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Sample records for behandling af den

  1. Two New Letters by Denning

    NASA Astrophysics Data System (ADS)

    Beech, Martin

    2010-06-01

    Two letters written by W. F. Denning to R. P. Greg in March and April of 1879 that had been tucked into the folds of an 1876 edition of the British Association for the Advancement of Science Reports were recently found at the Carnegie Institution in Washington D.C. The letters are wonderfully preserved, and offer us a snap-shot of the work being performed by a young Denning at the time when his influence in the field of meteor studies was in its ascendency. The contents of these two letters is analyzed and placed within context to Denning's other publications and private life.

  2. The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development

    PubMed Central

    Schinke, Josua; Kolog Gulko, Miriam; Christmann, Martin; Valerius, Oliver; Stumpf, Sina Kristin; Stirz, Margarita; Braus, Gerhard H.

    2016-01-01

    DenA/DEN1 and the COP9 signalosome (CSN) represent two deneddylases which remove the ubiquitin-like Nedd8 from modified target proteins and are required for distinct fungal developmental programmes. The cellular DenA/DEN1 population is divided into a nuclear and a cytoplasmatic subpopulation which is especially enriched at septa. DenA/DEN1 stability control mechanisms are different for the two cellular subpopulations and depend on different physical interacting proteins and the C-terminal DenA/DEN1 phosphorylation pattern. Nuclear DenA/DEN1 is destabilized during fungal development by five of the eight CSN subunits which target nuclear DenA/DEN1 for degradation. DenA/DEN1 becomes stabilized as a phosphoprotein at S243/S245 during vegetative growth, which is necessary to support further asexual development. After the initial phase of development, the newly identified cytoplasmatic DenA/DEN1 interacting phosphatase DipA and an additional developmental specific C-terminal phosphorylation site at serine S253 destabilize DenA/DEN1. Outside of the nucleus, DipA is co-transported with DenA/DEN1 in the cytoplasm between septa and nuclei. Deletion of dipA resulted in increased DenA/DEN1 stability in a strain which is unresponsive to illumination. The mutant strain is dysregulated in cytokinesis and impaired in asexual development. Our results suggest a dual phosphorylation-dependent DenA/DEN1 stability control with stabilizing and destabilizing modifications and physical interaction partner proteins which function as control points in the nucleus and the cytoplasm. PMID:27010942

  3. Dens in dente: A minimally invasive nonsurgical approach!

    PubMed Central

    Hegde, Vivek; Morawala, Abdul; Gupta, Abhilasha; Khandwawala, Naqiyaa

    2016-01-01

    Dens invaginatus, also known as dens in dente, is a rare anomaly affecting human dentition. The condition results in invagination of an amelodental structure within the pulp. This case report discusses the current management protocol of dens invaginatus using a minimally invasive and nonsurgical treatment option. As with most conditions, early diagnosis and preventive measures help minimize complications in dens invaginatus cases. PMID:27656073

  4. A new AF gravitational instanton

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Teo, Edward

    2011-09-01

    It has long been conjectured that the Euclidean Schwarzschild and Euclidean Kerr instantons are the only non-trivial asymptotically flat (AF) gravitational instantons. In this Letter, we show that this conjecture is false by explicitly constructing a new two-parameter AF gravitational instanton with a U (1) × U (1) isometry group, using the inverse-scattering method. It has Euler number χ = 3 and Hirzebruch signature τ = 1, and its global topology is CP2 with a circle S1 removed appropriately. Various other properties of this gravitational instanton are also discussed.

  5. Dragons' Den: promoting healthcare research and innovation.

    PubMed

    Mazhindu, Deborah; Gregory, Siobhan

    2015-07-01

    The changing health and social care landscape, and, in particular, the financial challenges affecting the NHS, can present difficulties for staff looking for funding to support innovation and new ways of working. One method of competitive tendering that is becoming more accepted as a way of allocating funds, encouraging staff engagement and developing innovation for research is a format based the BBC television series, Dragons' Den. This article describes how Hounslow and Richmond Community Healthcare NHS Trust, London, has developed a 'Dragons' Den initiative' of annual competitive research funding allocation to ensure that some of the most dynamic practice in the trust is captured.

