pH of >7, the effect of sorption on CL-20 degradation was examined in alkaline soils. Sorption-desorption isotherms measured using five slightly acidic soils (5.1 < pH < 6.9) containing various amounts of total organic carbon (TOC) revealed a nonlinear sorption that increased with TOC [K(d) (0.33% TOC) = 2.4 L kg(-1); K(d) (20% TOC) = 311 L kg(-1)]. Sorption to minerals (Fe(2)O(3), silica, kaolinite, montmorillonite, illite) was very low (0 < K(d) < 0.6 L kg(-1)), suggesting that mineral phases do not contribute significantly to CL-20 sorption. Degradation of CL-20 in sterile soils having different pH values increased as follows: sandy agricultural topsoil from Varennes, QC, Canada (VT) (pH = 5.6; K(d) = 15 L kg(-1); 8% loss) < clay soil from St. Sulpice, QC, Canada (CSS) (pH = 8.1; K(d) = 1 L kg(-1); 82% loss) < sandy soil provided by Agriculture Canada (SAC) (pH = 8.1, K(d) = approximately 0 L kg(-1); 100% loss). The faster degradation in SAC soil compared with CSS soil was attributed to the absence of sorption in the former. In summary, CL-20 is highly immobilized by soils rich in organic matter. Although sorption retards abiotic degradation, CL-20 still decomposes in soils where pH is >7.5, suggesting that it will not persist in even slightly alkaline soils.

Anti-nuclear liberals and the bomb: A comparative history of Kampf dem Atomtod and the Committee for a Sane Nuclear Policy, 1957-1963

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

Thiede, B.

The premises of Kampf dem Atomtod (KdA) and Citizens for a Sane Nuclear Policy (SANE) were based on nineteenth century traditions of liberal peace advocacy. Both groups gained substantial public support for their goals to prevent the nuclear armament of the Bundeswehr and to stop nuclear testing. Both organizations won well-educated middle-class and mostly white supporter. The dissertation examines the role of women: whether housewife or doctor, women stressed their special concerns as mothers. Both KdA and SANE had troubled relations with the labor movement. Their leaders hoped to gain government leaders' respect by winning a respectable, non-Communist constituency andmore » claiming their goals were reasonable ones. Government officials attacked KdA and SANE as dupes of Moscow. Many supporters left the organizations because of their strict anti-Communism. Local groups accused their leaders of lacking initative. KdA and SANE's leaders wasted time and energy rehashing issues and postponing decisions. After a period of providing initiatives and ideas local committees disintegrated. Both organizations considered education their paramount goal but their arguments primarily reached the converted, who often preferred more political action. KdA and SANE's leaders instead chose to support respectable projects based on humanitarian ideals. Since these projects offered little in the way of concrete action agendas, supporters defected to more active organizations or slipped into apathy. Neither organization achieved its national goals. Both governments generally denied them access to the policymaking process, ignored them as irrelavant, or attacked them as Communist sympathizers. While SANE and KdA were heard by those concerned by nuclear policy, and while members of SANE's National Board did help muster support for the Partial Test Ban Treaty, both organizations failed to make liberal peace values productive in the nuclear decisionmaking process.« less

Experimental determination of Pb partitioning between sulfide melt and basalt melt as a function of P, T and X

NASA Astrophysics Data System (ADS)

Hart, Stanley R.; Gaetani, Glenn A.

2016-07-01

We have measured the partition coefficient of Pb (KdPb) between FeS melt and basalt melt at temperatures of 1250-1523 °C, pressures of 1.0-3.5 GPa and oxygen fugacities at iron-wustite and wustite-magnetite. The total observed range of KdPb is 4.0-66.6, with a strong negative dependence on pressure and a strong negative dependence on FeO of the silicate melt (Fe+2 only). The FeO control was constrained over a wide range of FeO (4.2-39.5%). We found that the effect of oxygen fugacity can be subsumed under the FeO control parameter. Prior work has established the lack of a significant effect of temperature (Kiseeva and Wood, 2015; Li and Audétat, 2015). Our data are parameterized as: KdPb = 4.8 + (512 - 119*P in GPa)*(1/FeO - 0.021). We also measured a single value of KdPb between clinopyroxene and basalt melt at 2.0 GPa of 0.020 ± 0.001. This experimental data supports the ;natural; partitioning of Pb measured on sulfide globules in MORB (Patten et al., 2013), but not the low KdPb of ∼3 inferred from sulfides in abyssal peridotites by Warren and Shirey (2012). It also quantitatively affirms the modeling of Hart and Gaetani (2006) with respect to using sulfide to buffer the canonical Nd/Pb ratio for MORB and OIB (Hofmann, 2003). For the low FeO and pressure of segregation typical of MORB, KdPb ∼ 45, and the Nd/Pb ratio of erupted basalts will be the same as the Nd/Pb ratio of the mantle source. The remaining puzzle is why MORB and OIB have the same Nd/Pb when they clearly have different FeO and pressure of melt segregation.

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

Sorption behaviour of perfluoroalkyl substances in soils.

PubMed

Milinovic, Jelena; Lacorte, Silvia; Vidal, Miquel; Rigol, Anna

2015-04-01

The sorption behaviour of three perfluoroalkyl substances (PFASs), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorobutane sulfonic acid (PFBS), was studied in six soils with contrasting characteristics, especially in the organic carbon content. Sorption isotherms were obtained by equilibrating the soil samples with 0.01 mol L(-1) CaCl2 solutions spiked with increasing concentrations of the target PFAS. The sorption reversibility of PFASs was also tested for some of the samples. Liquid chromatography coupled to tandem mass spectrometry was used to quantify the target PFASs in the solutions. Both the Freundlich and linear models were appropriate to describe the sorption behaviour of PFASs in soils, and enabled us to derive solid-liquid distribution coefficients (Kd) for each compound in each soil. Kd values increased from 19 to 295 mL g(-1) for PFOS, from 2.2 to 38 mL g(-1) for PFOA and from 0.4 to 6.8 mL g(-1) for PFBS, and were positively correlated with the organic carbon content of the soil. KOC values obtained from the correlations were 710, 96 and 17 mL g(-1) for PFOS, PFOA and PFBS, respectively. Whereas Kd values decreased in the sequence PFOS>PFOA>PFBS, desorption yields were lower than 13% for PFOS, from 24 to 58% for PFOA, and from 32 to 60% for PFBS. This shows that the physicochemical characteristics of PFASs, basically their hydrophobicity, controlled their sorption behaviour in soils, with PFOS being the most irreversibly sorbed PFAS. Copyright © 2014 Elsevier B.V. All rights reserved.

Alternating carrier models of asymmetric glucose transport violate the energy conservation laws.

PubMed

Naftalin, Richard J

2008-11-01

Alternating access transporters with high-affinity externally facing sites and low-affinity internal sites relate substrate transit directly to the unliganded asymmetric "carrier" (Ci) distribution. When both bathing solutions contain equimolar concentrations of ligand, zero net flow of the substrate-carrier complex requires a higher proportion of unliganded low-affinity inside sites (proportional, variant 1/KD(in)) and slower unliganded "free" carrier transit from inside to outside than in the reverse direction. However, asymmetric rates of unliganded carrier movement, kij, imply that an energy source, DeltaGcarrier = RT ln (koi/kio) = RT ln (Cin/Cout) = RT ln (KD(in)/KD(out)), where R is the universal gas constant (8.314 Joules/M/K degrees), and T is the temperature, assumed here to be 300 K degrees , sustains the asymmetry. Without this invalid assumption, the constraints of carrier path cyclicity, combined with asymmetric ligand affinities and equimolarity at equilibrium, are irreconcilable, and any passive asymmetric uniporter or cotransporter model system, e.g., Na-glucose cotransporters, espousing this fundamental error is untenable. With glucose transport via GLUT1, the higher maximal rate and Km of net ligand exit compared to net ligand entry is only properly simulated if ligand transit occurs by serial dissociation-association reactions between external high-affinity and internal low-affinity immobile sites. Faster intersite transit rates occur from lower-affinity sites than from higher-affinity sites and require no other energy source to maintain equilibrium. Similar constraints must apply to cotransport.

Modified Atkins diet vs classic ketogenic formula in intractable epilepsy.

PubMed

El-Rashidy, O F; Nassar, M F; Abdel-Hamid, I A; Shatla, R H; Abdel-Hamid, M H; Gabr, S S; Mohamed, S G; El-Sayed, W S; Shaaban, S Y

2013-12-01

The study was designed to evaluate the efficacy, safety, and tolerability of the ketogenic diet (KD) whether classic 4:1 formula or the modified Atkins diet (MAD) in intractable childhood epilepsy. Anthropometric measurements and serum lipid profile were measured upon enrollment and after 3 and 6 months in 40 patients with symptomatic intractable epilepsy. Fifteen were given MAD diet, ten were kept on classic 4:1 ketogenic liquid formula, and the rest were allowed to eat as desired. The liquid ketogenic formula group showed significantly higher body mass index compared with those who did not receive KD after 6 months. The lipid profile of KD patients was within normal limits for age and sex during the study period. The rate of change of frequency and severity of seizures showed best improvement in ketogenic liquid formula patients followed by the MAD group than the patients on anti-epileptic medications alone. The KD whether classic 4:1 or MAD is a tolerable, safe, and effective adjuvant therapy for intractable symptomatic childhood epilepsy with limited adverse effects on the growth parameters and accepted changes in the lipid profile. The liquid ketogenic formula patients showed better growth pattern and significantly more seizure control. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.

PubMed Central

Tsoulfa, G; Rook, G A; Van-Embden, J D; Young, D B; Mehlert, A; Isenberg, D A; Hay, F C; Lydyard, P M

1989-01-01

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat. PMID:2930263

Ligand-receptor binding affinities from saturation transfer difference (STD) NMR spectroscopy: the binding isotherm of STD initial growth rates.

PubMed

Angulo, Jesús; Enríquez-Navas, Pedro M; Nieto, Pedro M

2010-07-12

The direct evaluation of dissociation constants (K(D)) from the variation of saturation transfer difference (STD) NMR spectroscopy values with the receptor-ligand ratio is not feasible due to the complex dependence of STD intensities on the spectral properties of the observed signals. Indirect evaluation, by competition experiments, allows the determination of K(D), as long as a ligand of known affinity is available for the protein under study. Herein, we present a novel protocol based on STD NMR spectroscopy for the direct measurements of receptor-ligand dissociation constants (K(D)) from single-ligand titration experiments. The influence of several experimental factors on STD values has been studied in detail, confirming the marked impact on standard determinations of protein-ligand affinities by STD NMR spectroscopy. These factors, namely, STD saturation time, ligand residence time in the complex, and the intensity of the signal, affect the accumulation of saturation in the free ligand by processes closely related to fast protein-ligand rebinding and longitudinal relaxation of the ligand signals. The proposed method avoids the dependence of the magnitudes of ligand STD signals at a given saturation time on spurious factors by constructing the binding isotherms using the initial growth rates of the STD amplification factors, in a similar way to the use of NOE growing rates to estimate cross relaxation rates for distance evaluations. Herein, it is demonstrated that the effects of these factors are cancelled out by analyzing the protein-ligand association curve using STD values at the limit of zero saturation time, when virtually no ligand rebinding or relaxation takes place. The approach is validated for two well-studied protein-ligand systems: the binding of the saccharides GlcNAc and GlcNAcbeta1,4GlcNAc (chitobiose) to the wheat germ agglutinin (WGA) lectin, and the interaction of the amino acid L-tryptophan to bovine serum albumin (BSA). In all cases, the experimental K(D) measured under different experimental conditions converged to the thermodynamic values. The proposed protocol allows accurate determinations of protein-ligand dissociation constants, extending the applicability of the STD NMR spectroscopy for affinity measurements, which is of particular relevance for those proteins for which a ligand of known affinity is not available.

Hypoxia-induced ANGPTL4 sustains tumour growth and anoikis resistance through different mechanisms in scirrhous gastric cancer cell lines.

PubMed

Baba, Koichi; Kitajima, Yoshihiko; Miyake, Shuusuke; Nakamura, Jun; Wakiyama, Kota; Sato, Hirofumi; Okuyama, Keiichiro; Kitagawa, Hiroshi; Tanaka, Tomokazu; Hiraki, Masatsugu; Yanagihara, Kazuyoshi; Noshiro, Hirokazu

2017-09-11

Patients with scirrhous gastric cancer (SGC) frequently develop peritoneal dissemination, which leads to poor prognosis. The secreted protein angiopoietin-like-4 (ANGPTL4), which is induced by hypoxia, exerts diverse effects on cancer progression. Here, we aimed to determine the biological function of ANGPTL4 in SGC cells under hypoxia. ANGPTL4 levels were higher in SGC cells under hypoxia than in other types of gastric cancer cells. Hypoxia-induced ANGPTL4 mRNA expression was regulated by hypoxia-inducible factor-1α (HIF-1α). Under hypoxic conditions, monolayer cultures of ANGPTL4 knockdown (KD) 58As9 SGC (58As9-KD) cells were arrested in the G 1 phase of the cell cycle through downregulation of c-Myc and upregulation of p27, in contrast to control 58As9-SC cells. Moreover, the ability of 58As9-KD xenografts to form tumours in nude mice was strongly suppressed. When 58As9-KD cells were cultured in suspension, hypoxia strongly increased their susceptibility to anoikis through suppression of the FAK/Src/PI3K-Akt/ERK pro-survival pathway, followed by activation of the apoptotic factors caspases-3, -8 and -9. The development of peritoneal dissemination by 58As9-KD cells was completely inhibited compared with that by 58As9-SC cells. In conclusion, ANGPTL4 is uniquely induced by hypoxia in cultured SGC cells and is essential for tumour growth and resistance to anoikis through different mechanisms.

Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter

NASA Astrophysics Data System (ADS)

Nicola, Juan P.; Carrasco, Nancy; Mario Amzel, L.

2014-06-01

The Na+/I- symporter (NIS) mediates active I- transport—the first step in thyroid hormonogenesis—with a 2Na+:1I- stoichiometry. NIS-mediated 131I- treatment of thyroid cancer post-thyroidectomy is the most effective targeted internal radiation cancer treatment available. Here to uncover mechanistic information on NIS, we use statistical thermodynamics to obtain Kds and estimate the relative populations of the different NIS species during Na+/anion binding and transport. We show that, although the affinity of NIS for I- is low (Kd=224 μM), it increases when Na+ is bound (Kd=22.4 μM). However, this Kd is still much higher than the submicromolar physiological I- concentration. To overcome this, NIS takes advantage of the extracellular Na+ concentration and the pronounced increase in its own affinity for I- and for the second Na+ elicited by binding of the first. Thus, at physiological Na+ concentrations, ~79% of NIS molecules are occupied by two Na+ ions and ready to bind and transport I-.

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

Chen, Junchao; Xin, Xiangpeng; Chen, Yong, E-mail: ychen@sei.ecnu.edu.cn

The nonlocal symmetry is derived from the known Darboux transformation (DT) of the Hirota-Satsuma coupled Korteweg-de Vries (HS-cKdV) system, and infinitely many nonlocal symmetries are given by introducing the internal parameters. By extending the HS-cKdV system to an auxiliary system with five dependent variables, the prolongation is found to localize the so-called seed nonlocal symmetry related to the DT. By applying the general Lie point symmetry method to this enlarged system, we obtain two main results: a new type of finite symmetry transformation is derived, which is different from the initial DT and can generate new solutions from old ones;more » some novel exact interaction solutions among solitons and other complicated waves including periodic cnoidal waves and Painlevé waves are computed through similarity reductions. In addition, two kinds of new integrable models are proposed from the obtained nonlocal symmetry: the negative HS-cKdV hierarchy by introducing the internal parameters; the integrable models both in lower and higher dimensions by restricting the symmetry constraints.« less

A novel method for the determination of adsorption partition coefficients of minor gases in a shale sample by headspace gas chromatography.

PubMed

Zhang, Chun-Yun; Hu, Hui-Chao; Chai, Xin-Sheng; Pan, Lei; Xiao, Xian-Ming

2013-10-04

A novel method has been developed for the determination of adsorption partition coefficient (Kd) of minor gases in shale. The method uses samples of two different sizes (masses) of the same material, from which the partition coefficient of the gas can be determined from two independent headspace gas chromatographic (HS-GC) measurements. The equilibrium for the model gas (ethane) was achieved in 5h at 120°C. The method also involves establishing an equation based on the Kd at higher equilibrium temperature, from which the Kd at lower temperature can be calculated. Although the HS-GC method requires some time and effort, it is simpler and quicker than the isothermal adsorption method that is in widespread use today. As a result, the method is simple and practical and can be a valuable tool for shale gas-related research and applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Association of Kawasaki disease with tropospheric wind patterns.

PubMed

Rodó, Xavier; Ballester, Joan; Cayan, Dan; Melish, Marian E; Nakamura, Yoshikazu; Uehara, Ritei; Burns, Jane C

2011-01-01

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols.

Association of Kawasaki disease with tropospheric wind patterns

PubMed Central

Rodó, Xavier; Ballester, Joan; Cayan, Dan; Melish, Marian E.; Nakamura, Yoshikazu; Uehara, Ritei; Burns, Jane C.

2011-01-01

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols. PMID:22355668

The α7-nicotinic acetylcholine receptor mediates the sensitivity of gastric cancer cells to taxanes.

PubMed

Tu, Chao-Chiang; Huang, Chien-Yu; Cheng, Wan-Li; Hung, Chin-Sheng; Uyanga, Batzorig; Wei, Po-Li; Chang, Yu-Jia

2016-04-01

Gastric cancer is difficult to cure because most patients are diagnosed at an advanced disease stage. Systemic chemotherapy remains an important therapy for gastric cancer, but both progression-free survival and disease-free survival associated with various combination regimens are limited because of refractoriness and chemoresistance. Accumulating evidence has revealed that the homomeric α7-nicotinic acetylcholine receptor (A7-nAChR) promotes human gastric cancer by driving cancer cell proliferation, migration, and metastasis. Therefore, A7-nAChR may serve as a potential therapeutic target for gastric cancer. However, the role of A7-nAChR in taxane therapy for gastric cancer was unclear. Cells were subjected to A7-nAChR knockdown (A7-nAChR KD) using short interfering RNA (siRNA). The anti-proliferative effects of taxane were assessed via 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL), and cell cycle distribution assays. A7-nAChR-KD cells exhibited low resistance to docetaxel and paclitaxel treatment, as measured by the MTT assay. Following paclitaxel treatment, the proportion of apoptotic cells was higher among A7-nAChR-KD cells than among scrambled control cells, as measured by cell cycle distribution and TUNEL assays. Further molecular analyses showed a reduction in the pAKT levels and a dramatic increase in the Bad levels in paclitaxel-treated A7-nAChR-KD cells but not in scrambled control cells. Following paclitaxel treatment, the level of Bax was slightly increased in both cell populations, whereas Poly (ADP-ribose) polymerase (PARP) cleavage was increased only in A7-nAChR-KD cells. These findings indicate that A7-nAChR-KD cells are more sensitive to paclitaxel treatment. We conclude that A7-nAChR may be a key biomarker for assessing the chemosensitivity of gastric cancer cells to taxane.

GEMAS: prediction of solid-solution phase partitioning coefficients (Kd) for oxoanions and boric acid in soils using mid-infrared diffuse reflectance spectroscopy.

PubMed

Janik, Leslie J; Forrester, Sean T; Soriano-Disla, José M; Kirby, Jason K; McLaughlin, Michael J; Reimann, Clemens

2015-02-01

The authors' aim was to develop rapid and inexpensive regression models for the prediction of partitioning coefficients (Kd), defined as the ratio of the total or surface-bound metal/metalloid concentration of the solid phase to the total concentration in the solution phase. Values of Kd were measured for boric acid (B[OH]3(0)) and selected added soluble oxoanions: molybdate (MoO4(2-)), antimonate (Sb[OH](6-)), selenate (SeO4(2-)), tellurate (TeO4(2-)) and vanadate (VO4(3-)). Models were developed using approximately 500 spectrally representative soils of the Geochemical Mapping of Agricultural Soils of Europe (GEMAS) program. These calibration soils represented the major properties of the entire 4813 soils of the GEMAS project. Multiple linear regression (MLR) from soil properties, partial least-squares regression (PLSR) using mid-infrared diffuse reflectance Fourier-transformed (DRIFT) spectra, and models using DRIFT spectra plus analytical pH values (DRIFT + pH), were compared with predicted log K(d + 1) values. Apart from selenate (R(2)  = 0.43), the DRIFT + pH calibrations resulted in marginally better models to predict log K(d + 1) values (R(2)  = 0.62-0.79), compared with those from PSLR-DRIFT (R(2)  = 0.61-0.72) and MLR (R(2)  = 0.54-0.79). The DRIFT + pH calibrations were applied to the prediction of log K(d + 1) values in the remaining 4313 soils. An example map of predicted log K(d + 1) values for added soluble MoO4(2-) in soils across Europe is presented. The DRIFT + pH PLSR models provided a rapid and inexpensive tool to assess the risk of mobility and potential availability of boric acid and selected oxoanions in European soils. For these models to be used in the prediction of log K(d + 1) values in soils globally, additional research will be needed to determine if soil variability is accounted on the calibration. © 2014 SETAC.

YC-1 BINDING TO THE BETA SUBUNIT OF SOLUBLE GUANYLYL CYCLASE OVERCOMES ALLOSTERIC INHIBITION BY THE ALPHA SUBUNIT

PubMed Central

Purohit, Rahul; Fritz, Bradley G.; The, Juliana; Issaian, Aaron; Weichsel, Andrzej; David, Cynthia L.; Campbell, Eric; Hausrath, Andrew C.; Rassouli-Taylor, Leida; Garcin, Elsa D.; Gage, Matthew J.; Montfort, William R.

2014-01-01

Soluble guanylate cyclase (sGC) is a heterodimeric heme protein and the primary nitric oxide receptor. NO binding stimulates cyclase activity, leading to regulation of cardiovascular physiology and making sGC an attractive target for drug discovery. YC-1 and related compounds stimulate sGC both independently and synergistically with NO and CO binding; however, where the compounds bind and how they work remains unknown. Using linked-equilibria binding measurements, surface plasmon resonance, and domain truncations in Manduca sexta and bovine sGC, we demonstrate that YC-1 binds near or directly to the heme-containing domain of the beta subunit. In the absence of CO, YC-1 binds with Kd = 9–21 μM, depending on construct. In the presence of CO, these values decrease to 0.6–1.1 μM. Pfizer compound 25 bound ~10-fold weaker than YC-1 in the absence of CO whereas compound BAY 41–2272 bound particularly tightly in the presence of CO (Kd = 30–90 nM). Additionally, we found that CO binding is much weaker to heterodimeric sGC proteins (Kd = 50–100 μM) than to the isolated heme domain (Kd = 0.2 μM for Manduca beta H-NOX/PAS). YC-1 greatly enhanced CO binding to heterodimeric sGC, as expected (Kd = ~1 μM). These data indicate the alpha subunit induces a heme pocket conformation with lower affinity for CO and NO. YC-1 family compounds bind near the heme domain, overcoming the alpha subunit effect and inducing a heme pocket conformation with high affinity. We propose this high-affinity conformation is required for the full-length protein to achieve high catalytic activity. PMID:24328155

Highly Selective Polypyrrole MIP-Based Gravimetric and Electrochemical Sensors for Picomolar Detection of Glyphosate

PubMed Central

Mazouz, Zouhour; Rahali, Seyfeddine; Fourati, Najla; Zerrouki, Chouki; Aloui, Nadia; Seydou, Mahamadou; Yaakoubi, Nourdin; Chehimi, Mohamed M.; Othmane, Ali; Kalfat, Rafik

2017-01-01

There is a global debate and concern about the use of glyphosate (Gly) as an herbicide. New toxicological studies will determine its use in the future under new strict conditions or its replacement by alternative synthetic or natural herbicides. In this context, we designed biomimetic polymer sensing layers for the selective molecular recognition of Gly. Towards this end, complementary surface acoustic wave (SAW) and electrochemical sensors were functionalized with polypyrrole (PPy)-imprinted polymer for the selective detection of Gly. Their corresponding limits of detection were on the order of 1 pM, which are among the lowest values ever reported in literature. The relevant dissociation constants between PPy and Gly were estimated at [Kd1 = (0.7 ± 0.3) pM and Kd2 = (1.6 ± 1.4) µM] and [Kd1 = (2.4 ± 0.9) pM and Kd2 = (0.3 ± 0.1) µM] for electrochemical and gravimetric measurements, respectively. Quantum chemical calculations permitted to estimate the interaction energy between Gly and PPy film: ΔE = −145 kJ/mol. Selectivity and competitivity tests were investigated with the most common pesticides. This work conclusively shows that gravimetric and electrochemical results indicate that both MIP-based sensors are perfectly able to detect and distinguish glyphosate without any ambiguity. PMID:29120397

[The role of Cd-binding proteins and phytochelatins in the formation of cadmium resistance in Nicotiana plumbaginifolia cell lines].

PubMed

Fenik, S I; Solodushko, V G; Kaliniak, T B; Blium, Ia B

2007-01-01

Nicotiana plumbaginifolia callus lines with the equal resistance to cadmium have been produced under different selective conditions--either without inhibition of the phytochelatin synthesis (line Cd-R) or in the presence of the inhibitor butionine sulfoximine (line Cd-Ri). The level of phytochelatin synthesis in the line Cd-R five-fold exceeded the control value and in the line Cd-Ri it was twice as much as in the control. It was shown that in the control line mainly three cadmium-binding proteins are expressed of the molecular weihgts 41, 34 and 19 kD. The common feature of the both resistant lines is the expression of the cadmium-binding proteins of 40, 37 and 19 kD. The resistant lines differ with respect to the synthesis of relatively low-molecular cadmium-binding proteins. The proteins of the molecular weights 12.5, 11.5 and 9 kD are expressed in the line Cd-R, while the proteins of 13 and 10 kD are expressed in the line Cd-Ri. It was supposed that both the phytochelatins and the Cd-binding proteins contribute to the resisitance of N. plumbaginifolia callus lines to cadmium and the lack of the phytochelatins can be equilibrated by the changes in the low-molecular Cd-binding protein synthesis.

Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism.

PubMed

Bonilla-Ramirez, Leonardo; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

2013-01-10

Previous studies have shown that polyphenols might be potent neuroprotective agents in Drosophila melanogaster wild type Canton-S acutely or chronically treated with paraquat (PQ), a selective toxin for elimination of dopaminergic (DAergic) neurons by oxidative stress (OS), as model of Parkinson's disease (PD). This study reports for the first time that knock-down (K-D) parkin Drosophila melanogaster (TH-GAL4; UAS-RNAi-parkin) chronically exposed to PQ (0.1-0.25 mM), FeSO(4) (Fe, 0.1mM), deferoxamine (DFO, 0.01 mM) alone or (0.1mM) PQ in combination with polyphenols propyl gallate (PG, 0.1mM) and epigallocathecin gallate (EGCG, 0.1, 0.5mM) showed significantly higher life span and locomotor activity than untreated K-D flies or treated with (1, 5, 20mM) PQ alone. Whilst gallic acid (GA, 0.1, 0.5mM) alone or in the presence of PQ provoked no effect on K-D flies, epicathecin (EC, 0.5mM) only showed a positive effect on prolonging K-D flies' life span. It is shown that PG (and EGCG) protected protocerebral posterolateral 1 (PPL1) DAergic neurons against PQ. Interestingly, the protective effect of low PQ concentrations, DFO and iron might be explained by a phenomenon known as "hormesis." However, pre-fed K-D flies with (0.1mM) PQ for 7 days and then exposed to (0.25 mM) for additional 8 days affect neither survival nor climbing of K-D Drosophila compared to flies treated with (0.25 mM) PQ alone. Remarkably, K-D flies treated with 0.1mM PQ (7 days) and then with (0.25 mM) PQ plus PG (8 days) behaved almost as flies treated with (0.25 mM) PQ. Taken these data suggest that antioxidant supplements that synergistically act with low pro-oxidant stimuli to prolong and increase locomotor activity become inefficient once a threshold of OS has been reached in K-D flies. Our present findings support the notion that genetically altered Drosophila melanogaster as suitable model to study genetic and environmental factors as causal and/or modulators in the development of autosomal recessive juvenile Parkinsonism (AR-JD)/PD. Most importantly, we have shown for the first time that low amounts of stressors induce a health-promoting extending effect in K-D parkin flies. Altogether our present results open new avenues for the screening, testing and development of novel antioxidant drugs against OS stimuli in neurodegenerative disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Competitive sorption of organic contaminants in chalk.

PubMed

Graber, E R; Borisover, M

2003-12-01

In the Negev desert, Israel, a chemical industrial complex is located over fractured Eocene chalk formations where transfer of water and solutes between fracture voids and matrix pores affects migration of contaminants in the fractures due to diffusion into the chalk matrix. This study tests sorption and sorption competition between contaminants in the chalk matrix to make it possible to evaluate the potential for contaminant attenuation during transport in fractures. Single solute sorption isotherms on chalk matrix material for five common contaminants (m-xylene, ametryn, 1,2-dichloroethane, phenanthrene, and 2,4,6-tribromophenol) were found to be nonlinear, as confirmed in plots of Kd versus initial solution concentration. Over the studied concentration ranges, m-xylene Kd varied by more than a factor of 100, ametryn Kd by a factor of 4, 1,2-dichloroethane Kd by more than a factor of 3, phenanthrene Kd by about a factor of 2, and 2,4,6-tribromophenol Kd by a factor of 10. It was earlier found that sorption is to the organic matter component of the chalk matrix and not to the mineral phases (Chemosphere 44 (2001) 1121). Nonlinear sorption isotherms indicate that there is at least some finite sorption domain. Bi-solute competition experiments with 2,4,6-tribromophenol as the competitor were designed to explore the nature of the finite sorption domain. All of the isotherms in the bi-solute experiments are more linear than in the single solute experiments, as confirmed by smaller variations in Kd as a function of initial solution concentration. For both m-xylene and ametryn, there is a small nonlinear component or domain that was apparently not susceptible to competition by 2,4,6-tribromophenol. The nonlinear sorption domain(s) is best expressed at low solution concentrations. Inert-solvent-normalized single and bi-solute sorption isotherms demonstrate that ametryn undergoes specific force interactions with the chalk sorbent. The volume percent of phenanthrene sorbed at the liquid solubility limit is calculated to be 13% v:v in both the single and bi-solute experiments. This value exceeds what may be reasonably interpreted as partitioning of phenanthrene into organic matter, despite the relative linearity of the phenanthrene sorption isotherm (compared with other compounds) in both single and bi-solute systems.

Modeling Cd and Cu mobility in soils amended by long-term urban waste compost applications

NASA Astrophysics Data System (ADS)

Filipović, Vilim; Cambier, Philippe; Matijević, Lana; Coquet, Yves; Pot, Valérie; Houot, Sabine; Benoit, Pierre

2016-04-01

Urban waste compost application to soil is an effective way for organic waste disposal and at the same time may have a positive effect on various soil rhizosphere processes. However, long term applications of organic waste amendments may lead to a noteworthy accumulation of micropollutants in soil. The long-term field experiment QualiAgro, an INRA-Veolia partnership (https://www6.inra.fr/qualiagro_eng/), has been conducted since 1998 with the objectives to characterize the agronomic value of urban composts and the environmental impacts of their application. Numerical modeling was performed using HYDRUS-2D to estimate the movement of Cd and Cu from compost incroporation in the tilled layer. Experimental plots regularly amended with co-compost of sewage sludge and green wastes (SGW), or a municipal solid waste compost (MSW) have been compared to control plot without any organic amendment (CONT). Field site was equipped with wicks lysimeters, TDR probes and tensiometers in order to determine water balance and trace metal concentrations during a 6 years' time period (2004-2010). In the tilled layer different structures (Δ - compacted clods, Γ - macroporous zone, IF - interfurrows, PP - plough pan) corresponding to the tillage and compost incorporation were delimited and reproduced in a 2-D model. The increase of Cd and Cu concentrations due to each compost addition was assumed to be located in IFs for further modeling. Four compost additions were performed during 2004-2010 period which increased the Cd and Cu concentrations in the IF zones considerably. After successful model description of water flow in highly heterogeneous soil profiles, Cd and Cu were added into the model and their fate was simulated during the same time period. Two approaches were followed to estimate plausible trace metals sorption coefficients (Kd), both while assuming equilibrium between dissolved and EDTA-extractable metals. The first approach was based on Kd estimated from ratios between EDTA and CaCl2-extracted metals (Kd-1). In the second approach we have calculated Kd from generic equations (literature), using soil organic carbon (SOC) and pH for Cd, and SOM, pH and DOC for Cu (Kd-2). Lysimeter data of Cu leaching were successfully reproduced by using first Kd-1 approach for three plots (model efficiency ESGW=0.97, EMSW=0.37; ECONT=0.95). Smaller agreement in MSW plot could be explained by the less stabile organic matter of MSW composts which increased its Cu mobile fraction after soil incorporation. The Cd leaching could be reproduced with the second Kd-2 approach for the two amended plots (ESGW=0.55, EMSW=0.80) while control plot simulations produced poorer fitting (ECONT=-0.57), probably due to an overestimation of the influence of the low pH of that plot on Kd-2(Cd). However, numerical modeling revealed interesting results in which, even with the high values of hydraulic conductivity in the interfurrow zones, the Cd and Cu showed low mobility. Although, the amended plots showed increased metal leaching below the tilled layer in both amended plots, their mobility in the tilled layer is reduced due to retention capacity of the applied composts. Acknowledgements: the involvement of INRA and Veolia members in the QualiAgro experiment and the financial support of Veolia are gratefully acknowledged Keywords: Compost amendments; Soil heterogeneity; Trace metals; Sorption; HYDRUS-2D

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents.

PubMed

Santoshi, Seneha; Manchukonda, Naresh Kumar; Suri, Charu; Sharma, Manya; Sridhar, Balasubramanian; Joseph, Silja; Lopus, Manu; Kantevari, Srinivas; Baitharu, Iswar; Naik, Pradeep Kumar

2015-03-01

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔG(bind, pred)) of these derivatives (ranging from -5.568 to -5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (-5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔG(bind, expt) (calculated from the Kd value) are consistent with the predicted value of ΔG(bind, pred) calculated based on LIE-SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents

NASA Astrophysics Data System (ADS)

Santoshi, Seneha; Manchukonda, Naresh Kumar; Suri, Charu; Sharma, Manya; Sridhar, Balasubramanian; Joseph, Silja; Lopus, Manu; Kantevari, Srinivas; Baitharu, Iswar; Naik, Pradeep Kumar

2015-03-01

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔGbind, pred) of these derivatives (ranging from -5.568 to -5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (-5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔGbind, expt (calculated from the Kd value) are consistent with the predicted value of ΔGbind, pred calculated based on LIE-SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

Synthesis, characterization, and sol-gel entrapment of a crown ether-styryl fluoroionophore

PubMed Central

Sui, Zhijie; Hanan, Nathan J.; Phimphivong, Sam; Wysocki, Ronald J.; Saavedra, S. Scott

2011-01-01

The synthesis and initial evaluation of a new dye-functionalized crown-ether, 2-[2-(2,3,5,6,8,9,11,12,14,15-decahydro-1,4,7,10.13.16-benzohexaoxacyclooctadecin)ethenyl]-3-methyl benzothiazolium iodide (denoted BSD), is reported. This molecule contains a benzyl 18-crown-6 moiety as the ionophore and a benzothiazolium to spectrally transduce ion binding. Binding of K+ to BSD in methanol causes shifts in the both absorbance and fluorescence emission maxima, as well as changes in the molar absorptivity and the emission intensity. Apparent dissociation constants (Kd) in the range of 30 – 65 μM were measured. In water and neutral buffer, Kd values were approximately 1 mM. BSD was entrapped in sol-gel films composed of methyltriethoxysilane (MTES) and tetraethylorthosilicate (TEOS) with retention of its spectral properties and minimal leaching. K+ binding to BSD in sol-gels films immersed in pH 7.4 buffer causes significant fluorescence quenching, with an apparent response time of approximately 2 min and an apparent Kd of 1.5 mM. PMID:19253273

Molecular modelling for the design of chimaeric biomimetic dye-ligands and their interaction with bovine heart mitochondrial malate dehydrogenase.

PubMed Central

Labrou, N E; Eliopoulos, E; Clonis, Y D

1996-01-01

Molecular modelling and kinetic inhibition studies, as well as KD determinations by both difference-spectra and enzyme-inactivation studies, were employed to assess the ability of purpose-designed chimaeric biomimetic dyes (BM dyes) to act as affinity ligands for bovine heart L-malate dehydrogenase (MDH). Each BM dye was composed of two enzyme-recognition moieties. The terminal biomimetic moiety bore a carboxyl or a keto acid structure linked to the triazine ring, thus mimicking the substrate of MDH. The chromophore anthraquinone moiety remained unchanged and the same as that of the parent dye Vilmafix Blue A-R (VBAR), recognizing the nucleotide-binding site of MDH. The monochlorotriazine BM dyes did not inactivate MDH but competitively inhibited inactivation by the parent dichlorotriazine dye VBAR. Dye binding to MDH was accompanied by a characteristic spectral change in the range 500-850 nm. This phenomenon was reversed after titration with increasing amounts of NADH. When compared with VBAR, Cibacron Blue 3GA and two control non-biomimetic anthraquinone dyes, all BM dyes exhibited lower KD values and therefore higher affinity for MDH. The enzyme bound preferably to BM ligands substituted with a biomimetic aromatic moiety bearing an alpha-keto acid group and an amide linkage, rather than a monocarboxyl group. Thus the biomimetic dye bearing p-aminobenzyloxanilic acid as its terminal biomimetic moiety (BM5) exhibited the highest affinity (KD 1.3 microM, which corresponded to a 219-fold decrease over the KD of a control dye). BM5 displayed competitive inhibition with respect to both NADH (Ki 2.7 microM) and oxaloacetate (Ki 9.6 microM). A combination of molecular modelling and experimental studies has led to certain conclusions. The positioning of the dye in the enzyme is primarily achieved by the recognition and positioning of the nucleotide-pseudomimetic anthraquinone moiety. The hydrophobic groups of the dye provide the driving force for positioning of the ketocarboxyl biomimetic moiety. A match between the alternating polar and hydrophobic regions of the enzyme binding site with those of the biomimetic moiety is desirable. The length of the biomimetic moiety should be conserved in order for the keto acid to approach the enzyme active site and form charge-charge interactions. PMID:8615849

Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus.

PubMed

Arya, Ravindra; Peariso, Katrina; Gaínza-Lein, Marina; Harvey, Jessica; Bergin, Ann; Brenton, J Nicholas; Burrows, Brian T; Glauser, Tracy; Goodkin, Howard P; Lai, Yi-Chen; Mikati, Mohamad A; Fernández, Iván Sánchez; Tchapyjnikov, Dmitry; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2018-04-27

To describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE). RSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug. Ketosis was defined as serum beta-hydroxybutyrate levels >20 mg/dl (1.9 mmol/l). Outcomes included proportion of patients with electrographic (EEG) seizure resolution within 7 days of starting KD, defined as absence of seizures and ≥50% suppression below 10 μV on longitudinal bipolar montage (suppression-burst ratio ≥50%); time to start KD after onset of RSE; time to achieve ketosis after starting KD; and the proportion of patients weaned off continuous infusions 2 weeks after KD initiation. Treatment-emergent adverse effects (TEAEs) were also recorded. Fourteen patients received KD for treatment of RSE (median age 4.7 years, interquartile range [IQR] 5.6). KD was started via enteral route in 11/14 (78.6%) patients. KD was initiated a median of 13 days (IQR 12.5) after the onset of RSE, at 4:1 ratio in 8/14 (57.1%) patients. Ketosis was achieved within a median of 2 days (IQR 2.0) after starting KD. EEG seizure resolution was achieved within 7 days of starting KD in 10/14 (71.4%) patients. Also, 11/14 (78.6%) patients were weaned off their continuous infusions within 2 weeks of starting KD. TEAEs, potentially attributable to KD, occurred in 3/14 (21.4%) patients, including gastro-intestinal paresis and hypertriglyceridemia. Three month outcomes were available for 12/14 (85.7%) patients, with 4 patients being seizure-free, and 3 others with decreased seizure frequency compared to pre-RSE baseline. This series suggests efficacy and safety of KD for treatment of pediatric RSE. Copyright © 2018. Published by Elsevier B.V.

Decoy Plasminogen Receptor Containing a Selective Kunitz-Inhibitory Domain

PubMed Central

2015-01-01

Kunitz domain 1 (KD1) of tissue factor pathway inhibitor-2 in which P2′ residue Leu17 (bovine pancreatic trypsin inhibitor numbering) is mutated to Arg selectively inhibits the active site of plasmin with ∼5-fold improved affinity. Thrombin cleavage (24 h extended incubation at a 1:50 enzyme-to-substrate ratio) of the KD1 mutant (Leu17Arg) yielded a smaller molecule containing the intact Kunitz domain with no detectable change in the active-site inhibitory function. The N-terminal sequencing and MALDI-TOF/ESI data revealed that the starting molecule has a C-terminal valine (KD1L17R-VT), whereas the smaller molecule has a C-terminal lysine (KD1L17R-KT). Because KD1L17R-KT has C-terminal lysine, we examined whether it could serve as a decoy receptor for plasminogen/plasmin. Such a molecule might inhibit plasminogen activation as well as the active site of generated plasmin. In surface plasmon resonance experiments, tissue plasminogen activator (tPA) and Glu-plasminogen bound to KD1L17R-KT (Kd ∼ 0.2 to 0.3 μM) but not to KD1L17R-VT. Furthermore, KD1L17R-KT inhibited tPA-induced plasma clot fibrinolysis more efficiently than KD1L17R-VT. Additionally, compared to ε-aminocaproic acid KD1L17R-KT was more effective in reducing blood loss in a mouse liver-laceration injury model, where the fibrinolytic system is activated. In further experiments, the micro(μ)-plasmin–KD1L17R-KT complex inhibited urokinase-induced plasminogen activation on phorbol-12-myristate-13-acetate-stimulated U937 monocyte-like cells, whereas the μ-plasmin–KD1L17R-VT complex failed to inhibit this process. In conclusion, KD1L17R-KT inhibits the active site of plasmin as well as acts as a decoy receptor for the kringle domain(s) of plasminogen/plasmin; hence, it limits both plasmin generation and activity. With its dual function, KD1L17R-KT could serve as a preferred agent for controlling plasminogen activation in pathological processes. PMID:24383758

Decoy plasminogen receptor containing a selective Kunitz-inhibitory domain.

PubMed

Kumar, Yogesh; Vadivel, Kanagasabai; Schmidt, Amy E; Ogueli, Godwin I; Ponnuraj, Sathya M; Rannulu, Nalaka; Loo, Joseph A; Bajaj, Madhu S; Bajaj, S Paul

2014-01-28

Kunitz domain 1 (KD1) of tissue factor pathway inhibitor-2 in which P2' residue Leu17 (bovine pancreatic trypsin inhibitor numbering) is mutated to Arg selectively inhibits the active site of plasmin with ∼5-fold improved affinity. Thrombin cleavage (24 h extended incubation at a 1:50 enzyme-to-substrate ratio) of the KD1 mutant (Leu17Arg) yielded a smaller molecule containing the intact Kunitz domain with no detectable change in the active-site inhibitory function. The N-terminal sequencing and MALDI-TOF/ESI data revealed that the starting molecule has a C-terminal valine (KD1L17R-VT), whereas the smaller molecule has a C-terminal lysine (KD1L17R-KT). Because KD1L17R-KT has C-terminal lysine, we examined whether it could serve as a decoy receptor for plasminogen/plasmin. Such a molecule might inhibit plasminogen activation as well as the active site of generated plasmin. In surface plasmon resonance experiments, tissue plasminogen activator (tPA) and Glu-plasminogen bound to KD1L17R-KT (Kd ∼ 0.2 to 0.3 μM) but not to KD1L17R-VT. Furthermore, KD1L17R-KT inhibited tPA-induced plasma clot fibrinolysis more efficiently than KD1L17R-VT. Additionally, compared to ε-aminocaproic acid KD1L17R-KT was more effective in reducing blood loss in a mouse liver-laceration injury model, where the fibrinolytic system is activated. In further experiments, the micro(μ)-plasmin-KD1L17R-KT complex inhibited urokinase-induced plasminogen activation on phorbol-12-myristate-13-acetate-stimulated U937 monocyte-like cells, whereas the μ-plasmin-KD1L17R-VT complex failed to inhibit this process. In conclusion, KD1L17R-KT inhibits the active site of plasmin as well as acts as a decoy receptor for the kringle domain(s) of plasminogen/plasmin; hence, it limits both plasmin generation and activity. With its dual function, KD1L17R-KT could serve as a preferred agent for controlling plasminogen activation in pathological processes.

Multivariate functions for predicting the sorption of 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitro-1,3,5-tricyclohexane (RDX) among taxonomically distinct soils.

PubMed

Katseanes, Chelsea K; Chappell, Mark A; Hopkins, Bryan G; Durham, Brian D; Price, Cynthia L; Porter, Beth E; Miller, Lesley F

2016-11-01

After nearly a century of use in numerous munition platforms, TNT and RDX contamination has turned up largely in the environment due to ammunition manufacturing or as part of releases from low-order detonations during training activities. Although the basic knowledge governing the environmental fate of TNT and RDX are known, accurate predictions of TNT and RDX persistence in soil remain elusive, particularly given the universal heterogeneity of pedomorphic soil types. In this work, we proposed a new solution for modeling the sorption and persistence of these munition constituents as multivariate mathematical functions correlating soil attribute data over a variety of taxonomically distinct soil types to contaminant behavior, instead of a single constant or parameter of a specific absolute value. To test this idea, we conducted experiments measuring the sorption of TNT and RDX on taxonomically different soil types that were extensively physical and chemically characterized. Statistical decomposition of the log-transformed, and auto-scaled soil characterization data using the dimension-reduction technique PCA (principal component analysis) revealed a strong latent structure based in the multiple pairwise correlations among the soil properties. TNT and RDX sorption partitioning coefficients (KD-TNT and KD-RDX) were regressed against this latent structure using partial least squares regression (PLSR), generating a 3-factor, multivariate linear functions. Here, PLSR models predicted KD-TNT and KD-RDX values based on attributes contributing to endogenous alkaline/calcareous and soil fertility criteria, respectively, exhibited among the different soil types: We hypothesized that the latent structure arising from the strong covariance of full multivariate geochemical matrix describing taxonomically distinguished soil types may provide the means for potentially predicting complex phenomena in soils. The development of predictive multivariate models tuned to a local soil's taxonomic designation would have direct benefit to military range managers seeking to anticipate the environmental risks of training activities on impact sites. Published by Elsevier Ltd.

An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice.

PubMed

Ma, Sihui; Huang, Qingyi; Yada, Koichi; Liu, Chunhong; Suzuki, Katsuhiko

2018-05-25

Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

Affinity, Avidity, and Kinetics of Target Sequence Binding to LC8 Dynein Light Chain Isoforms*

PubMed Central

Radnai, László; Rapali, Péter; Hódi, Zsuzsa; Süveges, Dániel; Molnár, Tamás; Kiss, Bence; Bécsi, Bálint; Erdödi, Ferenc; Buday, László; Kardos, József; Kovács, Mihály; Nyitray, László

2010-01-01

LC8 dynein light chain (DYNLL) is a highly conserved eukaryotic hub protein with dozens of binding partners and various functions beyond being a subunit of dynein and myosin Va motor proteins. Here, we compared the kinetic and thermodynamic parameters of binding of both mammalian isoforms, DYNLL1 and DYNLL2, to two putative consensus binding motifs (KXTQTX and XG(I/V)QVD) and report only subtle differences. Peptides containing either of the above motifs bind to DYNLL2 with micromolar affinity, whereas a myosin Va peptide (lacking the conserved Gln) and the noncanonical Pak1 peptide bind with Kd values of 9 and 40 μm, respectively. Binding of the KXTQTX motif is enthalpy-driven, although that of all other peptides is both enthalpy- and entropy-driven. Moreover, the KXTQTX motif shows strikingly slower off-rate constant than the other motifs. As most DYNLL partners are homodimeric, we also assessed the binding of bivalent ligands to DYNLL2. Compared with monovalent ligands, a significant avidity effect was found as follows: Kd values of 37 and 3.5 nm for a dimeric myosin Va fragment and a Leu zipper dimerized KXTQTX motif, respectively. Ligand binding kinetics of DYNLL can best be described by a conformational selection model consisting of a slow isomerization and a rapid binding step. We also studied the binding of the phosphomimetic S88E mutant of DYNLL2 to the dimeric myosin Va fragment, and we found a significantly lower apparent Kd value (3 μm). We conclude that the thermodynamic and kinetic fine-tuning of binding of various ligands to DYNLL could have physiological relevance in its interaction network. PMID:20889982

Organic pollutant levels in an agricultural watershed: the importance of analyzing multiple matrices for assessing stream water pollution.

PubMed

Gonzalez, Mariana; Miglioranza, Karina S B; Grondona, Sebastían I; Silva Barni, Maria Florencia; Martinez, Daniel E; Peña, Aránzazu

2013-04-01

This study is aimed at analyzing the occurrence and transport of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in the Quequén Grande river basin, as representative of a catchment under diffuse pollution sources. Pollutant levels in soils, river bottom sediments (RBS), streamwater (Sw), suspended particle materials (SPMs), macrophytes and muscle of silverside were determined by GC-ECD. Soil K(d) values for the current-used insecticides, endosulfans and cypermethrin, were established. Total levels (ng g(-1) dry weight) in soil ranged between 0.07–0.9 for OCPs, 0.03–0.37 for PCBs and 0.01–0.05 for PBDEs. Endosulfan insecticide (α- + b- + sulfate metabolite) represented up to 72.5% of OCPs. The low soil retention for α-endosulfan (K(d): 77) and endosulfan sulfate (K(d): 100) allows their transport to Sw, SPM and RBS. Levels of endosulfan in Sw in some cases exceeded the value postulated by international guidelines for aquatic biota protection (3 ng L(-1)). PCB and PBDE pollution was related to harbour, dumping sites and pile tire burning. Tri and hexa PCB congeners predominated in all matrices and exceeded the quality guideline value of 0.04 ng L(-1) in Sw. Considering levels in silverside muscle, none of the oral reference doses were exceeded, however, PCBs accounted for 18.6% of the total daily allowed ingest for a 70 kg individual. Although the levels of PCBs and OCPs in soil and RBS were low and did not go beyond quality guidelines, these compounds could still represent a risk to aquatic biota and humanbeings, and thus actions towards preventing this situation should be undertaken.

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

Alvarez, P; Gonzalez, S; McDonald, L

Purpose: Analysis of the performance of the microSTARii reader for optically stimulated luminescence dosimeters (OSLD) used by the IROC Houston Quality Assurance Center (IROC HQAC) for external audits compare to the characteristics of the Microstar reader. Methods: The IROC HQAC uses the Microstar reader for the OSLD program for verification of output of photon, electron and proton beams. The calculation of dose from the OSLD system is based on a group of factors defined at time of the commissioning of a batch of detectors. Factors like system sensitivity (SS), depletion (KD), element correction factor (ECF), linearity (KL), energy correction (KE).more » The new microSTARii unit presents many hardware and software upgrades that were considered useful for this program. Based on these changes many factors, that were considered reader dependent, were revised in order to analyze the effect of the new reading process. The SS, KD, ECF and KL were evaluated and compared with data defined based on reading done on Microstar reader. Results: The SS is reader specific and specified at 100 cGy dose level. This value is define per reading session and monitored over time. The KD factor was found to be different because of reading procedure are different. The ECF values changed for a group of nano dots compare to values defined based on reading done on the Microstar reader. The KL was defined for the reader. Conclusion: The new microSTARii reader presents new features that improve the efficiency of the OSLD program at the IROC HQAC. New characterization is needed before final implementation is done to match the requirements of the existing OSLD system defined for the Microstar reader. Changes in uncertainty of the results has not been analized.« less

Distribution pattern of rare earth ions between water and montmorillonite and its relation to the sorbed species of the ions.

PubMed

Takahashi, Yoshio; Tada, Akisa; Shimizu, Hiroshi

2004-09-01

REE (rare earth element) distribution coefficients (Kd) between the aqueous phase and montmorillonite surface were obtained to investigate the relation between the REE distribution patterns and the species of REE sorbed on the solid-water interface. It was shown that the features in the REE patterns, such as the slope of the REE patterns, the tetrad effect, and the Y/Ho ratio, were closely related to the REE species at the montmorillonite-water interface. In a binary system (REE-montmorillonite) below pH 5, three features (a larger Kd value for a lighter REE, the absence of the tetrad effect, and the Y/Ho ratio being unchanged from its initial value) suggest that hydrated REE are directly sorbed as an outer-sphere complex at the montmorillonite-water interface. Above pH 5.5, the features in the REE patterns, the larger Kd value for heavier REE, the M-type tetrad effect, and the reduced Y/Ho ratio, showed the formation of an inner-sphere complex of REE with -OH group at the montmorillonite surface. In addition, the REE patterns in the presence of humic acid at pH 5.9 were also studied, where the REE patterns became flat, suggesting that the humate complex is dominant as both dissolved and sorbed species of REE in the ternary system. All of these results were consistent with the spectroscopic data (laser-induced fluorescence spectroscopy) showing the local structure of Eu(III) conducted in the same experimental system. The present results suggest that the features in the REE distribution patterns include information on the REE species at the solid-water interface.

Apparent optical properties of the Canadian Beaufort Sea - Part 1: Observational overview and water column relationships

NASA Astrophysics Data System (ADS)

Antoine, D.; Hooker, S. B.; Bélanger, S.; Matsuoka, A.; Babin, M.

2013-07-01

A data set of radiometric measurements collected in the Beaufort Sea (Canadian Arctic) in August 2009 (Malina project) is analyzed in order to describe apparent optical properties (AOPs) in this sea, which has been subject to dramatic environmental changes for several decades. The two properties derived from the measurements are the spectral diffuse attenuation coefficient for downward irradiance, Kd, and the spectral remote sensing reflectance, Rrs. The former controls light propagation in the upper water column. The latter determines how light is backscattered out of the water and becomes eventually observable from a satellite ocean color sensor. The data set includes offshore clear waters of the Beaufort Basin as well as highly turbid waters of the Mackenzie River plumes. In the clear waters, we show Kd values that are much larger in the ultraviolet and blue parts of the spectrum than what could be anticipated considering the chlorophyll concentration. A larger contribution of absorption by colored dissolved organic matter (CDOM) is responsible for these high Kd values, as compared to other oligotrophic areas. In turbid waters, attenuation reaches extremely high values, driven by high loads of particulate materials and also by a large CDOM content. In these two extreme types of waters, current satellite chlorophyll algorithms fail. This questions the role of ocean color remote sensing in the Arctic when Rrs from only the blue and green bands are used. Therefore, other parts of the spectrum (e.g., the red) should be explored if one aims at quantifying interannual changes in chlorophyll in the Arctic from space. The very peculiar AOPs in the Beaufort Sea also advocate for developing specific light propagation models when attempting to predict light availability for photosynthesis at depth.

Apparent optical properties of the Canadian Beaufort Sea - Part 1: Observational overview and water column relationships

NASA Astrophysics Data System (ADS)

Antoine, D.; Hooker, S. B.; Belanger, S.; Matsuoka, A.; Babin, M.

2013-03-01

A data set of radiometric measurements collected in the Beaufort Sea (Canadian Arctic) in August 2009 (MALINA project) is analysed in order to describe apparent optical properties (AOPs) in this sea, which is subject to dramatic environmental changes for several decades. The two properties derived from the measurements are the spectral diffuse attenuation coefficient for downward irradiance, Kd, and the spectral remote sensing reflectance, Rrs. The former controls light propagation in the upper water column. The latter determines how light is backscattered out of the water and becomes eventually observable from a satellite ocean colour sensor. The data set includes offshore clear waters of the Beaufort basin as well as highly turbid waters of the Mackenzie River plumes. In the clear waters, we show Kd values that are much larger in the ultraviolet and blue parts of the spectrum than what could be anticipated considering the chlorophyll concentration. A larger contribution of absorption by coloured dissolved organic matter (CDOM) is responsible for this high Kd values, as compared to other oligotrophic areas. In turbid waters, attenuation reaches extremely high values, driven by high loads of particulate materials and also by a large CDOM content. In these two extreme types of waters, current satellite chlorophyll algorithms fail. This is questioning the role of ocean colour remote sensing in the Arctic when Rrs from only the blue and green bands are used. Therefore, other parts of the spectrum (e.g. the red) should be explored if one aims at quantifying interannual changes in chlorophyll in the Arctic from space. The very peculiar AOPs in the Beaufort Sea also advocate for developing specific light propagation models when attempting to predict light availability for photosynthesis at depth.

Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet

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

Zhang, Yu-Kun Jennifer; Yeager, Ronnie L.; Tanaka, Yuji

Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione andmore » exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gst{alpha}1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.« less

Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet.

PubMed

Zhang, Yu-Kun Jennifer; Yeager, Ronnie L; Tanaka, Yuji; Klaassen, Curtis D

2010-06-15

Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstalpha1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities. Copyright 2010. Published by Elsevier Inc.

Physicochemical properties of soils in the sago palm (Metroxylon spp.) growing area of Surat Thani province Thailand

NASA Astrophysics Data System (ADS)

Ruairuen, W.; Sparrow, E. B.; Fochesatto, G. J.

2016-12-01

Sago palm is one of the most important plants for sustainable agriculture and rural development in tropical swampy and peaty soils. Where no major crops can grow without drainage or soil improvement. It stores large quantities of starch which can be further processed into various basic raw materials for food, animal feed, industrial uses and alternative energy. This study aims to investigate the physicochemical properties of soil across the sago palm growing areas at Surat Thani province Thailand, where major of sago palms growth naturally exists. The soil samples from three districts Khiri Rat Nikhom (KR; 9 sampling sites), Kanchanadit (KD; 5 sampling sites), and Khian Sa (KS; 2 sampling sites) were studied and compared at 0-15 cm depth during March to June 2016. Observations indicated that the physicochemical properties of soil varied in each growing area. Soil bulk densities averages were lower in KD (0.52 g cm-3) than those in KR (0.58 g cm-3) and KS (0.57 g cm-3). Soil texture around KD and KS were dominated by silty loam. While in KR soil texture was dominated by sandy loam. The average soil conductivity in KS (5.68 mS m-1) was higher than KR (2.62 mS m-1) and KD (1.65 mS m-1). Furthermore, we found the sago palms grow well in a range of soil pH from 5.52 to 7.15, average soil pH: KS (6.8) and KD (6.96), while acid in KR (5.84). We also discuss the conservation activities to adequately protect sago palm, most of which are significantly threatened by habitat destruction and unsustainable harvesting.

The Role of Vacuolar Malate-Transport Capacity in Crassulacean Acid Metabolism and Nitrate Nutrition. Higher Malate-Transport Capacity in Ice Plant after Crassulacean Acid Metabolism-Induction and in Tobacco under Nitrate Nutrition1

PubMed Central

Lüttge, Ulrich; Pfeifer, Tanja; Fischer-Schliebs, Elke; Ratajczak, Rafael

2000-01-01

Anion uptake by isolated tonoplast vesicles was recorded indirectly via increased H+-transport by H+-pumping of the V-ATPase due to dissipation of the electrical component of the electrochemical proton gradient, ΔμH+, across the membrane. ATP hydrolysis by the V-ATPase was measured simultaneously after the Palmgren test. Normalizing for ATP-hydrolysis and effects of chloride, which was added to the assays as a stimulating effector of the V-ATPase, a parameter, Jmalrel, of apparent ATP-dependent malate-stimulated H+-transport was worked out as an indirect measure of malate transport capacity. This allowed comparison of various species and physiological conditions. Jmalrel was high in the obligate crassulacean acid metabolism (CAM) species Kalanchoë daigremontiana Hamet et Perrier, it increased substantially after CAM induction in ice plant (Mesembryanthemum crystallinum), and it was positively correlated with NO3− nutrition in tobacco (Nicotiana tabacum). For tobacco this was confirmed by measurements of malate transport energized via the V-PPase. In ice plant a new polypeptide of 32-kD apparent molecular mass appeared, and a 33-kD polypeptide showed higher levels after CAM induction under conditions of higher Jmalrel. It is concluded that tonoplast malate transport capacity plays an important role in physiological regulation in CAM and NO3− nutrition and that a putative malate transporter must be within the 32- to 33-kD polypeptide fraction of tonoplast proteins. PMID:11080309

Focal Adhesion Kinase (FAK) tyrosine 397E mutation restores the vascular leakage defect in endothelium-specific FAK-kinase dead mice.

PubMed

Alexopoulou, Annika N; Lees, Delphine M; Bodrug, Natalia; Lechertier, Tanguy; Fernandez, Isabelle; D'Amico, Gabriela; Dukinfield, Matthew; Batista, Silvia; Tavora, Bernardo; Serrels, Bryan; Hodivala-Dilke, Kairbaan

2017-07-01

Focal adhesion kinase (FAK) inhibitors have been developed as potential anticancer agents and are undergoing clinical trials. In vitro activation of the FAK kinase domain triggers autophosphorylation of Y397, Src activation, and subsequent phosphorylation of other FAK tyrosine residues. However, how FAK Y397 mutations affect FAK kinase-dead (KD) phenotypes in tumour angiogenesis in vivo is unknown. We developed three Pdgfb-iCre ert -driven endothelial cell (EC)-specific, tamoxifen-inducible homozygous mutant mouse lines: FAK wild-type (WT), FAK KD, and FAK double mutant (DM), i.e. KD with a putatively phosphomimetic Y397E mutation. These ECCre+;FAK WT / WT , ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice were injected subcutaneously with syngeneic B16F0 melanoma cells. Tumour growth and tumour blood vessel functions were unchanged between ECCre+;FAK WT / WT and ECCre-;FAK WT / WT control mice. In contrast, tumour growth and vessel density were decreased in ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice, as compared with Cre - littermates. Despite no change in the percentage of perfused vessels or pericyte coverage in either genotype, tumour hypoxia was elevated in ECCre+;FAK KD / KD and ECCre+;FAK DM / DM mice. Furthermore, although ECCre+;FAK KD / KD mice showed reduced blood vessel leakage, ECCre+;FAK DM / DM and ECCre-;FAK DM / DM mice showed no difference in leakage. Mechanistically, fibronectin-stimulated Y397 autophosphorylation was reduced in Cre+;FAK KD / KD ECs as compared with Cre+;FAK WT / WT cells, with no change in phosphorylation of the known Src targets FAK-Y577, FAK-Y861, FAK-Y925, paxillin-Y118, p130Cas-Y410. Cre+;FAK DM / DM ECs showed decreased Src target phosphorylation levels, suggesting that the Y397E substitution actually disrupted Src activation. Reduced VE-cadherin-pY658 levels in Cre+;FAK KD / KD ECs were rescued in Cre+FAK DM / DM ECs, corresponding with the rescue in vessel leakage in the ECCre+;FAK DM / DM mice. We show that EC-specific FAK kinase activity is required for tumour growth, angiogenesis, and vascular permeability. The ECCre+;FAK DM/DM mice restored the KD-dependent tumour vascular leakage observed in ECCre+;FAK KD/KD mice in vivo. This study opens new fields in in vivo FAK signalling. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Factors affecting the viscosity in high concentration solutions of different monoclonal antibodies.

PubMed

Yadav, Sandeep; Shire, Steven J; Kalonia, Devendra S

2010-12-01

The viscosity profiles of four different IgG(1) molecules were studied as a function of concentration at pH 6.0. At high concentrations, MAb-H and -A showed significantly higher viscosities as compared to MAb-G and -E. Zeta Potential (ξ) measurements showed that all the IgG(1) molecules carried a net positive charge at this pH. MAb-G showed the highest positive zeta potential followed by MAb-E, -H, and -A. A consistent interpretation of the impact of net charge on viscosity for these MAbs is not possible, suggesting that electroviscous effects cannot explain the differences in viscosity. Values of k(D) (dynamic light scattering) indicated that the intermolecular interactions were repulsive for MAb-E and -G; and attractive for MAb-H and -A. Solution storage modulus (G') in high concentration solutions was consistent with attractive intermolecular interactions for MAb-H and -A, and repulsive interactions for MAb-G and -E. Effect of salt addition on solution G' and k(D) indicated that the interactions were primarily electrostatic in nature. The concentration dependent viscosity data were analyzed using a modified Ross and Minton equation. The analysis explicitly differentiates between the effect of molecular shape, size, self-crowding, and electrostatic intermolecular interactions in governing high concentration viscosity behavior. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Study of Resource Recovery and Epidemiology in an Anaerobic Digester

NASA Technical Reports Server (NTRS)

Li, K. Y.; Cao, Song; Hunt, M. D.; Fu, Xuping

1995-01-01

Three 4-liter packed bed anaerobic digesters were fabricated and operated at 35 degrees C, pH around 7, and hydraulic retention time (HRT) of 20, 10 and 5 days to study the resource recovery and epidemiology in a controlled ecological life support system (CELSS). A simulated wastewater, consisted of shower water, clothwash water, dishwasher water, handwash water, and urine flush water was used as the feeding solution. Under steady-state operation, chemical oxygen demand (COD), total organic carbon (TOC), pH, nitrogen, phosphorus, and potassium wer monitored in the digester input and output solutions. The volume and the CH4/CO2 ratios in the biogas produced from the anaerobic digesters were measured. The results indicate about 90 percent of TOC is converted while only 5-8 percent of N-P-K are consumed in the digester. A multi-drug resistant strain of Salmonella choleraesuis was used as the indicator bacterium in the epidemiology study. The levels of Salmonella choleraesuis in the influent and the effluent wer determined and decimal decay rate constants, k(d), were estimated. The k(d) values were greater at higher initial doses than lower doses for the same HR, and greater for batch digestion (7.89/d) than for continuous digestion (4.28, 3.82, and 3.82/d for 20, 10, and 5 d HRT, respectively).

Absolute configuration of acremoxanthone C, a potent calmodulin inhibitor from Purpureocillium lilacinum.

PubMed

Madariaga-Mazón, Abraham; González-Andrade, Martín; González, María Del Carmen; Glenn, Anthony E; Cerda-García-Rojas, Carlos M; Mata, Rachel

2013-08-23

Bioassay-guided fractionation of an extract prepared from the culture medium and mycelium of Purpureocillium lilacinum allowed the isolation of two calmodulin (CaM) inhibitors, namely, acremoxanthone C (1) and acremonidin A (2). The absolute configuration of 1 was established as 2R, 3R, 1'S, 11'S, and 14'R through extensive NMR spectroscopy and molecular modeling calculations at the DFT B3LYP/DGDZVP level, which included the comparison between theoretical and experimental specific rotation, ³J(C,H), and ³J(H,H) values. Compounds 1 and 2 bind to the human calmodulin (hCaM) biosensor hCaM M124C-mBBr, with dissociation constants (Kd) of 18.25 and 19.40 nM, respectively, 70-fold higher than that of chlorpromazine (Kd = 1.24 μM), used as positive control. Docking analysis using AutoDock 4.2 predicted that 1 and 2 bind to CaM at a similar site to that which KAR-2 binds, which is unusual. Furthermore, a novel, sensible, and specific fluorescent biosensor of hCaM, i.e., hCaM T110C-mBBr, was constructed; this device is labeled at a site where classical inhibitors do not interact and was successfully applied to measure the interaction of 1 with CaM. This is the first report of xanthone-anthraquinone heterodimers in species of Paecilomyces or Purpureocillium genera.

Rapid characterization of a novel taspine derivative-HMQ1611 binding to EGFR by a cell membrane chromatography method.

PubMed

Du, Hui; Lv, Nan; Wang, Sicen; He, Langchong

2013-05-01

A new high-expression endothelial growth factor receptor (EGFR) cell membrane chromatography (CMC) method was applied to recognize the ligands acting on EGFR specifically, and investigate the affinity of gefitinib/HMQ1611 to EGFR. In the self and direct competitive assay, gefitinib/HMQ1611 was used as a competitor in the mobile phase to evaluate the effect of the competitor's concentrations on the retention of the ligands, respectively, and the competition between gefitinib and HMQ1611 binding to EGFR was also been examined. The retention behavior indicated that gefitinib had one type of binding sites on the EGFR, and the equilibrium dissociation constant (K(D)) was (9.11 ± 1.89) × 10(-6) M; HMQ1611 had two major binding regions on the EGFR, and the K(D) values obtained from the model were (2.39 ± 0.33) × 10(-7) and (3.87 ± 0.93) × 10(-5) M for HMQ1611 at the high- and low-affinity sites, respectively. The competition between gefitinib and HMQ1611 occurred at the low-affinity sites on the EGFR. The low-affinity sites were of higher concentrations and contributed to a much larger part of retention of HMQ1611. The results suggested that gefitinib and HMQ1611 competed for the common binding sites on the EGFR, no matter the ligand was used as an analyte or a competitor.

Sorption of fluoroquinolones and sulfonamides in 13 Brazilian soils.

PubMed

Leal, Rafael Marques Pereira; Alleoni, Luis Reynaldo Ferracciú; Tornisielo, Valdemar Luiz; Regitano, Jussara Borges

2013-08-01

Animal production is a leading economic activity in Brazil and antibiotics are widely used. However, the occurrence, behavior, and impacts of antibiotics in Brazilian soils are still poorly known. We evaluated the sorption behavior of four fluoroquinolones (norfloxacin, ciprofloxacin, danofloxacin, and enrofloxacin) and five sulfonamides (sulfadiazine, sulfachloropyridazine, sulfamethoxazole, sulfadimidine, and sulfathiazole) in 13 Brazilian soils with contrasting physical, chemical, and mineralogical properties. Fluoroquinolone sorption was very high (Kd≥544 L kg(-1)) whereas sulfonamide sorption ranged from low to high (Kd=0.7-70.1 L kg(-1)), consistent with previous reports in the literature. Soil texture and cation exchange capacity were the soil attributes that most affected sorption. Cation exchange was the most important sorption mechanism for the fluoroquinolones in highly weathered tropical soils, although cation bridging and ion pairing could not be ruled out. Hydrophobic partition played an important role in the sorption of the sulfonamides, but sorption was also affected by non-hydrophobic interactions with organic and/or mineral surfaces. Sorption for both compound classes tended to be higher in soils with high Al and Fe oxihydroxide contents, but they were not correlated with Kd values. No direct effect of soil pH was seen. The fluoroquinolones are not expected to leach even in worst-case scenarios (soils rich in sand and poor in organic carbon), whereas soil attributes dictate leaching potential for the sulfonamides. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modelling of Tc migration in an un-oxidized fractured drill core from Äspö, Sweden

NASA Astrophysics Data System (ADS)

Huber, F. M.; Totskiy, Y.; Montoya Garcia, V.; Enzmann, F.; Trumm, M.; Wenka, A.; Geckeis, H.; Schaefer, T.

2015-12-01

The radionuclide retention of redox sensitive radionuclides (e.g. Pu, Np, U, Tc) in crystalline host rock greatly depends on the rock matrix and the rock redox capacity. Preservation of drill cores concerning oxidation is therefore of paramount importance to reliably predict the near-natural radionuclide retention properties. Here, experimental results of HTO and Tc laboratory migration experiments in a naturally single fractured Äspö un-oxidized drill core are modelled using two different 2D models. Both models employ geometrical information obtained by μ-computed tomography (μCT) scanning of the drill core. The models differ in geometrical complexity meaning the first model (PPM-MD) consists of a simple parallel plate with a porous matrix adjacent to the fracture whereas the second model (MPM) uses the mid-plane of the 3D fracture only (no porous matrix). Simulation results show that for higher flow rates (Peclet number > 1), the MPM satisfactorily describes the HTO breakthrough curves (BTC) whereas the PPM-MD model nicely reproduces the HTO BTC for small Pe numbers (<1). These findings clearly highlight the influence of fracture geometry/flow field complexity on solute transport for Pe numbers > 1 and the dominating effect of matrix diffusion for Peclet numbers < 1. Retention of Tc is modelled using a simple Kd-approach in case of the PPM-MD and including 1st order sorptive reduction/desorption kinetics in case of the MPM. Batch determined sorptive reduction/desorption kinetic rates and Kd values for Tc on non-oxidized Äspö diorite are used in the model and compared to best fit values. By this approach, the transferability of kinetic data concerning sorptive reduction determined in static batch experiments to dynamic transport experiments is examined.

Reversible and irreversible sorption of perfluorinated compounds (PFCs) by sediments of an urban reservoir.

PubMed

Chen, Huiting; Reinhard, Martin; Nguyen, Viet Tung; Gin, Karina Yew-Hoong

2016-02-01

Uncertainty about the extent to which contaminant sorption by suspended solids and bed sediments is irreversible is a major impediment for modeling and managing the water quality of surface water resources. This study examined reversible and irreversible sorption of several perfluorinated compounds (PFCs) to bed sediments from an urban reservoir. PFCs investigated include C4, C6, C8, C9 and C10 perfluoroalkanoate homologues (PFBA, PFHxA, PFOA, PFNA and PFDA, respectively) and perfluorooctane and hexane sulfonate (PFOS and PFHxS, respectively). Although sorption branches of the PFOS, PFNA and PFDA isotherms were nearly linear (implying a partitioning-like process), desorption experiments indicated that a fraction of the sorbed PFCs were entrapped and resistant to desorption. The hysteretic desorption branches were approximately linear. Irreversibility increased with chain length and was nearly complete for PFDA (thermodynamic irreversibility index (TII) 0.98). For the weakly sorbing PFOA and PFHxS, sorption was largely reversible. Data suggest that (1) for the strongly sorbing PFCs, e.g. PFNA, PFDA and PFOS, bed sediments acted predominantly as irreversible sinks, (2) aqueous concentrations of the moderately sorbing PFCs (PFOA and PFHxS) are buffered by reversibly sorbing suspended solids, and (3) the short-chain PFCs (PFBA and PFHxA) are not significantly sorbed and therefore not expected to be significantly influenced by sediment transport. Situations in which highly contaminated particles entering relatively clean water bodies, equilibrium is approached from the reverse (desorption) direction. For irreversibly sorbed contaminants field-based K(D) values will be higher than the K(D) values derived from laboratory sorption data obtained from forward sorption experiments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Azole affinity of sterol 14α-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens.

PubMed

Warrilow, Andrew G; Parker, Josie E; Kelly, Diane E; Kelly, Steven L

2013-03-01

Candida albicans CYP51 (CaCYP51) (Erg11), full-length Homo sapiens CYP51 (HsCYP51), and truncated Δ60HsCYP51 were expressed in Escherichia coli and purified to homogeneity. CaCYP51 and both HsCYP51 enzymes bound lanosterol (K(s), 14 to 18 μM) and catalyzed the 14α-demethylation of lanosterol using Homo sapiens cytochrome P450 reductase and NADPH as redox partners. Both HsCYP51 enzymes bound clotrimazole, itraconazole, and ketoconazole tightly (dissociation constants [K(d)s], 42 to 131 nM) but bound fluconazole (K(d), ~30,500 nM) and voriconazole (K(d), ~2,300 nM) weakly, whereas CaCYP51 bound all five medical azole drugs tightly (K(d)s, 10 to 56 nM). Selectivity for CaCYP51 over HsCYP51 ranged from 2-fold (clotrimazole) to 540-fold (fluconazole) among the medical azoles. In contrast, selectivity for CaCYP51 over Δ60HsCYP51 with agricultural azoles ranged from 3-fold (tebuconazole) to 9-fold (propiconazole). Prothioconazole bound extremely weakly to CaCYP51 and Δ60HsCYP51, producing atypical type I UV-visible difference spectra (K(d)s, 6,100 and 910 nM, respectively), indicating that binding was not accomplished through direct coordination with the heme ferric ion. Prothioconazole-desthio (the intracellular derivative of prothioconazole) bound tightly to both CaCYP51 and Δ60HsCYP51 (K(d), ~40 nM). These differences in binding affinities were reflected in the observed 50% inhibitory concentration (IC(50)) values, which were 9- to 2,000-fold higher for Δ60HsCYP51 than for CaCYP51, with the exception of tebuconazole, which strongly inhibited both CYP51 enzymes. In contrast, prothioconazole weakly inhibited CaCYP51 (IC(50), ~150 μM) and did not significantly inhibit Δ60HsCYP51.

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι*

PubMed Central

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F. Peter

2016-01-01

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn2+ than Mg2+. The human germline R96G variant impairs both Mn2+-dependent and Mg2+-dependent activities of pol ι, whereas the Δ1–25 variant selectively enhances its Mg2+-dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1–445) proteins. The presence of Mn2+ (0.15 mm) instead of Mg2+ (2 mm) caused a 770-fold increase in efficiency (kpol/Kd,dCTP) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in Kd,dCTP. The R96G and Δ1–25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in kpol/Kd,dCTP for dCTP insertion opposite G with Mg2+ when compared with wild type, substantially attenuated by substitution with Mn2+. Crystal structures of pol ι ternary complexes, including the primer terminus 3′-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg2+ or Mn2+, revealed that Mn2+ achieves more optimal octahedral coordination geometry than Mg2+, with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. PMID:27555320

ARSENITE BINDING TO SUBSETS OF THE HUMAN ESTROGEN RECEPTOR-ALPHA

EPA Science Inventory

Enzyme inhibition by arsenicals has been described many times, but the underlying binding of trivalent arsenicals to peptides and proteins has received little attention. The purpose of this study was to determine Kd and Bmax values for arsenite binding to nine synthetic peptides ...

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage.

PubMed

Wang, Shuangyong; Li, Liangliang; Liu, Ying; Li, Chaoyang; Zhang, Min; Wang, Bowen; Huang, Zheqian; Gao, Xinbo; Wang, Zhichong

2015-03-01

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterization of the three different states of the cholecystokinin (CCK) receptor in pancreatic acini.

PubMed

Talkad, V D; Patto, R J; Metz, D C; Turner, R J; Fortune, K P; Bhat, S T; Gardner, J D

1994-10-20

By measuring binding of [125I]CCK-8 and [3H]L-364,718 to rat pancreatic acini we demonstrated directly that the pancreatic CCK receptor can exist in three different affinity states with respect to CCK--high affinity, low affinity and very low affinity. Binding of [125I]CCK-8 reflects interaction of the tracer with the high and low affinity states, whereas binding of [3H]L-364,718 reflects interaction of the tracer with the low and very low affinity states. Treating acini with carbachol abolished the high affinity state of the CCK receptor and converted approximately 25% of the low affinity receptors to the very low affinity state. Carbachol treatment was particularly useful in establishing the values of Kd for the high and low affinity states for different CCK receptor agonists and antagonists. Of the various CCK receptor agonists tested, CCK-8 had the highest affinity for the high affinity state (Kd approximately 1 nM), whereas CCK-JMV-180 had the highest affinity for the low (Kd 7 nM) and very low affinity (Kd 200 nM) states. Gastrin and de(SO4)CCK-8 had affinities for the high and low affinity states of the receptor that were 100- to 400-fold less than those of CCK-8 but had affinities for the very low affinity state that were only 3- to 10-fold less than that of CCK-8. CCK receptor antagonists showed several patterns in interacting with the different states of the CCK receptor. L-364,718 had the same affinity for each state of the CCK receptor. CR1409 and Bt2cGMP each had similar affinities for the high and low affinity states and lower affinity for the very low affinity state. L-365,260 and CCK-JMV-179 had the highest affinity for the low affinity state and lower affinities for the high and very low affinity states. Different CCK receptor agonists caused the same maximal stimulation of amylase secretion but showed different degrees of amplification in terms of the relationship between their abilities to stimulate amylase secretion and their abilities to occupy the low affinity state of the CCK receptor. When amplification was expressed quantitatively as the value of Kd for the low affinity state divided by the corresponding EC50 for stimulating amylase secretion the values were CCK-8 (1000), de(SO)CCK-8 (1500), gastrin (100) and CCK-JMV-180 (Menozzi, D., Vinayek, R., Jensen, R.T. and Gardner, J.D. (1991) J. Biol. Chem. 266, 10385-1091).(ABSTRACT TRUNCATED AT 400 WORDS)

Sorption of biodegradation end products of nonylphenol polyethoxylates onto activated sludge.

PubMed

Hung, Nguyen Viet; Tateda, Masafumi; Ike, Michihiko; Fujita, Masanori; Tsunoi, Shinji; Tanaka, Minoru

2004-01-01

Nonylphenol(NP), nonylphenoxy acetic acid (NP1EC), nonylphenol monoethoxy acetic acid (NP2EC), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate (NP2EO) are biodegradation end products (BEPs) of nonionic surfactant nonylphenolpolyethoxylates (NPnEO). In this research, sorption of these compounds onto model activated sludge was characterized. Sorption equilibrium experiments showed that NP, NP1EO and NP2EO reached equilibrium in about 12 h, while equilibrium of NP1EC and NP2EC were reached earlier, in about 4 h. In sorption isotherm experiments, obtained equilibrium data at 28 degrees C fitted well to Freundlich sorption model for all investigated compounds. For NP1EC, in addition to Freundlich, equilibrium data also fitted well to Langmuir model. Linear sorption model was also tried, and equilibrium data of all NP, NP1EO, NP2EO and NP2EC except NP1EC fitted well to this model. Calculated Freundlich coefficient (K(F)) and linear sorption coefficient (K(D)) showed that sorption capacity of the investigated compounds were in order NP > NP2EO > NP1EO > NP1EC approximately NP2EC. For NP, NP1EO and NP2EO, high values of calculated K(F) and K(D) indicated an easy uptake of these compounds from aqueous phase onto activated sludge. Whereas, NP1EC and NP2EC with low values of K(F) and K(D) absorbed weakly to activated sludge and tended to preferably remain in aqueous phase.