  6. Polar bear maternity denning in the Beaufort Sea

    USGS Publications Warehouse

    Amstrup, S.; Gardner, C.

    1994-01-01

    The distribution of polar bears (Ursus maritimus) is circumpolar in the NOrthern Hemisphere, but known locations of maternal dens are concentrated in relatively few, widely scattered locations. Denning is either uncommon or unknown within gaps. To understand effects of industrial development and propose increases in hunting, the temporal and spatial distribution of denning in the Beaufort Sea must be known. We caputred and radiocollared polar bears between 1981 and 1991 and determined tht denning in the Beaufort Sea region was sufficient to account for the estimated population there. Of 90 dend, 48 were on drifting pack ice, 38 on land, and 4 on land-fast ice. The portions of dens on land was higher (P= 0.029) in later compared with earlier years of the study. Bears denning on pack ice drifting as far as 997 km (x=385km) while in dens. there was no difference in cun production by bears denning on land and pack ice (P =0.66). Mean entry and exit dates were 11 November and 5 April for land dens and 22 November and 26 March for pack-ice dens. Female polar bears captured in the Beaufort Sea appeared to be isolated from those caught eat of Cape Bathurst in Canada. Of 35 polar bears that denned along the mainland coast of Alaska and Canada 80% denned between 137 00'W snf 146 59'W. Bears followed to >1 den did not reuse sites and consecutive dens were 20-1,304 km apart. However radio-collared bears are largely faithful to substrate (pack-ice, land, and land-fast ice) and the general geographic area of previous dens. Bears denning on land may be vunerable to human activities such as hunting and industrial development. However, predictable denning chronology and alck of site fidelity indicate that many potential impacts on denning polar bears could be mitigated.

  7. Installation Restoration Program. Phase 1 - Records Search AAC-Northern Region, Galena AFS, Campion AFS, Cape Lisburne AFS, Fort Yukon AFS, Indian Mountain AFS, Kotzebue AFS, Murphy Dome AFS, and Tin City AFS

    DTIC Science & Technology

    1985-09-01

    registered with Defense Technical Information Center should direct requests for copies of this report to: Defense Technical Information Center Cameron Station ...Information Center should direct requests for copies of this report to: Defense Technical Information Center Cameron Station Alexandria, Virginia 22314 U’ B...Contract No. F08637 84 C0070. The locations of these installations are shown in Figure 1. INSTALLATION DESCRIPTION Galena AFS * Galena Air Force Station

  8. A rare presentation of multiple dens invaginatus in maxillary dentition.

    PubMed

    Purani, Jigar M; Purani, Hiral J

    2014-08-01

    Dens invaginatus is a developmental disturbance of the tooth and usually occurs in the maxillary lateral incisor of permanent dentition. In this article, a rare case of dens invaginatus affecting multiple permanent maxillary teeth is described.

  9. Dens Evaginatus: A Problem-Based Approach

    PubMed Central

    Ayer, A.; Vikram, M.; Suwal, P.

    2015-01-01

    Dens evaginatus is an uncommon developmental anomaly of human dentition characterized by the presence of tubercle on the occlusal surface of mandibular premolars and lingual surface of anterior teeth. Due to occlusal trauma this tubercle tends to fracture thus exposing the pathway to the pulp chamber of teeth. This case report is about the presentation of dens evaginatus in mandibular premolars bilaterally; among them tooth 44 was associated with chronic apical periodontitis. Fractured tubercle of three premolars was sealed with composite resin. Root canal treatment was performed with tooth 44. Routine endodontic treatment did not result in remission of infection. Therefore, culture and sensitivity tests were performed to identify the cause and modify treatment plan accordingly. Triple antibiotic paste was used as an intracanal medicament to disinfect the root canal that resulted in remission of infection. PMID:26779353

  10. Dysplastic dens of the axis: case report.

    PubMed

    Payer, M; Bijlenga, P; Delavelle, J

    2003-09-01

    In a patient injured in a bicycle accident, radiological evaluation of the cervical spine revealed an oblique orientation of a dysplastic dens of the axis, which, to our knowledge, has not been reported in the literature. There were no other bony or soft tissue anomalies and no associated instability. This case should draw attention to congenital anomalies of the cranio-cervical junction in trauma patients.

  11. Den use by arctic foxes in northern Alaska

    SciTech Connect

    Eberhardt, L.E.; Garrott, R.A.; Hanson, W.C.

    1983-01-01

    Den use by arctic foxes (Alopex lagopus) was examined near the Prudhoe Bay oil field and on a nearby undisturbed area on the Colville River Delta in northern Alaska. The density of dens at Prudhoe Bay (1 den/12 km/sup 2/) was approximately three times that on Colville Delta (1 den/34 km/sup 2/). Thirty-three percent of the Prudhoe Bay dens appeared to be of recent origin compared to 11% on the Colville Delta. Survival or production of juvenile foxes decreased on both study areas in 1977 when densities of lemmings (Dicrostonyx torquatus and Lemmus sibiricus) were low, but the decrease was less pronounced at Prudhoe Bay. Foxes that raised young at Prudhoe Bay in 1977 were those living near petroleum development facilities. The utilization of garbage by Prudhoe Bay foxes probably accounted for many of the observed differences between study sites. Common features of spring and summer den use by arctic foxes included a selection of historically preferred den sites, splitting litters into multiple dens, and the fidelity of some adult and juvenile foxes to dens in successive years. Winter use of dens was common at Prudhoe Bay. 24 references, 2 tables.

  12. Control of multicellular development by the physically interacting deneddylases DEN1/DenA and COP9 signalosome.

    PubMed

    Christmann, Martin; Schmaler, Tilo; Gordon, Colin; Huang, Xiaohua; Bayram, Ozgür; Schinke, Josua; Stumpf, Sina; Dubiel, Wolfgang; Braus, Gerhard H

    2013-01-01

    Deneddylases remove the ubiquitin-like protein Nedd8 from modified proteins. An increased deneddylase activity has been associated with various human cancers. In contrast, we show here that a mutant strain of the model fungus Aspergillus nidulans deficient in two deneddylases is viable but can only grow as a filament and is highly impaired for multicellular development. The DEN1/DenA and the COP9 signalosome (CSN) deneddylases physically interact in A. nidulans as well as in human cells, and CSN targets DEN1/DenA for protein degradation. Fungal development responds to light and requires both deneddylases for an appropriate light reaction. In contrast to CSN, which is necessary for sexual development, DEN1/DenA is required for asexual development. The CSN-DEN1/DenA interaction that affects DEN1/DenA protein levels presumably balances cellular deneddylase activity. A deneddylase disequilibrium impairs multicellular development and suggests that control of deneddylase activity is important for multicellular development.

  13. An update of dens invaginatus in the diagnosis and treatment.

    PubMed

    Zhu, Jingjing; Wang, Xinhuan; Fang, Yanjun; Von den Hoff, Johannes W; Meng, Liuyan

    2017-03-17

    Dens invaginatus is a malformation with varying anatomical features, posing challenges to treatment. Early and accurate diagnosis plays a significant role in selecting the appropriate treatment. The diagnosis of teeth with a complex root canal system including dens invaginatus has made progress with the application of three-dimensional imaging techniques in endodontics. Advanced treatment options provide hope for teeth that could not be saved before. This review discusses diagnostic methods and treatment options for teeth with dens invaginatus, and provides guidelines for the management of dens invaginatus cases in clinic. Current as well as traditional diagnostic techniques are summarised. Treatment options including state-of-the-art alternatives are presented for coronal dens invaginatus and radicular dens invaginatus. This article is protected by copyright. All rights reserved.