Distributions of polycyclic aromatic hydrocarbons in surface waters, sediments and soils of Hangzhou City, China.

PubMed

Chen, Baoliang; Xuan, Xiaodong; Zhu, Lizhong; Wang, Jing; Gao, Yanzheng; Yang, Kun; Shen, Xueyou; Lou, Baofeng

2004-09-01

Ten polycyclic aromatic hydrocarbons (PAHs) were simultaneously measured in 17 surface water samples and 11 sediments of four water bodies, and 3 soils near the water-body bank in Hangzhou, China in December 2002. It was observed that the sum of PAHs concentrations ranged from 0.989 to 9.663 microg/L in surface waters, from 132.7 to 7343 ng/g dry weight in sediments, and from 59.71 to 615.8 ng/g dry weight in soils. The composition pattern of PAHs by ring size in water, sediment and soil were surveyed. Three-ring PAHs were dominated in surface waters and soils, meanwhile sediments were mostly dominated by four-ring PAHs. Furthermore, PAHs apparent distribution coefficients (K(d)) and solid f(oc)-normalized K(d) (e.g. K(oc)= K(d) / f(oc)) were calculated. The relationship between logK(oc) and logK(ow) of PAHs for field data on sediments and predicted values were compared. The sources of PAHs in different water bodies were evaluated by comparison of K (oc) values in sediments of the river downstream with that in soils. Hangzhou section of the Great Canal was heavily polluted by PAHs released from industrial wastewater in the past and now PAHs in sediment may serve as sources of PAHs in surface water. PAHs in Qiantang River were contributed from soil runoff. Municipal road runoff was mostly contributed to West Lake PAHs.

Bridging the gap between batch and column experiments: A case study of Cs adsorption on granite.

PubMed

Wang, Tsing-Hai; Li, Ming-Hsu; Teng, Shi-Ping

2009-01-15

Both batch and column methods are conventionally utilized to determine some critical parameters for assessing the transport of contaminants of concern. The validity of using these parameters is somewhat confusing, however, since outputs such as distribution coefficient (Kd) from these two approaches are often discrepant. To bridge this gap, all possible factors that might contribute to this discrepancy were thoroughly investigated in this report by a case study of Cs sorption to crushed granite under various conditions. Our results confirm an important finding that solid/liquid (S/L) ratio is the dominant factor responsible for this discrepancy. As long as the S/L ratio exceeds 0.25, a consistent Kd value can be reached by the two methods. Under these conditions (S/L ratios>0.25), the sorption capacity of the solid is about an order of magnitude less than that in low S/L ratios (<0.25). Although low sorption capacity is observed in the cases of high S/L ratios, the sorption usually takes place preferentially on the most favorable (thermodynamically stable) sorption sites to form a stronger binding. This is verified by our desorption experiments in which a linear isotherm feature is shown either in deionized water or in 1M of ammonium acetate solutions. It may be concluded that batch experiment with an S/L ratio exceeding 0.25 is crucial to obtain convincing Kd values for safety assessment of radioactive waste repository.

Modulation of the platelet serotonin transporter by thermal balneotherapy: a study in healthy subjects.

PubMed

Baroni, S; Marazziti, D; Consoli, G; Picchetti, M; Catena-Dell'Osso, M; Galassi, A

2012-05-01

Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 30 healthy volunteers before (t0) and 30 minutes after (t1) thermal balneotherapy with ozonized water, as compared with a similar group who underwent a bath in non-mineral water. MATERIALS AN METHODS: The SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of 3H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.

Thermal balneotherapy induces changes of the platelet serotonin transporter in healthy subjects.

PubMed

Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Catena Dell'Osso, Mario; Consoli, Giorgio; Picchetti, Michela; Carlini, Marina; Massimetti, Gabriele; Provenzano, Serafina; Galassi, Antonio

2007-10-01

Although the beneficial effects of balneotherapy have been recognized since a long time, a few information is available on the biological mechanisms underlying them and the subjective feelings of increased well-being and mood. The links between the serotonin (5-HT) system and mood prompted us to investigate the 5-HT platelet transporter (SERT), which is considered a reliable, peripheral marker of the same structure present in presynaptic neurons, in 20 healthy volunteers before (t0) and 30 min after (t1) thermal balneotherapy with ozonized water of Montecatini spa, as compared with a similar group who underwent a bath in non-mineral water. The SERT was evaluated by means of the specific binding of (3)H-paroxetine ((3)H-Par) to platelet membranes. Equilibrium-saturation binding data, the maximal binding capacity (Bmax) and the dissociation constant (Kd), were obtained by means of the Scatchard analysis. The results showed that, while Bmax values did not change in both groups, the Kd values decreased significantly at t1 only in those subjects who bathed in ozonized water. The results of this study, while showing a decrease of the dissociation constant (Kd) which is the inverse of affinity constant, of (3)H-Par binding to SERT in all subjects after balneotherapy and not in those bathing in normal water, suggest that SERT modifications may be related to a specific effect of ozonized water and, perhaps, also to the increased sense of well-being.

Bisphenol A in Solid Waste Materials, Leachate Water, and Air Particles from Norwegian Waste-Handling Facilities: Presence and Partitioning Behavior.

PubMed

Morin, Nicolas; Arp, Hans Peter H; Hale, Sarah E

2015-07-07

The plastic additive bisphenol A (BPA) is commonly found in landfill leachate at levels exceeding acute toxicity benchmarks. To gain insight into the mechanisms controlling BPA emissions from waste and waste-handling facilities, a comprehensive field and laboratory campaign was conducted to quantify BPA in solid waste materials (glass, combustibles, vehicle fluff, waste electric and electronic equipment (WEEE), plastics, fly ash, bottom ash, and digestate), leachate water, and atmospheric dust from Norwegian sorting, incineration, and landfill facilities. Solid waste concentrations varied from below 0.002 mg/kg (fly ash) to 188 ± 125 mg/kg (plastics). A novel passive sampling method was developed to, for the first time, establish a set of waste-water partition coefficients, KD,waste, for BPA, and to quantify differences between total and freely dissolved concentrations in waste-facility leachate. Log-normalized KD,waste (L/kg) values were similar for all solid waste materials (from 2.4 to 3.1), excluding glass and metals, indicating BPA is readily leachable. Leachate concentrations were similar for landfills and WEEE/vehicle sorting facilities (from 0.7 to 200 μg/L) and dominated by the freely dissolved fraction, not bound to (plastic) colloids (agreeing with measured KD,waste values). Dust concentrations ranged from 2.3 to 50.7 mg/kgdust. Incineration appears to be an effective way to reduce BPA concentrations in solid waste, dust, and leachate.

Interaction of Sr-90 with site candidate soil for demonstration disposal facility at Serpong

NASA Astrophysics Data System (ADS)

Setiawan, Budi; Mila, Oktri; Safni

2014-03-01

Interaction of radiostrontium (Sr-90) with site candidate soil for demonstration disposal facility to be constructed in the near future at Serpong has been done. This activity is to anticipate the interim storage facility at Serpong nuclear area becomes full off condition, and show to the public how radioactive waste can be well managed with the existing technology. To ensure that the location is save, a reliability study of site candidate soil becomes very importance to be conducted through some experiments consisted some affected parameters such as contact time, effect of ionic strength, and effect of Sr+ ion in solution. Radiostrontium was used as a tracer on the experiments and has role as radionuclide reference in low-level radioactive waste due to its long half-live and it's easy to associate with organism in nature. So, interaction of radiostrontium and soil samples from site becomes important to be studied. Experiment was performed in batch method, and soil sample-solution containing radionuclide was mixed in a 20 ml of PE vial. Ratio of solid: liquid was 10-2 g/ml. Objective of the experiment is to collect the specific characteristics data of radionuclide sorption onto soil from site candidate. Distribution coefficient value was used as indicator where the amount of initial and final activities of radiostrontium in solution was compared. Result showed that equilibrium condition was reached after contact time 10 days with Kd values ranged from 1600-2350 ml/g. Increased in ionic strength in solution made decreased of Kd value into soil sample due to competition of background salt and radiostrontium into soil samples, and increased in Sr ion in solution caused decreased of Kd value in soil sample due to limitation of sorption capacity in soil samples. Fast condition in saturated of metal ion into soil samples was reached due to a simple reaction was occurred.

Kawasaki Disease-Specific Molecules in the Sera Are Linked to Microbe-Associated Molecular Patterns in the Biofilms

PubMed Central

Murata, Kenji; Kanno, Shunsuke; Nishio, Hisanori; Saito, Mitsumasa; Tanaka, Tamami; Yamamura, Kenichiro; Sakai, Yasunari; Takada, Hidetoshi; Miyamoto, Tomofumi; Mizuno, Yumi; Ouchi, Kazunobu; Waki, Kenji; Hara, Toshiro

2014-01-01

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The innate immune system is involved in its pathophysiology at the acute phase. We have recently established a novel murine model of KD coronary arteritis by oral administration of a synthetic microbe-associated molecular pattern (MAMP). On the hypothesis that specific MAMPs exist in KD sera, we have searched them to identify KD-specific molecules and to assess the pathogenesis. Methods We performed liquid chromatography-mass spectrometry (LC-MS) analysis of fractionated serum samples from 117 patients with KD and 106 controls. Microbiological and LC-MS evaluation of biofilm samples were also performed. Results KD samples elicited proinflammatory cytokine responses from human coronary artery endothelial cells (HCAECs). By LC-MS analysis of KD serum samples collected at 3 different periods, we detected a variety of KD-specific molecules in the lipophilic fractions that showed distinct m/z and MS/MS fragmentation patterns in each cluster. Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (common MAMPs from Bacillus cereus, Yersinia pseudotuberculosis and Staphylococcus aureus) at the 1st study period, and from the biofilms formed in vivo (common MAMPs from Bacillus cereus, Bacillus subtilis/Bacillus cereus/Yersinia pseudotuberculosis and Staphylococcus aureus) at the 2nd and 3rd periods. The biofilm extracts from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus also induced proinflammatory cytokines by HCAECs. By the experiments with IgG affinity chromatography, some of these serum KD-specific molecules bound to IgG. Conclusions We herein conclude that serum KD-specific molecules were mostly derived from biofilms and possessed molecular structures common to MAMPs from Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis and Staphylococcus aureus. Discovery of these KD-specific molecules might offer novel insight into the diagnosis and management of KD as well as its pathogenesis. PMID:25411968

Mobility of radionuclides and trace elements in soil from legacy NORM and undisturbed naturally 232Th-rich sites.

PubMed

Mrdakovic Popic, Jelena; Meland, Sondre; Salbu, Brit; Skipperud, Lindis

2014-05-01

Investigation of radionuclides (232Th and 238U) and trace elements (Cr, As and Pb) in soil from two legacy NORM (former mining sites) and one undisturbed naturally 232Th-rich site was conducted as a part of the ongoing environmental impact assessment in the Fen Complex area (Norway). The major objectives were to determine the radionuclide and trace element distribution and mobility in soils as well as to analyze possible differences between legacy NORM and surrounding undisturbed naturally 232Th-rich soils. Inhomogeneous soil distribution of radionuclides and trace elements was observed for each of the investigated sites. The concentration of 232Th was high (up to 1685 mg kg(-1), i.e., ∼7000 Bq kg(-1)) and exceeded the screening value for the radioactive waste material in Norway (1 Bq g(-1)). Based on the sequential extraction results, the majority of 232Th and trace elements were rather inert, irreversibly bound to soil. Uranium was found to be potentially more mobile, as it was associated with pH-sensitive soil phases, redox-sensitive amorphous soil phases and soil organic compounds. Comparison of the sequential extraction datasets from the three investigated sites revealed increased mobility of all analyzed elements at the legacy NORM sites in comparison with the undisturbed 232Th-rich site. Similarly, the distribution coefficients Kd (232Th) and Kd (238U) suggested elevated dissolution, mobility and transportation at the legacy NORM sites, especially at the decommissioned Nb-mining site (346 and 100 L kg(-1) for 232Th and 238U, respectively), while the higher sorption of radionuclides was demonstrated at the undisturbed 232Th-rich site (10,672 and 506 L kg(-1) for 232Th and 238U, respectively). In general, although the concentration ranges of radionuclides and trace elements were similarly wide both at the legacy NORM and at the undisturbed 232Th-rich sites, the results of soil sequential extractions together with Kd values supported the expected differences between sites as the consequences of previous mining operations. Hence, mobility and possible elevated bioavailability at the legacy NORM site could be expected and further risk assessment should take this into account when decisions about the possible intervention measures are made.

Quasimodular instanton partition function and the elliptic solution of Korteweg-de Vries equations

NASA Astrophysics Data System (ADS)

He, Wei

2015-02-01

The Gauge/Bethe correspondence relates Omega-deformed N = 2 supersymmetric gauge theories to some quantum integrable models, in simple cases the integrable models can be treated as solvable quantum mechanics models. For SU(2) gauge theory with an adjoint matter, or with 4 fundamental matters, the potential of corresponding quantum model is the elliptic function. If the mass of matter takes special value then the potential is an elliptic solution of KdV hierarchy. We show that the deformed prepotential of gauge theory can be obtained from the average densities of conserved charges of the classical KdV solution, the UV gauge coupling dependence is assembled into the Eisenstein series. The gauge theory with adjoint mass is taken as the example.

Chemical and ruminal in vitro evaluation of Canadian canola meals produced over 4 years.

PubMed

Broderick, Glen A; Colombini, Stefania; Costa, Sara; Karsli, Mehmet A; Faciola, Antonio P

2016-10-01

To test the effects of year and processing plant on the nutritional value of canola meal (CM), 3 CM samples/yr were collected from each of 12 Canadian production plants over 4yr (total=144). Samples of CM were analyzed for differences in chemical composition and for in vitro ruminal protein degradability using the Michaelis-Menten inhibitor in vitro (MMIIV) method. In the MMIIV method, protein degradation rate (kd) was estimated by 2 methods: from net release (i.e., blank corrected) of (1) ammonia plus AA determined by o-phthaldialdehyde fluorescence (OPAF) assay or (2) ammonia, AA, plus oligopeptides determined by o-phthaldialdehyde absorbance (OPAA) assay; rumen-undegradable protein (RUP) was computed assuming passage rates of 0.16 and 0.06/h for, respectively, soluble and insoluble protein. Casein, solvent soybean meal (SSBM), and expeller soybean meal (ESBM) were included in all incubations as standard proteins. Differences among years and plants were assessed using the mixed procedures of SAS. Small but significant differences were found in CM among years for chemical composition, including N solubility; some of these differences may have been related to changes in our analytical methods over time. However, adjustment of degradation activity of individual in vitro incubations based on the mean degradation activity over all incubations yielded kd and RUP that did not differ by year using either assay. Simultaneously incubating CM samples from 2yr in the same in vitro runs confirmed that no year effects existed for kd or RUP. Differences existed in chemical composition of CM among the 12 processing plants over the 4yr of sample collection. Moreover, consistent differences in kd and RUP were observed among plants: kd ranged from 0.069 to 0.113/h (OPAA assay) and 0.075 to 0.120/h (OPAF assay), and RUP estimates ranged from 51 to 43% (OPAA assay) and 49 to 41% (OPAF assay). Regression of kd on insoluble N content of CM yielded correlation coefficients (R(2))=0.40 (OPAA assay) and 0.42 (OPAF assay), and regressions of kd on NDIN and N-fraction B3 yielded R(2)<0.02. Mean estimates from both OPAA and OPAF assays for casein, SSBM, ESBM, and CM were, respectively, kd=0.764, 0.161, 0.050, and 0.093/h and RUP=18, 33, 56, and 45%. A range of 8 percentage units from lowest to highest RUP suggests that substantial differences exist in metabolizable protein content of CM produced by different processing plants. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Autism spectrum disorder and epilepsy: the role of ketogenic diet].

PubMed

Garcia-Penas, J J

2016-01-01

Between 5-40% of autistic patients will develop epilepsy. Most individuals with autism and epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. For this population, alternative treatments such as ketogenic diet (KD) can be highly efficacious and should be seriously considered. To discuss the use of the KD in refractory pediatric epilepsy and its role in patients with autism and epilepsy. KD is an effective and well-tolerated treatment for refractory childhood epilepsy, including those patients who associate autism and epilepsy. Accurate characterization of the electroclinical epilepsy syndrome is the key to deciding when to consider the KD. Otherwise, the positive effect of KD for treating mitochondrial oxidative disorders and different models of autistic animals suggest that KD could be a good alternative treatment for autistic patients. Based on the demonstrated efficacy of KD in patients who associate both epilepsy and autism, KD treatment has been recently used in the treatment of autism spectrum disorders; however, there is lacking of controlled studies to define the real efficacy of this therapy. A well designed randomized controlled study is needed to determine whether KD is really efficacious for these patients.

Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein.

PubMed

Toth, Karoly; Tarakanova, Vera; Doronin, Konstantin; Ward, Peter; Kuppuswamy, Mohan; Locke, Jacob E; Dawson, Julie E; Kim, Han J; Wold, William S M

2003-03-01

We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3-11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and spread of virus from cell to cell, and thus its overexpression increases the oncolytic activity of the vectors. KD1 and KD3 contain mutations in the Ad5 E1A gene that knock out binding of the E1A proteins to cellular p300/CBP and pRB; these mutations allow KD1 and KD3 to grow well in cancer cells but not in normal cells. VRX-007 has wild-type E1A. Here we report that radiation increases the oncolytic activity of KD1, KD3, and VRX-007. This increased activity was observed in cultured cells, and it was not because of radiation-induced replication of the vectors. The combination of radiation plus KD3 suppressed the growth of A549 lung adenocarcinoma xenografts in nude mice more efficiently than radiation alone or KD3 alone. The combination of ADP-overexpressing vectors and radiation may have potential in treating cancer.

Ketogenic diet in endocrine disorders: Current perspectives

PubMed Central

Gupta, L; Khandelwal, D; Kalra, S; Gupta, P; Dutta, D; Aggarwal, S

2017-01-01

Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.” PMID:29022562

Predicting links based on knowledge dissemination in complex network

NASA Astrophysics Data System (ADS)

Zhou, Wen; Jia, Yifan

2017-04-01

Link prediction is the task of mining the missing links in networks or predicting the next vertex pair to be connected by a link. A lot of link prediction methods were inspired by evolutionary processes of networks. In this paper, a new mechanism for the formation of complex networks called knowledge dissemination (KD) is proposed with the assumption of knowledge disseminating through the paths of a network. Accordingly, a new link prediction method-knowledge dissemination based link prediction (KDLP)-is proposed to test KD. KDLP characterizes vertex similarity based on knowledge quantity (KQ) which measures the importance of a vertex through H-index. Extensive numerical simulations on six real-world networks demonstrate that KDLP is a strong link prediction method which performs at a higher prediction accuracy than four well-known similarity measures including common neighbors, local path index, average commute time and matrix forest index. Furthermore, based on the common conclusion that an excellent link prediction method reveals a good evolving mechanism, the experiment results suggest that KD is a considerable network evolving mechanism for the formation of complex networks.

Kid depletion in mouse oocytes associated with multinucleated blastomere formation and inferior embryo development.

PubMed

Egashira, Akiyoshi; Yamauchi, Nobuhiko; Islam, Md Rashedul; Yamagami, Kazuki; Tanaka, Asami; Suyama, Hikaru; El-Sayed, El-Sharawy Mohamed; Tabata, Shoji; Kuramoto, Takashi

2016-08-01

This study investigated the knockdown (KD) of Kid on maturation developmental competence and multinucleation of mouse germinal vesicle (GV) oocytes after parthenogenetic activation. Data revealed that Kid messenger RNA (mRNA) was expressed in GV and MII stage oocyte and 1- and 2-cell embryos. Additionally, Kid mRNA expression in the Kid KD group decreased by nearly 46% compared to the control small interfering RNA (siRNA) groups. The rate of multinucleated embryos in the Kid KD group (52.4%) was significantly higher (P < 0.05) than the control siRNA group (4.7%). Finally, the developmental rates were significantly lower in the Kid siRNA group at > 4-cell stage (28.6% vs. 53.5%) and the blastocyst stage (2.4% vs. 23.3%) compared to the control siRNA groups. Suppression of Kid using siRNA caused multinucleation in early embryos with high frequency and it may increase 2- to 4-cell arrested embryos and reduce the developmental competence to blastocyst. © 2016 Japanese Society of Animal Science.

Endogenous Acetylcholine Controls the Severity of Polymicrobial Sepsisassociated Inflammatory Response in Mice.

PubMed

Amaral, Flávio Almeida; Fagundes, Caio Tavares; Miranda, Aline Silva; Costa, Vivian Vasconceios; Resende, Livia; Gloria de Souza, Danielle da; Prado, Vania Ferreira; Teixeira, Mauro Martins; Maximo Prado, Marco Antonio; Teixeira, Antonio Lucio

2016-01-01

Acetylcholine (ACh) is the main mediator associated with the anti-inflammatory cholinergic pathway. ACh plays an inhibitory role in several inflammatory conditions. Sepsis is a severe clinical syndrome characterized by bacterial dissemination and overproduction of inflammatory mediators. The aim of the current study was to investigate the participation of endogenous ACh in the modulation of inflammatory response induced by a model of polymicrobial sepsis. Wild type (WT) and vesicular acetylcholine transporter knockdown (VAChT(KD)) mice were exposed to cecal ligation and perforation- induced sepsis. Levels of Tumor Necrosis Factor Alpha (TNF-α) and bacterial growth in peritoneal cavity and serum, and neutrophil recruitment into peritoneal cavity were assessed. The concentration of TNF-α in both compartments was higher in VAChT(KD) in comparison with WT mice. VAChT(KD) mice presented elevated burden of bacteria in peritoneum and blood, and impairment of neutrophil migration to peritoneal cavity. This phenotype was reversed by treatment with nicotine salt. These findings suggest that endogenous ACh plays a major role in the control of sepsis-associated inflammatory response.

Few-cycle optical rogue waves: complex modified Korteweg-de Vries equation.

PubMed

He, Jingsong; Wang, Lihong; Li, Linjing; Porsezian, K; Erdélyi, R

2014-06-01

In this paper, we consider the complex modified Korteweg-de Vries (mKdV) equation as a model of few-cycle optical pulses. Using the Lax pair, we construct a generalized Darboux transformation and systematically generate the first-, second-, and third-order rogue wave solutions and analyze the nature of evolution of higher-order rogue waves in detail. Based on detailed numerical and analytical investigations, we classify the higher-order rogue waves with respect to their intrinsic structure, namely, fundamental pattern, triangular pattern, and ring pattern. We also present several new patterns of the rogue wave according to the standard and nonstandard decomposition. The results of this paper explain the generalization of higher-order rogue waves in terms of rational solutions. We apply the contour line method to obtain the analytical formulas of the length and width of the first-order rogue wave of the complex mKdV and the nonlinear Schrödinger equations. In nonlinear optics, the higher-order rogue wave solutions found here will be very useful to generate high-power few-cycle optical pulses which will be applicable in the area of ultrashort pulse technology.

Mouse models: the ketogenic diet and polyunsaturated fatty acids.

PubMed

Borges, Karin

2008-11-01

Literature on the anticonvulsant effects of the ketogenic diet (KD) in mouse seizure models is summarized. Recent data show that a KD balanced in vitamin, mineral, and antioxidant content is anticonvulsant in mice, confirming that the KD's effect in mice can be attributed to the composition of the diet and not other dietary factors. Given that the anticonvulsant mechanism of the KD is still unknown, the anticonvulsant profile of the diet in different seizure models may help to decipher this mechanism. The implications of the findings that the KD is anticonvulsant in electrical seizure models are indicated. Further, the potential involvement of polyunsaturated fatty acids (PUFA) in the KD's anticonvulsant mechanism is discussed.

Ketogenic diet and childhood neurological disorders other than epilepsy: an overview.

PubMed

Verrotti, Alberto; Iapadre, Giulia; Pisano, Simone; Coppola, Giangennaro

2017-05-01

In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). The aim of this review is to analyze how KD can target these different medical conditions, highlighting possible mechanisms involved. Areas covered: We have conducted an analysis on literature concerning KD use in mitochondriopathies, AHC, brain tumors, migraine, and ASD. Expert commentary: The role of KD in reducing seizure activity in some mitochondriopathies and its efficacy in pyruvate dehydrogenase deficiency is known. Recently, few cases suggest the potentiality of KD in decreasing paroxysmal activity in children affected by AHC. A few data support its potential use as co-adjuvant and alternative therapeutic option for brain cancer, while any beneficial effect of KD on migraine remains unclear. KD could improve cognitive and social skills in a subset of children with ASD.

Amyloid Precursor-like Protein 2 Increases the Endocytosis, Instability, and Turnover of the H2-Kd MHC Class I Molecule1

PubMed Central

Tuli, Amit; Sharma, Mahak; McIlhaney, Mary M.; Talmadge, James E.; Naslavsky, Naava; Caplan, Steve; Solheim, Joyce C.

2008-01-01

The defense against the invasion of viruses and tumors relies on the presentation of viral and tumor-derived peptides to cytotoxic T lymphocytes by cell surface major histocompatibility complex (MHC) class I molecules. Previously, we showed that the ubiquitously expressed protein amyloid precursor-like protein 2 (APLP2) associates with the folded form of the MHC class I molecule Kd. In the current study, APLP2 was found to associate with folded Kd molecules following their endocytosis and to increase the amount of endocytosed Kd. In addition, increased expression of APLP2 was shown to decrease Kd surface expression and thermostability. Correspondingly, Kd thermostability and surface expression were increased by down-regulation of APLP2 expression. Overall, these data suggest that APLP2 modulates the stability and endocytosis of Kd molecules. PMID:18641335

A Super mKdV Equation: Bosonization, Painlevé Property and Exact Solutions

NASA Astrophysics Data System (ADS)

Ren, Bo; Lou, Sen-Yue

2018-04-01

The symmetry of the fermionic field is obtained by means of the Lax pair of the mKdV equation. A new super mKdV equation is constructed by virtue of the symmetry of the fermionic form. The super mKdV system is changed to a system of coupled bosonic equations with the bosonization approach. The bosonized SmKdV (BSmKdV) equation admits Painlevé property by the standard singularity analysis. The traveling wave solutions of the BSmKdV system are presented by the mapping and deformation method. We also provide other ideas to construct new super integrable systems. Supported by the National Natural Science Foundation of China under Grant Nos. 11775146, 11435005, and 11472177, Shanghai Knowledge Service Platform for Trustworthy Internet of Things under Grant No. ZF1213 and K. C. Wong Magna Fund in Ningbo University

Desorption of biocides from renders modified with acrylate and silicone.

PubMed

Styszko, Katarzyna; Bollmann, Ulla E; Wangler, Timothy P; Bester, Kai

2014-01-01

Biocides are used in the building industry to prevent algal, bacterial and fungal growth on polymericrenders and thus to protect buildings. However, these biocides are leached into the environment. To better understand this leaching, the sorption/desorption of biocides in polymeric renders was assessed. In this study the desorption constants of cybutryn, carbendazim, iodocarb, isoproturon, diuron, dichloro-N-octylisothiazolinone and tebuconazole towards acrylate and silicone based renders were assessed at different pH values. At pH 9.5 (porewater) the constants for an acrylate based render varied between 8 (isoproturon) and 9634 (iodocarb) and 3750 (dichloro-N-octylisothiazolinone), respectively. The values changed drastically with pH value. The results for the silicone based renders were in a similar range and usually the compounds with high sorption constants for one polymer also had high values for the other polymer. Comparison of the octanol water partitioning constants (Kow) with the render/water partitioning constants (Kd) revealed similarities, but no strong correlation. Adding higher amounts of polymer to the render material changed the equilibria for dichloro-N-octylisothiazolinone, tebuconazole, cybutryn, carbendazim but not for isoproturon and diuron. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of soil biochar aging on sorption of the herbicides MCPA, nicosulfuron, terbuthylazine, indaziflam, and fluoroethyldiaminotriazine

USDA-ARS?s Scientific Manuscript database

Sorption of four herbicides and a metabolite of indaziflam on a fresh macadamia nut biochar and biochars aged one or two years in soil was characterized. On fresh biochar, the sorption was terbuthylazine (Kd = 595) > indaziflam (Kd = 162) > MCPA (Kd = 7.5) > fluoroethyldiaminotriazine (Kd = 0.26) a...

Direct Connection between the RII Chain and the Nonautonomous Discrete Modified KdV Lattice

NASA Astrophysics Data System (ADS)

Maeda, Kazuki; Tsujimoto, Satoshi

2013-11-01

The spectral transformation technique for symmetric RII polynomials is developed. Use of this technique reveals that the nonautonomous discrete modified KdV (nd-mKdV) lattice is directly connected with the RII chain. Hankel determinant solutions to the semi-infinite nd-mKdV lattice are also presented.

Lytic and Chemotactic Features of the Plaque-Forming Bacterium KD531 on Phaeodactylum tricornutum

PubMed Central

Chen, Zhangran; Zheng, Wei; Yang, Luxi; Boughner, Lisa A.; Tian, Yun; Zheng, Tianling; Xu, Hong

2017-01-01

Phaeodactylum tricornutum is a dominant bloom forming species and potential biofuel feedstock. To control P. tricornutum bloom or to release lipids from P. tricornutum, we previously screened and identified the lytic bacterium Labrenzia sp. KD531 toward P. tricornutum. In the present study, we evaluated the lytic activity of Labrenzia sp. KD531 on microalgae and investigated its lytic mechanism. The results indicated that the lytic activity of KD531 was temperature- and pH-dependent, but light-independent. In addition to P. tricornutum, KD531 also showed lytic activity against other algal species, especially green algae. A quantitative analysis of algal cellular protein, carbohydrate and lipid content together with measurements of dry weight after exposure to bacteria-infected algal lysate indicated that the bacterium KD531 influenced the algal biomass by disrupting the algal cells. Both chemotactic analysis and microscopic observations of subsamples from different regions of formed plaques showed that KD531 could move toward and then directly contact algal cells. Direct contact between P. tricornutum and KD531 cells was essential for the lytic process. PMID:29312256

State-of-the-art acute phase management of Kawasaki disease after 2017 scientific statement from the American Heart Association.

PubMed

Liu, Yi-Ching; Lin, Ming-Tai; Wang, Jou-Kou; Wu, Mei-Hwan

2018-03-30

Kawasaki disease (KD) has become the most common form of pediatric systemic vasculitis. Although patients with KD received intravenous immunoglobulin (IVIG) therapy, coronary arterial lesions (CALs) still occurred in 5%-10% of these patients during the acute stage. CALs may persist and even progress to stenosis or obstruction. Therefore, CALs following KD are currently the leading cause of acquired heart diseases in children. The etiology of CALs remains unknown despite more than four decades of research. Two unsolved problems are IVIG unresponsiveness and the diagnosis of incomplete KD. The two subgroups of KD patients with these problems have a high risk of CAL. In April 2017, the American Heart Association (AHA) updated the guidelines for the diagnosis, treatment, and long-term management of KD. Compared with the previous KD guidelines published in 2004, the new guidelines provide solutions to the aforementioned two problems and emphasize risk stratification by using coronary artery Z score systems, as well as coronary severity-based management and long-term follow-up. Therefore, in this study, we merged the AHA Scientific Statement in 2017 with recent findings for Taiwanese KD patients to provide potential future care directions for Taiwanese patients with KD. Copyright © 2018. Published by Elsevier B.V.

Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.

PubMed

Diep, Duy Trong Vien; Hong, Kyungki; Khun, Triyeng; Zheng, Mei; Ul-Haq, Asad; Jun, Hee-Sook; Kim, Young-Bum; Chun, Kwang-Hoon

2018-02-06

Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK's activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent.

Efficacy of a ketogenic diet in resistant myoclono-astatic epilepsy: A French multicenter retrospective study.

PubMed

Stenger, Elodie; Schaeffer, Mickael; Cances, Claude; Motte, Jacques; Auvin, Stéphane; Ville, Dorothée; Maurey, Hélène; Nabbout, Rima; de Saint-Martin, Anne

2017-03-01

Recent studies have suggested that the early introduction of a ketogenic diet (KD) could improve seizure control in myoclono-astatic epilepsy (MAE). This multicenter study sought to identify the benefits of KD use on seizure control and epilepsy and on developmental outcomes in children with resistant MAE. Fifty children who were diagnosed with severe MAE in the French network of Reference Centers for Rare Epilepsies and who were treated with KD between 2000 and 2013 were included in this study. The seizure frequency and EEG recordings were assessed two weeks before KD introduction, 2 and 6 months after, and during the last follow-up, which also included an assessment of developmental outcome. Patients had a median follow up of 52 months (range 13-136) and received 4.3 antiepileptic drugs [2-9] before KD introduction. Fifty-four percent (54%) of our patients were seizure-free after 6 months of KD or more, and 86% experienced more than a 70% seizure reduction after 2 months of KD. Forty-four percent (44%) of them had a clear benefit of early KD treatment (after four AEDs failed). Early KD treatment did not result in a greater seizure reduction (p=0.055), but significantly resulted in remission (p<0.028). Fifty percent of patients with resistant MAE had normal development outcomes. Earlier KD treatment, after three AEDs failed, was correlated with a better cognitive outcome (p<0.01). Early introduction of KD treatment in resistant MAE has a strong, persistent anticonvulsant effect with long-term remission and better cognitive outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

PubMed

Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

2017-04-01

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.

PubMed

Chang, Chia-Jung; Kuo, Ho-Chang; Chang, Jeng-Sheng; Lee, Jong-Keuk; Tsai, Fuu-Jen; Khor, Chiea Chuen; Chang, Li-Ching; Chen, Shih-Ping; Ko, Tai-Ming; Liu, Yi-Min; Chen, Ying-Ju; Hong, Young Mi; Jang, Gi Young; Hibberd, Martin L; Kuijpers, Taco; Burgner, David; Levin, Michael; Burns, Jane C; Davila, Sonia; Chen, Yuan-Tsong; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lee, Yi-Ching

2013-01-01

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

Ketogenic diet exposure during the juvenile period increases social behaviors and forebrain neural activation in adult Engrailed 2 null mice.

PubMed

Verpeut, Jessica L; DiCicco-Bloom, Emanuel; Bello, Nicholas T

2016-07-01

Prolonged consumption of ketogenic diets (KD) has reported neuroprotective benefits. Several studies suggest KD interventions could be useful in the management of neurological and developmental disorders. Alterations in the Engrailed (En) genes, specifically Engrailed 2 (En2), have neurodevelopmental consequences and produce autism-related behaviors. The following studies used En2 knockout (KO; En2(-/-)), and wild-type (WT; En2(+/+)), male mice fed either KD (80% fat, 0.1% carbohydrates) or control diet (CD; 10% fat, 70% carbohydrates). The objective was to determine whether a KD fed from weaning at postnatal day (PND) 21 to adulthood (PND 60) would alter brain monoamines concentrations, previously found dysregulated, and improve social outcomes. In WT animals, there was an increase in hypothalamic norepinephrine content in the KD-fed group. However, regional monoamines were not altered in KO mice in KD-fed compared with CD-fed group. In order to determine the effects of juvenile exposure to KD in mice with normal blood ketone levels, separate experiments were conducted in mice removed from the KD or CD and fed standard chow for 2days (PND 62). In a three-chamber social test with a novel mouse, KO mice previously exposed to the KD displayed similar social and self-grooming behaviors compared with the WT group. Groups previously exposed to a KD, regardless of genotype, had more c-Fos-positive cells in the cingulate cortex, lateral septal nuclei, and anterior bed nucleus of the stria terminalis. In the novel object condition, KO mice previously exposed to KD had similar behavioral responses and pattern of c-Fos immunoreactivity compared with the WT group. Thus, juvenile exposure to KD resulted in short-term consequences of improving social interactions and appropriate exploratory behaviors in a mouse model that displays autism-related behaviors. Such findings further our understanding of metabolic-based therapies for neurological and developmental disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Tissue-specific, tumor-selective, replication-competent adenovirus vector for cancer gene therapy.

PubMed

Doronin, K; Kuppuswamy, M; Toth, K; Tollefson, A E; Krajcsi, P; Krougliak, V; Wold, W S

2001-04-01

We have previously described two replication-competent adenovirus vectors, named KD1 and KD3, for potential use in cancer gene therapy. KD1 and KD3 have two small deletions in the E1A gene that restrict efficient replication of these vectors to human cancer cell lines. These vectors also have increased capacity to lyse cells and spread from cell to cell because they overexpress the adenovirus death protein, an adenovirus protein required for efficient cell lysis and release of adenovirus from the cell. We now describe a new vector, named KD1-SPB, which is the KD1 vector with the E4 promoter replaced by the promoter for surfactant protein B (SPB). SPB promoter activity is restricted in the adult to type II alveolar epithelial cells and bronchial epithelial cells. Because KD1-SPB has the E1A mutations, it should replicate within and destroy only alveolar and bronchial cancer cells. We show that KD1-SPB replicates, lyses cells, and spreads from cell to cell as well as does KD1 in H441 cells, a human cancer cell line where the SPB promoter is active. KD1-SPB replicates, lyses cells, and spreads only poorly in Hep3B liver cancer cells. Replication was determined by expression of the E4ORF3 protein, viral DNA accumulation, fiber synthesis, and virus yield. Cell lysis and vector spread were measured by lactate dehydrogenase release and a "vector spread" assay. In addition to Hep3B cells, KD1-SPB also did not express E4ORF3 in HT29.14S (colon), HeLa (cervix), KB (nasopharynx), or LNCaP (prostate) cancer cell lines, in which the SPB promoter is not expected to be active. Following injection into H441 or Hep3B tumors growing in nude mice, KD1-SPB caused a three- to fourfold suppression of growth of H441 tumors, similar to that seen with KD1. KD1-SPB had only a minimal effect on the growth of Hep3B tumors, whereas KD1 again caused a three- to fourfold suppression. These results establish that the adenovirus E4 promoter can be replaced by a tissue-specific promoter in a replication-competent vector. The vector has three engineered safety features: the tissue-specific promoter, the mutations in E1A that preclude efficient replication in nondividing cells, and a deletion of the E3 genes which shield the virus from attack by the immune system. KD1-SPB may have use in treating human lung cancers in which the SPB promoter is active.

The King-Devick test is a valid and reliable tool for assessing sport-related concussion in Australian football: A prospective cohort study.

PubMed

Hecimovich, Mark; King, Doug; Dempsey, Alasdair R; Murphy, Myles

2018-03-28

Sport-related concussion (SRC) research has focused on impaired oculomotor function. The King-Devick (K-D) test measures oculomotor performance and is reported to identify suboptimal brain function. The use of the K-D test in Australian football (AF), a sport involving body contact and tackling, has not been documented. Therefore, the objective of this study was to determine the test-retest reliability and diagnostic accuracy of the K-D test on a sub-elite AF team. Prospective cohort study METHODS: In total, 22 male players (19.6+2.3 years) were tested and re-tested on the K-D test. Those suspected of having a SRC secondary to a significant head impact were tested. Randomly selected additional players without SRC were assessed for comparison. There were observable learning effects between the first and second baseline testing (48 vs. 46s). The ICC for the first and second baseline tests was 0.91. Post-match test times were longer than the baseline times for players with SRC (n=7) (-1.9s; z=-5.08; p<0.0001). Players tested with no signs of SRC (n=13) had an improvement in time when compared with their baseline score (3.0s; z=-4.38; p<0.0001). The overall sensitivity was 0.98, specificity 0.96, and a kappa of κ=0.94. The positive likelihood ratio was 11.6 and the positive predictive value was 89.0%. This study supports the use of the K-D test due to its test-retest reliability, high sensitivity and specificity, and fast and simple use that is ideal for sports medicine professionals to make quick judgement on management and playability. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Optical Properties of Otago Shelf Waters: South Island New Zealand

NASA Astrophysics Data System (ADS)

Pfannkuche, J.