  14. Denning behaviour of non-gravid wolves, Canis lupus

    USGS Publications Warehouse

    Mech, L.D.; Phillips, M.K.; Smith, D.W.; Kreeger, T.J.

    1996-01-01

    Wild wolves (Canis lupus) that had produced pups in earlier years but were not currently pregnant, and ovariectomized captive wolves, dug dens during and after the whelping season even though they produced no pups. These observations suggest that den digging is not a function of pregnancy or of ovarian estrogen or progesterone. We hypothesize that increasing prolactin in spring elicits or mediates den-digging behavior.

  15. Health Information in Somali (af Soomaali): MedlinePlus

    MedlinePlus

    ... af Soomaali (Somali) Bilingual PDF Health Information Translations Wildfires Wildfires - English Dabka duurka - af Soomaali (Somali) Multimedia Healthy Roads Media Wildfires - English Dabka duurka - af Soomaali (Somali) PDF Healthy ...

  16. STBC AF relay for unmanned aircraft system

    NASA Astrophysics Data System (ADS)

    Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

    2015-01-01

    If a large scale disaster similar to the Great East Japan Earthquake 2011 happens, some areas may be isolated from the communications network. Recently, unmanned aircraft system (UAS) based wireless relay communication has been attracting much attention since it is able to quickly re-establish the connection between isolated areas and the network. However, the channel between ground station (GS) and unmanned aircraft (UA) is unreliable due to UA's swing motion and as consequence, the relay communication quality degrades. In this paper, we introduce space-time block coded (STBC) amplify-and-forward (AF) relay for UAS based wireless relay communication to improve relay communication quality. A group of UAs forms single frequency network (SFN) to perform STBC-AF cooperative relay. In STBC-AF relay, only conjugate operation, block exchange and amplifying are required at UAs. Therefore, STBC-AF relay improves the relay communication quality while alleviating the complexity problem at UAs. It is shown by computer simulation that STBC-AF relay can achieve better throughput performance than conventional AF relay.

  17. Evaluation Studies of the DEN-2/S-1 Vaccine.

    DTIC Science & Technology

    1981-08-01

    Urbana, IL 61801). This drug was found to have antiviral activity against herpes s.mplex viruses (types I and II), vaccinia, influenza PR8...painfluenza 3, coxsackie A-21 and equine rhinovirus (Dr. Rinehart, personal communication). We have found that Didemnin A reduces plaque formation by DEN-i, DEN...3 and herpes simplex virus type 2 (see figures I and 2). Fifty percent inu- bition of plaque formation by these viruses was observed at drug

  18. Dental abscess in a tooth with intact dens evaginatus.

    PubMed

    Cho, S Y

    2006-03-01

    This article reports a case of dental abscess in a mandibular premolar with intact dens evaginatus. Dentists are advised to critically evaluate those teeth with dens evaginatus, both clinically and radiographically, before attempting prophylactic treatments. This is particularly important medicolegally in case the tooth develops symptoms shortly after the prophylactic treatment. Dentists practising in Western countries should also be aware of this dental anomaly because of the increasing global migration of people from Asia.

  19. Patterns of den occupation by the spotted hyaena (Crocuta crocuta)

    USGS Publications Warehouse

    Boydston, E.E.; Kapheim, K.M.; Holekamp, K.E.

    2006-01-01

    Spotted hyaenas utilize isolated natal dens (NDs) and communal dens (CDs) for rearing their cubs. Here we describe patterns of natal and CD occupation by hyaenas belonging to one well-studied clan in the Maasai Mara National Reserve during a 10-year period. Locations of 98 den sites that were used as natal or CDs by hyaenas in the study clan were digitized in a Geographic Information System, and the duration of use of each den site, frequency of re-use, and distances involved in den moves were quantified. Hyaenas moved their CD monthly on average. Most CD sites were occupied only once during the study, but several sites were used repeatedly. On rare occasions, the movement of hyaenas to a new den site could be attributed to a disturbance event at the CD, but factors regularly prompting hyaenas to move to new CD sites were unclear. High-ranking female hyaenas were more likely to rear their cubs from birth in a CD than low-ranking females. Low-ranking females almost always utilized isolated NDs for the first few weeks of a litter's development, and low-ranking females transferred their cubs over longer distances than did high-ranking females. ?? 2006 East African Wild Life Society.