2002-10-01

The optical properties and concentrations of optically active water components were measured at 31 stations on the Otago coast. For the broad-band (PAR), diffuse light attenuation decreased 15-fold ( Kd=0·76 to 0·05 m -1) and reflectance 7-fold ( R=11·95 to 1·45%) from the most turbid harbour water to the clearest oceanic sites 30 km offshore. The Kd values therefore suggested, that Otago shelf waters were appreciably clearer than at first thought. The absorption and scattering coefficients ( a and b, respectively) for PAR were calculated using published nomograms. Multiple linear regression showed the dependence of a and b on changes in the concentration of gilvin, g 440, chlorophyll a, [ C], and inorganic particles, [ I]: a (PAR)=0·019+0·221 g440 +0·037[ C]+0·018[ I] b (PAR)=0·239[ C]+0·342[ I] Substituting the mean concentrations of gilvin (0·078 m -1), chlorophyll a (1·58 mg m -3) and inorganic particles (3·23 g m -3) into the above equations suggested that gilvin absorbed 11%, phytoplankton 39%, inorganic particles 38% and water itself 12% of PAR and on average. Phytoplankton cells caused 25% and inorganic sediments 75% of the scattering. Spectral irradiance measurements showed, that absorption by gilvin and suspended sediments could dominate absorption in the blue-green waveband for the most turbid harbour waters. Gilvin and phytoplankton levels were lowest in winter and inorganic sediment concentration were generally low offshore (<1 g m -3). Thus, oceanic waters were clearer and brighter in winter when compared to spring (July: Kd=0·05 m -1; R=3·1%; November: Kd=0·11 m -1; R=2·1% on average). However, spectral irradiance measurements showed anomalous features in R (λ) and Kd(λ) spectra above ˜590 nm which suggested light emission resulting from Raman scattering and chlorophyll fluorescence.

A novel noncommutative KdV-type equation, its recursion operator, and solitons

NASA Astrophysics Data System (ADS)

Carillo, Sandra; Lo Schiavo, Mauro; Porten, Egmont; Schiebold, Cornelia

2018-04-01

A noncommutative KdV-type equation is introduced extending the Bäcklund chart in Carillo et al. [Symmetry Integrability Geom.: Methods Appl. 12, 087 (2016)]. This equation, called meta-mKdV here, is linked by Cole-Hopf transformations to the two noncommutative versions of the mKdV equations listed in Olver and Sokolov [Commun. Math. Phys. 193, 245 (1998), Theorem 3.6]. For this meta-mKdV, and its mirror counterpart, recursion operators, hierarchies, and an explicit solution class are derived.

On the conservation laws and solutions of a (2+1) dimensional KdV-mKdV equation of mathematical physics

NASA Astrophysics Data System (ADS)

Motsepa, Tanki; Masood Khalique, Chaudry

2018-05-01

In this paper, we study a (2+1) dimensional KdV-mKdV equation, which models many physical phenomena of mathematical physics. This equation has two integral terms in it. By an appropriate substitution, we convert this equation into two partial differential equations, which do not have integral terms and are equivalent to the original equation. We then work with the system of two equations and obtain its exact travelling wave solutions in form of Jacobi elliptic functions. Furthermore, we employ the multiplier method to construct conservation laws for the system. Finally, we revert the results obtained into the original variables of the (2+1) dimensional KdV-mKdV equation.

Multiphase wavetrains, singular wave interactions and the emergence of the Korteweg–de Vries equation

PubMed Central

Bridges, Thomas J.

2016-01-01

Multiphase wavetrains are multiperiodic travelling waves with a set of distinct wavenumbers and distinct frequencies. In conservative systems, such families are associated with the conservation of wave action or other conservation law. At generic points (where the Jacobian of the wave action flux is non-degenerate), modulation of the wavetrain leads to the dispersionless multiphase conservation of wave action. The main result of this paper is that modulation of the multiphase wavetrain, when the Jacobian of the wave action flux vector is singular, morphs the vector-valued conservation law into the scalar Korteweg–de Vries (KdV) equation. The coefficients in the emergent KdV equation have a geometrical interpretation in terms of projection of the vector components of the conservation law. The theory herein is restricted to two phases to simplify presentation, with extensions to any finite dimension discussed in the concluding remarks. Two applications of the theory are presented: a coupled nonlinear Schrödinger equation and two-layer shallow-water hydrodynamics with a free surface. Both have two-phase solutions where criticality and the properties of the emergent KdV equation can be determined analytically. PMID:28119546

ITC-derived binding affinity may be biased due to titrant (nano)-aggregation. Binding of halogenated benzotriazoles to the catalytic domain of human protein kinase CK2

PubMed Central

Winiewska, Maria; Bugajska, Ewa

2017-01-01

The binding of four bromobenzotriazoles to the catalytic subunit of human protein kinase CK2 was assessed by two complementary methods: Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC). New algorithm proposed for the global analysis of MST pseudo-titration data enabled reliable determination of binding affinities for two distinct sites, a relatively strong one with the Kd of the order of 100 nM and a substantially weaker one (Kd > 1 μM). The affinities for the strong binding site determined for the same protein-ligand systems using ITC were in most cases approximately 10-fold underestimated. The discrepancy was assigned directly to the kinetics of ligand nano-aggregates decay occurring upon injection of the concentrated ligand solution to the protein sample. The binding affinities determined in the reverse ITC experiment, in which ligands were titrated with a concentrated protein solution, agreed with the MST-derived data. Our analysis suggests that some ITC-derived Kd values, routinely reported together with PDB structures of protein-ligand complexes, may be biased due to the uncontrolled ligand (nano)-aggregation, which may occur even substantially below the solubility limit. PMID:28273138

High-affinity 3H-substance P binding to longitudinal muscle membranes of the guinea pig small intestine.

PubMed

Buck, S H; Maurin, Y; Burks, T F; Yamamura, H I

1984-01-30

The binding of 3H-substance P (3H-SP) to longitudinal muscle membranes of the guinea pig small intestine has been characterized. The binding of 3H-SP exhibited a high affinity (Kd = 0.5nM). It was saturable (Bmax = 2 fmoles/mg tissue), reversible, and temperature-dependent. Kinetic studies and competition of 3H-SP binding by unlabeled SP yielded Kd and Ki values, respectively, which were in good agreement with the Kd calculated from saturation studies. The binding of 3H-SP appeared to be dependent on the presence of divalent cations in the incubation buffer. It was displaced by SP and various analogs and fragments in the rank order of SP greater than SP-(2-11) = SP-(3-11) greater than Nle11- SP = physalaemin greater than SP-(4-11) greater than SP-(5-11) greater than eledoisin much greater than SP-(7-11). Our results indicate that 3H-SP binds in longitudinal muscle of the guinea pig small intestine to a biologically relevant receptor which in many respects resembles the SP receptor characterized in the brain and the salivary gland of the rat.

Glacial influences on solar radiation in a subarctic sea.

PubMed

Barron, Mace G; Barron, Kyle J

2005-01-01

Understanding macroscale processes controlling solar radiation in marine systems will be important in interpreting the potential effects of global change from increasing ultraviolet radiation (UV) and glacial retreat. This study provides the first quantitative assessment of UV in the water column of Prince William Sound, a subarctic, semienclosed sea surrounded by mountains, glaciers, rivers, bays and fjords in south central Alaska. Glacial influences on diffuse attenuation coefficients (Kd) were determined along an approximate 120 km transect running NE (61 degrees 07'43''N, 146 degrees 17'1''W) to SW (60 degrees 27'25''N, 148 degrees 05'27'' W). Glacial meltwater and flour caused a 10-fold increase in Kd for visible light, UV-A and UV-B, whereas high optical clarity was present in a diversity of areas away from glacial influences. Transition areas and locations affected by calving of a tidewater glacier had intermediate Kd values. Depths at 99% attenuation ranged from less than 0.2 m near glacial streams to greater than 5 m in bays and open ocean distant from sources of glacial sediments. These results suggest that potential global change from increasing UV and glacial retreat may have heterogeneous effects on subarctic marine systems.

Detection of the human 70-kD and 60-kD heat shock proteins in the vagina: relation to microbial flora, vaginal pH, and method of contraception.

PubMed Central

Giraldo, P; Neuer, A; Ribeiro-Filho, A; Linhares, I; Witkin, S S

1999-01-01

The expression of the 60-kD and 70-kD heat shock proteins (hsp60 and hsp70) in the vaginas of 43 asymptomatic women of reproductive age with or without a history of recurrent vulvovaginitis (RVV) were compared. Vaginal wash samples were obtained and assayed by enzyme-linked immunosorbent assay (ELISA) for human hsp60 and hsp70. Heat shock protein 70 was not detected in any of the 19 women with no history of RVV, and hsp60 was present in only one woman in this group. In contrast, in the RVV group, 11 (45.8%) were hsp60-positive and eight (33.3%) were hsp70-positive. The presence of either heat shock protein in the vagina was associated with an elevated vaginal pH (>4.5). Bacterial vaginosis or Candida was identified in some of the asymptomatic subjects; their occurrence was significantly higher in women with vaginal hsp70 than in women with no heat shock proteins. Oral contraceptives were used by 35.7% of subjects who were negative for vaginal heat shock proteins, as opposed to only 12.5% of women who were positive for hsp70 and 8.3% who were positive for hsp60. Expression of heat shock proteins in the vagina may indicate an altered vaginal environment and a susceptibility to vulvovaginal symptoms. PMID:10231004

Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol.

PubMed

Zoghbi, Abdelmoumin; Geng, Tianjiao; Wang, Bo

2017-11-01

Carvedilol (CAR) is a non-selective α and β blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-β-cyclodextrin (HPβCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPβCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPβCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPβCD and PLX/PVP on water solubility and bioavailability of CAR.

Fifth-order complex Korteweg-de Vries-type equations

NASA Astrophysics Data System (ADS)

Khanal, Netra; Wu, Jiahong; Yuan, Juan-Ming

2012-05-01

This paper studies spatially periodic complex-valued solutions of the fifth-order Korteweg-de Vries (KdV)-type equations. The aim is at several fundamental issues including the existence, uniqueness and finite-time blowup problems. Special attention is paid to the Kawahara equation, a fifth-order KdV-type equation. When a Burgers dissipation is attached to the Kawahara equation, we establish the existence and uniqueness of the Fourier series solution with the Fourier modes decaying algebraically in terms of the wave numbers. We also examine a special series solution to the Kawahara equation and prove the convergence and global regularity of such solutions associated with a single mode initial data. In addition, finite-time blowup results are discussed for the special series solution of the Kawahara equation.

Hypoxic inactivation of glycogen synthase kinase-3β promotes gastric tumor growth and angiogenesis by facilitating hypoxia-inducible factor-1 signaling.

PubMed

Ko, Young San; Cho, Sung Jin; Park, Jinju; Choi, Yiseul; Lee, Jae-Seon; Youn, Hong-Duk; Kim, Woo Ho; Kim, Min A; Park, Jong-Wan; Lee, Byung Lan

2016-09-01

Since the molecular mechanism of hypoxic adaptation in cancer cells is cell-type specific, we investigated whether glycogen synthase kinase-3β (GSK-3β) activation is involved in hypoxia-induced gastric tumor promotion. Stable gastric cancer cell lines (SNU-638, SNU-484, MKN1, and MKN45) were cultured under hypoxic conditions. Cells overexpressing wild-type GSK-3β (WT-GSK-3β) or kinase-dead mutant of GSK-3β (KD-GSK-3β) were generated and used for cell culture and animal studies. In cell culture experiments, hypoxia decreased GSK-3β activation in gastric cancer cells. Cell viability and the expressions of HIF-1α protein and VEGF mRNA in gastric cancer cells were higher in KD-GSK-3β transfectants than in WT-GSK-3β transfectants under hypoxic conditions, but not under normoxic conditions. Gastric cancer xenografts showed that tumor growth, microvessel area, HIF-1α activation, and VEGF expression were higher in KD-GSK-3β tumors than in WT-GSK-3β tumors in vivo. In addition, the expression of hypoxia-induced HIF-1α protein was regulated by GSK-3β at the translational level. Our data suggest that GSK-3β is involved in hypoxic adaptation of gastric cancer cells as an inhibitory upstream regulator of the HIF-1α/VEGF signaling pathway. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Customized Peptide Biomaterial Synthesis via an Environment-Reliant Auto-Programmer Stigmergic Approach

PubMed Central

Choonara, Yahya E.; du Toit, Lisa C.; Bijukumar, Divya; Chejara, Dharmesh R.

2018-01-01

Stigmergy, a form of self-organization, was employed here to engineer a self-organizing peptide capable of forming a nano- or micro-structure and that can potentially be used in various drug delivery and biomedical applications. These self-assembling peptides exhibit several desirable qualities for drug delivery, tissue engineering, cosmetics, antibiotics, food science, and biomedical surface engineering. In this study, peptide biomaterial synthesis was carried out using an environment-reliant auto-programmer stigmergic approach. A model protein, α-gliadin (31, 36, and 38 kD), was forced to attain a primary structure with free –SH groups and broken down enzymatically into smaller fragments using chymotrypsin. This breakdown was carried out at different environment conditions (37 and 50 °C), and the fragments were allowed to self-organize at these temperatures. The new peptides so formed diverged according to the environmental conditions. Interestingly, two peptides (with molecular weights of 13.8 and 11.8 kD) were isolated when the reaction temperature was maintained at 50 °C, while four peptides with molecular weights of 54, 51, 13.8, and 12.8 kD were obtained when the reaction was conducted at 37 °C. Thus, at a higher temperature (50 °C), the peptides formed, compared to the original protein, had lower molecular weights, whereas, at a lower temperature (37 °C), two peptides had higher molecular weights and two had lower molecular weights. PMID:29659507

Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis

PubMed Central

1990-01-01

Immunization with the 69-kD outer membrane protein (OMP) of Bordetella pertussis protected neonatal mice against lethal respiratory challenge with B. pertussis 18323. Active immunization elicited a serum IgG anti- 69-kD OMP response at the time of challenge, with IgG anti-69-kD OMP antibodies detected in bronchoalveolar lavage fluid after challenge. Intravenous administration of BPE8, a monoclonal IgG1 anti-69-kD OMP, also protected young mice against B. pertussis challenge. Intravenously injected BPE8 was detected in the lungs of mice at the time of aerosol challenge, suggesting that the presence of specific antibody in the lungs may mediate protection. Thus the 69-kD OMP of B. pertussis is a protective antigen in mice that elicits specific serum antibody that can transude to the lung. The 69-kD OMP was detected in a preparation of a Takeda acellular vaccine by immunoblot analysis and a serum antibody response to the 69-kD OMP was observed in 18-mo-old children boosted with this preparation of Japanese acellular vaccine. Our results demonstrate that the B. pertussis 69-kD OMP is a protective antigen in animals, is immunogenic in humans, and is present in a preparation of acellular pertussis vaccine that is widely used in Japan. These findings indicate that the 69-kD OMP should be seriously considered as a candidate for inclusion in new formulations of antigenically defined acellular pertussis vaccines. PMID:2295882

A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease.

PubMed

Kim, Jae-Jung; Hong, Young Mi; Sohn, Saejung; Jang, Gi Young; Ha, Kee-Soo; Yun, Sin Weon; Han, Myung Ki; Lee, Kyung-Yil; Song, Min Seob; Lee, Hyoung Doo; Kim, Dong Soo; Lee, Jong-Eun; Shin, Eun-Soon; Jang, Ji-Hyun; Lee, Yeon-Su; Kim, Sook-Young; Lee, Jong-Young; Han, Bok-Ghee; Wu, Jer-Yuarn; Kim, Kwi-Joo; Park, Young-Mi; Seo, Eul-Joo; Park, In-Sook; Lee, Jong-Keuk

2011-05-01

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p < 1 × 10(-5)). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85-4.54, P (combined) = 1.46 × 10(-6)); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77-4.12, P (combined) = 2.00 × 10(-6)). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.

Residency Training: The King-Devick test and sleep deprivation

PubMed Central

Davies, Emma C.; Henderson, Sam; Galetta, Steven L.

2012-01-01

Objective: The current study investigates the effect of sleep deprivation on the speed and accuracy of eye movements as measured by the King-Devick (K-D) test, a <1-minute test that involves rapid number naming. Methods: In this cohort study, neurology residents and staff from the University of Pennsylvania Health System underwent baseline followed by postcall K-D testing (n = 25); those not taking call (n = 10) also completed baseline and follow-up K-D testing. Differences in the times and errors between baseline and follow-up K-D scores were compared between the 2 groups. Results: Residents taking call had less improvement from baseline K-D times when compared to participants not taking call (p < 0.0001, Wilcoxon rank sum test). For both groups, the change in K-D time from baseline was correlated to amount of sleep obtained (rs = −0.50, p = 0.002) and subjective evaluation of level of alertness (rs = 0.33, p = 0.05) but had no correlation to time since last caffeine consumption (rs = −0.13, p = 0.52). For those residents on their actual call night, the duration of sleep obtained did not correlate with change in K-D scores from baseline (rs = 0.13, p = 0.54). Conclusions: The K-D test is sensitive to the effects of sleep deprivation on cognitive functioning, including rapid eye movements, concentration, and language function. As with other measures of sleep deprivation, K-D performance demonstrated significant interindividual variability in vulnerability to sleep deprivation. Severe fatigue appears to reduce the degree of improvement typically observed in K-D testing. PMID:22529208

Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

PubMed Central

Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

2012-01-01

Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

Kinematic dynamo, supersymmetry breaking, and chaos

NASA Astrophysics Data System (ADS)

Ovchinnikov, Igor V.; Enßlin, Torsten A.

2016-04-01

The kinematic dynamo (KD) describes the growth of magnetic fields generated by the flow of a conducting medium in the limit of vanishing backaction of the fields onto the flow. The KD is therefore an important model system for understanding astrophysical magnetism. Here, the mathematical correspondence between the KD and a specific stochastic differential equation (SDE) viewed from the perspective of the supersymmetric theory of stochastics (STS) is discussed. The STS is a novel, approximation-free framework to investigate SDEs. The correspondence reported here permits insights from the STS to be applied to the theory of KD and vice versa. It was previously known that the fast KD in the idealistic limit of no magnetic diffusion requires chaotic flows. The KD-STS correspondence shows that this is also true for the diffusive KD. From the STS perspective, the KD possesses a topological supersymmetry, and the dynamo effect can be viewed as its spontaneous breakdown. This supersymmetry breaking can be regarded as the stochastic generalization of the concept of dynamical chaos. As this supersymmetry breaking happens in both the diffusive and the nondiffusive cases, the necessity of the underlying SDE being chaotic is given in either case. The observed exponentially growing and oscillating KD modes prove physically that dynamical spectra of the STS evolution operator that break the topological supersymmetry exist with both real and complex ground state eigenvalues. Finally, we comment on the nonexistence of dynamos for scalar quantities.

Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A2A receptors in mice.

PubMed

Dziubina, Anna; Szmyd, Karina; Zygmunt, Małgorzata; Sapa, Jacek; Dudek, Magdalena; Filipek, Barbara; Drabczyńska, Anna; Załuski, Michał; Pytka, Karolina; Kieć-Kononowicz, Katarzyna

2016-12-01

It has recently been suggested that the adenosine A 2A receptor plays a role in several animal models of depression. Additionally, A 2A antagonists have reversed behavioral deficits and exhibited a profile similar to classical antidepressants. In the present study, imidazo- and pyrimido[2,1-f]purinedione derivatives (KD 66, KD 167, KD 206) with affinity to A 2A receptors but poor A 1 affinity were evaluated for their antidepressant- and anxiolytic-like activity. The activity of these derivatives was tested using a tail suspension and forced swim test, two widely-used behavioral paradigms for the evaluation of antidepressant-like activity. In turn, the anxiolytic activity was evaluated using the four-plate test. The results showed the antidepressant-like activity of pyrimido- and imidazopurinedione derivatives (i.e. KD 66, KD 167 and KD 206) in acute and chronic behavioral tests in mice. KD 66 revealed an anxiolytic-like effect, while KD 167 increased anxiety behaviors. KD 206 had no effect on anxiety. Furthermore, none of the tested compounds increased locomotor activity. Available data support the proposition that the examined compounds with adenosine A 2A receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

PHYSICS OF GASES, PLASMAS, AND ELECTRIC DISCHARGES Dust Acoustic Solitary Waves in Saturn F-ring's Region

NASA Astrophysics Data System (ADS)

E. K., El-Shewy; M. I. Abo el, Maaty; H. G., Abdelwahed; M. A., Elmessary

2011-01-01

Effect of hot and cold dust charge on the propagation of dust-acoustic waves (DAWs) in unmagnetized plasma having electrons, singly charged ions, hot and cold dust grains has been investigated. The reductive perturbation method is employed to reduce the basic set of fluid equations to the Kortewege-de Vries (KdV) equation. At the critical hot dusty plasma density Nh0, the KdV equation is not appropriate for describing the system. Hence, a set of stretched coordinates is considered to derive the modified KdV equation. It is found that the presence of hot and cold dust charge grains not only significantly modifies the basic properties of solitary structure, but also changes the polarity of the solitary profiles. In the vicinity of the critical hot dusty plasma density Nh0, neither KdV nor mKdV equation is appropriate for describing the DAWs. Therefore, a further modified KdV (fmKdV) equation is derived, which admits both soliton and double layer solutions.

Development of a Surface Plasmon Resonance Assay for the Characterization of Small-Molecule Binding Kinetics and Mechanism of Binding to Kynurenine 3-Monooxygenase.

PubMed

Poda, Suresh B; Kobayashi, Masakazu; Nachane, Ruta; Menon, Veena; Gandhi, Adarsh S; Budac, David P; Li, Guiying; Campbell, Brian M; Tagmose, Lena

2015-10-01

Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the kynurenine pathway, was identified as a potential therapeutic target for treating neurodegenerative and psychiatric disorders. In this article, we describe a surface plasmon resonance (SPR) assay that delivers both kinetics and the mechanism of binding (MoB) data, enabling a detailed characterization of KMO inhibitors for the enzyme in real time. SPR assay development included optimization of the protein construct and the buffer conditions. The stability and inhibitor binding activity of the immobilized KMO were significantly improved when the experiments were performed at 10°C using a buffer containing 0.05% n-dodecyl-β-d-maltoside (DDM) as the detergent. The KD values of the known KMO inhibitors (UPF648 and RO61-8048) from the SPR assay were in good accordance with the biochemical LC/MS/MS assay. Also, the SPR assay was able to differentiate the binding kinetics (k(a) and k(d)) of the selected unknown KMO inhibitors. For example, the inhibitors that showed comparable IC50 values in the LC/MS/MS assay displayed differences in their residence time (τ = 1/k(d)) in the SPR assay. To better define the MoB of the inhibitors to KMO, an SPR-based competition assay was developed, which demonstrated that both UPF648 and RO61-8048 bound to the substrate-binding site. These results demonstrate the potential of the SPR assay for characterizing the affinity, the kinetics, and the MoB profiles of the KMO inhibitors.

Decreased striatal and enhanced thalamic dopaminergic responsivity in detoxified cocaine abusers

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

Volkow, N.D.; Wang, G.J.; Fowler, J.S.

It has been hypothesized that cocaine addiction could result from decreased brain dopamine (DA) function. However, little is known about changes in (DA) neurotransmission in human cocaine addiction. We used PET and [C-11]raclopride, a DA D2 receptor ligand sensitive to competition with endogenous DA, to measure relative changes in extracellular DA induced by methylphenidate (MP) in 20 cocaine abusers (3-6 weeks after cocaine discontinuation) and 23 controls. MP did not affect the transport of [C-11]raclopride from blood to brain (K1); however it induced a significant reduction in DA D2 receptor availability (Bmax/Kd) in striatum. The magnitude of ND-induced changes inmore » striatal [C-11]raclopride binding were significantly larger in controls (21 + 13% change from baseline) than in cocaine abusers (9 {+-} 13 %) (ANOVA p < 0.005). In cocaine abusers, but not in controls, MP also decreased Bmax/Kd values in thalamus (29 {+-} 35 %) (ANOVA p < 0.005). There were no differences in plasma MP concentration between the groups. In striatum MP-induced changes in Bmax/Kd were significantly correlated with MP-induced changes in self reports of restlessness (r = 0.49, df 42, p < 0.002). In thalamus MP-induced changes in Bmax/Kd were significantly correlated with ND-induced changes in self reports of cocaine craving (r = 0.57, df 42, p < 0.0001). These results are compatible with a decrease in striatal DA brain function in cocaine abusers. They also suggest a participation of thalamic DA pathways in cocaine addiction.« less

Parameter sensitivity analysis of a 1-D cold region lake model for land-surface schemes

NASA Astrophysics Data System (ADS)

Guerrero, José-Luis; Pernica, Patricia; Wheater, Howard; Mackay, Murray; Spence, Chris

2017-12-01

Lakes might be sentinels of climate change, but the uncertainty in their main feedback to the atmosphere - heat-exchange fluxes - is often not considered within climate models. Additionally, these fluxes are seldom measured, hindering critical evaluation of model output. Analysis of the Canadian Small Lake Model (CSLM), a one-dimensional integral lake model, was performed to assess its ability to reproduce diurnal and seasonal variations in heat fluxes and the sensitivity of simulated fluxes to changes in model parameters, i.e., turbulent transport parameters and the light extinction coefficient (Kd). A C++ open-source software package, Problem Solving environment for Uncertainty Analysis and Design Exploration (PSUADE), was used to perform sensitivity analysis (SA) and identify the parameters that dominate model behavior. The generalized likelihood uncertainty estimation (GLUE) was applied to quantify the fluxes' uncertainty, comparing daily-averaged eddy-covariance observations to the output of CSLM. Seven qualitative and two quantitative SA methods were tested, and the posterior likelihoods of the modeled parameters, obtained from the GLUE analysis, were used to determine the dominant parameters and the uncertainty in the modeled fluxes. Despite the ubiquity of the equifinality issue - different parameter-value combinations yielding equivalent results - the answer to the question was unequivocal: Kd, a measure of how much light penetrates the lake, dominates sensible and latent heat fluxes, and the uncertainty in their estimates is strongly related to the accuracy with which Kd is determined. This is important since accurate and continuous measurements of Kd could reduce modeling uncertainty.

Dressed soliton in quantum dusty pair-ion plasma

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

Chatterjee, Prasanta; Muniandy, S. V.; Wong, C. S.

Nonlinear propagation of a quantum ion-acoustic dressed soliton is studied in a dusty pair-ion plasma. The Korteweg-de Vries (KdV) equation is derived using reductive perturbation technique. A higher order inhomogeneous differential equation is obtained for the higher order correction. The expression for a dressed soliton is calculated using a renormalization method. The expressions for higher order correction are determined using a series solution technique developed by Chatterjee et al. [Phys. Plasmas 16, 072102 (2009)].

Lie Symmetry Analysis and Explicit Solutions of the Time Fractional Fifth-Order KdV Equation

PubMed Central

Wang, Gang wei; Xu, Tian zhou; Feng, Tao

2014-01-01

In this paper, using the Lie group analysis method, we study the invariance properties of the time fractional fifth-order KdV equation. A systematic research to derive Lie point symmetries to time fractional fifth-order KdV equation is performed. In the sense of point symmetry, all of the vector fields and the symmetry reductions of the fractional fifth-order KdV equation are obtained. At last, by virtue of the sub-equation method, some exact solutions to the fractional fifth-order KdV equation are provided. PMID:24523885

Bilinear approach to Kuperschmidt super-KdV type equations

NASA Astrophysics Data System (ADS)

Babalic, Corina N.; Carstea, A. S.

2018-06-01

Hirota bilinear form and soliton solutions for the super-KdV (Korteweg–de Vries) equation of Kuperschmidt (Kuper–KdV) are given. It is shown that even though the collision of supersolitons is more complicated than in the case of the supersymmetric KdV equation of Manin–Radul, the asymptotic effect of the interaction is simpler. As a physical application it is shown that the well-known FPU problem, having a phonon-mediated interaction of some internal degrees of freedom expressed through Grassmann fields, transforms to the Kuper–KdV equation in a multiple-scale approach.

Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats.

PubMed

de Almeida Rabello Oliveira, Marcela; da Rocha Ataíde, Terezinha; de Oliveira, Suzana Lima; de Melo Lucena, Ana Luíza; de Lira, Carla Emmanuela Pereira Rodrigues; Soares, Anderson Acioli; de Almeida, Clarissa Beatriz Santos; Ximenes-da-Silva, Adriana

2008-03-21

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.

[Complete nucleotide sequences and genome structure of two Chinese tobacco mosaic virus isolates deduced from full-length infectious cDNA clones].

PubMed

Yang, G; Liu, X G; Qiu, B S

2000-07-01

The complete nucleotides of two Chinese tobacco mosaic virus (TMV) isolates, TMV-Cv (vulgare strain) and TMV-N14 (an attenuated virus originated from a tomato strain), were determined from their respective full-length infectious cDNA clones and compared with published TMV sequences. The genome structure of TMV-Cv contained 6395 nucleotides, in which four functional open reading frames (ORF), coding for replicase (126 kD/183 kD), movement protein (MP, 30 kD) and coat protein (CP, 17.6 kD) respectively, could be recognized. TMV-N14 contained 6384 nucleotides in its genome. In contrast to TMV-Cv, five functional ORFs encoding the replicase 98.5 kD/126 kD/183 kD, MP(27 kD) and CP(17.6 kD), respectively, were detected in the TMV-N14 genome. TMV-Cv is 99% homologous to a Korean TMV isolate belonging to the vulgare strain at the nucleotide level. TMV-N14 is 99% homologous to a highly virulent Japanese isolate TMV-L (tomato strain) at the nucleotide level. In TMV-N14, one opal nulation (UGA) occurred in the replicase gene and one ochre nutation (UAA) in the MP gene. The former mutation created a potential, additional ORF within the replicase gene, the latter reduced the size of the MP to 27 kD. In addition, there were also 13 amino acid substitutions in the replicase gene of TMV-N14 when compared to that of TMV-L. Collectively, these changes may have significant implications in the attenuation of the virulence of TMV-N14.

CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.

PubMed

Noval Rivas, Magali; Lee, Youngho; Wakita, Daiko; Chiba, Norika; Dagvadorj, Jargalsaikhan; Shimada, Kenichi; Chen, Shuang; Fishbein, Michael C; Lehman, Thomas J A; Crother, Timothy R; Arditi, Moshe

2017-02-01

Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD. We addressed the function of T cell subsets in KD development by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies. LCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis. The LCWE-induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans. © 2016, American College of Rheumatology.

Pathophysiologic insights into motor axonal function in Kennedy disease.

PubMed

Vucic, Steve; Kiernan, Matthew C

2007-11-06

Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p < 0.01) and the hyperpolarizing current/threshold gradient (KD 0.42 +/- 0.01; controls, 0.37 +/- 0.01, p < 0.05) were significantly increased in KD. Strength-duration time constant correlated with the CMAP amplitude (R = 0.68) and the fasciculation frequency (R = 0.62). Threshold electrotonus revealed greater changes in response to subthreshold depolarizing (KD TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

Residency training: the King-Devick test and sleep deprivation: study in pre- and post-call neurology residents.

PubMed

Davies, Emma C; Henderson, Sam; Balcer, Laura J; Galetta, Steven L

2012-04-24

The current study investigates the effect of sleep deprivation on the speed and accuracy of eye movements as measured by the King-Devick (K-D) test, a <1-minute test that involves rapid number naming. In this cohort study, neurology residents and staff from the University of Pennsylvania Health System underwent baseline followed by postcall K-D testing (n = 25); those not taking call (n = 10) also completed baseline and follow-up K-D testing. Differences in the times and errors between baseline and follow-up K-D scores were compared between the 2 groups. Residents taking call had less improvement from baseline K-D times when compared to participants not taking call (p < 0.0001, Wilcoxon rank sum test). For both groups, the change in K-D time from baseline was correlated to amount of sleep obtained (r(s) = -0.50, p = 0.002) and subjective evaluation of level of alertness (r(s) = 0.33, p = 0.05) but had no correlation to time since last caffeine consumption (r(s) = -0.13, p = 0.52). For those residents on their actual call night, the duration of sleep obtained did not correlate with change in K-D scores from baseline (r(s) = 0.13, p = 0.54). The K-D test is sensitive to the effects of sleep deprivation on cognitive functioning, including rapid eye movements, concentration, and language function. As with other measures of sleep deprivation, K-D performance demonstrated significant interindividual variability in vulnerability to sleep deprivation. Severe fatigue appears to reduce the degree of improvement typically observed in K-D testing.

Susceptibility of Adult Mosquitoes to Insecticides in Aqueous Sucrose Baits

DTIC Science & Technology

2010-01-01

imidacloprid, followed by spinosad, thiamethoxam , bifenthrin, permethrin, and cyfluthrin. The least effective ingredients were chlorfenapyr and ivermectin...effective active ingredients were fipronil, deltamethrin and imidacloprid, followed by spinosad, thiamethoxam , bifenthrin, permethrin, and cyfluthrin. The...presented. Based on KD50 values, Cx. quinquefasciatus were most suscepti- ble to fipronil > imidacloprid > deltamethrin, spinosad, thiamethoxam , and

Design and synthesis of biotin analogues reversibly binding with streptavidin.

PubMed

Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

2015-04-01

Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measuring the steady-state properties of Ca²⁺ indicators with a set of calibrated [Ca²⁺] solutions.

PubMed

Faas, Guido C; Mody, Istvan

2014-07-01

Fluorescent Ca(2+) indicators are widely used to measure the concentration of free Ca(2+) ([Ca(2+)]free) in biological processes. By calibrating the dye under the same experimental conditions as employed during its planned use, the actual [Ca(2+)] can be calculated from the measured fluorescence. When using non ratiometric dyes, such as the Oregon Green BAPTA (OGB) family of dyes or the Fluo dyes, the steady-state affinity (K(d)) and the ratio between the maximal and minimal fluorescence (F(ratio) = F(max)/F(min)) of the particular dye are needed for this conversion. Although these values are usually given by the manufacturer, we consistently find that the actual values can differ between various batches delivered by the companies that make the dyes. In this protocol, we provide the recipe for a series of solutions with a known and tightly buffered [Ca(2+)](free) and describe how to use these mixtures to determine the exact K(d) and F(ratio) of a fluorescent Ca(2+) dye. © 2014 Cold Spring Harbor Laboratory Press.

Kinetic study of the effects of calcium ions on cationic artichoke (Cynara scolymus L.) peroxidase: calcium binding, steady-state kinetics and reactions with hydrogen peroxide.

PubMed

Hiner, Alexander N P; Sidrach, Lara; Chazarra, Soledad; Varón, Ramón; Tudela, José; García-Cánovas, Francisco; Rodríguez-López, José Neptuno

2004-01-01

The apparent catalytic constant (k(cat)) of artichoke (Cynara scolymus L.) peroxidase (AKPC) with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) increased 130-fold in the presence of calcium ions (Ca2+) but the affinity (K(m)) of the enzyme for ABTS was 500 times lower than for Ca2+-free AKPC. AKPC is known to exhibit an equilibrium between 6-aquo hexa-coordinate and penta-coordinate forms of the haem iron that is modulated by Ca2+ and affects compound I formation. Measurements of the Ca2+ dissociation constant (K(D)) were complicated by the water-association/dissociation equilibrium yielding a global value more than 1000 times too high. The value for the Ca2+ binding step alone has now been determined to be K(D) approximately 10 nM. AKPC-Ca2+ was more resistant to inactivation by hydrogen peroxide (H(2)O(2)) and exhibited increased catalase activity. An analysis of the complex H(2)O(2) concentration dependent kinetics of Ca2+-free AKPC is presented.

Pregnancy in women with a history of Kawasaki disease: management and outcomes.

PubMed

Gordon, C T; Jimenez-Fernandez, S; Daniels, L B; Kahn, A M; Tarsa, M; Matsubara, T; Shimizu, C; Burns, J C; Gordon, J B

2014-10-01

To characterise the obstetrical management and outcomes in a series of women with a history of Kawasaki disease (KD) in childhood. Retrospective case series. Tertiary healthcare setting in the USA. Women with a history of KD in childhood. Women completed a detailed health questionnaire and participated in research imaging studies as part of the San Diego Adult KD Collaborative Study. Obstetrical management, complications during pregnancy and delivery, and infant outcomes. Ten women with a history of KD in childhood carried a total of 21 pregnancies to term. There were no cardiovascular complications during labour and delivery despite important cardiovascular abnormalities in four of the ten subjects. Pregnancy was complicated by pre-eclampsia and the post-partum course was complicated by haemorrhage in one subject each. Two of the 21 progeny subsequently developed KD. Women with important cardiovascular sequelae from KD in childhood should be managed by a team that includes both a maternal-fetal medicine specialist and a cardiologist. Pre-pregnancy counselling should include delineation of the woman's current functional and structural cardiovascular status and appropriate adjustment of medications, but excellent outcomes are possible with appropriate care. Review of the English and Japanese literature on KD and pregnancy revealed the occurrence of myocardial infarction during pregnancy in women with missed KD and aneurysms that were not diagnosed until their acute event. Our study highlights the need for counselling with regard to the increased genetic risk of KD in offspring born to these mothers. © 2014 Royal College of Obstetricians and Gynaecologists.

The ketogenic diet as a treatment for traumatic brain injury: a scoping review.

PubMed

McDougall, Alexandre; Bayley, Mark; Munce, Sarah Ep

2018-01-01

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. The ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after TBI. The purpose of this study is to complete a scoping review and synthesize the evidence regarding the KD and its therapeutic effects in TBI. The methodological framework of Arksey and O'Malley was employed. Databases searched include Medline, EMBASE, CCRCT, CINAHL and WebOfScience. Two reviewers independently screened titles, abstracts and full texts in a two-step screening protocol to determine inclusion. Abstracted data included study setting and therapeutic mechanism. The KD was demonstrated to reduce cerebral oedema, apoptosis, improve cerebral metabolism and behavioural outcomes in rodent TBIs. Additionally, the KD affected rodent TBIs in an age-dependent manner. Due to a lack of relevant outcome measures, the human trials did not establish much evidence with respect to the KD as a treatment for TBI; only its safety was established. The KD is an effective treatment for TBI recovery in rats and shows potential in humans. Future research should aim to better elucidate the KD's mechanisms of action in human TBIs and determine if the KD's effectiveness on clinical outcomes can be reproduced in humans.

Light and electron microscopic immunocytochemical localization of two major proteins in garlic bulb.

PubMed

Wen, G Y; Mato, A; Wisniewski, H M; Malik, M N; Jenkins, E C; Sheikh, A M; Kim, K S

1995-08-01

Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, antidiabetic, and anticoagulant. Two major proteins of 40 KD and 14 KD constituting approximately 96% of total garlic proteins have been recently purified at our Institute. This immunocytochemical and ultrastructural study revealed that the 40 KD protein was localized in the parenchyma sheath cells (PSC) of garlic bulbs, whereas the 14 KD protein was present in the cortical cells (CC). Immunogold electron microscopy study indicated that the 40 KD protein was specifically localized in the globular granules of the cytoplasmic area of PSC. Each globular granule was amorphous and homogenous with membrane limiting its outermost layer. The yellowish color of PSC in freshly cut slices of garlic bulb suggested that PSC may have sulfur-containing compounds such as allicin, the primary contributor of the pungency and medicinal properties of garlic. Ellman's reagent test quantitatively revealed that there were 17.8 n moles sulfhydryl (SH)/ml of 40 KD garlic protein. Microtubule tubulin in mitotic figures from PHA-stimulated human short-term whole blood cultures reacted strongly with antitubulin antibody but reacted negatively with anti-40 KD garlic protein antibodies and therefore was not related to the 40 KD garlic protein immunocytochemically.

Ketogenic diet in migraine: rationale, findings and perspectives.

PubMed

Barbanti, Piero; Fofi, Luisa; Aurilia, Cinzia; Egeo, Gabriella; Caprio, Massimiliano

2017-05-01

Ketogenic diet (KD) is an established treatment for refractory pediatric epilepsy and a promising therapy for diverse neurological diseases. Clinical data on KD in migraine-obtained from 150 patients investigated in case reports and prospective studies-suggest that KD may be a rapid onset effective prophylaxis for episodic and chronic migraine. KD would contribute to restore brain excitability and metabolism and to counteract neuroinflammation in migraine, although its precise mechanism is still unclear. Randomized controlled studies are needed to confirm the usefulness of KD in migraine and to investigate its optimal duration, repeatability, feasibility in normal weight subjects, efficacy in pediatric population and association to conventional migraine prophylaxis.

Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine

PubMed Central

Ross, Ruth A; Brockie, Heather C; Fernando, Susanthi R; Saha, Bijali; Razdan, Raj K; Pertwee, Roger G

1998-01-01

We have investigated the nature of cannabinoid receptors in guinea-pig small intestine by establishing whether this tissue contains cannabinoid receptors with similar binding properties to those of brain CB1 receptors. The cannabinoids used were the CB1-selective antagonist SR141716A, the CB2-selective antagonist SR144528, the novel cannabinoid receptor ligand, 6′-azidohex-2′-yne-Δ8-tetrahydrocannabinol (O-1184), and the agonists CP55940, which binds equally well to CB1 and CB2 receptors, and WIN55212-2, which shows marginal CB2 selectivity.[3H]-CP55940 (1 nM) underwent extensive specific binding both to forebrain membranes (76.3%) and to membranes obtained by sucrose density gradient fractionation of homogenates of myenteric plexus-longitudinal muscle of guinea-pig small intestine (65.2%).Its binding capacity (Bmax) was higher in forebrain (4281 fmol mg−1) than in intestinal membranes (2092 fmol mg−1). However, the corresponding KD values were not significantly different from each other (2.29 and 1.75 nM respectively). Nor did the Ki values for its displacement by CP55940, WIN55212-2, O-1184, SR141716A and SR144528 from forebrain membranes (0.87, 4.15, 2.85, 5.32 and 371.9 respectively) differ significantly from the corresponding Ki values determined in experiments with intestinal membranes (0.99, 5.03, 3.16, 4.95 and 361.5 nM respectively).The Bmax values of [3H]-CP55940 and [3H]-SR141716A in forebrain membranes did not differ significantly from each other (4281 and 5658 fmol mg−1) but were both greater than the Bmax of [3H]-WIN55212-2 (2032 fmol mg−1).O-1184 (10 or 100 nM) produced parallel dextral shifts in the log concentration-response curves of WIN55212-2 and CP55940 for inhibition of electrically-evoked contractions of the myenteric plexus-longitudinal muscle preparation, its KD values being 0.20 nM (against WIN55212-2) and 0.89 nM (against CP55940).We conclude that cannabinoid binding sites in guinea-pig small intestine closely resemble CB1 binding sites of guinea-pig brain and that O-1184 behaves as a cannabinoid receptor antagonist in the guinea-pig myenteric plexus-longitudinal muscle preparation. PMID:9863666

Localization of the human 64kD autoantigen D1 to myofibrils in a subset of extraocular muscle fibers

NASA Technical Reports Server (NTRS)

Conley, C. A.; Fowler, V. M.

1999-01-01

PURPOSE. To evaluate the tissue-specific expression pattern of the 64kD human autoantigen D1, a tropomodulin-related protein that may be involved in thyroid-associated ophthalmopathy. METHODS. Recombinant 64kD human autoantigen D1 was generated in a bacterial expression system and used to immunize rabbits. Specific antibodies were affinity-purified and used for Western blots on normal and hyperthyroid rat and rabbit tissue, and immunofluorescence localization on cryosections of rat tissue. RESULTS. Anti-64kD human autoantigen D1 antibodies recognize specifically a approximately 70kD polypeptide in western blots of extraocular muscle, sternothyroid muscle, and smooth muscle. Immunofluorescence staining demonstrates that the 64kD human autoantigen D1 localizes to myofibrils in slow fibers from rat extraocular and sternothyroid muscle. The level of this protein is not altered in extraocular muscles from hyperthyroid rabbits. CONCLUSIONS. The 64kD human autoantigen D1 is expressed in slow fibers of extraocular and sternothyroid muscles as a component of myofibrils, and is not upregulated in conditions of hyperthyroidism.

The alpha3(betaMet222Ser/Tyr345Trp)3gamma subcomplex of the TF1-ATPase does not hydolyze ATP at a significant rate until the substrate binds to the catalytic site of the lowest affinity.

PubMed

Ren, Huimiao; Bandyopadhyay, Sanjay; Allison, William S

2006-05-16

The alpha(3)(betaM(222)S/Y(345)W)(3)gamma double-mutant subcomplex of the F(1)-ATPase from the thermophilic Bacillus PS3 (TF(1)), free of endogenous nucleotides, does not entrap inhibitory MgADP in a catalytic site during turnover. It hydrolyzes 100 nM-2 mM ATP with a K(m) of 31 microM and a k(cat) of 220 s(-)(1). Fluorescence titrations of the introduced tryptophans with MgADP or MgATP revealed that both Mg-nucleotide complexes bind to the catalytic site of the highest affinity with K(d)()1 values of less than 1 nM and bind to the site of intermediate affinity with a common K(d)2 value of about 12 nM. The K(d)3 values obtained for the catalytic site of the lowest affinity from titrations with MgADP and MgATP are 25 and 37 microM, respectively. The double mutant hydrolyzes 200 nM ATP with a first-order rate of 1.5 s(-)(1), which is 0.7% of k(cat). Hence, it does not hydrolyze ATP at a significant rate when the catalytic site of intermediate affinity is saturated and the catalytic site of the lowest affinity is minimally occupied. After the addition of stoichiometric MgATP to the alpha(3)(betaM(222)S/Y(345)W)(3)gamma subcomplex, one-third of the tryptophan fluorescence remains quenched after 10 min. The product [(3)H]ADP remains bound when the wild-type and double-mutant subcomplexes hydrolyze substoichiometric [(3)H]ATP. In contrast, (32)P(i) is not retained when the wild-type subcomplex hydrolyzes substoichiometric [gamma-(32)P]ATP. This precludes assessment of the equilibrium at the high-affinity catalytic site when the wild-type TF(1) subcomplex hydrolyzes substoichiometric ATP.

Methanogenic degradation kinetics of phenolic compounds in aquifer-derived microcosms

USGS Publications Warehouse

Godsy, E.M.; Goerlitz, D.F.; Grbic-Galic, D.

1992-01-01

In this segment of a larger multidisciplinary study of the movement and fate of creosote derived compounds in a sand-and-gravel aquifer, we present evidence that the methanogenic degradation of the major biodegradable phenolic compounds and concomitant microbial growth in batch microcosms derived from contaminated aquifer material can be described using Monod kinetics. Substrate depletion and bacterial growth curves were fitted to the Monod equations using nonlinear regression analysis. The method of Marquardt was used for the determination of parameter values that best fit the experimental data by minimizing the residual sum of squares. The Monod kinetic constants (??max, Ks, Y, and kd) that describe phenol, 2-, 3-, and 4-methylphenol degradation and concomitant microbial growth were determined under conditions that were substantially different from those previously reported for microcosms cultured from sewage sludge. The Ks values obtained in this study are approximately two orders of magnitude lower than values obtained for the anaerobic degradation of phenol in digesting sewage sludge, indicating that the aquifer microorganisms have developed enzyme systems that are adapted to low nutrient conditions. The values for kd are much less than ??max, and can be neglected in the microcosms. The extremely low Y values, approximately 3 orders of magnitude lower than for the sewage sludge derived cultures, and the very low numbers of microorganisms in the aquifer derived microcosms suggest that these organisms use some unique strategies to survive in the subsurface environment. ?? 1992 Kluwer Academic Publishers.

Activity and Differential Induction of Chitinase Isozymes in Soybean Cultivars Resistant or Susceptible to Root-knot Nematodes.

PubMed

Qtu, J; Hallmann, J; Kokalis-Burelle, N; Weaver, D B; Rodríguez-Kábana, R; Tuzun, S

1997-12-01

Host physiological events in relation to infestation by parasitic nematodes are not well documented. Soybean plant responses to Meloidogyne incognita infestation were compared to resistant (Bryan) and susceptible (Brim) cultivars at 0, 1, 3, 10, 20, and 34 days after infestation (DAI). The resistant cultivar had higher chitinase activity than the susceptible cultivar at every sample time beginning at 3 DAI. Results from isoelectric focusing gel electrophoresis analyses indicated that three acidic chitinase isozymes with isoelectric points (pIs) of 4.8, 4.4, and 4.2 accumulated to a greater extent in the resistant compared to the susceptible cultivar following challenge. SDS-PAGE analysis of root proteins revealed that two proteins with molecular weights of approximately 31 and 46 kD accumulated more rapidly and to a higher level in the resistant than in the susceptible cultivar. Additionally, three major protein bands (33, 22, and 20 kD) with chitinase activity were detected with a modified SDS-PAGE analysis in which glycolchitin was added into the gel matrix. These results indicate that higher chitinase activity and early induction of specific chitinase isozymes may be associated with resistance to root-knot nematode in soybean.

The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions

PubMed Central

Hallman, Troy M.; Peng, Min; Meade, Ray; Hancock, Wayne W.; Madaio, Michael P.; Gasser, David L.

2008-01-01

Interstitial nephritis occurs spontaneously in kd/kd mice, but the mechanisms leading to this disease have not been fully elucidated. The earliest manifestation of a phenotype is the appearance of ultrastructural defects in the mitochondria of mice as young as 42 days of age. To examine the influence of the environment on the phenotype, homozygous B6.kd/kd mice were transferred from specific pathogen-free (SPF) conditions to a germfree (GF) environment, and the development of the disease was observed. The GF state resulted in a highly significant reduction in the frequency of tubulointerstitial nephritis. In addition, GF conditions markedly reduced the appearance of the mitochondrial phenotype, with no sign of mitochondrial abnormalities in GF mice of up to 155 days of age. These results suggest that environmental factors are involved in the progression of all known manifestations of this disease phenotype. PMID:16337774

Vaccines and Kawasaki disease.

PubMed

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

Dust acoustic cnoidal waves in a polytropic complex plasma

NASA Astrophysics Data System (ADS)

El-Labany, S. K.; El-Taibany, W. F.; Abdelghany, A. M.

2018-01-01

The nonlinear characteristics of dust acoustic (DA) waves in an unmagnetized collisionless complex plasma containing adiabatic electrons and ions and negatively charged dust grains (including the effects of modified polarization force) are investigated. Employing the reductive perturbation technique, a Korteweg-de Vries-Burgers (KdVB) equation is derived. The analytical solution for the KdVB equation is discussed. Also, the bifurcation and phase portrait analyses are presented to recognize different types of possible solutions. The dependence of the properties of nonlinear DA waves on the system parameters is investigated. It has been shown that an increase in the value of the modified polarization parameter leads to a fast decay and diminishes the oscillation amplitude of the DA damped cnoidal wave. The relevance of our findings and their possible applications to laboratory and space plasma situations is discussed.

Electrostatic Rate Enhancement and Transient Complex of Protein-Protein Association

PubMed Central

Alsallaq, Ramzi; Zhou, Huan-Xiang

2012-01-01

The association of two proteins is bounded by the rate at which they, via diffusion, find each other while in appropriate relative orientations. Orientational constraints restrict this rate to ~105 – 106 M−1s−1. Proteins with higher association rates generally have complementary electrostatic surfaces; proteins with lower association rates generally are slowed down by conformational changes upon complex formation. Previous studies (Zhou, Biophys. J. 1997;73:2441–2445) have shown that electrostatic enhancement of the diffusion-limited association rate can be accurately modeled by kD = kD0 exp(−*/ kBT), where kD and kD0 are the rates in the presence and absence of electrostatic interactions, respectively, * is the average electrostatic interaction energy in a “transient-complex” ensemble, and kBT is thermal energy. The transient-complex ensemble separates the bound state from the unbound state. Predictions of the transient-complex theory on four protein complexes were found to agree well with experiment when the electrostatic interaction energy was calculated with the linearized Poisson-Boltzmann (PB) equation (Alsallaq and Zhou, Structure 2007, 15:215–224). Here we show that the agreement is further improved when the nonlinear PB equation is used. These predictions are obtained with the dielectric boundary defined as the protein van der Waals surface. When the dielectric boundary is instead specified as the molecular surface, electrostatic interactions in the transient complex become repulsive and are thus predicted to retard association. Together these results demonstrate that the transient-complex theory is predictive of electrostatic rate enhancement and can help parameterize PB calculations. PMID:17932929

Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding.

PubMed

More, Vijay R; Xu, Jialin; Shimpi, Prajakta C; Belgrave, Clyde; Luyendyk, James P; Yamamoto, Masayuki; Slitt, Angela L

2013-08-01

The nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis and Properties of Asante Calcium Red –a Novel Family of Long Excitation Wavelength Calcium Indicators

PubMed Central

Hyrc, Krzysztof L.; Minta, Akwasi; Escamilla, P. Rogelio; Chan, Patrick P.L.; Meshik, Xenia A.; Goldberg, Mark P.

2013-01-01

Although many synthetic calcium indicators are available, a search for compounds with improved characteristics continues. Here, we describe the synthesis and properties of Asante Calcium Red-1 (ACR-1) and its low affinity derivative (ACR-1-LA) created by linking BAPTA to seminaphthofluorescein. The indicators combine a visible light (450–540 nm) excitation with deep-red fluorescence (640 nm). Upon Ca2+ binding, the indicators raise their fluorescence with longer excitation wavelengths producing higher responses. Although the changes occur without any spectral shifts, it is possible to ratio Ca2+-dependent (640 nm) and quasi-independent (530 nm) emission when using visible (<490 nm) or multiphoton (~780 nm) excitation. Therefore, both probes can be used as single wavelength or, less dynamic, ratiometric indicators. Long indicator emission might allow easy [Ca2+]i measurement in GFP expressing cells. The indicators bind Ca2+ with either high (Kd=0.49±0.07 μM; ACR-1) or low affinity (Kd=6.65±0.13 μM; ACR-1-LA). Chelating Zn2+ (Kd =0.38±0.02 nM) or Mg2+ (Kd ~5 mM) slightly raises and binding Co2+ quenches dye fluorescence. New indicators are somewhat pH-sensitive (pKa=6.31±0.07), but fairly resistant to bleaching. The probes are rather dim, which combined with low AM ester loading efficiency, might complicate in situ imaging. Despite potential drawbacks, ACR-1 and ACR-1-LA are promising new calcium indicators. PMID:24017967

Numerical solution of the generalized, dissipative KdV-RLW-Rosenau equation with a compact method

NASA Astrophysics Data System (ADS)

Apolinar-Fernández, Alejandro; Ramos, J. I.

2018-07-01

The nonlinear dynamics of the one-dimensional, generalized Korteweg-de Vries-regularized-long wave-Rosenau (KdV-RLW-Rosenau) equation with second- and fourth-order dissipative terms subject to initial Gaussian conditions is analyzed numerically by means of three-point, fourth-order accurate, compact finite differences for the discretization of the spatial derivatives and a trapezoidal method for time integration. By means of a Fourier analysis and global integration techniques, it is shown that the signs of both the fourth-order dissipative and the mixed fifth-order derivative terms must be negative. It is also shown that an increase of either the linear drift or the nonlinear convection coefficients results in an increase of the steepness, amplitude and speed of the right-propagating wave, whereas the speed and amplitude of the wave decrease as the power of the nonlinearity is increased, if the amplitude of the initial Gaussian condition is equal to or less than one. It is also shown that the wave amplitude and speed decrease and the curvature of the wave's trajectory increases as the coefficients of the second- and fourth-order dissipative terms are increased, while an increase of the RLW coefficient was found to decrease both the damping and the phase velocity, and generate oscillations behind the wave. For some values of the coefficients of both the fourth-order dissipative and the Rosenau terms, it has been found that localized dispersion shock waves may form in the leading part of the right-propagating wave, and that the formation of a train of solitary waves that result from the breakup of the initial Gaussian conditions only occurs in the absence of both Rosenau's, Kortweg-de Vries's and second- and fourth-order dissipative terms, and for some values of the amplitude and width of the initial condition and the RLW coefficient. It is also shown that negative values of the KdV term result in steeper, larger amplitude and faster waves and a train of oscillations behind the wave, whereas positive values of that coefficient may result in negative phase and group velocities, no wave breakup and oscillations ahead of the right-propagating wave.

How Can a Ketogenic Diet Improve Motor Function?

PubMed Central

Veyrat-Durebex, Charlotte; Reynier, Pascal; Procaccio, Vincent; Hergesheimer, Rudolf; Corcia, Philippe; Andres, Christian R.; Blasco, Hélène

2018-01-01

A ketogenic diet (KD) is a normocaloric diet composed by high fat (80–90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction. PMID:29434537

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan.

PubMed

Rodó, Xavier; Curcoll, Roger; Robinson, Marguerite; Ballester, Joan; Burns, Jane C; Cayan, Daniel R; Lipkin, W Ian; Williams, Brent L; Couto-Rodriguez, Mara; Nakamura, Yosikazu; Uehara, Ritei; Tanimoto, Hiroshi; Morguí, Josep-Anton

2014-06-03

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987-2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD.

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

PubMed Central

Rodó, Xavier; Curcoll, Roger; Robinson, Marguerite; Ballester, Joan; Burns, Jane C.; Cayan, Daniel R.; Lipkin, W. Ian; Williams, Brent L.; Couto-Rodriguez, Mara; Nakamura, Yosikazu; Uehara, Ritei; Tanimoto, Hiroshi; Morguí, Josep-Anton

2014-01-01

Evidence indicates that the densely cultivated region of northeastern China acts as a source for the wind-borne agent of Kawasaki disease (KD). KD is an acute, coronary artery vasculitis of young children, and still a medical mystery after more than 40 y. We used residence times from simulations with the flexible particle dispersion model to pinpoint the source region for KD. Simulations were generated from locations spanning Japan from days with either high or low KD incidence. The postepidemic interval (1987–2010) and the extreme epidemics (1979, 1982, and 1986) pointed to the same source region. Results suggest a very short incubation period (<24 h) from exposure, thus making an infectious agent unlikely. Sampling campaigns over Japan during the KD season detected major differences in the microbiota of the tropospheric aerosols compared with ground aerosols, with the unexpected finding of the Candida species as the dominant fungus from aloft samples (54% of all fungal strains). These results, consistent with the Candida animal model for KD, provide support for the concept and feasibility of a windborne pathogen. A fungal toxin could be pursued as a possible etiologic agent of KD, consistent with an agricultural source, a short incubation time and synchronized outbreaks. Our study suggests that the causative agent of KD is a preformed toxin or environmental agent rather than an organism requiring replication. We propose a new paradigm whereby an idiosyncratic immune response, influenced by host genetics triggered by an environmental exposure carried on winds, results in the clinical syndrome known as acute KD. PMID:24843117

Epidemiologic Features of Kawasaki Disease in Shanghai From 2008 Through 2012.

PubMed

Chen, Jing-Jing; Ma, Xiao-Jing; Liu, Fang; Yan, Wei-Li; Huang, Mei-Rong; Huang, Min; Huang, Guo-Ying

2016-01-01

This study was to investigate the epidemiologic trends of Kawasaki disease (KD) and coronary arterial lesions (CALs) in Shanghai from 2008 through 2012. Data were collected by using the network of the KD research group established during the first survey in Shanghai to conduct the third survey, covering the period from 2008 through 2012. Clinical records of 2304 patients with acute KD were retrospectively reviewed. Epidemiologic features of KD were investigated. Univariate and multivariate analyses were performed to identify the risk factors for CAL in patients with KD. The data were compared with the previous 2 surveys covering the periods from 1998 to 2002 and 2003 to 2007, respectively. The average incidence of KD was 30.3 to 71.9 per 100,000 children aged 0-4 years from 2008 through 2012. Age at onset ranged from 32 days to 11.7 years (median: 2.3 years). The occurrence of KD was more common in summer and spring. A total of 365 (15.9%) cases developed CAL defined as ectasia or aneurysm. Male, age ≤ 1 year, intravenous immunoglobulin (IVIG) unresponsiveness, a smaller administrative dosage and the delayed administration of IVIG (>10 days) were independent risk factors for CAL. The occurrence of CAL seemed less frequent in patients who received IVIG within 5 days after onset of illness. The incidence of KD in children has increased over time, and the development of CAL decreased in the past 5 years in Shanghai. Earlier treatment with IVIG (<5 days) was associated with reduced CAL among patients with KD.

Suppressed plasmablast responses in febrile infants, including children with Kawasaki disease

PubMed Central

Martin, Meghan; Wrotniak, Brian H.

2018-01-01

Background Kawasaki disease (KD), the leading cause of acquired heart disease in children, primarily affects infants and toddlers. Investigations on immune responses during KD are hampered by a limited understanding of normal immune responses in these ages. It’s well known that Infants have poorer vaccine responses and difficulty with maintaining prolonged serum immunity, but there are few studies on human infants detailing immune deficiencies. Limited studies propose an inability to maintain life-long bone marrow plasma cells. Plasmablasts are a transitional cell form of B cells that lead to long-term Plasma cells. Plasmablasts levels rise in the peripheral blood after exposure to a foreign antigen. In adult studies, these responses are both temporally and functionally well characterized. To date, there have been few studies on plasmablasts in the predominant age range of KD. Methods Children presenting to an urban pediatric emergency room undergoing laboratory evaluation, who had concern of KD or had fever and symptoms overlapping those of KD, were recruited. Peripheral blood mononuclear cells were isolated and evaluated utilizing flow cytometry with specific B cell markers from 18 KD subjects and 69 febrile controls. Results Plasmablast numbers and temporal formation are similar between infectious disease controls and KD subjects. In both groups, infants have diminished plasmablast responses compared to older children. Conclusion In this single-time point survey, infants have a blunted peripheral plasmablast response. Overall, similar plasmablast responses in KD and controls support an infectious disease relationship to KD. Future time-course studies of plasmablasts in infants are warranted as this phenomenon may contribute to observed immune responses in this age group. PMID:29579044

Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats.

PubMed

Zhao, Ming; Huang, Xin; Cheng, Xiang; Lin, Xiao; Zhao, Tong; Wu, Liying; Yu, Xiaodan; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

2017-01-01

Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.

Reaction rates of α-tocopheroxyl radicals confined in micelles and in human plasma lipoproteins.

PubMed

Vanzani, Paola; Rigo, Adelio; Zennaro, Lucio; Di Paolo, Maria Luisa; Scarpa, Marina; Rossetto, Monica

2014-08-01

α-Tocopherol, the main component of vitamin E, traps highly reactive radicals which otherwise might react with lipids present in plasmatic lipoproteins or in cell membranes. The α-tocopheroxyl radicals generated by this process have also a pro-oxidant action which is contrasted by their reaction with ascorbate or by bimolecular self-reaction (dismutation). The kinetics of this bimolecular self-reaction were explored in solution such as ethanol, and in heterogeneous systems such as deoxycholic acid micelles and in human plasma. According to ESR measurements, the kinetic rate constant (2k(d)) of the bimolecular self-reaction of α-tocopheroxyl radicals in micelles and in human plasma was calculated to be of the order of 10(5) M(-1) s(-1) at 37 °C. This value was obtained considering that the reactive radicals are confined into the micellar pseudophase and is one to two orders of magnitude higher than the value we found in homogeneous phase. The physiological significance of this high value is discussed considering the competition between bimolecular self-reaction and the α-tocopheroxyl radical recycling by ascorbate. Copyright © 2014 Elsevier B.V. All rights reserved.

A new integrable equation combining the modified KdV equation with the negative-order modified KdV equation: multiple soliton solutions and a variety of solitonic solutions

NASA Astrophysics Data System (ADS)

Wazwaz, Abdul-Majid

2018-07-01

A new third-order integrable equation is constructed via combining the recursion operator of the modified KdV equation (MKdV) and its inverse recursion operator. The developed equation will be termed the modified KdV-negative order modified KdV equation (MKdV-nMKdV). The complete integrability of this equation is confirmed by showing that it nicely possesses the Painlevé property. We obtain multiple soliton solutions for the newly developed integrable equation. Moreover, this equation enjoys a variety of solutions which include solitons, peakons, cuspons, negaton, positon, complexiton and other solutions.

Kawasaki disease: A brief history.

PubMed

Burns, J C; Kushner, H I; Bastian, J F; Shike, H; Shimizu, C; Matsubara, T; Turner, C L

2000-08-01

Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause of acquired heart disease among children in North America and Japan. Although an infectious agent is suspected, the cause remains unknown. However, significant progress has been made toward understanding the natural history of the disease and therapeutic interventions have been developed that halt the immune-mediated destruction of the arterial wall. We present a brief history of KD, review progress in research on the disease, and suggest avenues for future study. Kawasaki saw his first case of KD in January 1961 and published his first report in Japanese in 1967. Whether cases existed in Japan before that time is currently under study. The most significant controversy in the 1960s in Japan was whether the rash and fever sign/symptom complex described by Kawasaki was connected to subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka and pediatrician Takajiro Yamamoto disputed the early assertion of Kawasaki that KD was a self-limited illness with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases of sudden cardiac death after KD. By the time of the first English-language publication by Kawasaki in 1974, the link between KD and coronary artery vasculitis was well-established. KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles Children's Hospital, retrospectively diagnosed a 1971 autopsy case as KD. The similarity between KD and infantile periarteritis nodosa (IPN) was apparent to these pathologists, as it had been to Tanaka earlier. What remains unknown is the reason for the simultaneous recognition of this disease around the world in the 1960s and 1970s. There are several possible explanations. KD may have been a new disease that emerged in Japan and emanated to the Western World through Hawaii, where the disease is prevalent among Asian children. Alternatively, KD and IPN may be part of the spectrum of the same disease and clinically mild KD masqueraded as other diseases, such as scarlet fever in the preantibiotic era. Case reports of IPN from Western Europe extend back to at least the 19th century, but, thus far, cases of IPN have not been discovered in Japan before World War II. Perhaps the factors responsible for KD were introduced into Japan after the World War II and then reemerged in a more virulent form that subsequently spread through the industrialized Western world. It is also possible that improvements in health care and, in particular, the use of antibiotics to treat infections caused by organisms including toxin-producing bacteria reduced the burden of rash/fever illness and allowed KD to be recognized as a distinct clinical entity. Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide surveys in Japan. These have indicated that: 1) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; 2) there are approximately 5,000 to 6,000 new cases each year; 3) current estimates of incidence rates are 120 to 150 cases per 100,000 children <5 years old; 4) KD is 1.5 times more common in males and 85% of cases occur in children <5 years old; and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for Disease Control and Prevention published a case definition based on Kawasaki's original criteria. The Centers for Disease Control and Prevention developed a computerized database in 1984, and a passive reporting system currently exists in 22 states. Regional investigations and national surveys suggest an annual incidence of 4 to 15 cases per 100 000 children <5 years o

Intermittent fasting: A “new” historical strategy for controlling seizures?

PubMed Central

Hartman, Adam L.; Rubenstein, James E.; Kossoff, Eric H.

2013-01-01

Summary In antiquity, fasting was a treatment for epilepsy and a rationale for the ketogenic diet (KD). Preclinical data indicate the KD and intermittent fasting do not share identical anticonvulsant mechanisms. We implemented an intermittent fasting regimen in six children with an incomplete response to a KD. Three patients adhered to the combined intermittent fasting/KD regimen for 2 months and four had transient improvement in seizure control, albeit with some hunger-related adverse reactions. PMID:23206889

Tissue-specific expression of the gene coding for human Clara cell 10-kD protein, a phospholipase A2-inhibitory protein.

PubMed Central

Peri, A; Cordella-Miele, E; Miele, L; Mukherjee, A B

1993-01-01

Clara cell 10-kD protein (cc10kD), a secretory phospholipase A2 inhibitor, is suggested to be the human counterpart of rabbit uteroglobin (UG). Because cc10kD is expressed constitutively at a very high level in the human respiratory epithelium, the 5' region of its gene may be useful in achieving organ-specific expression of recombinant DNA in gene therapy of diseases such as cystic fibrosis. However, it is important to establish the tissue-specific expression of this gene before designing gene transfer experiments. Since the UG gene in the rabbit is expressed in many other organs besides the lung and the endometrium, we investigated the organ and tissue specificity of human cc10kD gene expression using polymerase chain reaction, nucleotide sequence analysis, immunofluorescence, and Northern blotting. Our results indicate that, in addition to the lung, cc10kD is expressed in several nonrespiratory organs, with a distribution pattern very similar, if not identical, to that of UG in the rabbit. These results underscore the necessity for more detailed analyses of the 5' region of the human cc10kD gene before its usefulness in gene therapy could be fully assessed. These data also suggest that cc10kD and UG may have similar physiological function(s). Images PMID:8227325

Lack of association between miR-218 rs11134527 A>G and Kawasaki disease susceptibility.

PubMed

Pi, Lei; Fu, Lanyan; Xu, Yufen; Che, Di; Deng, Qiulian; Huang, Xijing; Li, Meiai; Zhang, Li; Huang, Ping; Gu, Xiaoqiong

2018-05-01

Abstract Kawasaki disease (KD) is a type of disease that includes the development of a fever that lasts at least five days and involves the clinical manifestation of multicellular vasculitis. KD has become one of the most common pediatric cardiovascular diseases. Previous studies have reported that miR-218 rs11134527 A>G is associated with susceptibility to various cancer risks. However, there is a lack of evidence regarding the relationship between this polymorphism and KD risk. This study explored the correlation between the miR-218 rs11134527 A>G polymorphism and the risk of KD. We recruited 532 patients with KD and 623 controls to genotype the miR-218 rs11134527 A>G polymorphism with a TaqMan allelic discrimination assay. Our results illustrated that the miR-218 rs11134527 A>G polymorphism was not associated with KD risk. In an analysis stratified by age, sex, and coronary artery lesions, we found only that the risk of KD was significantly decreased for children older than 5 years (GG vs. AA/AG: adjusted OR=0.26, 95% CI=0.07-0.94, P =0.041). This study demonstrated that the miR-218 rs1113452 A>G polymorphism may have an age-related relationship with KD susceptibility that has not previously been revealed. ©2018 The Author(s).

Psoriasiform Eruptions During Kawasaki Disease: A Distinct Phenotype

PubMed Central

Haddock, Ellen S.; Calame, Antoanella; Shimizu, Chisato; Tremoulet, Adriana H.; Burns, Jane C.; Tom, Wynnis L.

2016-01-01

Background A psoriasis-like eruption develops in a subset of patients with Kawasaki disease (KD). Objective To systematically compare KD-associated psoriasiform eruptions with classic psoriasis and the outcomes of KD in children with and without this rash. Methods This was a retrospective study of 11 KD cases with a psoriasiform eruption matched 1:2 by age, gender, and ethnicity with psoriasis-only and KD-only controls. Genotyping was performed in 10 cases for a deletion of two late cornified envelope (LCE) genes, LCE3C_LCE3B-del, associated with increased risk for pediatric-onset psoriasis. Results Similar to classic psoriasis, KD-associated eruptions were characterized clinically by well-demarcated, scaly pink plaques and histopathologically by intraepidermal neutrophils, suprabasilar keratin 16 expression, and increased Ki-67 expression. They showed less frequent diaper area involvement, more crust and serous exudate, and an enduring remission (91% vs. 23% with confirmed resolution; p < 0.001). Frequency of LCE3C_LCE3B-del and major KD outcomes were similar between cases and controls. Limitations The study was limited by the small number of cases, treatment variation, and availability of skin biopsy specimens. Conclusions Although the overall clinical and histopathologic findings were similar to conventional psoriasis, this appears to be a distinct phenotype with significantly greater propensity for remission. No adverse effect on KD outcomes was noted. PMID:26946987

Completing the Feedback Loop: The Impact of Chlorophyll Data Assimilation on the Ocean State

NASA Technical Reports Server (NTRS)

Borovikov, Anna; Keppenne, Christian; Kovach, Robin

2015-01-01

In anticipation of the integration of a full biochemical model into the next generation GMAO coupled system, an intermediate solution has been implemented to estimate the penetration depth (1Kd_PAR) of ocean radiation based on the chlorophyll concentration. The chlorophyll is modeled as a tracer with sources-sinks coming from the assimilation of MODIS chlorophyll data. Two experiments were conducted with the coupled ocean-atmosphere model. In the first, climatological values of Kpar were used. In the second, retrieved daily chlorophyll concentrations were assimilated and Kd_PAR was derived according to Morel et al (2007). No other data was assimilated to isolate the effects of the time-evolving chlorophyll field. The daily MODIS Kd_PAR product was used to validate the skill of the penetration depth estimation and the MERRA-OCEAN re-analysis was used as a benchmark to study the sensitivity of the upper ocean heat content and vertical temperature distribution to the chlorophyll input. In the experiment with daily chlorophyll data assimilation, the penetration depth was estimated more accurately, especially in the tropics. As a result, the temperature bias of the model was reduced. A notably robust albeit small (2-5 percent) improvement was found across the equatorial Pacific ocean, which is a critical region for seasonal to inter-annual prediction.

The Interaction Affinity between Vascular Cell Adhesion Molecule-1 (VCAM-1) and Very Late Antigen-4 (VLA-4) Analyzed by Quantitative FRET

PubMed Central

Wu, Shu-Han; Karmenyan, Artashes; Chiou, Arthur

2015-01-01

Very late antigen-4 (VLA-4), a member of integrin superfamily, interacts with its major counter ligand vascular cell adhesion molecule-1 (VCAM-1) and plays an important role in leukocyte adhesion to vascular endothelium and immunological synapse formation. However, irregular expressions of these proteins may also lead to several autoimmune diseases and metastasis cancer. Thus, quantifying the interaction affinity of the VCAM-1/VLA-4 interaction is of fundamental importance in further understanding the nature of this interaction and drug discovery. In this study, we report an ‘in solution’ steady state organic fluorophore based quantitative fluorescence resonance energy transfer (FRET) assay to quantify this interaction in terms of the dissociation constant (Kd). We have used, in our FRET assay, the Alexa Fluor 488-VLA-4 conjugate as the donor, and Alexa Fluor 546-VCAM-1 as the acceptor. From the FRET signal analysis, Kd of this interaction was determined to be 41.82 ± 2.36 nM. To further confirm our estimation, we have employed surface plasmon resonance (SPR) technique to obtain Kd = 39.60 ± 1.78 nM, which is in good agreement with the result obtained by FRET. This is the first reported work which applies organic fluorophore based ‘in solution’ simple quantitative FRET assay to obtain the dissociation constant of the VCAM-1/VLA-4 interaction, and is also the first quantification of this interaction. Moreover, the value of Kd can serve as an indicator of abnormal protein-protein interactions; hence, this assay can potentially be further developed into a drug screening platform of VLA-4/VCAM-1 as well as other protein-ligand interactions. PMID:25793408

Quasiprobability behind the out-of-time-ordered correlator

NASA Astrophysics Data System (ADS)

Yunger Halpern, Nicole; Swingle, Brian; Dressel, Justin

2018-04-01

Two topics, evolving rapidly in separate fields, were combined recently: the out-of-time-ordered correlator (OTOC) signals quantum-information scrambling in many-body systems. The Kirkwood-Dirac (KD) quasiprobability represents operators in quantum optics. The OTOC was shown to equal a moment of a summed quasiprobability [Yunger Halpern, Phys. Rev. A 95, 012120 (2017), 10.1103/PhysRevA.95.012120]. That quasiprobability, we argue, is an extension of the KD distribution. We explore the quasiprobability's structure from experimental, numerical, and theoretical perspectives. First, we simplify and analyze Yunger Halpern's weak-measurement and interference protocols for measuring the OTOC and its quasiprobability. We decrease, exponentially in system size, the number of trials required to infer the OTOC from weak measurements. We also construct a circuit for implementing the weak-measurement scheme. Next, we calculate the quasiprobability (after coarse graining) numerically and analytically: we simulate a transverse-field Ising model first. Then, we calculate the quasiprobability averaged over random circuits, which model chaotic dynamics. The quasiprobability, we find, distinguishes chaotic from integrable regimes. We observe nonclassical behaviors: the quasiprobability typically has negative components. It becomes nonreal in some regimes. The onset of scrambling breaks a symmetry that bifurcates the quasiprobability, as in classical-chaos pitchforks. Finally, we present mathematical properties. We define an extended KD quasiprobability that generalizes the KD distribution. The quasiprobability obeys a Bayes-type theorem, for example, that exponentially decreases the memory required to calculate weak values, in certain cases. A time-ordered correlator analogous to the OTOC, insensitive to quantum-information scrambling, depends on a quasiprobability closer to a classical probability. This work not only illuminates the OTOC's underpinnings, but also generalizes quasiprobability theory and motivates immediate-future weak-measurement challenges.

Quantifying Protein-Ligand Binding Constants using Electrospray Ionization Mass Spectrometry: A Systematic Binding Affinity Study of a Series of Hydrophobically Modified Trypsin Inhibitors

NASA Astrophysics Data System (ADS)

Cubrilovic, Dragana; Biela, Adam; Sielaff, Frank; Steinmetzer, Torsten; Klebe, Gerhard; Zenobi, Renato

2012-10-01

NanoESI-MS is used for determining binding strengths of trypsin in complex with two different series of five congeneric inhibitors, whose binding affinity in solution depends on the size of the P3 substituent. The ligands of the first series contain a 4-amidinobenzylamide as P1 residue, and form a tight complex with trypsin. The inhibitors of the second series have a 2-aminomethyl-5-chloro-benzylamide as P1 group, and represent a model system for weak binders. The five different inhibitors of each group are based on the same scaffold and differ only in the length of the hydrophobic side chain of their P3 residue, which modulates the interactions in the S3/4 binding pocket of trypsin. The dissociation constants (KD) for high affinity ligands investigated by nanoESI-MS ranges from 15 nM to 450 nM and decreases with larger hydrophobic P3 side chains. Collision-induced dissociation (CID) experiments of five trypsin and benzamidine-based complexes show a correlation between trends in KD and gas-phase stability. For the second inhibitor series we could show that the effect of imidazole, a small stabilizing additive, can avoid the dissociation of the complex ions and as a result increases the relative abundance of weakly bound complexes. Here the KD values ranging from 2.9 to 17.6 μM, some 1-2 orders of magnitude lower than the first series. For both ligand series, the dissociation constants (KD) measured via nanoESI-MS were compared with kinetic inhibition constants (Ki) in solution.

Kinetic studies on strand displacement in de novo designed parallel heterodimeric coiled coils† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc05342h

PubMed Central

Groth, Mike C.; Rink, W. Mathis; Meyer, Nils F.

2018-01-01

Among the protein folding motifs, which are accessible by de novo design, the parallel heterodimeric coiled coil is most frequently used in bioinspired applications and chemical biology in general. This is due to the straightforward sequence-to-structure relationships, which it has in common with all coiled-coil motifs, and the heterospecificity, which allows control of association. Whereas much focus was laid on designing orthogonal coiled coils, systematic studies on controlling association, for instance by strand displacement, are rare. As a contribution to the design of dynamic coiled-coil-based systems, we studied the strand-displacement mechanism in obligate heterodimeric coiled coils to investigate the suitability of the dissociation constants (KD) as parameters for the prediction of the outcome of strand-displacement reactions. We use two sets of heterodimeric coiled coils, the previously reported N-AxBy and the newly characterized C-AxBy. Both comprise KD values in the μM to sub-nM regime. Strand displacement is explored by CD titration and a FRET-based kinetic assay and is proved to be an equilibrium reaction with half-lifes from a few seconds up to minutes. We could fit the displacement data by a competitive binding model, giving rate constants and overall affinities of the underlying association and dissociation reactions. The overall affinities correlate well with the ratios of KD values determined by CD-thermal denaturation experiments and, hence, support the dissociative mechanism of strand displacement in heterodimeric coiled coils. From the results of more than 100 different displacement reactions we are able to classify three categories of overall affinities, which allow for easy prediction of the equilibrium of strand displacement in two competing heterodimeric coiled coils. PMID:29780562

Combined processing and mutual interpretation of radiometry and fluorometry from autonomous profiling Bio-Argo floats: 2. Colored dissolved organic matter absorption retrieval

NASA Astrophysics Data System (ADS)

Xing, Xiaogang; Morel, André; Claustre, Hervé; D'Ortenzio, Fabrizio; Poteau, Antoine

2012-04-01

Eight autonomous profiling "Bio-Argo" floats were deployed offshore during about 2 years (2008-2010) in Pacific, Atlantic, and Mediterranean zones. They were equipped with miniaturized bio-optical sensors, namely a radiometer measuring within the upper layer the downward irradiance at 412, 490, and 555 nm, and two fluorometers for detection of chlorophyll-a (Chla) and colored dissolved organic matter (CDOM; profiles from 400 m to surface). A first study dealt with the interpretation of the Chla fluorescence signal in terms of concentration, using for this purpose the diffuse attenuation coefficient for irradiance at 490 nm, Kd(490), taken as a proxy for the Chla absorption. The present study examines the possibility of similarly using the Kd(412) values combined with retrieved Chla profiles to convert the CDOM fluorometric qualitative information into a CDOM absorption coefficient (ay). The rationale is to take advantage of the fact that Kd is more sensitive to CDOM presence at 412 nm than at 490 nm. A validation of this method is tested through its application to field data, collected from a ship over a wide range of trophic conditions (Biogeochemistry and Optics South Pacific Experiment (BIOSOPE) cruise); these data include both in situ fluorescence profiles and CDOM absorption as measured on discrete samples. In addition, near-surface ay values retrieved from the floats agree with those derivable from ocean color imagery (Moderate Resolution Imaging Spectroradiometer (MODIS-A)). The low sensitivity of commercially available CDOM fluorometers presently raises difficulties when applying this technique to open ocean waters. It was nevertheless possible to derive from the floats records meaningful time series of CDOM vertical distribution.