  20. Den use by arctic foxes (Alopex lagopus) in a subarctic region of western Alaska

    USGS Publications Warehouse

    Anthony, R. Michael

    1996-01-01

    Distribution, abundance, and use of arctic fox dens located in coastal tundra communities of the Yukon–Kuskokwim delta were determined in studies from 1985 to 1990. Dens were denser and less complex than those described in studies conducted above the Arctic Circle. Eighty-three dens of varying complexity were found in the 52-km2 study area. Nineteen dens were used by arctic foxes for whelping or rearing pups. Three females relocated litters to multiple dens; a maximum of four dens were used concurrently by pups from one litter. Although red foxes (Vulpes vulpes) were common in the region, their use of dens in the study area was minimal. Differences in vegetation at den sites and nearby unoccupied sites were minimal. Furthermore, den sites could not be distinguished from non-den sites during aerial surveys.

  1. Denning chronology and design of effective bear management units

    USGS Publications Warehouse

    Inman, R.M.; Costello, C.M.; Jones, D.E.; Inman, K.H.; Thompson, B.C.; Quigley, H.B.

    2007-01-01

    Reports on the effectiveness of using late fall hunting seasons to reduce the proportion of female black bears (Ursus americanus) in the harvest are limited, and the geographic scale over which the technique functions as intended has not been examined. During 1992-2000, we radio-equipped black bears in New Mexico, USA, obtained estimates of 175 den entry and 137 den emergence dates, and used New Mexico Department of Game and Fish harvest data (1985-2000) to test for differences in proportion of females in the harvest relative to denning chronology. Bears in northern New Mexico entered dens earlier and emerged later than bears in southern New Mexico (P ??? 0.001). In northern New Mexico bears displayed the typical pattern of earlier entry and later emergence by reproductive females, proportion of females in the harvest varied over time as expected, and late fall seasons were effective (P ??? 0.10). In contrast, denning chronology did not differ by sex in southern New Mexico, proportion of females in the harvest did not change over time, and late fall seasons were not effective (P ??? 0.18). Manipulation of hunting season dates to influence female mortality can be an effective tool, however our study provides an example of an area where denning chronology did not differ by sex and late seasons were not effective. We also observed regional differences in timing of entrance and emergence, which suggest that scale of application may be key. In management jurisdictions that encompass ecologically distinct areas, cover a wide range of latitudes, or are mountainous, successful use of the technique may depend on knowledge of denning chronology at multiple locations and appropriate designation of hunting unit boundaries, season dates, and data analysis units.

  2. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  3. AFS Estuaries Section - A Successful Partnership

    EPA Science Inventory

    The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

  4. Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

    PubMed

    Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

    2014-08-21

    Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

  5. AF fixer: new incremental OPC method for optimizing assist feature

    NASA Astrophysics Data System (ADS)

    Jung, Sung-Gon; Kim, Sang-Wook; Suh, Sung-Soo; Kim, Young-Chang; Lee, Suk-Joo; Choi, Sung-Woon; Han, Woo-Sung; Moon, Joo-Tae; Barnes, Levi D.; Li, Xiaohai; Lugg, Robert M.; Lee, Sooryong; Koo, Kyoil; Do, Munhoe; Amoroso, Frank P.; Painter, Benjamin