Impact of defects on percolation in random sequential adsorption of linear k-mers on square lattices.

PubMed

Tarasevich, Yuri Yu; Laptev, Valeri V; Vygornitskii, Nikolai V; Lebovka, Nikolai I

2015-01-01

The effect of defects on the percolation of linear k-mers (particles occupying k adjacent sites) on a square lattice is studied by means of Monte Carlo simulation. The k-mers are deposited using a random sequential adsorption mechanism. Two models L(d) and K(d) are analyzed. In the L(d) model it is assumed that the initial square lattice is nonideal and some fraction of sites d is occupied by nonconducting point defects (impurities). In the K(d) model the initial square lattice is perfect. However, it is assumed that some fraction of the sites in the k-mers d consists of defects, i.e., is nonconducting. The length of the k-mers k varies from 2 to 256. Periodic boundary conditions are applied to the square lattice. The dependences of the percolation threshold concentration of the conducting sites p(c) vs the concentration of defects d are analyzed for different values of k. Above some critical concentration of defects d(m), percolation is blocked in both models, even at the jamming concentration of k-mers. For long k-mers, the values of d(m) are well fitted by the functions d(m)∝k(m)(-α)-k(-α) (α=1.28±0.01 and k(m)=5900±500) and d(m)∝log(10)(k(m)/k) (k(m)=4700±1000) for the L(d) and K(d) models, respectively. Thus, our estimation indicates that the percolation of k-mers on a square lattice is impossible even for a lattice without any defects if k⪆6×10(3).

Using nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) for simultaneous determination of concentration and equilibrium constant.

PubMed

Kanoatov, Mirzo; Galievsky, Victor A; Krylova, Svetlana M; Cherney, Leonid T; Jankowski, Hanna K; Krylov, Sergey N

2015-03-03

Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) is a versatile tool for studying affinity binding. Here we describe a NECEEM-based approach for simultaneous determination of both the equilibrium constant, K(d), and the unknown concentration of a binder that we call a target, T. In essence, NECEEM is used to measure the unbound equilibrium fraction, R, for the binder with a known concentration that we call a ligand, L. The first set of experiments is performed at varying concentrations of T, prepared by serial dilution of the stock solution, but at a constant concentration of L, which is as low as its reliable quantitation allows. The value of R is plotted as a function of the dilution coefficient, and dilution corresponding to R = 0.5 is determined. This dilution of T is used in the second set of experiments in which the concentration of T is fixed but the concentration of L is varied. The experimental dependence of R on the concentration of L is fitted with a function describing their theoretical dependence. Both K(d) and the concentration of T are used as fitting parameters, and their sought values are determined as the ones that generate the best fit. We have fully validated this approach in silico by using computer-simulated NECEEM electropherograms and then applied it to experimental determination of the unknown concentration of MutS protein and K(d) of its interactions with a DNA aptamer. The general approach described here is applicable not only to NECEEM but also to any other method that can determine a fraction of unbound molecules at equilibrium.

Metolachlor Sorption and Degradation in Soil Amended with Fresh and Aged Biochars.

PubMed

Trigo, Carmen; Spokas, Kurt A; Hall, Kathleen E; Cox, Lucia; Koskinen, William C

2016-04-27

Addition of organic amendments such as biochar to soils can influence pesticide sorption-desorption processes and, in turn, the amount of pesticide readily availability for transport and biodegradation. Sorption-desorption processes are affected by both the physical and chemical properties of soils and pesticides, as well as soil-pesticide contact time, or aging. Changes in sorption-desorption of metolachlor with aging in soil amended with three macadamia nut shell biochars aged 0 (BCmac-fr), 1 year (BCmac-1yr), and 2 years (BCmac-2yr) and two wood biochars aged 0 (BCwood-fr) and 5 years (BCwood-5yr) were determined. Apparent sorption coefficient (Kd-app) values increased with incubation time to a greater extent in amended soil as compared to unamended soils; Kd-app increased by 1.2-fold for the unamended soil, 2.0-fold for BCwood-fr, 1.4-fold for BCwood-5yr, 2.4-fold for BCmac-fr, 2.5-fold for BCmac-1yr, and 1.9-fold for BCmac-4yr. The increase in calculated Kd-app value was the result of a 15% decrease in the metolachlor solution concentration extractable with CaCl2 solution with incubation time in soil as compared to a 50% decrease in amended soil with very little change in the sorbed concentration. Differences could possibly be due to diffusion to less accessible or stronger binding sites with time, a faster rate of degradation (in solution and on labile sites) than desorption, or a combination of the two in the amended soils. These data show that transport models would overpredict the depth of movement of metolachlor in soil if effects of aging or biochar amendments are not considered.

Anaerobic Biotransformation and Mobility of Pu and of Pu-EDTA

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

Xun, Luying

2009-11-20

The enhanced mobility of radionuclides by co-disposed chelating agent, ethylenediaminetetraacetate (EDTA), is likely to occur only under anaerobic conditions. Our extensive effort to enrich and isolate anaerobic EDTA-degrading bacteria has failed. Others has tried and also failed. To explain the lack of anaerobic biodegradation of EDTA, we proposed that EDTA has to be transported into the cells for metabolism. A failure of uptake may contribute to the lack of EDTA degradation under anaerobic conditions. We demonstrated that an aerobic EDTA-degrading bacterium strain BNC1 uses an ABC-type transporter system to uptake EDTA. The system has a periplasmic binding protein that bindmore » EDTA and then interacts with membrane proteins to transport EDTA into the cell at the expense of ATP. The bind protein EppA binds only free EDTA with a Kd of 25 nM. The low Kd value indicates high affinity. However, the Kd value of Ni-EDTA is 2.4 x 10^(-10) nM, indicating much stronger stability. Since Ni and other trace metals are essential for anaerobic respiration, we conclude that the added EDTA sequestrates all trace metals and making anaerobic respiration impossible. Thus, the data explain the lack of anaerobic enrichment cultures for EDTA degradation. Although we did not obtain an EDTA degrading culture under anaerobic conditions, our finding may promote the use of certain metals that forms more stable metal-EDTA complexes than Pu(III)-EDTA to prevent the enhanced mobility. Further, our data explain why EDTA is the most dominant organic pollutant in surface waters, due to the lack of degradation of certain metal-EDTA complexes.« less

miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease

PubMed Central

He, Ming; Chen, Zhen; Martin, Marcy; Zhang, Jin; Sangwung, Panjamaporn; Woo, Brian; Tremoulet, Adriana H.; Shimizu, Chisato; Jain, Mukesh K.; Burns, Jane C.; Shyy, John Y-J.

2016-01-01

Rationale Endothelial-to-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. Objective We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied. Methods and Results Sera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells (HUVECs). Cardiovascular disease-related miRNAs, CTGF, and EndoMT markers were quantified using RT-qPCR, ELISA, and Western blotting. Compared to healthy controls, HUVEC incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3′ untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in ECs in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a Phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in ECs. Conclusions KD sera suppress the KLF4-miR-483 axis in ECs leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part through the restoration of KLF4-miR-483 expression. Clinical Trial Registration NCT01431105 PMID:27923814

Epidemiologic survey of Kawasaki disease in Inner Mongolia, China, between 2001 and 2013

PubMed Central

Zhang, Xiaomei; Liang, Yanyan; Feng, Wanyu; Su, Xuewen; Zhu, Hua

2016-01-01

The epidemiologic features of Kawasaki disease (KD) in the Inner Mongolia Autonomous Region of China has not been previously determined, to the best of our knowledge. Therefore, the aim of the present study was to investigate the epidemiology of KD in Inner Mongolia. Clinical data from 518 patients treated for KD in Inner Mongolia between January 2001 and December 2013 were analyzed. The results indicated that the mean annual incidence rate was 3.55±2.96 per 100,000 children under the age of 5 years between 2001 and 2013. The age at diagnosis ranged between 49 days and 14 years, while the disease occurred more frequently in the spring and summer. In addition, the incidence of coronary artery lesion (CAL) was reported to be 40.2% in the present survey. KD patients in the Han Chinese ethnic group were more likely to be complicated by CAL, whereas patients with incidence of KD in July were less likely to be complicated by CAL. In conclusion, the incidence of KD was observed to be increasing in Inner Mongolia, while the ethnic group and month of onset may be associated with the incidence of CAL in KD patients. PMID:27446347

Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

PubMed

Nagao, Y; Urabe, C; Nakamura, H; Hatano, N

2016-02-01

Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

Intermittent fasting: a "new" historical strategy for controlling seizures?

PubMed

Hartman, Adam L; Rubenstein, James E; Kossoff, Eric H

2013-05-01

In antiquity, fasting was a treatment for epilepsy and a rationale for the ketogenic diet (KD). Preclinical data indicate the KD and intermittent fasting do not share identical anticonvulsant mechanisms. We implemented an intermittent fasting regimen in six children with an incomplete response to a KD. Three patients adhered to the combined intermittent fasting/KD regimen for 2 months and four had transient improvement in seizure control, albeit with some hunger-related adverse reactions. Copyright © 2012 Elsevier B.V. All rights reserved.

Use of the King-Devick test for sideline concussion screening in junior rugby league.

PubMed

King, D; Hume, P; Gissane, C; Clark, T

2015-10-15

To determine whether the King-Devick (K-D) test used as a sideline test in junior rugby league players over 12 matches in a domestic competition season could identify witnessed and incidentally identified episodes of concussion. A prospective observational cohort study of a club level junior rugby league team (n=19) during the 2014 New Zealand competition season involved every player completing two pre-competition season baseline trials of the K-D test. Players removed from match participation, or who reported any signs or symptoms of concussion were assessed on the sideline with the K-D test and referred for further medical assessment. Players with a pre- to post-match K-D test difference >3s were referred for physician evaluation. The baseline test-retest reliability of the K-D test was high (rs=0.86; p<0.0001). Seven concussions were medically identified in six players who recorded pre- to post-match K-D test times greater than 3s (mean change of 7.4s). Post-season testing of players demonstrated improvement of K-D time scores consistent with learning effects of using the K-D test (67.7s vs. 62.2s). Although no witnessed concussions occurred during rugby play, six players recorded pre- to post-match changes with a mean delay of 4s resulting in seven concussions being subsequently confirmed post-match by health practitioners. All players were medically managed for a return to sports participation. The K-D test was quickly and easily administered making it a practical sideline tool as part of the continuum of concussion assessment tools for junior rugby league players. Copyright © 2015 Elsevier B.V. All rights reserved.

Changes in the Polypeptide Patterns of Barley Seedlings Exposed to Jasmonic Acid and Salinity 1

PubMed Central

Maslenkova, Liliana Todorova; Miteva, Tania Simeonova; Popova, Losanka P.

1992-01-01

Soluble and thylakoid membrane proteins of jasmonic acid (JA)-treated and salt-stressed barley (Hordeum vulgare L.) seedlings were investigated using 15% sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. High JA concentrations induced marked quantitative and qualitative changes in polypeptide profiles concerning mainly the proteins with approximately equal mobility, as in NaCl-stressed plants. The most obvious increase in thylakoid polypeptide band intensity was at 55 to 57 kilodaltons (kD). The relative share of some polypeptides with apparent molecular masses above 66 kD and of polypeptides with lower molecular masses in the region of 20.5 to 15 kD was enhanced. At the same time, one new band at 31 to 31.5 kD was well expressed at 25 and 250 micromolar JA concentrations and became discernible in the 100 micromolar NaCl-treated plants. The intensity of some polypeptides of soluble proteins (molecular masses of 60, 47, 37, 30, and 23.4 kD) increased with increasing JA concentration, whereas the intensities of other polypeptide bands (55, 21.4, and 15 kD) decreased. Enhanced levels of 60-, 47-, 34-, and 30-kD polypeptides and reduced levels of 55- and 15-kD polypeptides were present in NaCl-treated plants. The appearance of one new polypeptide, of 25.1 kD, was observed only in NaCl-treated plants. At 100 millimolar NaCl, an eightfold increase in proline content was observed while at 250 micromolar JA, the proline content was threefold over the control. It is hypothesized that exogenously applied jasmonates act as stress agents. As such, they provoke alterations in the proline content and they can modulate typical stress responses by induction of stress proteins. ImagesFigure 1Figure 4Figure 5 PMID:16668698

The biophysical properties of the aorta are altered following Kawasaki disease.

PubMed

Vaujois, Laurence; Dallaire, Frédéric; Maurice, Roch L; Fournier, Anne; Houde, Christine; Thérien, Johanne; Cartwright, Daniel; Dahdah, Nagib

2013-12-01

The long-term sequelae of Kawasaki disease (KD) are based on the coronary complications. Because KD causes generalized vasculitis, with documented aneurysms in the femoral, iliac, renal, axillary, and brachial arteries, the aim of this study was to assess the biophysical properties of the aorta (BPA) after KD. The BPA are biometric measurements representing vascular structural and dynamic changes in response to cardiac work. Anthropometric and echocardiographic measurements of the aorta in a series of patients with KD were compared with those of healthy subjects. The BPA were calculated noninvasively by extrapolating previously validated equations that were conceived for invasive measurements. Because BPA vary with body habitus, control subjects were used to normalize BPA parameters for height to compute BPA Z-score equations. Between June 2007 and February 2010, BPA were recorded in 57 patients with KD >1 year after the onset of the disease, 45 without and 12 with coronary artery sequelae. The mean intervals between the acute onset of KD and enrollment were 10.0 ± 5.0 and 5.8 ± 4.5 years for patients with and without coronary artery sequelae, respectively (P = .008). Patients with KD with coronary artery sequelae had significantly altered Z scores of aortic diameter modulation, Peterson's elastic modulus, and β stiffness index (P = .001-.016). Patients with KD without coronary artery sequelae also exhibited altered elasticity, stiffness, and pulse-wave velocity (P = .001-.026). Altered BPA after KD are detectible despite apparent resolution of acute vasculitis. Future directions toward determining multilevel and multilayer vascular impact, including vascular autonomous homeostasis, require thorough investigation. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

The King-Devick test as a concussion screening tool administered by sports parents.

PubMed

Leong, D F; Balcer, L J; Galetta, S L; Liu, Z; Master, C L

2014-02-01

Sports-related concussion has received increasing awareness due to short- and long-term neurologic sequelae seen among athletes. The King-Devick (K-D) test captures impairment of eye movements and other correlates of suboptimal brain function. We investigated the K-D test as a screening for concussion when administered by layperson sports parents in a cohort of amateur boxers. The K-D test was administered pre-fight and post-fight by laypersons masked to the head trauma status of each athlete. Matches were watched over by a ringside physician and boxing trainer. Athletes with suspected head trauma received testing with the Military Acute Concussion Evaluation (MACE) by the ringside physician to determine concussion status. Athletes sustaining concussion were compared to the athletes screened using the K-D test. Post-fight K-D scores were lower (better) than the best baseline score (41 vs. 39.3 s, P=0.34, Wilcoxon signed-rank test), in the absence of concussion. One boxer sustained a concussion as determined by the ringside physician. This boxer was accurately identified by the layperson K-D testers due to a worsening in K-D test compared to baseline (3.2 seconds) and an increased number of errors. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.90 [95% CI 0.84-0.97]). Additionally, 6 boxers who participated in multiple bouts showed no worsening of their K-D times further supporting that scores are not affected by the fatigue associated with sparring. The K-D test is a rapid sideline screening tool for concussion that can be effectively administered by non-medically trained laypersons.

Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.

PubMed

Wakita, Daiko; Kurashima, Yosuke; Crother, Timothy R; Noval Rivas, Magali; Lee, Youngho; Chen, Shuang; Fury, Wen; Bai, Yu; Wagner, Shawn; Li, Debiao; Lehman, Thomas; Fishbein, Michael C; Hoffman, Hal M; Shah, Prediman K; Shimada, Kenichi; Arditi, Moshe

2016-05-01

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated AAA. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease. © 2016 American Heart Association, Inc.

Soy isoflavone intake is associated with risk of Kawasaki disease

PubMed Central

Portman, Michael A.; Navarro, Sandi L.; Bruce, Margaret E.; Lampe, Johanna W.

2016-01-01

Kawasaki disease (KD) is an acute vasculitis affecting children. Incidence of KD varies according to ethnicity and is highest in Asian populations. Although genetic differences may explain this variation, dietary or environmental factors could also be responsible. The objectives of this study were to determine dietary soy and isoflavone consumption in a cohort of KD children just before disease onset and their mothers' intake during pregnancy and nursing. We tested the hypothesis that soy isoflavone consumption is associated with risk of KD in US children, potentially explaining some of the ethnic-cultural variation in incidence. We evaluated soy food intake and isoflavone consumption in nearly 200 US KD cases and 200 age-matched controls using a food frequency questionnaire for children and in their mothers. We used a logistic regression model to test the association of isoflavones and KD. Maternal surveys on soy intake during pregnancy and nursing showed no significant differences in isoflavone consumption between groups. However, we identified significantly increased KD risk in children for total isoflavone (odds ratio [OR], 2.33; 95%confidence interval [CI], 1.37–3.96) and genistein (OR, 2.46; 95% CI, 1.46–4.16) intakes, when comparing high soy consumers vs nonconsumers. In addition, significantly increased KD risk occurred in Asian-American children with the highest consumption (total isoflavones: OR, 7.29; 95% CI, 1.73–30.75; genistein: OR, 8.33; 95% CI, 1.92–36.24) compared to whites. These findings indicate that childhood dietary isoflavone consumption, but not maternal isoflavone intake during pregnancy and nursing, relates to KD risk in an ethnically diverse US population. PMID:27440537

Occurrence and distribution of perfluoroalkyl acids (PFAAs) in surface water and sediment of a tropical coastal area (Bay of Bengal coast, Bangladesh).

PubMed

Habibullah-Al-Mamun, Md; Ahmed, Md Kawser; Raknuzzaman, Mohammad; Islam, Md Saiful; Negishi, Junya; Nakamichi, Shihori; Sekine, Makoto; Tokumura, Masahiro; Masunaga, Shigeki

2016-11-15

This study reports the first evidence of perfluoroalkyl acids (PFAAs) in surface waters and sediments collected from the coastal area of Bangladesh. Fifteen target PFAAs, including C4-14-PFCAs (perfluoroalkyl carboxylates) and C4, C6, C8, and C10-PFSAs (perfluoroalkyl sulfonates), were quantified by HPLC-MS/MS. The ΣPFAAs in surface water and sediment samples were in the range of 10.6 to 46.8ng/L and 1.07 to 8.15ng/gdw, respectively. PFOA in water (3.17-27.8ng/L) and PFOS in sediment samples (0.60-1.14ng/gdw) were found to be the most abundant PFAAs, and these concentrations were comparable to or less than most other reported values, particularly those recorded from the coastal areas of China, Japan, Korea and Spain. The majority of the monitored PFAAs did not show clear seasonal variation. The southeastern part (Cox's Bazar and Chittagong) of the Bangladeshi coastal area was more contaminated with PFAAs than the southern (Meghna Estuary) and southwestern parts (Sundarbans). Industrial and municipal wastewater effluents, ship breaking and port activities were identified as potential sources of the PFAA contamination in this region. Field-based sediment water distribution coefficients (KD) were calculated and corrected for organic carbon content (KOC), which reduced the variability between samples. The values of log KD (1.63-2.88) and log KOC (4.02-5.16) were higher than previously reported values, which may indicate that the partitioning of PFAAs in a tropical coastal ecosystem is different from other ecosystems, such as temperate and sub-tropical regions. Although a preliminary environmental hazard assessment indicated that PFOA or PFOS levels do not currently exceed the acute safety thresholds, we should keep in mind that they are bioavailable and can accumulate in the food chain. Therefore, the ubiquity of PFAAs in the coastal area of Bangladesh warrants further studies characterizing their specific sources and the potential long-term risks they present to both humans and wildlife. Copyright © 2016 Elsevier B.V. All rights reserved.

A saxitoxin-binding aptamer with higher affinity and inhibitory activity optimized by rational site-directed mutagenesis and truncation.

PubMed

Zheng, X; Hu, B; Gao, S X; Liu, D J; Sun, M J; Jiao, B H; Wang, L H

2015-07-01

Saxitoxin (STX), a member of the family of paralytic shellfish poisoning toxins, poses toxicological and ecotoxicological risks. To develop an analytical recognition element for STX, a DNA aptamer (APT(STX1)) was previously discovered via an iterative process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) by Handy et al. Our study focused on generating an improved aptamer based on APT(STX1) through rational site-directed mutation and truncation. In this study, we generated the aptamer, M-30f, with a 30-fold higher affinity for STX compared with APT(STX1). The Kd value for M-30f was 133 nM, which was calculated by Bio-Layer Interferometry. After optimization, we detected and compared the interaction of STX with aptamers (APT(STX1) or M-30f) through several techniques (ELISA, cell bioassay, and mouse bioassay). Both aptamers' STX-binding ability was demonstrated in all three methods. Moreover, M-30f performs better than its parent sequence with higher suppressive activity against STX. As a molecular recognition element, M-30f has good prospects for practical application. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.

PubMed

Newman, John C; Covarrubias, Anthony J; Zhao, Minghao; Yu, Xinxing; Gut, Philipp; Ng, Che-Ping; Huang, Yu; Haldar, Saptarsi; Verdin, Eric

2017-09-05

Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies downregulation of insulin, protein synthesis, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, upregulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice. Published by Elsevier Inc.

New analytical exact solutions of time fractional KdV-KZK equation by Kudryashov methods

NASA Astrophysics Data System (ADS)

S Saha, Ray

2016-04-01

In this paper, new exact solutions of the time fractional KdV-Khokhlov-Zabolotskaya-Kuznetsov (KdV-KZK) equation are obtained by the classical Kudryashov method and modified Kudryashov method respectively. For this purpose, the modified Riemann-Liouville derivative is used to convert the nonlinear time fractional KdV-KZK equation into the nonlinear ordinary differential equation. In the present analysis, the classical Kudryashov method and modified Kudryashov method are both used successively to compute the analytical solutions of the time fractional KdV-KZK equation. As a result, new exact solutions involving the symmetrical Fibonacci function, hyperbolic function and exponential function are obtained for the first time. The methods under consideration are reliable and efficient, and can be used as an alternative to establish new exact solutions of different types of fractional differential equations arising from mathematical physics. The obtained results are exhibited graphically in order to demonstrate the efficiencies and applicabilities of these proposed methods of solving the nonlinear time fractional KdV-KZK equation.

Diffusion of Na(I), Cs(I), Sr(II) and Eu(III) in smectite rich natural clay.

PubMed

Kasar, Sharayu; Kumar, Sumit; Bajpai, R K; Tomar, B S

2016-01-01

Diffusion of Na(I), Cs(I), Sr(II) and Eu(III) in smectite rich natural clay, proposed as a backfill material in the Indian geological repository, was studied using the out-diffusion method. Radiotracers (22)Na, (137)Cs, (85)Sr and (154)Eu were used; the first three are carrier-free enabling experimental work at sub-micromolar metal ion concentration, and Eu(III) tracer (154)Eu was used at sub millimolar concentration. An out-diffusion methodology, wherein a thin planar source of radioactivity placed between two clay columns diffuses out, was used to obtain the apparent diffusion coefficient (Da) values. This methodology enabled determination of diffusion coefficient even for strongly sorbing (154)Eu. Da values for (22)Na, (137)Cs, (85)Sr and (154)Eu were 2.35 (±0.14) × 10(-11), 2.65 (±0.09) × 10(-12), 3.32 (±0.15) × 10(-11) and 1.23 (±0.15) × 10(-13) m(2) s(-1), respectively. Da values were found to be in fair agreement with literature data reported for similar mineralogical sediments. Sorption of radionuclides on the clay was also determined in the present study and differences in Da values were rationalized on the basis of sorption data. Distribution ratios (Kd) for Cs(I) and Eu(III) were higher than that for Sr(II), which in turn was higher than that for Na(I). Copyright © 2015 Elsevier Ltd. All rights reserved.

[Kawasaki disease is more prevalent in rural areas of Catalonia (Spain)].

PubMed

Sánchez-Manubens, Judith; Antón, Jordi; Bou, Rosa; Iglesias, Estibaliz; Calzada-Hernandez, Joan; Rodó, Xavier; Morguí, Josep-Antón

2017-10-01

Kawasaki disease (KD) is an acute self-limited systemic vasculitis relatively common in childhood. The etiology of KD is still unknown, although clinical, laboratory and epidemiological features suggest an infectious origin or trigger. Differences on incidence between countries have been related to specific genetic factors, ethnicity, country of birth and some other sociocultural and environmental factors. We present a population-based study on incidence of KD in Catalonia (Spain), focusing on differences between patients in rural and non-rural areas of the region. Observational population-based study including all Pediatric Units in Catalan hospitals, between 2004 and 2014. A 12-month (March 2013-March 2014) prospective collection of new cases of KD was carried out to determine the incidence of KD. The rest of the data was retrieved retrospectively. Data from 399 patients over the 10-year study period was analyzed. Among the total KD patients, 353 (88.5%) lived in non-rural areas and 46 (11.5%) in rural areas. It was found that there is a significant difference (P<.001) between the percentage of rural population observed in patients with KD (11.5%), and the expected 5% of the Catalan population. This is the first population-based study showing significant differences on KD incidence rates between rural and non-rural areas. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Characterization of lipoproteins from the turtle, Trachemys scripta elegans, in fasted and fed states.

PubMed

Cain, William; Song, Li; Stephens, Gregory; Usher, David

2003-04-01

The lipid and apolipoprotein composition of VLDL, IDL, LDL, HDL(2) and HDL(3) were examined in the turtle, Trachemys scripta elegans, in fasted and fed states. The lipid composition of turtle lipoproteins was very similar to their human counterparts. The major apolipoprotein found in LDL, IDL and VLDL, which has a molecular weight of approximately 550 kD, is a homologue of apoB100. The major apolipoprotein found in both HDL(2) and HDL(3), has a molecular weight of 28-kD and is homologous to human apoA-I. HDL(3) also contains a 6.5 kD protein that is homologous to apoA-II, while HDL(2) has two low molecular weight proteins of 6 kD and 7 kD which are also found on the triglyceride rich lipoproteins (TRL). The 7 kD protein is homologous to apoC-III, while the 6 kD protein has a similar size and distribution as apoC-II or apoC-I. In addition, HDL(2) also possesses a protein of 15.8 kD that has no obvious mammalian homologue. In both size and apolipoprotein composition, turtle HDL(2) resembles human HDL(2b) while turtle HDL(3) resembles human HDL(3). In the fasted state, turtles contained very little TRL. When fed a high fat diet, the amount of IDL and LDL sized particles increased significantly.

Epilepsy Treatment Simplified through Mobile Ketogenic Diet Planning.

PubMed

Li, Hanzhou; Jauregui, Jeffrey L; Fenton, Cagla; Chee, Claire M; Bergqvist, A G Christina

2014-07-01

The Ketogenic Diet (KD) is an effective, alternative treatment for refractory epilepsy. This high fat, low protein and carbohydrate diet mimics the metabolic and hormonal changes that are associated with fasting. To maximize the effectiveness of the KD, each meal is precisely planned, calculated, and weighed to within 0.1 gram for the average three-year duration of treatment. Managing the KD is time-consuming and may deter caretakers and patients from pursuing or continuing this treatment. Thus, we investigated methods of planning KD faster and making the process more portable through mobile applications. Nutritional data was gathered from the United States Department of Agriculture (USDA) Nutrient Database. User selected foods are converted into linear equations with n variables and three constraints: prescribed fat content, prescribed protein content, and prescribed carbohydrate content. Techniques are applied to derive the solutions to the underdetermined system depending on the number of foods chosen. The method was implemented on an iOS device and tested with varieties of foods and different number of foods selected. With each case, the application's constructed meal plan was within 95% precision of the KD requirements. In this study, we attempt to reduce the time needed to calculate a meal by automating the computation of the KD via a linear algebra model. We improve upon previous KD calculators by offering optimal suggestions and incorporating the USDA database. We believe this mobile application will help make the KD and other dietary treatment preparations less time consuming and more convenient.

Growth regulation of the mammalian ocular lens by vitreous humor.

PubMed

Banerjee, A; Parafina, J; Bagchi, M

1992-05-01

Experiments were performed in our laboratory to study the effects of a mammalian 8 kD vitreous humor (VH) factor on the DNA synthesis and mitosis of the epithelial cells of organ cultured rabbit lens. The 8 kD polypeptide factor was purified from mature rabbit vitreous humor by liquid chromatography. Proliferative activities of the epithelial cells of organ cultured lenses were stimulated by 3% rabbit serum. The data from our experiments depicted that the 8 kD VH factor effectively inhibits DNA synthesis and mitosis by the epithelial cells of the organ cultured lens. Our experiments also showed that this 8 kD VH factor can maintain its growth inhibitory activity even when heated for 3 min at 95 degrees C. The growth inhibitory effect of the 8 kD VH factor was dose dependent. Using iodinated vitreal proteins it was demonstrated that the VH proteins are able to enter or bind to lens epithelial cells. The growth inhibitory effect of the 8 kD VH factor was also tested on tissue cultured lens epithelial cells. These experiments showed that the 8 kD VH factor has no growth inhibitory effect on the tissue cultured lens epithelial cells. This experiment has been repeated many times using different concentrations of the factor. These observations suggest that the 8 kD VH factor may have receptors in the lens capsular material (extracellular matrix) and the factor-receptor binding is essential for the growth inhibitory effect.

Molecular cloning of a ripening-specific lipoxygenase and its expression during wild-type and mutant tomato fruit development.

PubMed Central

Kausch, K D; Handa, A K

1997-01-01

A 94-kD protein that accumulates predominately in tomato (Ly-copersicon esculentum) fruit during ripening was purified, and antibodies specific for the purified protein were used to isolate cDNA clones from a red-ripe fruit cDNA library. A sequence analysis of these cDNAs and cross-reactivity of the 94-kD-specific antibodies to the soybean lipoxygenase (LOX) L-1, L-2, and L-3 proteins and soybean LOX L-1-specific antibodies to the 94-kD protein identified it as a member of the LOX gene family. Maximum levels of the 94-kD LOX mRNA and protein are present in breaker to ripe and red-ripe stages, respectively. Expression of 94-kD LOX in different tissues from mature green and red-ripe tomato fruits was found to be greatest in the radial walls of ripe fruit, but immunocytolocalization using tissue printing suggests that the highest accumulation of its protein occurs in locular jelly. None of 94-kD LOX is expressed in nonripening mutant fruits of any age. Never-ripe mutant fruit accumulate the 94-kD LOX mRNA to levels similar to those obtained in wild-type fruit, but fail to accumulate the 94-kD LOX protein. Collectively, the results show that expression of 94-kD LOX is regulated by the ripening process, and ethylene may play a role in its protein accumulation. PMID:9112767

Management of Kawasaki disease

PubMed Central

Eleftheriou, D; Levin, M; Shingadia, D; Tulloh, R; Klein, NJ; Brogan, PA

2014-01-01

Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances. PMID:24162006

Muscarinic receptor occupation and receptor activation in the guinea-pig ileum by some acetamides related to oxotremorine.

PubMed Central

Ringdahl, B.

1984-01-01

The dissociation constants (KD values) and relative efficacies of seven acetamide analogues of oxotremorine, including two enantiomeric pairs, at muscarinic receptors in the guinea-pig isolated ileum were determined. The method used involved analysis of dose-response data before and after fractional inactivation of receptors with propylbenzilylcholine mustard. All of the compounds studied had lower affinities than oxotremorine, but some had substantially higher relative efficacies. Replacement of the pyrrolidine ring of N-methyl-N-(4- pyrrolidino -2- butynyl )acetamide(I), the parent compound in the series, by a dimethylamino or a trimethylammonium group decreased the affinity 32 and 4.5 fold, respectively, whereas the relative efficacy increased 5.7-8.3 times. There was no correlation between relative efficacies and affinities of the compounds. The structural requirements for high affinity and high efficacy appeared to be quite different. PMID:6733356

Analysis of the generalized (2+1)-dimensional Nizhnik-Novikov-Veselov equations with variable coefficients in an inhomogeneous medium

NASA Astrophysics Data System (ADS)

Chai, Han-Peng; Tian, Bo; Zhen, Hui-Ling; Chai, Jun; Guan, Yue-Yang

2017-08-01

Korteweg-de Vries (KdV)-type equations are seen to describe the shallow-water waves, lattice structures and ion-acoustic waves in plasmas. Hereby, we consider an extension of the KdV-type equations called the generalized (2+1)-dimensional Nizhnik-Novikov-Veselov equations with variable coefficients in an inhomogeneous medium. Via the Hirota bilinear method and symbolic computation, we derive the bilinear forms, N-soliton solutions and Bäcklund transformation. Effects of the first- and higher-order dispersion terms are investigated. Soliton evolution and interaction are graphically presented and analyzed: Both the propagation velocity and direction of the soliton change when the dispersion terms are time-dependent; The interactions between/among the solitons are elastic, independent of the forms of the coefficients in the equations.

A mRNA-Responsive G-Quadruplex-Based Drug Release System

PubMed Central

Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

2015-01-01

G-quadruplex-based drug delivery carriers (GDDCs) were designed to capture and release a telomerase inhibitor in response to a target mRNA. Hybridization between a loop on the GDDC structure and the mRNA should cause the G-quadruplex structure of the GDDC to unfold and release the bound inhibitor, anionic copper(II) phthalocyanine (CuAPC). As a proof of concept, GDDCs were designed with a 10-30-mer loop, which can hybridize with a target sequence in epidermal growth factor receptor (EGFR) mRNA. Structural analysis using circular dichroism (CD) spectroscopy showed that the GDDCs form a (3 + 1) type G-quadruplex structure in 100 mM KCl and 10 mM MgCl2 in the absence of the target RNA. Visible absorbance titration experiments showed that the GDDCs bind to CuAPC with Ka values of 1.5 × 105 to 5.9 × 105 M−1 (Kd values of 6.7 to 1.7 μM) at 25 °C, depending on the loop length. Fluorescence titration further showed that the G-quadruplex structure unfolds upon binding to the target RNA with Ka values above 1.0 × 108 M−1 (Kd values below 0.01 μM) at 25 °C. These results suggest the carrier can sense and bind to the target RNA, which should result in release of the bound drug. Finally, visible absorbance titration experiments demonstrated that the GDDC release CuAPC in response to the target RNA. PMID:25905703

Differential processing of the two subunits of human choriogonadotropin (hCG) by granulosa cells. I. Preparation and characterization of selectively labeled hCG

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

Landefeld, T.D.; Byrne, M.D.; Campbell, K.L.

1981-12-01

The alpha- and beta-subunits of hCG were radioiodinated and recombined with unlabeled complementary subunits. The resultant recombined hormones, selectively labeled in either the alpha- or beta-subunit, were separated from unrecombined subunit by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, extracted with Triton X-100, and characterized by binding analysis. The estimates of maximum binding (active fraction) of the two resultant selectively labeled, recombined hCG preparations, determined with excess receptor were 0.41 and 0.59. These values are similar to those obtained when hCG is labeled as an intact molecule. The specific activities of the recombined preparations were estimated by four different methods, and themore » resulting values were used in combination with the active fraction estimates to determine the concentrations of active free and bound hormone. Binding analyses were run using varying concentrations of both labeled and unlabeled hormone. Estimates of the equilibrium dissociation binding constant (Kd) and receptor capacity were calculated in three different ways. The mean estimates of capacity (52.6 and 52.7 fmol/mg tissue) and Kd (66.6 and 65.7 pM) for the two preparations were indistinguishable. Additionally, these values were similar to values reported previously for hCG radioiodinated as an intact molecule. The availability of well characterized, selectively labeled hCG preparations provides new tools for studying the mechanism of action and the target cell processing of the subunits of this hormone.« less

Diagnostic accuracy of the clinical and CT findings for differentiating Kikuchi's disease and tuberculous lymphadenitis presenting with cervical lymphadenopathy.

PubMed

Baek, Hye Jin; Lee, Jeong Hyun; Lim, Hyun Kyung; Lee, Ha Young; Baek, Jung Hwan

2014-11-01

To determine the optimal clinical and CT findings for differentiating Kikuchi's disease (KD) and tuberculous lymphadenitis (TB) in patients presenting with cervical lymphadenopathy. From 2006 to 2010, 87 consecutive patients who were finally diagnosed with KD or TB were enrolled. Two radiologists performed independent analysis of contrast-enhanced neck CT images with regard to the involvement pattern, nodal or perinodal changes, and evidence of the previous infection. Significant clinical and CT findings of KD were determined by statistical analyses. Of the 87 patients, 27 (31%) were classified as having KD and 60 (69%) as having TB. Statistically significant findings of KD patients were younger age, presence of fever, involvement of ≥5 nodal levels or the bilateral neck, no or minimal nodal necrosis, marked perinodal infiltration, and no evidence of upper lung lesion or mediastinal lymphadenopathy. The presence of four or more statistically significant clinical and CT findings of KD had the largest area under the receiver-operating characteristic curve (A z = 0.861; 95% confidence intervals 0.801, 0.909), with a sensitivity of 89% and specificity of 83%. CT can be a helpful tool for differentiating KD from TB, especially when it is combined with the clinical findings.

An optimal serum-free defined condition for in vitro culture of kidney organoids.

PubMed

Nishikawa, Masaki; Kimura, Hiroshi; Yanagawa, Naomi; Hamon, Morgan; Hauser, Peter; Zhao, Lifu; Jo, Oak D; Yanagawa, Norimoto

2018-07-02

Kidney organoid is an emerging topic of importance for research in kidney development and regeneration. Conventional culture systems for kidney organoids reported thus far use culture media containing serum, which may compromise our understanding and the potential clinical applicability of the organoid system. In our present study, we tested two serum-free culture conditions and compared their suitability for the maintenance and growth of kidney organoids in culture. One of the serum-free culture conditions was the combination of keratinocytes serum free medium (KSFM) with knockout serum replacement (KSR) (KSFM + KSR), and the other was the combination of knockout DMEM/F12 (KD/F12) and KSR (KD/F12 + KSR). With cell aggregates derived from E12.5 mouse embryonic kidneys, we found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2 + nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis. With KD/F12 + KSR, we found that lower concentrations of KSR at 5-10% were superior to a higher concentration (20%) in promoting the growth of aggregates without affecting the expression levels of NPC marker genes. We also found that NPC in aggregates retained their differentiation potential to develop nephron tubules through mesenchyme-to-epithelial transition (MET), after being maintained in culture under these conditions for up to 7 days. In conclusion, we have identified a defined serum-free culture condition suitable for the maintenance and growth of kidney organoids that retain the differentiation potential to develop nephron structures. This defined serum-free culture condition may serve as a useful platform for further investigation of kidney organoids in vitro. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS.

PubMed

Dohmen, Luuk C T; Navas, Adriana; Vargas, Deninson Alejandro; Gregory, David J; Kip, Anke; Dorlo, Thomas P C; Gomez, Maria Adelaida

2016-04-29

Within its mammalian host, Leishmania resides and replicates as an intracellular parasite. The direct activity of antileishmanials must therefore depend on intracellular drug transport, metabolism, and accumulation within the host cell. In this study, we explored the role of human macrophage transporters in the intracellular accumulation and antileishmanial activity of miltefosine (MLF), the only oral drug available for the treatment of visceral and cutaneous leishmaniasis (CL). Membrane transporter gene expression in primary human macrophages infected in vitro with Leishmania Viannia panamensis and exposed to MLF showed modulation of ABC and solute liquid carrier transporters gene transcripts. Among these, ABCA3, a lipid transporter, was significantly induced after exposure to MLF, and this induction was confirmed in primary macrophages from CL patients. Functional validation of MLF as a substrate for ABCA3 was performed by shRNA gene knockdown (KD) in THP-1 monocytes. Intracellular accumulation of radiolabeled MLF was significantly higher in ABCA3(KD) macrophages. ABCA3(KD) resulted in increased cytotoxicity induced by MLF exposure. ABCA3 gene expression inversely correlated with intracellular MLF content in primary macrophages from CL patients. ABCA3(KD) reduced parasite survival during macrophage infection with an L. V. panamensis strain exhibiting low in vitro susceptibility to MLF. Confocal microscopy showed ABCA3 to be located in the cell membrane of resting macrophages and in intracellular compartments in L. V. panamensis-infected cells. These results provide evidence of ABCA3 as an MLF efflux transporter in human macrophages and support its role in the direct antileishmanial effect of this alkylphosphocholine drug. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Acute anticonvulsant effects of capric acid in seizure tests in mice.

PubMed

Wlaź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Żarnowski, Tomasz; Żarnowska, Iwona; Czuczwar, Stanisław J; Gasior, Maciej

2015-03-03

Capric acid (CA10) is a 10-carbon medium-chain fatty acid abundant in the medium-chain triglyceride ketogenic diet (MCT KD). The purpose of this study was to characterize acute anticonvulsant effects of CA10 across several seizure tests in mice. Anticonvulsant effects of orally (p.o.) administered CA10 were assessed in the maximal electroshock seizure threshold (MEST), 6-Hz seizure threshold, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests in mice. Acute effects of CA10 on motor coordination were assessed in the grip and chimney tests. Plasma and brain concentrations of CA10 were measured. Co-administration studies with CA10 and another abundant medium-chain fatty acid, caprylic acid (CA8) were performed. CA10 showed significant and dose-dependent anticonvulsant properties by increasing seizure thresholds in the 6-Hz and MEST seizure tests; it was ineffective in the i.v. PTZ seizure test. At higher doses than those effective in the 6-Hz and MEST seizure tests, CA10 impaired motor performance in the grip and chimney tests. An enhanced anticonvulsant response in the 6-Hz seizure test was produced when CA8 and CA10 were co-administered. An acute p.o. administration of CA10 resulted in dose-proportional increases in its plasma and brain concentrations. CA10 exerted acute anticonvulsant effects at doses that produce plasma exposures comparable to those reported in epileptic patients on the MCT KD. An enhanced anticonvulsant effect is observed when CA10 and the other main constituent of the MCT KD, CA8, were co-administered. Thus, acute anticonvulsant properties of CA10 and CA8 may influence the overall clinical efficacy of the MCT KD. Copyright © 2014. Published by Elsevier Inc.

Bio-optical anomalies in the world's oceans: An investigation on the diffuse attenuation coefficients for downward irradiance derived from Biogeochemical Argo float measurements

NASA Astrophysics Data System (ADS)

Organelli, Emanuele; Claustre, Hervé; Bricaud, Annick; Barbieux, Marie; Uitz, Julia; D'Ortenzio, Fabrizio; Dall'Olmo, Giorgio

2017-05-01

Identification of oceanic regions characterized by particular optical properties is extremely important for ocean color applications. The departure from globally established bio-optical models (i.e., anomaly) introduces uncertainties in the retrieval of biogeochemical quantities from satellite observations. Thanks to an array of 105 Biogeochemical Argo floats acquiring almost daily downward irradiance measurements at selected wavelengths in the UV and blue region of the spectrum, we reexamined the natural variability of the spectral diffuse attenuation coefficients, Kd(λ), among the world's oceans and compared them to previously established bio-optical models. The analysis of 2847 measurements of Kd(λ) at 380 and 490 nm, within the first optical depth, provided a classification of the examined regions into three groups. The first one included the Black Sea, a water body characterized by a very high content of colored dissolved organic matter (CDOM). The second group was essentially composed by the subtropical gyres (Atlantic and Pacific Oceans), with optical properties consistent with previous models (i.e., no anomalies). High latitude (North Atlantic and Southern oceans) and temperate (Mediterranean Sea) seas formed the third group, in which optical properties departed from existing bio-optical models. Annual climatologies of the Kd(380)/Kd(490) ratio evidenced a persistent anomaly in the Mediterranean Sea, that we attributed to a higher-than-average CDOM contribution to total light absorption. In the North Atlantic subpolar gyre, anomalies were observed only in wintertime and were also attributed to high CDOM concentrations. In the Southern Ocean, the anomaly was likely related to high phytoplankton pigment packaging rather than to CDOM.

Impaired binding affinity of electronegative low-density lipoprotein (LDL) to the LDL receptor is related to nonesterified fatty acids and lysophosphatidylcholine content.

PubMed

Benítez, Sonia; Villegas, Virtudes; Bancells, Cristina; Jorba, Oscar; González-Sastre, Francesc; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

2004-12-21

The binding characteristics of electropositive [LDL(+)] and electronegative LDL [LDL(-)] subfractions to the LDL receptor (LDLr) were studied. Saturation kinetic studies in cultured human fibroblasts demonstrated that LDL(-) from normolipemic (NL) and familial hypercholesterolemic (FH) subjects had lower binding affinity than their respective LDL(+) fractions (P < 0.05), as indicated by higher dissociation constant (K(D)) values. FH-LDL(+) also showed lower binding affinity (P < 0.05) than NL-LDL(+) (K(D), sorted from lower to higher affinity: NL-LDL(-), 33.0 +/- 24.4 nM; FH-LDL(-), 24.4 +/- 7.1 nM; FH-LDL(+), 16.6 +/- 7.0 nM; NL-LDL(+), 10.9 +/- 5.7 nM). These results were confirmed by binding displacement studies. The impaired affinity binding of LDL(-) could be attributed to altered secondary and tertiary structure of apolipoprotein B, but circular dichroism (CD) and tryptophan fluorescence (TrpF) studies revealed no structural differences between LDL(+) and LDL(-). To ascertain the role of increased nonesterified fatty acids (NEFA) and lysophosphatidylcholine (LPC) content in LDL(-), LDL(+) was enriched in NEFA or hydrolyzed with secretory phospholipase A(2). Modification of LDL gradually decreased the affinity to LDLr in parallel to the increasing content of NEFA and/or LPC. Modified LDLs with a NEFA content similar to that of LDL(-) displayed similar affinity. ApoB structure studies of modified LDLs by CD and TrpF showed no difference compared to LDL(+) or LDL(-). Our results indicate that NEFA loading or phospholipase A(2) lipolysis of LDL leads to changes that affect the affinity of LDL to LDLr with no major effect on apoB structure. Impaired affinity to the LDLr shown by LDL(-) is related to NEFA and/or LPC content rather than to structural differences in apolipoprotein B.

Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix

PubMed Central

Mohammadi, Hamid; Pinto, Vanessa I.; Wang, Yongqiang; Hinz, Boris; Janmey, Paul A.; McCulloch, Christopher A.

2016-01-01

Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~ 4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported collagen gels that create lateral boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix. PMID:26134946

Colloid-Mediated Transport of PPCPs through Porous Media

NASA Astrophysics Data System (ADS)

Chen, Xijuan; Xing, Yingna; Chen, Xin; Zhuang, Jie

2017-04-01

Pharmaceutical and personal care products (PPCPs) enter the soil through reclaimed water irrigation and biosolid land application. Colloids, such as clays that are present in soil, may interact with PPCPs to affect their fate and transport in the subsurface environment. This study addresses how soil colloids mediate the sorption and transport behaviors of PPCPs through laboratory column experiments. The affinities of PPCPs for colloids as well as the influence factors were investigated. For PPCPs that have high sorption (e.g., ciprofloxacin with Kd ˜104-5 L/kg) on soil colloids, the transport is dominantly controlled by colloids, with a higher extent of colloid-facilitated effect at lower ionic strength. For PPCPs that have intermediate sorption (e.g., tetracycline with Kd ˜103-4 L/kg) on soil colloids, the mobility of dissolved and colloid-bound PPCPs respond oppositely to the effect of changes in solution ionic strength, making the net effect of soil colloids on PPCP transport variable with soil solution chemistry. For PPCPs with low sorption (e.g., ibuprofen with Kd ˜102-3 L/kg) on soil colloids, other measures (such as pre-filtration) must be taken. This study suggested that colloids are significant carriers of PPCPs in the subsurface environment and could affect their off-site environmental risks.

Classification of coronary artery tissues using optical coherence tomography imaging in Kawasaki disease

NASA Astrophysics Data System (ADS)

Abdolmanafi, Atefeh; Prasad, Arpan Suravi; Duong, Luc; Dahdah, Nagib

2016-03-01

Intravascular imaging modalities, such as Optical Coherence Tomography (OCT) allow nowadays improving diagnosis, treatment, follow-up, and even prevention of coronary artery disease in the adult. OCT has been recently used in children following Kawasaki disease (KD), the most prevalent acquired coronary artery disease during childhood with devastating complications. The assessment of coronary artery layers with OCT and early detection of coronary sequelae secondary to KD is a promising tool for preventing myocardial infarction in this population. More importantly, OCT is promising for tissue quantification of the inner vessel wall, including neo intima luminal myofibroblast proliferation, calcification, and fibrous scar deposits. The goal of this study is to classify the coronary artery layers of OCT imaging obtained from a series of KD patients. Our approach is focused on developing a robust Random Forest classifier built on the idea of randomly selecting a subset of features at each node and based on second- and higher-order statistical texture analysis which estimates the gray-level spatial distribution of images by specifying the local features of each pixel and extracting the statistics from their distribution. The average classification accuracy for intima and media are 76.36% and 73.72% respectively. Random forest classifier with texture analysis promises for classification of coronary artery tissue.

Innovative In-Situ Remediation of Contaminated Sediments for Simultaneous Control of Contamination and Erosion. Part 1

DTIC Science & Technology

2010-12-27

Erosion Rates and Critical Shear Stress ......................... 45 Erosion Rate Ratio Analysis...inductively coupled plasma – mass spectrometry Kd – partition coefficient Meq – milliequivalents MNR – monitored natural recovery SRNL-STI-2010...186 Figure 82. Critical Shear Stress Comparison among Biopolymer Materials at 2, 10, and 175 Days. Each value is an average of

Behaviour of pharmaceuticals in spiked lake sediments - effects and interactions with benthic invertebrates.

PubMed

Gilroy, Ève A M; Balakrishnan, Vimal K; Solomon, Keith R; Sverko, Ed; Sibley, Paul K

2012-02-01

The behaviour and effects of atorvastatin (ATO), carbamazepine (CBZ), and 17α-ethinylestradiol (EE2) were investigated in spiked lake sediments, at concentrations up to 56.5 mg kg(-1)dry weight (dw), with the benthic invertebrates Chironomus dilutus and Hyalella azteca. Desorption constants were calculated in the presence and absence of animals, using linear isotherms, yielding K(d) values of 28.2, 189.0 and 125.1 L kg(-1) (ATO), 73.7, 201.7 and 263.2 L kg(-1) (CBZ), and 114.9, 114.2 and 519.2 L kg(-1) (EE2) for C. dilutus, H. azteca, and without animals, respectively. For ATO and CBZ, K(d) values were smaller in the presence of C. dilutus, indicating greater desorption to the overlying water from bioturbation, which is consistent with the predominantly benthic occurrence of C. dilutus compared to H. azteca. In contrast, due to its greater hydrophobicity, bioturbation did not significantly affect desorption of EE2. No significant toxicity was observed, indicating decreased bioavailability of the chemicals sorbed to sediments compared with water-only toxicity assays. Copyright © 2011 Elsevier Ltd. All rights reserved.

The application and properties of composite sorbents of inorganic ion exchangers and polyacrylonitrile binding matrix.

PubMed

Nilchi, A; Khanchi, A; Atashi, H; Bagheri, A; Nematollahi, L

2006-10-11

A description is given of the preparation and properties of potassium hexacyanocobalt (II) ferrate (II) (KCFC) and the composite, potassium hexacyanocobalt (II) ferrate (II)-polyacrylonitrile (KCFC-PAN). The materials were dried at high temperatures and characterized by chemical analysis, scanning electron microscope, X-ray diffraction, inductively coupled plasma and infrared. The ion exchange of alkaline earth metals and molybdenum on a nonstoichiometric compound K(2)[CoFe(CN)(6)] and its PAN based absorber was examined by batch methods. The adsorption of molybdenum from aqueous solutions on KCFC-PAN was investigated and optimized as a function of equilibration time and pH. The materials which were dried at optimum high temperature of 110 degrees C were found to be stable in water, dilute acids, alkaline solutions and relatively high temperature. The distribution coefficient values K(d) for alkaline earth metals, followed the same trend of increase for both sets of absorbers studied, i.e. Ba(2+)>Sr(2+)>Ca(2+)>Mg(2+), which closely resembles to the order of the size of the hydrated cations. However, the K(d) values show a significant increase for PAN based absorbers in comparison to KCFC absorbers.

Evaluating the potential for remote bathymetric mapping of a turbid, sand-bed river: 1. field spectroscopy and radiative transfer modeling

USGS Publications Warehouse

Legleiter, Carl J.; Kinzel, Paul J.; Overstreet, Brandon T.

2011-01-01

Remote sensing offers an efficient means of mapping bathymetry in river systems, but this approach has been applied primarily to clear-flowing, gravel bed streams. This study used field spectroscopy and radiative transfer modeling to assess the feasibility of spectrally based depth retrieval in a sand-bed river with a higher suspended sediment concentration (SSC) and greater water turbidity. Attenuation of light within the water column was characterized by measuring the amount of downwelling radiant energy at different depths and calculating a diffuse attenuation coefficient, Kd. Attenuation was strongest in blue and near-infrared bands due to scattering by suspended sediment and absorption by water, respectively. Even for red wavelengths with the lowest values of Kd, only a small fraction of the incident light propagated to the bed, restricting the range of depths amenable to remote sensing. Spectra recorded above the water surface were used to establish a strong, linear relationship (R2 = 0.949) between flow depth and a simple band ratio; even under moderately turbid conditions, depth remained the primary control on reflectance. Constraints on depth retrieval were examined via numerical modeling of radiative transfer within the atmosphere and water column. SSC and sensor radiometric resolution limited both the maximum detectable depth and the precision of image-derived depth estimates. Thus, although field spectra indicated that the bathymetry of turbid channels could be remotely mapped, model results implied that depth retrieval in sediment-laden rivers would be limited to shallow depths (on the order of 0.5 m) and subject to a significant degree of uncertainty.

The King-Devick test and sports-related concussion: study of a rapid visual screening tool in a collegiate cohort.

PubMed

Galetta, Kristin M; Brandes, Lauren E; Maki, Karl; Dziemianowicz, Mark S; Laudano, Eric; Allen, Megan; Lawler, Kathy; Sennett, Brian; Wiebe, Douglas; Devick, Steve; Messner, Leonard V; Galetta, Steven L; Balcer, Laura J

2011-10-15

Concussion, defined as an impulse blow to the head or body resulting in transient neurologic signs or symptoms, has received increasing attention in sports at all levels. The King-Devick (K-D) test is based on the time to perform rapid number naming and captures eye movements and other correlates of suboptimal brain function. In a study of boxers and mixed martial arts (MMA) fighters, the K-D test was shown to have high degrees of test-retest and inter-rater reliability and to be an accurate method for rapidly identifying boxers and mixed martial arts fighters with concussion. We performed a study of the K-D test as a rapid sideline screening tool in collegiate athletes to determine the effect of concussion on K-D scores compared to a pre-season baseline. In this longitudinal study, athletes from the University of Pennsylvania varsity football, sprint football, and women's and men's soccer and basketball teams underwent baseline K-D testing prior to the start of the 2010-11 playing season. Post-season testing was also performed. For athletes who had concussions during the season, K-D testing was administered immediately on the sidelines and changes in score from baseline were determined. Among 219 athletes tested at baseline, post-season K-D scores were lower (better) than the best pre-season scores (35.1 vs. 37.9s, P=0.03, Wilcoxon signed-rank test), reflecting mild learning effects in the absence of concussion. For the 10 athletes who had concussions, K-D testing on the sidelines showed significant worsening from baseline (46.9 vs. 37.0s, P=0.009), with all except one athlete demonstrating worsening from baseline (median 5.9s). This study of collegiate athletes provides initial evidence in support of the K-D test as a strong candidate rapid sideline visual screening tool for concussion. Data show worsening of scores following concussion, and ongoing follow-up in this study with additional concussion events and different athlete populations will further examine the effectiveness of the K-D test. Copyright © 2011 Elsevier B.V. All rights reserved.

PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

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

Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp; Uchida, Daisuke; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki

Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD).more » To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR{alpha}-null mice. PPAR{gamma} activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression in the fatty liver.« less

Effect of N-benzoyl-D-phenylalanine and metformin on insulin receptors in neonatal streptozotocin-induced diabetic rats: studies on insulin binding to erythrocytes.

PubMed

Ashokkumar, N; Pari, L; Rao, Ch Appa

2006-07-01

In the present study, we focused on the insulin-receptor binding in circulating erythrocytes of N-benzoyl-D-phenylalanine (NBDP) and metformin in neonatal streptozotocin (nSTZ)-induced male Wistar rats. We measured blood levels of glucose and plasma insulin and the binding of insulin to cell-membrane ER receptors in NBDP and metformin-treated diabetic rats. The mean specific binding of insulin to ER was significantly lower in diabetic control rats (DC) (53.0 +/- 3.1%) than in NBDP (62.0 +/- 3.1%), metformin (66.0 +/- 3.3%) and NBDP and metformin combination-treated (72.0 +/- 4.2%) diabetic rats, resulting in a significant decrease in plasma insulin. Scatchard plot analysis demonstrated that the decrease in insulin binding was accounted for by a lower number of insulin receptor sites per cell in DC rats when compared with NBDP and metformin-treated rats. High-affinity (Kd1), low-affinity (Kd2), and kinetic analysis revealed an increase in the average receptor affinity in ER from NBDP and metformin-treated diabetic rats having NBDP 2.0 +/- 0.10 x 10(-10) M(-1) (Kd1); 12.0 +/- 0.85 x 10(-8) M(-1) (Kd2), Metformin 2.1 +/- 0.15 x 10(-10) M(-1) (Kd1); 15.0 +/- 0.80 x 10(-8) M(-1) (Kd2), NBDP and metformin 2.7 +/- 0.10 x 10(-10) M(-1) (Kd1); 20.0 +/- 1.2 x 10(-8) M(-1) (Kd2) compared with 0.9 +/- 0.06 x 10(-10) M(-1) (Kd1); 6.0 +/- 0.30 x 10(-8) M(-1) (Kd2) in DC rats. The results suggest an acute alteration in the number of insulin receptors on ER membranes in nSTZ induced diabetic control rats. Treatment with NBDP along with metformin significantly improved specific insulin binding, with receptor number and affinity binding reaching almost normal non-diabetic levels. The data presented here show that NBDP along with metformin increase total ER membrane insulin binding sites with a concomitant significant increase in plasma insulin.

Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet.

PubMed

Hu, Xiao-Ling; Cheng, Xuewen; Fei, Jian; Xiong, Zhi-Qi

2011-09-01

The ketogenic diet (KD) has been used as an effective antiepileptic treatment for nearly a century. Inhibition of glycolysis and increased levels of ketone bodies are both known to contribute to the antiepileptic effects of the KD. Neuron-restrictive silencer factor (NRSF), also known as RE-1 silencing transcription factor (REST), is implicated in the antiepileptic effects of the glycolytic inhibitor 2-deoxy-d-glucose (2DG). Glycolytic inhibition is a common feature of the KD and 2DG treatment, leading to the hypothesis that NRSF might also be involved in the antiepileptic effect of the KD. To test this hypothesis, the present study was designed to investigate the role of NRSF in the antiepileptic effect of 2DG, the KD, and acetone in vivo. Kindling was used as a model to test the antiepileptic effects of 2DG, the KD, and acetone on control and NRSF conditional knockout mice (NRSF-cKO; from the intercross of CamKIIα-iCre and NRSF exon 2 floxed mice). After recovery from electrode implantation, adult mice were stimulated twice a day at afterdischarge threshold (ADT) current intensity. In the 2DG- (500 mg/kg) and acetone- (10 mmol/kg) treated groups, drugs were injected intraperitoneally 20 min before each stimulus. In the 2DG group, mice were pretreated with intraperitoneal injections for 3 days in addition to the injections administered before the regular kindling stimulation. In the KD group, mice were fed the KD instead of a control diet until the end of stimulations. Compared with control mice, the antiepileptic effect of 2DG was abolished in NRSF-cKO mice, indicating that NRSF is required for the antiepileptic effect of 2DG. In the KD-fed group, kindling development was retarded in both control and NRSF-cKO mice. In the acetone-treated group, inhibition of kindling-induced epileptogenesis was observed in both control and NRSF-cKO mice, similar to the action of the KD. These findings imply that NRSF repression complex is not essential for the antiepileptic effect of the ketogenic diet. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Soluble scute proteins of healthy and ill desert tortoises (Gopherus agassizii)

USGS Publications Warehouse

Homer, B.L.; Li, C.; Berry, K.H.; Denslow, N.D.; Jacobson, E.R.; Sawyer, R.H.; Williams, J.E.

2001-01-01

Objectives - To characterize protein composition of shell scute of desert tortoises and to determine whether detectable differences could be used to identify healthy tortoises from tortoises with certain illnesses. Animals - 20 desert tortoises. Procedures - Complete postmortem examinations were performed on all tortoises. Plastron scute proteins were solubilized, scute proteins were separated by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and proteins were analyzed, using densitometry. Two-dimensional immobilized pH gradient-PAGE (2D IPG-PAGE) and immunoblot analysis, using polyclonal antisera to chicken-feather ?? keratin and to alligator-scale ?? keratin, were conducted on representative samples. The 14-kd proteins were analyzed for amino acid composition. Results - The SDS-PAGE and densitometry revealed 7 distinct bands, each with a mean relative protein concentration of > 1 %, ranging from 8 to 47 kd, and a major protein component of approximately 14 kd that constituted up to 75% of the scute protein. The 2D IPG-PAGE revealed additional distinct 62-and 68-kd protein bands. On immunoblot analysis, the 14-, 32-, and 45-kd proteins reacted with both antisera. The 14-kd proteins had an amino acid composition similar to that of chicken ?? keratins. There was a substantial difference in the percentage of the major 14-kd proteins from scute of ill tortoises with normal appearing shells, compared with 14-kd proteins of healthy tortoises. Conclusions and Clinical Relevance - The major protein components of shell scute of desert tortoises have amino acid composition and antigenic features of ?? keratins. Scute protein composition may be altered in tortoises with certain systemic illnesses.

Monoclonal antibodies to the light-harvesting chlorophyll a/b protein complex of photosystem II

PubMed Central

1986-01-01

A collection of 17 monoclonal antibodies elicited against the light- harvesting chlorophyll a/b protein complex which serves photosystem II (LHC-II) of Pisum sativum shows six classes of binding specificity. Antibodies of two of the classes recognize a single polypeptide (the 28- or the 26- kD polypeptides), thereby suggesting that the two proteins are not derived from a common precursor. Other classes of antibodies cross-react with several polypeptides of LHC-II or with polypeptides of both LHC-II and the light-harvesting chlorophyll a/b polypeptides of photosystem I (LHC-I), indicating that there are structural similarities among the polypeptides of LHC-II and LHC-I. The evidence for protein processing by which the 26-, 25.5-, and 24.5-kD polypeptides are derived from a common precursor polypeptide is discussed. Binding studies using antibodies specific for individual LHC- II polypeptides were used to quantify the number of antigenic polypeptides in the thylakoid membrane. 27 copies of the 26-kD polypeptide and two copies of the 28-kD polypeptide were found per 400 chlorophylls. In the chlorina f2 mutant of barley, and in intermittent light-treated barley seedlings, the amount of the 26-kD polypeptide in the thylakoid membranes was greatly reduced, while the amount of 28-kD polypeptide was apparently not affected. We propose that stable insertion and assembly of the 28-kD polypeptide, unlike the 26-kD polypeptide, is not regulated by the presence of chlorophyll b. PMID:3528171

Epilepsy Treatment Simplified through Mobile Ketogenic Diet Planning

PubMed Central

Li, Hanzhou; Jauregui, Jeffrey L.; Fenton, Cagla; Chee, Claire M.; Bergqvist, A.G. Christina

2017-01-01

Background The Ketogenic Diet (KD) is an effective, alternative treatment for refractory epilepsy. This high fat, low protein and carbohydrate diet mimics the metabolic and hormonal changes that are associated with fasting. Aims To maximize the effectiveness of the KD, each meal is precisely planned, calculated, and weighed to within 0.1 gram for the average three-year duration of treatment. Managing the KD is time-consuming and may deter caretakers and patients from pursuing or continuing this treatment. Thus, we investigated methods of planning KD faster and making the process more portable through mobile applications. Methods Nutritional data was gathered from the United States Department of Agriculture (USDA) Nutrient Database. User selected foods are converted into linear equations with n variables and three constraints: prescribed fat content, prescribed protein content, and prescribed carbohydrate content. Techniques are applied to derive the solutions to the underdetermined system depending on the number of foods chosen. Results The method was implemented on an iOS device and tested with varieties of foods and different number of foods selected. With each case, the application’s constructed meal plan was within 95% precision of the KD requirements. Conclusion In this study, we attempt to reduce the time needed to calculate a meal by automating the computation of the KD via a linear algebra model. We improve upon previous KD calculators by offering optimal suggestions and incorporating the USDA database. We believe this mobile application will help make the KD and other dietary treatment preparations less time consuming and more convenient. PMID:28794808

WAVE2 regulates epithelial morphology and cadherin isoform switching through regulation of Twist and Abl.

PubMed

Bryce, Nicole S; Reynolds, Albert B; Koleske, Anthony J; Weaver, Alissa M

2013-01-01

Epithelial morphogenesis is a dynamic process that involves coordination of signaling and actin cytoskeletal rearrangements. We analyzed the contribution of the branched actin regulator WAVE2 in the development of 3-dimensional (3D) epithelial structures. WAVE2-knockdown (WAVE2-KD) cells formed large multi-lobular acini that continued to proliferate at an abnormally late stage compared to control acini. Immunostaining of the cell-cell junctions of WAVE2-KD acini revealed weak and heterogeneous E-cadherin staining despite little change in actin filament localization to the same junctions. Analysis of cadherin expression demonstrated a decrease in E-cadherin and an increase in N-cadherin protein and mRNA abundance in total cell lysates. In addition, WAVE2-KD cells exhibited an increase in the mRNA levels of the epithelial-mesenchymal transition (EMT)-associated transcription factor Twist1. KD of Twist1 expression in WAVE2-KD cells reversed the cadherin switching and completely rescued the aberrant 3D morphological phenotype. Activity of the WAVE2 complex binding partner Abl kinase was also increased in WAVE2-KD cells, as assessed by tyrosine phosphorylation of the Abl substrate CrkL. Inhibition of Abl with STI571 rescued the multi-lobular WAVE2-KD 3D phenotype whereas overexpression of Abl kinase phenocopied the WAVE2-KD phenotype. The WAVE2 complex regulates breast epithelial morphology by a complex mechanism involving repression of Twist1 expression and Abl kinase activity. These data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis.

Monitoring System and Temperature Controlling on PID Based Poultry Hatching Incubator

NASA Astrophysics Data System (ADS)

Shafiudin, S.; Kholis, N.

2018-04-01

Poultry hatching cultivation is essential to be observed in terms of temperature stability by using artificial penetration incubator which applies On/Off control. The On/Off control produces relatively long response time to reach steady-state conditions. Moreover, how the system works makes the component worn out because the lamp is on-off periodically. Besides, the cultivation in the market is less suitable to be used in an environment which has fluctuating temperature because it may influence plant’s temperature stability. The study aims to design automatic poultry hatching cultivation that can repair the temperature’s response of plant incubator to keep stable and in line with the intended set-point temperature value by using PID controller. The method used in PID controlling is designed to identify plant using ARX (Auto Regressive eXogenous) MATLAB which is dynamic/non-linear to obtain mathematical model and PID constants value that is appropriate to system. The hardware design for PID-based egg incubator uses Arduino Uno R3, as the main controller that includes PID source, and PWM, to keep plant temperature stability, which is integrated with incandescent light actuators and sensors where DHTI 1 sensor as the reader as temperature condition and plant humidity. The result of the study showed that PID constants value of each plant is different. For parallel 15 Watt plant, Kp = 3.9956, Ki = 0.361, Kd = 0, while for parallel 25 Watt plant, the value of Kp = 5.714, Ki = 0.351, Kd = 0. The PID constants value were capable to produce stable system response which is based on set-point with steady state error’s value is around 5%, that is 2.7%. With hatching percentage of 70-80%, the hatching process is successful in air-conditioned environment (changeable).

Characterization of diadenosine tetraphosphate (Ap4A) binding sites in cultured chromaffin cells: evidence for a P2y site.

PubMed Central

Pintor, J.; Torres, M.; Castro, E.; Miras-Portugal, M. T.

1991-01-01

1. Diadenosine tetraphosphate (Ap4A) a dinucleotide, which is stored in secretory granules, presents two types of high affinity binding sites in chromaffin cells. A Kd value of 8 +/- 0.65 x 10(-11) M and Bmax value of 5420 +/- 450 sites per cell were obtained for the high affinity binding site. A Kd value of 5.6 +/- 0.53 x 10(-9) M and a Bmax value close to 70,000 sites per cell were obtained for the second binding site with high affinity. 2. The diadenosine polyphosphates, Ap3A, Ap4A, Ap5A and Ap6A, displaced [3H]-Ap4A from the two binding sites, the Ki values being 1.0 nM, 0.013 nM, 0.013 nM and 0.013 nM for the very high affinity binding site and 0.5 microM, 0.13 microM, 0.062 microM and 0.75 microM for the second binding site. 3. The ATP analogues displaced [3H]-Ap4A with the potency order of the P2y receptors, adenosine 5'-O-(2 thiodiphosphate) (ADP-beta-S) greater than 5'-adenylyl imidodiphosphate (AMP-PNP) greater than alpha, beta-methylene ATP (alpha, beta-MeATP), in both binding sites. The Ki values were respectively 0.075 nM, 0.2 nM and 0.75 nM for the very high affinity binding site and 0.125 microM, 0.5 microM and 0.9 microM for the second binding site. PMID:1912985

Exact Solutions, Symmetry Reductions, Painlevé Test and Bäcklund Transformations of A Coupled KdV Equation

NASA Astrophysics Data System (ADS)

Min-Hui, XU; Man, JIA

2017-10-01

A coupled KdV equation is studied in this manuscript. The exact solutions, such as the periodic wave solutions and solitary wave solutions by means of the deformation and mapping approach from the solutions of the nonlinear ϕ 4 model are given. Using the symmetry theory, the Lie point symmetries and symmetry reductions of the coupled KdV equation are presented. The results show that the coupled KdV equation possesses infinitely many symmetries and may be considered as an integrable system. Also, the Painlevé test shows the coupled KdV equation possesses Painlevé property. The Bäcklund transformations of the coupled KdV equation related to Painlevé property and residual symmetry are shown. Supported by the National Natural Science Foundation of China under Grant Nos. 11675084 and 11435005, Ningbo Natural Science Foundation under Grant No. 2015A610159 and granted by the Opening Project of Zhejiang Provincial Top Key Discipline of Physics Sciences in Ningbo University under Grant No. xkzwl1502, and the authors are sponsored by K. C. Wong Magna Fund in Ningbo University

Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study.

PubMed

Di Lorenzo, Cherubino; Coppola, Gianluca; Bracaglia, Martina; Di Lenola, Davide; Evangelista, Maurizio; Sirianni, Giulio; Rossi, Paolo; Di Lorenzo, Giorgio; Serrao, Mariano; Parisi, Vincenzo; Pierelli, Francesco

2016-01-01

Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine. Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs. After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks. KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

Extended Kd distributions for freshwater environment.

PubMed

Boyer, Patrick; Wells, Claire; Howard, Brenda

2018-06-18

Many of the freshwater K d values required for quantifying radionuclide transfer in the environment (e.g. ERICA Tool, Symbiose modelling platform) are either poorly reported in the literature or not available. To partially address this deficiency, Working Group 4 of the IAEA program MODARIA (2012-2015) has completed an update of the freshwater K d databases and K d distributions given in TRS 472 (IAEA, 2010). Over 2300 new values for 27 new elements were added to the dataset and 270 new K d values were added for the 25 elements already included in TRS 472 (IAEA, 2010). For 49 chemical elements, the K d values have been classified according to three solid-liquid exchange conditions (adsorption, desorption and field) as was previously carried out in TRS 472. Additionally, the K d values were classified into two environmental components (suspended and deposited sediments). Each combination (radionuclide x component x condition) was associated with log-normal distributions when there was at least ten K d values in the dataset and to a geometric mean when there was less than ten values. The enhanced K d dataset shows that K d values for suspended sediments are significantly higher than for deposited sediments and that the variability of K d distributions are higher for deposited than for suspended sediments. For suspended sediments in field conditions, the variability of K d distributions can be significantly reduced as a function of the suspended load that explains more than 50% of the variability of the K d datasets of U, Si, Mo, Pb, S, Se, Cd, Ca, B, K, Ra and Po. The distinction between adsorption and desorption conditions is justified for deterministic calculations because the geometric means are systematically greater in desorption conditions. Conversely, this distinction is less relevant for probabilistic calculations due to systematic overlapping between the K d distributions of these two conditions. Copyright © 2018. Published by Elsevier Ltd.

Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin.

PubMed

Kibata, Tetsuhiro; Suzuki, Yasuo; Hasegawa, Shunji; Matsushige, Takeshi; Kusuda, Takeshi; Hoshide, Madoka; Takahashi, Kazumasa; Okada, Seigo; Wakiguchi, Hiroyuki; Moriwake, Tadashi; Uchida, Masashi; Ohbuchi, Noriko; Iwai, Takashi; Hasegawa, Masanari; Ichihara, Kiyoshi; Yashiro, Mayumi; Makino, Nobuko; Nakamura, Yosikazu; Ohga, Shouichi

2016-07-01

Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial. Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months). The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders. IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cur l 3, a major allergen of Curvularia lunata-derived short synthetic peptides, shows promise for successful immunotherapy.

PubMed

Sharma, Vidhu; Singh, Bhanu Pratap; Arora, Naveen

2011-12-01

Allergens with reduced IgE binding and intact T cell reactivity are required for safety and efficacy of immunotherapy (IT). Curvularia lunata is an important fungus for respiratory allergic disorders having cross-reactive and specific allergens. Previously, we have identified major allergens-namely, Cur l 1 (31 kD, serine protease), Cur l 2 (48 kD, enolase), and Cur l 3 (12 kD, cytochrome c)-from this fungus. Furthermore, Cur l 3 epitope-peptide, P6, showed immunogenicity and higher IgE binding, where cysteine and histidine were observed to be vital for IgE binding. Thus, this peptide and three derivatives with reduced IgE binding were selected for analysis in mice. In the present study, the effect of IT was assessed with Cur l 3, P6, its derivatives (P6.1-6.3), and P10 in a mouse model of allergy. IT with P6.2 and P10 reduced IgE and IgG1 levels significantly (P < 0.05), with increase in IgG2a levels as compared to other antigens. There was a significant reduction of IL-4 level associated with increased IFN-γ after IT. Airway inflammation was reduced significantly in terms of eosinophil counts in lung tissue and bronchoalveolar lavage fluid. IT with P6 and P6.2 induced significantly higher IL-10 secretion than baseline after 40 days of treatment. Generally, the effect of IT was more pronounced after 40 days than after 10 days of treatment. In summary, the modified peptide, P6.2, with reduced IgE binding, but intact immunogenicity, showed promise for successful IT.

Septated pericarditis associated with Kawasaki disease: a brief case report.

PubMed

Sonçaği, Arzu; Devrim, Ilker; Karagöz, Tevfik; Dilber, Embiya; Celiker, Alpay; Ozen, Seza; Seçmeer, Gülten

2007-01-01

Kawasaki disease (KD) is primarily the systemic vasculitis of childhood that affects mainly the medium-sized arteries, such as the coronary arteries. KD is the leading cause of acquired heart disease, whereas the incidence of rheumatic fever has declined. The most serious complication is coronary artery involvement. Among the children with KD who developed cardiac complications, pericarditis is a rare complication, with an incidence of 0.07%. We report our experience in a 5.5-year-old child with KD complicated with aneurysm of the left anterior descendant coronary artery and septated pericardial effusion, which has not been reported in the literature. The pericardial effusion disappeared very dramatically with intravenous immunoglobulin (IVIG) therapy. We would like to point out that septated pericardial effusion in cases of KD do not need any further therapy other than IVIG and high-dose acetylsalicylic acid.

Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.

PubMed

Assari, Raheleh; Aghighi, Yahya; Ziaee, Vahid; Sadr, Maryam; Rahmani, Farzaneh; Rezaei, Arezou; Sadr, Zeinab; Moradinejad, Mohammad Hassan; Raeeskarami, Seyed Reza; Rezaei, Nima

2016-07-25

Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD. Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1β at -511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565. Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD. TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.

PubMed

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D

2012-01-01

Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes.

Augmented TLR2 Expression on Monocytes in both Human Kawasaki Disease and a Mouse Model of Coronary Arteritis

PubMed Central

Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D.

2012-01-01

Background Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Methods Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Results Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. Conclusion This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes. PMID:22737215

Soliton solution and gauge equivalence for an integrable nonlocal complex modified Korteweg-de Vries equation

NASA Astrophysics Data System (ADS)

Ma, Li-Yuan; Shen, Shou-Feng; Zhu, Zuo-Nong

2017-10-01

In this paper, we prove that an integrable nonlocal complex modified Korteweg-de Vries (mKdV) equation introduced by Ablowitz and Musslimani [Nonlinearity 29, 915-946 (2016)] is gauge equivalent to a spin-like model. From the gauge equivalence, one can see that there exists significant difference between the nonlocal complex mKdV equation and the classical complex mKdV equation. Through constructing the Darboux transformation for nonlocal complex mKdV equation, a variety of exact solutions including dark soliton, W-type soliton, M-type soliton, and periodic solutions are derived.

Exact periodic cross-kink wave solutions for the new (2+1)-dimensional KdV equation in fluid flows and plasma physics.

PubMed

Liu, Jian-Guo; Du, Jian-Qiang; Zeng, Zhi-Fang; Ai, Guo-Ping

2016-10-01

The Korteweg-de Vries (KdV)-type models have been shown to describe many important physical situations such as fluid flows, plasma physics, and solid state physics. In this paper, a new (2 + 1)-dimensional KdV equation is discussed. Based on the Hirota's bilinear form and a generalized three-wave approach, we obtain new exact solutions for the new (2 + 1)-dimensional KdV equation. With the help of symbolic computation, the properties for some new solutions are presented with some figures.

Establishment of Kawasaki disease database based on metadata standard.

PubMed

Park, Yu Rang; Kim, Jae-Jung; Yoon, Young Jo; Yoon, Young-Kwang; Koo, Ha Yeong; Hong, Young Mi; Jang, Gi Young; Shin, Soo-Yong; Lee, Jong-Keuk

2016-07-01

Kawasaki disease (KD) is a rare disease that occurs predominantly in infants and young children. To identify KD susceptibility genes and to develop a diagnostic test, a specific therapy, or prevention method, collecting KD patients' clinical and genomic data is one of the major issues. For this purpose, Kawasaki Disease Database (KDD) was developed based on the efforts of Korean Kawasaki Disease Genetics Consortium (KKDGC). KDD is a collection of 1292 clinical data and genomic samples of 1283 patients from 13 KKDGC-participating hospitals. Each sample contains the relevant clinical data, genomic DNA and plasma samples isolated from patients' blood, omics data and KD-associated genotype data. Clinical data was collected and saved using the common data elements based on the ISO/IEC 11179 metadata standard. Two genome-wide association study data of total 482 samples and whole exome sequencing data of 12 samples were also collected. In addition, KDD includes the rare cases of KD (16 cases with family history, 46 cases with recurrence, 119 cases with intravenous immunoglobulin non-responsiveness, and 52 cases with coronary artery aneurysm). As the first public database for KD, KDD can significantly facilitate KD studies. All data in KDD can be searchable and downloadable. KDD was implemented in PHP, MySQL and Apache, with all major browsers supported.Database URL: http://www.kawasakidisease.kr. © The Author(s) 2016. Published by Oxford University Press.

A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease.

PubMed

Kim, Jae-Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung-Yil; Kil, Hong-Ryang; Kim, Gi Beom; Han, Myung-Ki; Song, Min Seob; Lee, Hyoung Doo; Ha, Kee Soo; Sohn, Sejung; Johnson, Todd A; Takahashi, Atsushi; Kubo, Michiaki; Tsunoda, Tatsuhiko; Ito, Kaoru; Onouchi, Yoshihiro; Hong, Young Mi; Jang, Gi Young; Lee, Jong-Keuk

2017-12-01

Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10 -5 ), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10 -11 ). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10 -6 ) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10 -6 to 5.24 × 10 -8 ). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10 -6 ). These results provide new insights into the pathogenesis and pathophysiology of KD.

Ketogenic diet for high partial pressure oxygen diving.

PubMed

Valadao, Jason M; Vigilante, John A; DiGeorge, Nicholas W; O'Connor, Sunila E; Bear, Alexandria; Kenyon, Jeffrey; Annis, Heather; Dituri, Joseph; Dituri, Amy E; Whelan, Harry T

2014-01-01

A ketogenic diet (KD) may decrease central nervous system oxygen toxicity symptoms in divers, and in view of this implication a feasibility/ toxicity pilot study was performed to demonstrate tolerance of KD while performing normal diving profiles. The exact mechanism of neuroprotection from the KD remains unknown; however, evidence to support the efficacy of the KD in reducing seizures is present in epilepsy and oxygen toxicity studies, and may provide valuable insight in diving activities. Three divers (two males and one female ages 32-45 with a history of deep diving and high pO2 exposure) on the KD made dives to varying depths in Hawaii using fully closed-circuit MK-15 and Inspiration rebreathers. These rebreathers have an electronically controlled set point, allowing the divers to monitor and control the oxygen level in the breathing loop, which can be varied manually by the divers. Oxygen level was varied during descent, bottom depth and ascent (decompression). Divers fasted for 12-18 hours before diet initiation. The ketosis level was verified by urinating on a Ketostix (reagent strips for urinalysis). Ketosis was achieved and was easily monitored with Ketostix in the simulated operational environment. The KD did not interfere with the diving mission; no seizure activity or signs or symptoms of CNS toxicity were observed, and there were no adverse effects noted by the divers while on the KD.