    2008-05-01

    Due to shrinking design nodes and to some limitations of scanners, extreme off-axis illumination (OAI) required and its use and implementation of assist features (AF) to solve depth of focus (DOF) problems for isolated features and specific pitch regions is essential. But unfortunately, the strong periodic character of OAI illumination makes AF's print more easily. Present OPC flows generate AFs before OPC, which is also causes some AF printing problems. At present, mask manufacturers must downsize AF's below 30nm to solve this problem. This is challenging and increases mask cost. We report on an AF-fixer tool which is able to check AF printability and correct weak points with minimal cost in terms of DOF after OPC. We have devised an effective algorithm that removes printing AF's. It can not only search for the best non-printing AF condition to meet the DOF spec, but also reports uncorrectable spots, which could be marked as design errors. To limit correction times and to maximize DOF in full-chip correction, a process window (PW) model and incremental OPC method are applied. This AF fixer, which suggests optimum AF in only weak point region, solves AF printing problems economically and accurately.

  6. Remote identification of polar bear maternal den habitat in northern Alaska

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Ambrosius, Ken J.

    2001-01-01

    Polar bears (Ursus maritimus) give birth in dens of ice and snow to protect their altricial young. During the snow-free season, we visited 25 den sites located previously by radiotelemetry and characterized the den site physiognomy. Seven dens occurred in habitats with minimal relief. Eighteen dens (72%) were in coastal and river banks. These "banks" were identifiable on aerial photographs. We then searched high-resolution aerial photographs (n = 3000) for habitats similar to those of the 18 dens. On aerial photos, we mapped 1782 km of bank habitats suitable for denning. Bank habitats comprised 0.18% of our study area between the Colville River and the Tamayariak River in northern Alaska. The final map, which correctly identified 88% of bank denning habitat in this region, will help minimize the potential for disruptions of maternal dens by winter petroleum exploration activities.

  7. Detecting denning polar bears with Forward-Looking Infrared (FLIR) imagery

    USGS Publications Warehouse

    Amstrup, Steven C.; York, G.; McDonald, T.L.; Nielson, R.; Simac, K.

    2004-01-01

    Polar bears give birth in snow dens in midwinter and remain in dens until early spring. The survival and development of cubs is dependent on a stable environment within the maternal den. To mitigate potential disruption of polar bear denning by existing and proposed petroleum activities, we used forward-looking infrared (FLIR) viewing to try to detect heat rising from dens.We flew transects over dens of radio-collared females with FLIR imager-equipped aircraft, recorded weather conditions at each observation, and noted whether the den was detected.We surveyed 23 dens on 67 occasions (1 to 7 times each). Nine dens were always detected, and 10 dens visited more than once were detected on some flights but not on others. Four dens were never detected (17 percent), but three of those were visited only under marginal conditions. The odds of detecting a den were 4.8 times greater when airborne moisture (snow, blowing snow, fog, etc.) was absent than when it was present, and they increased 3-fold for every 1?C increase in temperature-dew point spread. The estimated probability of detecting dens in sunlight was 0. Data suggested that FLIR surveys conducted during optimal conditions for detection can produce detection rates approaching 90 percent and thus can be an important management and mitigation tool. polar bear, infrared imagery, maternal denning, human impacts, management

  8. American black bear denning behavior: Observations and applications using remote photography

    USGS Publications Warehouse

    Bridges, A.S.; Fox, J.A.; Olfenbuttel, C.; Vaughan, M.B.

    2004-01-01

    Researchers examining American black bear (Ursus americanus) denning behavior have relied primarily on den-site visitation and radiotelemetry to gather data. Repeated den-site visits are time-intensive and may disturb denning bears, possibly causing den abandonment, whereas radiotelemetry is sufficient only to provide gross data on den emergence. We used remote cameras to examine black bear denning behavior in the Allegheny Mountains of western Virginia during March-May 2003. We deployed cameras at 10 den sites and used 137 pictures of black bears. Adult female black bears exhibited greater extra-den activity than we expected prior to final den emergence, which occurred between April 12 and May 6, 2003. Our technique provided more accurate den-emergence estimation than previously published methodologies. Additionally, we observed seldom-documented behaviors associated with den exits and estimated cub age at den emergence. Remote cameras can provide unique insights into denning ecology, and we describe their potential application to reproductive, survival, and behavioral research.