MRA_1571 is required for isoleucine biosynthesis and improves Mycobacterium tuberculosis H37Ra survival under stress

PubMed Central

Sharma, Rishabh; Keshari, Deepa; Singh, Kumar Sachin; Yadav, Shailendra; Singh, Sudheer Kumar

2016-01-01

Threonine dehydratase is a pyridoxal 5-phosphate dependent enzyme required for isoleucine biosynthesis. Threonine dehydratase (IlvA) participates in conversion of threonine to 2-oxobutanoate and ammonia is released as a by-product. MRA_1571 is annotated to be coding for IlvA in Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a recombinant (KD) Mtb-Ra strain by down-regulating IlvA. The growth studies on different carbon sources suggested reduced growth of KD compared to wild-type (WT), also, isoleucine concentration dependent KD growth restoration was observed. The expression profiling of IlvA suggested increased expression of IlvA during oxygen, acid and oxidative stress. In addition, KD showed reduced survival under pH, starvation, nitric oxide and peroxide stresses. KD was more susceptible to antimycobacterial agents such as streptomycin (STR), rifampicin (RIF) and levofloxacin (LVF), while, no such effect was noticeable when exposed to isoniazid. Also, an increase in expression of IlvA was observed when exposed to STR, RIF and LVF. The dye accumulation studies suggested increased permeability of KD to ethidium bromide and Nile Red as compared to WT. TLC and Mass studies confirmed altered lipid profile of KD. In summary down-regulation of IlvA affects Mtb growth, increases its susceptibility to stress and leads to altered cell wall lipid profile. PMID:27353854

The Ketogenic Diet and Sport: A Possible Marriage?

PubMed

Paoli, Antonio; Bianco, Antonino; Grimaldi, Keith A

2015-07-01

The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/power performance negatively.

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

7 CFR 29.1080 - Variegated dark red (KD).

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Variegated dark red (KD). 29.1080 Section 29.1080..., 13, 14 and Foreign Type 92) § 29.1080 Variegated dark red (KD). A dark brownish-red discoloration... over extended periods of time. Any leaf of which 20 percent or more of its surface is dark brownish-red...

Extremely Fast Numerical Integration of Ocean Surface Wave Dynamics: Building Blocks for a Higher Order Method

DTIC Science & Technology

2006-09-30

equation known as the Kadomtsev - Petviashvili (KP) equation ): (ηt + coηx +αηηx + βη )x +γηyy = 0 (4) where γ = co / 2 . The KdV equation ...using the spectral formulation of the Kadomtsev - Petviashvili equation , a standard equation for nonlinear, shallow water wave dynamics that is a... Petviashvili and nonlinear Schroedinger equations and higher order corrections have been developed as prerequisites to coding the Boussinesq and Euler

Transforming Growth Factor-β Signaling Pathway in Patients with Kawasaki Disease

PubMed Central

Shimizu, Chisato; Jain, Sonia; Lin, Kevin O.; Molkara, Delaram; Frazer, Jeffrey R.; Sun, Shelly; Baker, Annette L.; Newburger, Jane W.; Rowley, Anne H.; Shulman, Stanford T.; Davila, Sonia; Hibberd, Martin L.; Burgner, David; Breunis, Willemijn B.; Kuijpers, Taco W.; Wright, Victoria J.; Levin, Michael; Eleftherohorinou, Hariklia; Coin, Lachlan; Popper, Stephen J.; Relman, David A.; Fury, Wen; Lin, Calvin; Mellis, Scott; Tremoulet, Adriana H.; Burns, Jane C.

2011-01-01

Background Transforming growth factor (TGF)-β is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-β signaling might be important in KD susceptibility and disease outcome. Methods and Results We investigated genetic variation in 15 genes belonging to the TGF-β pathway in a total 771 KD subjects of mainly European descendent from the US, UK, Australia and the Netherlands. We analyzed transcript abundance patterns using microarray and RT-PCR for these same genes and measured TGF-β2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2 and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in two independent cohorts and an intronic SNP in a separate haplotype block was also strongly associated (A/G, rs4776338) (p=0.000022, OR 1.50, 95% CI 1.25-1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-β pathway in KD pathogenesis. Whole blood transcript abundance for these genes and TGF-β2 plasma protein levels changed dynamically over the course of the illness. Conclusions These studies suggest that genetic variation in the TGF-β pathway influences KD susceptibility, disease outcome, and response to therapy and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis. PMID:21127203

Aflatoxin Toxicity Reduction in Feed by Enhanced Binding to Surface-Modified Clay Additives

PubMed Central

Jaynes, William F.; Zartman, Richard E.

2011-01-01

Animal feeding studies have demonstrated that clay additives, such as bentonites, can bind aflatoxins in ingested feed and reduce or eliminate the toxicity. Bentonite deposits are found throughout the world and mostly consist of expandable smectite minerals, such as montmorillonite. The surfaces of smectite minerals can be treated with organic compounds to create surface-modified clays that more readily bind some contaminants than the untreated clay. Montmorillonites treated with organic cations, such as hexadecyltrimethylammonium (HDTMA) and phenyltrimethylammonium (PTMA), more effectively remove organic contaminants, such as benzene and toluene, from water than untreated clay. Similarly, montmorillonite treated with PTMA (Kd = 24,100) retained more aflatoxin B1 (AfB1) from aqueous corn flour than untreated montmorillonite (Kd = 944). Feed additives that reduced aflatoxin toxicity in animal feeding studies adsorbed more AfB1 from aqueous corn flour than feed additives that were less effective. The organic cations HDTMA and PTMA are considered toxic and would not be suitable for clay additives used in feed or food, but other non-toxic or nutrient compounds can be used to prepare surface-modified clays. Montmorillonite (SWy) treated with choline (Kd = 13,800) and carnitine (Kd = 3960) adsorbed much more AfB1 from aqueous corn flour than the untreated clay (Kd = 944). A choline-treated clay prepared from a reduced-charge, high-charge montmorillonite (Kd = 20,100) adsorbed more AfB1 than the choline-treated high-charge montmorillonite (Kd = 1340) or the untreated montmorillonite (Kd = 293). Surface-modified clay additives prepared using low-charge smectites and nutrient or non-toxic organic compounds might be used to more effectively bind aflatoxins in contaminated feed or food and prevent toxicity. PMID:22069725

Genetic epistasis between killer immunoglobulin-like receptors and human leukocyte antigens in Kawasaki disease susceptibility.

PubMed

Bossi, G; Mannarino, S; Pietrogrande, M C; Salice, P; Dellepiane, R M; Cremaschi, A L; Corana, G; Tozzo, A; Capittini, C; De Silvestri, A; Tinelli, C; Pasi, A; Martinetti, M

2015-10-01

Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).

Fine specificities of natural regulatory T cells after IVIG therapy in patients with Kawasaki disease

PubMed Central

Burns, Jane C.; Touma, Ranim; Song, Yali; Padilla, Robert L.; Tremoulet, Adriana H.; Sidney, John; Sette, Alessandro; Franco, Alessandra

2016-01-01

The activation of natural regulatory T cells (nTreg) recognizing the heavy constant region (Fc) of IgG is an important mechanism of action of intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). Lack of circulating Fc-specific nTreg in the sub-acute phase of KD is correlated with the development of coronary artery abnormalities (CAA). Here, we characterize the fine specificity of nTreg in sub-acute (2- to 8-week post-IVIG) and convalescent (1- to 10-year post-IVIG) KD subjects by testing the immunogenicity of 64 peptides, 15 amino acids in length with a 10 amino acid-overlap spanning the entire Fc protein. About 12 Fc peptides (6 pools of 2 consecutive peptides) were recognized by nTreg in the cohorts studied, including two patients with CAA. To test whether IVIG expands the same nTreg populations that maintain vascular homeostasis in healthy subjects, we compared these results with results obtained in healthy adult controls. Similar nTreg fine specificities were observed in KD patients after IVIG and in healthy donors. These results suggest that T cell fitness rather than T cell clonal deletion or anergy is responsible for the lack of Fc-specific nTreg in KD patients who develop CAA. Furthermore, we found that adolescents and adults who had KD during childhood without developing CAA did not respond to the Fc protein in vitro, suggesting that the nTreg response induced by IVIG in KD patients is short-lived. Our results support the concept that peptide epitopes may be a viable therapeutic approach to expand Fc-specific nTreg and more effectively prevent CAA in KD patients. PMID:25822882

Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

PubMed

Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

2006-07-01

Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

[Prospective study of ketogenic diet in treatment of children with global developmental delay].

PubMed

Zhu, Deng-Na; Li, Ping; Wang, Jun; Yuan, Jun-Ying; Zhang, Guang-Yu; Liang, Jiang-Fang; Wang, Ming-Mei; Zhao, Yun-Xia; An, Shuang; Ma, Na; Ma, Dan-Dan

2017-10-01

To study the effect of ketogenic diet (KD) on neurobehavioral development, emotional and social behaviors, and life ability in children with global developmental delay (GDD). A prospective case-control study was performed for hospitalized children with GDD, who were randomly divided into KD treatment group (n=40) and conventional treatment group (n=37). The children in both groups were given comprehensive rehabilitation training, and those in the KD treatment group were given modified Atkins diet in addition to the comprehensive rehabilitation training. The children in both groups were assessed with the Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and Infants-Junior High School Students' Social Life Abilities Scale (S-M scale) before treatment and after 3, 6, and 9 months of treatment. The two groups were compared in terms of the improvements in neurobehavioral development, emotional and social behaviors, and social life ability. After 3, 6, and 9 months of treatment, the KD treatment group had significantly greater improvements in the scores of the adaptive, fine motor, and language quotients of the Gesell Developmental Scale compared with the conventional treatment group (P<0.05); the KD treatment group had significantly greater improvements in CITSEA/CBCL scores than the conventional treatment group (P<0.05). The KD treatment group had a greater improvement in the score of the S-M scale after 9 months of treatment (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1 experienced mild urinary stones. KD can improve the neurobehavioral development and behavioral and emotional behaviors in children with GDD, and it has few adverse effects.

Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: a case series.

PubMed

Bertoli, Simona; Trentani, Claudia; Ferraris, Cinzia; De Giorgis, Valentina; Veggiotti, Pierangelo; Tagliabue, Anna

2014-06-01

The only known treatment of glucose transporter 1 deficiency syndrome (GLUT-1 DS) is a ketogenic diet (KD), which provides the brain with an alternative fuel. Studies in children with intractable epilepsy have shown that a prolonged KD can induce a progressive loss of bone mineral content associated with poor bone health status, probably as a consequence of a chronic acidic environment. The aim of this study is to determine the long-term effects of a KD on body composition and bone mineral status of patients with GLUT-1 DS, is currently unknown. In this case series, we report the changes in body composition and bone mineral status observed in three adult patients with GLUT-1 DS who have been treated with a KD for more than 5 y. A long-term KD did not produce appreciable changes in weight and body composition of adults with GLUT-1 DS. Moreover, we found no evidence of potential adverse effects of a KD on bone health. In summary, this case series contributes to a small but growing body of literature that investigated the potential long-term effects of a KD on bone health. Our data suggest that maintaining a KD for more than 5 y does not pose any major negative effects on body composition, bone mineral content, and bone mineral density in adults with GLUT-1 DS, a finding that is at variance with previous reports focusing on children with intractable epilepsy. Further studies with larger sizes are needed to confirm and expand our findings. Copyright © 2014 Elsevier Inc. All rights reserved.

Aflatoxin toxicity reduction in feed by enhanced binding to surface-modified clay additives.

PubMed

Jaynes, William F; Zartman, Richard E

2011-06-01

Animal feeding studies have demonstrated that clay additives, such as bentonites, can bind aflatoxins in ingested feed and reduce or eliminate the toxicity. Bentonite deposits are found throughout the world and mostly consist of expandable smectite minerals, such as montmorillonite. The surfaces of smectite minerals can be treated with organic compounds to create surface-modified clays that more readily bind some contaminants than the untreated clay. Montmorillonites treated with organic cations, such as hexadecyltrimethylammonium (HDTMA) and phenyltrimethylammonium (PTMA), more effectively remove organic contaminants, such as benzene and toluene, from water than untreated clay. Similarly, montmorillonite treated with PTMA (K(d) = 24,100) retained more aflatoxin B1 (AfB1) from aqueous corn flour than untreated montmorillonite (K(d) = 944). Feed additives that reduced aflatoxin toxicity in animal feeding studies adsorbed more AfB1 from aqueous corn flour than feed additives that were less effective. The organic cations HDTMA and PTMA are considered toxic and would not be suitable for clay additives used in feed or food, but other non-toxic or nutrient compounds can be used to prepare surface-modified clays. Montmorillonite (SWy) treated with choline (K(d) = 13,800) and carnitine (K(d) = 3960) adsorbed much more AfB1 from aqueous corn flour than the untreated clay (K(d) = 944). A choline-treated clay prepared from a reduced-charge, high-charge montmorillonite (K(d) = 20,100) adsorbed more AfB1 than the choline-treated high-charge montmorillonite (K(d) = 1340) or the untreated montmorillonite (K(d) = 293). Surface-modified clay additives prepared using low-charge smectites and nutrient or non-toxic organic compounds might be used to more effectively bind aflatoxins in contaminated feed or food and prevent toxicity.

King-Devick Test identifies real-time concussion and asymptomatic concussion in youth athletes.

PubMed

Dhawan, Priya S; Leong, Danielle; Tapsell, Lisa; Starling, Amaal J; Galetta, Steven L; Balcer, Laura J; Overall, Trenton L; Adler, Jennifer S; Halker-Singh, Rashmi B; Vargas, Bert B; Dodick, David

2017-12-01

Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. Among 141 players tested, 20 had clinically diagnosed concussion. All 20 had immediate postconcussion K-D times >5 seconds from baseline (average 7.3 seconds) and all but 2 had worse postseason scores (46.4 seconds vs 52.4 seconds, p < 0.05, Wilcoxon signed rank test). Nonconcussed athletes saw minimal improvement postseason (43.9 seconds vs 42.1 seconds, p < 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

WAVE2 Regulates Epithelial Morphology and Cadherin Isoform Switching through Regulation of Twist and Abl

PubMed Central

Bryce, Nicole S.; Reynolds, Albert B.; Koleske, Anthony J.; Weaver, Alissa M.

2013-01-01

Background Epithelial morphogenesis is a dynamic process that involves coordination of signaling and actin cytoskeletal rearrangements. Principal Findings We analyzed the contribution of the branched actin regulator WAVE2 in the development of 3-dimensional (3D) epithelial structures. WAVE2-knockdown (WAVE2-KD) cells formed large multi-lobular acini that continued to proliferate at an abnormally late stage compared to control acini. Immunostaining of the cell-cell junctions of WAVE2-KD acini revealed weak and heterogeneous E-cadherin staining despite little change in actin filament localization to the same junctions. Analysis of cadherin expression demonstrated a decrease in E-cadherin and an increase in N-cadherin protein and mRNA abundance in total cell lysates. In addition, WAVE2-KD cells exhibited an increase in the mRNA levels of the epithelial-mesenchymal transition (EMT)-associated transcription factor Twist1. KD of Twist1 expression in WAVE2-KD cells reversed the cadherin switching and completely rescued the aberrant 3D morphological phenotype. Activity of the WAVE2 complex binding partner Abl kinase was also increased in WAVE2-KD cells, as assessed by tyrosine phosphorylation of the Abl substrate CrkL. Inhibition of Abl with STI571 rescued the multi-lobular WAVE2-KD 3D phenotype whereas overexpression of Abl kinase phenocopied the WAVE2-KD phenotype. Conclusions The WAVE2 complex regulates breast epithelial morphology by a complex mechanism involving repression of Twist1 expression and Abl kinase activity. These data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis. PMID:23691243

Dietary therapy is not the best option for refractory nonsurgical epilepsy.

PubMed

Vaccarezza, María Magdalena; Silva, Walter Horacio

2015-09-01

The ketogenic diet (KD) is currently a well-established treatment for patients with medically refractory, nonsurgical epilepsy. However, despite its efficacy, the KD is highly restrictive and constitutes a treatment with serious potential adverse effects, and often with difficulties in its implementation and compliance. Patients on the KD require strict follow-up and constant supervision by a medical team highly experienced in its management in order to prevent complications. Other alternative treatments for patients with refractory epilepsy include vagus nerve stimulation (VNS), new-generation antiepileptic drugs (AEDs), corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this review, we explain not only the difficulties of the KD as a therapeutic option for refractory epilepsy but also the benefits of other therapeutic strategies, which, in many cases, have proven to have better efficacy than the KD itself. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Membrane transport of amino acid enantiomers in protoscoleces of Echinococcus granulosus (Cestoda).

PubMed

Allen, J T; Arme, C

1991-02-01

Protoscoleces of Echinococcus granulosus absorb both L- and D-alanine. Concentration ratios exceed 1 with values for D-alanine exceeding those for the L-isomer, suggesting that both are absorbed by active mechanisms. Uptake of both isomers involves both diffusion and carrier-mediated components. Values for the diffusion component (Kd) for L- and D-alanine were 0.21 and 0.38 nmol mg-1 protein/1.5 min mM-1 respectively, and values for Kt, the transport constants, 0.17 mM and 0.21 mM respectively. Uptake of both isomers was inhibited competitively by a number of other amino acids.

A Bivariate Chebyshev Spectral Collocation Quasilinearization Method for Nonlinear Evolution Parabolic Equations

PubMed Central

Motsa, S. S.; Magagula, V. M.; Sibanda, P.

2014-01-01

This paper presents a new method for solving higher order nonlinear evolution partial differential equations (NPDEs). The method combines quasilinearisation, the Chebyshev spectral collocation method, and bivariate Lagrange interpolation. In this paper, we use the method to solve several nonlinear evolution equations, such as the modified KdV-Burgers equation, highly nonlinear modified KdV equation, Fisher's equation, Burgers-Fisher equation, Burgers-Huxley equation, and the Fitzhugh-Nagumo equation. The results are compared with known exact analytical solutions from literature to confirm accuracy, convergence, and effectiveness of the method. There is congruence between the numerical results and the exact solutions to a high order of accuracy. Tables were generated to present the order of accuracy of the method; convergence graphs to verify convergence of the method and error graphs are presented to show the excellent agreement between the results from this study and the known results from literature. PMID:25254252

A bivariate Chebyshev spectral collocation quasilinearization method for nonlinear evolution parabolic equations.

PubMed

Motsa, S S; Magagula, V M; Sibanda, P

2014-01-01

This paper presents a new method for solving higher order nonlinear evolution partial differential equations (NPDEs). The method combines quasilinearisation, the Chebyshev spectral collocation method, and bivariate Lagrange interpolation. In this paper, we use the method to solve several nonlinear evolution equations, such as the modified KdV-Burgers equation, highly nonlinear modified KdV equation, Fisher's equation, Burgers-Fisher equation, Burgers-Huxley equation, and the Fitzhugh-Nagumo equation. The results are compared with known exact analytical solutions from literature to confirm accuracy, convergence, and effectiveness of the method. There is congruence between the numerical results and the exact solutions to a high order of accuracy. Tables were generated to present the order of accuracy of the method; convergence graphs to verify convergence of the method and error graphs are presented to show the excellent agreement between the results from this study and the known results from literature.

NADP-dependent malate dehydrogenase (decarboxylating) from sugar cane leaves. Kinetic properties of different oligomeric structures.

PubMed

Iglesias, A A; Andreo, C S

1990-09-24

NADP-dependent malate dehydrogenase (decarboxylating) from sugar cane leaves was inhibited by increasing the ionic strength in the assay medium. The inhibitory effect was higher at pH 7.0 than 8.0, with median inhibitory concentrations (IC50) of 89 mM and 160 mM respectively, for inhibition by NaCl. Gel-filtration experiments indicated that the enzyme dissociated into dimers and monomers when exposed to high ionic strength (0.3 M NaCl). By using the enzyme-dilution approach in the absence and presence of 0.3 M NaCl, the kinetic properties of each oligomeric species of the protein was determined at pH 7.0 and 8.0. Tetrameric, dimeric and monomeric structures were shown to be active but with different V and Km values. The catalytic efficiency of the oligomers was tetramer greater than dimer greater than monomer, and each quaternary structure exhibited higher activity at pH 8.0 than 7.0. Dissociation constants for the equilibria between the different oligomeric forms of the enzyme were determined. It was established that Kd values were affected by pH and Mg2+ levels in the medium. Results suggest that the distinct catalytic properties of the different oligomeric forms of NADP-dependent malate dehydrogenase and changes in their equilibrium could be the molecular basis for an efficient physiological regulation of the decarboxylation step of C4 metabolism.

p-( sup 125 I)iodoclonidine is a partial agonist at the alpha 2-adrenergic receptor

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

Gerhardt, M.A.; Wade, S.M.; Neubig, R.R.

1990-08-01

The binding properties of p-(125I)iodoclonidine (( 125I)PIC) to human platelet membranes and the functional characteristics of PIC are reported. (125I)PIC bound rapidly and reversibly to platelet membranes, with a first-order association rate constant (kon) at room temperature of 8.0 +/- 2.7 x 10(6) M-1 sec-1 and a dissociation rate constant (koff) of 2.0 +/- 0.8 x 10(-3) sec-1. Scatchard plots of specific (125I)PIC binding (0.1-5 nM) were linear, with a Kd of 1.2 +/- 0.1 nM. (125I)PIC bound to the same number of high affinity sites as the alpha 2-adrenergic receptor (alpha 2-AR) full agonist (3H) bromoxidine (UK14,304), which representedmore » approximately 40% of the sites bound by the antagonist (3H)yohimbine. Guanosine 5'-(beta, gamma-imido)triphosphate greatly reduced the amount of (125I)PIC bound (greater than 80%), without changing the Kd of the residual binding. In competition experiments, the alpha 2-AR-selective ligands yohimbine, bromoxidine, oxymetazoline, clonidine, p-aminoclonidine, (-)-epinephrine, and idazoxan all had Ki values in the low nanomolar range, whereas prazosin, propranolol, and serotonin yielded Ki values in the micromolar range. Epinephrine competition for (125I)PIC binding was stereoselective. Competition for (3H)bromoxidine binding by PIC gave a Ki of 1.0 nM (nH = 1.0), whereas competition for (3H)yohimbine could be resolved into high and low affinity components, with Ki values of 3.7 and 84 nM, respectively. PIC had minimal agonist activity in inhibiting adenylate cyclase in platelet membranes, but it potentiated platelet aggregation induced by ADP with an EC50 of 1.5 microM. PIC also inhibited epinephrine-induced aggregation, with an IC50 of 5.1 microM. Thus, PIC behaves as a partial agonist in a human platelet aggregation assay. (125I)PIC binds to the alpha 2B-AR in NG-10815 cell membranes with a Kd of 0.5 +/- 0.1 nM.« less

Hamiltonian formulation of the KdV equation

NASA Astrophysics Data System (ADS)

Nutku, Y.

1984-06-01

We consider the canonical formulation of Whitham's variational principle for the KdV equation. This Lagrangian is degenerate and we have found it necessary to use Dirac's theory of constrained systems in constructing the Hamiltonian. Earlier discussions of the Hamiltonian structure of the KdV equation were based on various different decompositions of the field which is avoided by this new approach.

On a hierarchy of nonlinearly dispersive generalized Korteweg - de Vries evolution equations

DOE PAGES

Christov, Ivan C.

2015-08-20

We propose a hierarchy of nonlinearly dispersive generalized Korteweg–de Vries (KdV) evolution equations based on a modification of the Lagrangian density whose induced action functional the KdV equation extremizes. Two recent nonlinear evolution equations describing wave propagation in certain generalized continua with an inherent material length scale are members of the proposed hierarchy. Like KdV, the equations from the proposed hierarchy possess Hamiltonian structure. Unlike KdV, the solutions to these equations can be compact (i.e., they vanish outside of some open interval) and, in addition, peaked. Implicit solutions for these peaked, compact traveling waves (“peakompactons”) are presented.

WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells

PubMed Central

Sarmiento, Corina; Wang, Weigang; Dovas, Athanassios; Yamaguchi, Hideki; Sidani, Mazen; El-Sibai, Mirvat; DesMarais, Vera; Holman, Holly A.; Kitchen, Susan; Backer, Jonathan M.; Alberts, Art; Condeelis, John

2008-01-01

We examined the role of the actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion in response to epidermal growth factor (EGF), a key regulator in carcinoma cell invasion. We found that WAVE2 knockdown (KD) suppresses lamellipod formation and increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous KD of both proteins results in the formation of large jagged protrusions with lamellar properties and increased filopod formation. This suggests that another actin nucleation activity is at work in carcinoma cells in response to EGF. A mammalian Diaphanous–related formin, mDia1, localizes at the jagged protrusions in double KD cells. Constitutively active mDia1 recapitulated the phenotype, whereas inhibition of mDia1 blocked the formation of these protrusions. Increased RhoA activity, which stimulates mDia1 nucleation, was observed in the N-WASP/WAVE2 KD cells and was shown to be required for the N-WASP/WAVE2 KD phenotype. These data show that coordinate regulation between the WASP family and mDia proteins controls the balance between lamellar and lamellipodial protrusion activity. PMID:18362183

Temperature-sensitive high affinity (/sup 3/H)serotonin binding: characterization and effects of antidepressant treatment

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

Helmeste, D.M.; Tang, S.W.

1984-08-13

Characterization of temperature-sensitive (/sup 3/H)serotonin (5-HT) binding sites (1 and 4 nM Kd sites) revealed complex inhibition by neuroleptics and serotonin antagonists. There was no simple correlation with affinities for S/sub 1/ and S/sub 2/ receptors. In vivo pretreatment (48 h before) with mianserin did not alter B/sub max/ or Kd for the 1 nM Kd (/sup 3/H)5-HT site, although (/sup 3/H)ketanserin (S/sub 2/) densities were decreased by 50%. This suggested that possible S/sub 2/ components of (/sup 3/H)5-HT binding must be negligible, even though ketanserin competed with high affinity (IC/sub 50/ = 3 nM) for a portion of themore » 1 nM Kd (/sup 3/H)5-HT site. Low concentrations of mianserin inhibited the 1 nM Kd (/sup 3/H)5-HT site in a non-competitive manner, as shown by a decrease in B/sub max/ with no change in Kd after in vitro incubation. The complex inhibition data may therefore represent indirect interactions through another site.« less

Use of synthetic peptide libraries for the H-2Kd binding motif identification.

PubMed

Quesnel, A; Casrouge, A; Kourilsky, P; Abastado, J P; Trudelle, Y

1995-01-01

To identify Kd-binding peptides, an approach based on small peptide libraries has been developed. These peptide libraries correspond to all possible single-amino acid variants of a particular Kd-binding peptide, SYIPSAEYI, an analog of the Plasmodium berghei 252-260 antigenic peptide SYIPSAEKI. In the parent sequence, each position is replaced by all the genetically encoded amino acids (except cysteine). The multiple analog syntheses are performed either by the Divide Couple and Recombine method or by the Single Resin method and generate mixtures containing 19 peptides. The present report deals with the synthesis, the purification, the chemical characterization by amino acid analysis and electrospray mass spectrometry (ES-MS), and the application of such mixtures in binding tests with a soluble, functionally empty, single-chain H-2Kd molecule denoted SC-Kd. For each mixture, bound peptides were eluted and analyzed by sequencing. Since the binding tests were realized in noncompetitive conditions, our results show that a much broader set of peptides bind to Kd than expected from previous studies. This may be of practical importance when looking for low affinity peptides such as tumor peptides capable of eliciting protective immune response.

Disruption of PH–kinase domain interactions leads to oncogenic activation of AKT in human cancers

PubMed Central

Parikh, Chaitali; Janakiraman, Vasantharajan; Wu, Wen-I; Foo, Catherine K.; Kljavin, Noelyn M.; Chaudhuri, Subhra; Stawiski, Eric; Lee, Brian; Lin, Jie; Li, Hong; Lorenzo, Maria N.; Yuan, Wenlin; Guillory, Joseph; Jackson, Marlena; Rondon, Jesus; Franke, Yvonne; Bowman, Krista K.; Sagolla, Meredith; Stinson, Jeremy; Wu, Thomas D.; Wu, Jiansheng; Stokoe, David; Stern, Howard M.; Brandhuber, Barbara J.; Lin, Kui; Skelton, Nicholas J.; Seshagiri, Somasekar

2012-01-01

The protein kinase v-akt murine thymoma viral oncogene homolog (AKT), a key regulator of cell survival and proliferation, is frequently hyperactivated in human cancers. Intramolecular pleckstrin homology (PH) domain–kinase domain (KD) interactions are important in maintaining AKT in an inactive state. AKT activation proceeds after a conformational change that dislodges the PH from the KD. To understand these autoinhibitory interactions, we generated mutations at the PH–KD interface and found that most of them lead to constitutive activation of AKT. Such mutations are likely another mechanism by which activation may occur in human cancers and other diseases. In support of this likelihood, we found somatic mutations in AKT1 at the PH–KD interface that have not been previously described in human cancers. Furthermore, we show that the AKT1 somatic mutants are constitutively active, leading to oncogenic signaling. Additionally, our studies show that the AKT1 mutants are not effectively inhibited by allosteric AKT inhibitors, consistent with the requirement for an intact PH–KD interface for allosteric inhibition. These results have important implications for therapeutic intervention in patients with AKT mutations at the PH–KD interface. PMID:23134728

Claudin-31 contributes to corticosteroid-induced alterations in the barrier properties of the gill epithelium.

PubMed

Kolosov, Dennis; Donini, Andrew; Kelly, Scott P

2017-01-05

The contribution of Claudin-31 (Cldn-31) to corticosteroid-induced tightening of the trout gill epithelium was examined using a primary cultured model preparation. Cldn-31 is a ∼23 kDa protein that localizes to the periphery of gill epithelial cells and diffusely in select gill cells that are Na + -K + -ATPase-immunoreactive. Transcriptional knockdown (KD) of cldn-31 reduced Cldn-31 abundance and increased epithelium permeability. Under simulated in vivo conditions (apical freshwater), cldn-31 KD increased net ion flux rates (≡ efflux). Cortisol treatment increased Cldn-31 abundance and decreased epithelium permeability. This tightening effect was diminished, but not eliminated, by cldn-31 KD, most likely due to other cortisol-sensitive TJ proteins that were transcriptionally unperturbed or enhanced in cortisol-treated cldn-31 KD preparations. However, cldn-31 KD abolished a cortisol-induced increase in Cldn-8d abundance, which may contribute to compromised cldn-31 KD epithelium permeability. Data suggest an important barrier function for Cldn-31 and an integral role for Cldn-31 in corticosteroid-induced gill epithelium tightening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells.

PubMed

Sarmiento, Corina; Wang, Weigang; Dovas, Athanassios; Yamaguchi, Hideki; Sidani, Mazen; El-Sibai, Mirvat; Desmarais, Vera; Holman, Holly A; Kitchen, Susan; Backer, Jonathan M; Alberts, Art; Condeelis, John

2008-03-24

We examined the role of the actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion in response to epidermal growth factor (EGF), a key regulator in carcinoma cell invasion. We found that WAVE2 knockdown (KD) suppresses lamellipod formation and increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous KD of both proteins results in the formation of large jagged protrusions with lamellar properties and increased filopod formation. This suggests that another actin nucleation activity is at work in carcinoma cells in response to EGF. A mammalian Diaphanous-related formin, mDia1, localizes at the jagged protrusions in double KD cells. Constitutively active mDia1 recapitulated the phenotype, whereas inhibition of mDia1 blocked the formation of these protrusions. Increased RhoA activity, which stimulates mDia1 nucleation, was observed in the N-WASP/WAVE2 KD cells and was shown to be required for the N-WASP/WAVE2 KD phenotype. These data show that coordinate regulation between the WASP family and mDia proteins controls the balance between lamellar and lamellipodial protrusion activity.

The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine - FTIR microspectroscopy study

NASA Astrophysics Data System (ADS)

Skoczen, A.; Setkowicz, Z.; Janeczko, K.; Sandt, Ch.; Borondics, F.; Chwiej, J.

2017-09-01

The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm- 1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm- 1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress

PubMed Central

Guo, Min; Wang, Xun; Zhao, Yanxin; Yang, Qi; Ding, Hongyan; Dong, Qiang; Chen, Xingdong; Cui, Mei

2018-01-01

Background: Neuroprotective effects of ketogenic diets (KD) have been reported in stroke models, and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms. Methods: In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R)-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB) followed by oxygen–glucose deprivation/reoxygenation (OGD/R). NLRP3 inflammasome activation and related regulatory mechanisms were evaluated. Results: Mice fed with KD had increased tolerance to MCAO/R. KD inhibited endoplasmic reticulum (ER) stress and suppressed TXNIP/NLRP3 inflammasome activation in the brain. The in vitro study showed BHB (10 mM) prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1) to inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species (ROS) generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and suppressed ER stress-induced NLRP3 inflammasome activation. Conclusions: KD may suppress ER stress and protect mitochondrial integrity by suppressing the mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation, thus exerting neuroprotective effects. Our findings provide evidence for the potential application of KD in the prevention of ischemic stroke. PMID:29662437

The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma.

PubMed

Stafford, Phillip; Abdelwahab, Mohammed G; Kim, Do Young; Preul, Mark C; Rho, Jong M; Scheck, Adrienne C

2010-09-10

Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia. Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet. Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4. Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

Lupus autoantibodies target ribosomal P proteins

PubMed Central

1985-01-01

All nine SLE (systemic lupus erythematosus) sera with antiribosomal antibody activity targeted the same three ribosomal protein antigens, of molecular masses 38 and 17/19 kD when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. One serum reacted with an additional protein of approximately kD. Ribosomal subunit fractionation by composite gel electrophoresis and sucrose density ultracentrifugation showed that these proteins were part of the large subunit. Isoelectric focusing in agarose, and two-dimensional polyacrylamide gel electrophoresis revealed that the antigens had pI between 4.5 and 6.5, but that the 17/19 kD antigens were more acidic than the 38 kD antigen. Similarities in the molecular masses, charges, as well as the presence of highly conserved crossreactive epitopes, failure to bind to carboxymethylcellulose at pH 4.2, and extractability of the 17/19 kD proteins by 400 mM NH4Cl-ethanol at 0 degrees C indicated that these antigens were analogous to the proteins P0 (38 kD) and P1/P2 (17/19 kD) described previously (25, 36). Co-identity was confirmed using reference antibodies and antigen. Although antibodies to these proteins were only found in 5-10% of more than 50 sera screened by radioimmunoassay or Western blotting, the selective production of antibodies to epitopes on three (out of a total of more than 80) ribosomal proteins may provide further clues to autoantibody induction of SLE. PMID:2410526

High-density Genotyping of Immune Loci in Kawasaki Disease and IVIG Treatment Response in European-American Case-parent Trio Study

PubMed Central

Shendre, Aditi; Wiener, Howard W.; Zhi, Degui; Vazquez, Ana I; Portman, Michael A.; Shrestha, Sadeep

2014-01-01

Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children and has genetic and autoimmune components. We genotyped 112 case-parent trios of European decent (confirmed by AIMS) using the ImmunoChip array and performed association analyses with susceptibility to KD and IVIG non-response. KD susceptibility was assessed using the transmission disequilibrium test whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated SNPs in three gene regions (FCGR, CD40/CDH22, and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with potential pathway in KD pathogenesis. SNP rs838143 in the 3′ UTR of FUT1 gene (2.7×10-5) and rs9847915 in the intergenic region of LOC730109 ∣ BRD7P2 (6.81×10-7) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A ∣ C14orf19 (1.4×10-4) and rs4889606 in the intron of the STX1B gene (6.95×10-5) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases play an important role in the pathogenesis of KD and IVIG response mechanism. PMID:25101798

A Semianalytical Ocean Color Inversion Algorithm with Explicit Water Column Depth and Substrate Reflectance Parameterization

NASA Technical Reports Server (NTRS)

Mckinna, Lachlan I. W.; Werdell, P. Jeremy; Fearns, Peter R. C.; Weeks, Scarla J.; Reichstetter, Martina; Franz, Bryan A.; Shea, Donald M.; Feldman, Gene C.

2015-01-01

A semianalytical ocean color inversion algorithm was developed for improving retrievals of inherent optical properties (IOPs) in optically shallow waters. In clear, geometrically shallow waters, light reflected off the seafloor can contribute to the water-leaving radiance signal. This can have a confounding effect on ocean color algorithms developed for optically deep waters, leading to an overestimation of IOPs. The algorithm described here, the Shallow Water Inversion Model (SWIM), uses pre-existing knowledge of bathymetry and benthic substrate brightness to account for optically shallow effects. SWIM was incorporated into the NASA Ocean Biology Processing Group's L2GEN code and tested in waters of the Great Barrier Reef, Australia, using the Moderate Resolution Imaging Spectroradiometer (MODIS) Aqua time series (2002-2013). SWIM-derived values of the total non-water absorption coefficient at 443 nm, at(443), the particulate backscattering coefficient at 443 nm, bbp(443), and the diffuse attenuation coefficient at 488 nm, Kd(488), were compared with values derived using the Generalized Inherent Optical Properties algorithm (GIOP) and the Quasi-Analytical Algorithm (QAA). The results indicated that in clear, optically shallow waters SWIM-derived values of at(443), bbp(443), and Kd(443) were realistically lower than values derived using GIOP and QAA, in agreement with radiative transfer modeling. This signified that the benthic reflectance correction was performing as expected. However, in more optically complex waters, SWIM had difficulty converging to a solution, a likely consequence of internal IOP parameterizations. Whilst a comprehensive study of the SWIM algorithm's behavior was conducted, further work is needed to validate the algorithm using in situ data.

Formation and growth of embryos of the Earth-Moon system

NASA Astrophysics Data System (ADS)

Ipatov, Sergei I.

2016-07-01

Galimov and Krivtsov [1] made computer simulations of the formation of the embryos of the Earth and the Moon as a result of contraction of a rarefied condensation. The angular momentum needed for such contraction could not be acquired during formation of the condensation from a protoplanetary disk. Using the formulas presented in [2], we obtained that the angular momentum of the present Earth-Moon system could be acquired at a collision of two rarefied condensations with a total mass not smaller than 0.1M_{e}, where M_{e} is the Earth mass. In principle, the angular momentum of the condensation needed for formation of the Earth-Moon system could be acquired by accumulation only of small objects, but for such model, the parental condensations of Venus and Mars could also get the angular momentum that was enough for formation of large satellites. Probably, the condensations that contracted and formed the embryos of the terrestrial planets other than the Earth did not collide with massive condensations, and therefore they did not get a large enough angular momentum needed to form massive satellites. The embryos formed as a result of contraction of the condensation grew by accumulation of solid planetesimals. The mass of the rarefied condensation that was a parent for the embryos of the Earth and the Moon could be relatively small (0.02M_{e} or even less), if we take into account the growth of the angular momentum of the embryos at the time when they accumulated planetesimals. There could be also the second main collision of the parental rarefied condensation with another condensation, at which the radius of the Earth's embryo condensation was smaller than the semi-major axis of the orbit of the Moon's embryo. The second main collision (or a series of similar collisions) could change the tilt of the Earth to its present value. For large enough eccentricities of planetesimals, the effective radii of proto-Earth and proto-Moon were proportional to r (where r is the radius of a considered embryo), and at the growth of the mass of the Earth's embryo by 10 times, the mass of the Moon's embryo increased by a factor of 1.43 and 1.31 at the ratio k_d of the density of the growing Moon to that of the growing Earth equal to its present value (k_d=0.6) and for equal densities (k_d=1), respectively. For the case of small relative velocities of planetesimals, effective radii of the embryos are proportional to r^2, and at the growth of the Earth's embryo mass by 10 times, the Moon's embryo mass increased by a factor of 1.051 and 1.044 at k_d=0.6 and k_d=1, respectively. [1] Galimov E.M., Krivtsov A.M.: Origin of the Moon. New concept. / De Gruyter. Berlin. 2012. 168 p. [2] Ipatov S.I.: Mon. Not. R. Astron. Soc., 2010, vol. 403, pp. 405-414.