  9. Habitat characteristics of polar bear terrestrial maternal den sites in northern Alaska

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Fischbach, Anthony S.

    2003-01-01

    Polar bears (Ursus maritimus) give birth to and nurture their young in dens of ice and snow. During 1999-2001, we measured the structure of 22 dens on the coastal plain of northern Alaska after polar bear families had evacuated their dens in the spring. During the summers of 2001 and 2002, we revisited the sites of 42 maternal and autumn exploratory dens and recorded characteristics of the under-snow habitat. The structure of polar bear snow dens was highly variable. Most were simple chambers with a single entrance/egress tunnel. Others had multiple chambers and additional tunnels. Thickness of snow above and below dens was highly variable, but most dens were overlain by less than 1 m of snow. Dens were located on, or associated with, pronounced landscape features (primarily coastal and river banks, but also a lake shore and an abandoned oil field gravel pad) that are readily distinguished from the surrounding terrain in summer and catch snow in early winter. Although easily identified, den landforms in northern Alaska were more subtle than den habitats in many other parts of the Arctic. The structure of polar bear dens in Alaska was strikingly similar to that of dens elsewhere and has remained largely unchanged in northern Alaska for more than 25 years. Knowledge of den structure and site characteristics will allow resource managers to identify habitats with the greatest probability of holding dens. This information may assist resource managers in preventing negative impacts of mineral exploration and extraction on polar bears.

  10. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    NASA Technical Reports Server (NTRS)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  11. Denning habits of free-ranging dogs reveal preference for human proximity

    PubMed Central

    Sen Majumder, Sreejani; Paul, Manabi; Sau, Shubhra; Bhadra, Anindita

    2016-01-01

    Dens are crucial in the early development of many mammals, making den site selection an important component of parental care in such species. Resource availability and shelter from predators primarily govern den selection. Species inhabiting human-dominated landscapes typically den away from human disturbance, often shifting dens to avoid humans during the early life of their young. Domesticated dogs have evolved in human proximity over centuries, being bred and reared in human homes for generations. While pets rely on their owners for shelter and care, free-ranging dogs roam uncared, and typically whelp in dens. We conducted a study on 148 free-ranging dog dens in India to understand their denning habits. Distance from resources influenced den choice, but anthropogenic disturbance did not. Dens were found in areas of high human activity, and begging from humans was preferred over scavenging. A study on 15 pregnant females revealed that females actively searched for denning sites, rejecting several intermediate ones before selecting the final den. We propose that the obvious preference of dogs for denning close to humans is a behavioural adaptation that helps them to survive in the urban landscape, in spite of the high human induced mortality during the early life of pups. PMID:27535214

  12. Endodontic management of dens invaginatus Type IIIb: Case series

    PubMed Central

    Martins, Jorge N. R.; da Costa, Rui Pereira; Anderson, Craig; Quaresma, Sérgio André; Corte-Real, Luís S. M.; Monroe, Adam D.

    2016-01-01

    Dens invaginatus may be seen as a developmental malformation. It is characterized by an invagination of the enamel and dentin, creating a lumen inside the affected tooth, which may extend as deep as the apical foramen. Oehlers Type IIIb is considered the most challenging clinical conditions. The purpose of this study is to discuss the nonsurgical endodontic management of vital and necrotic dens invaginatus Type IIIb cases. Due to the complex anatomical consideration of dens invaginatus Type IIIb, endodontic treatment is extremely technique sensitive. A conservative approach was used in a vital case to treat the invaginated lumen only, to preserve the vitality of the pulp, and a more invasive approach was used in a necrotic case to debride the lumen and necrotic pulp for proper disinfection of the root canal system. Although different, all the approaches were successful. The clinical signs and symptoms were resolved. The vital case remains vital after 19 months, and the recall radiographs were able to show satisfactory periapical healing both in vital and necrotic cases. Due to the highly complex anatomy of dens invaginatus Type IIIb, the decision of preserving the pulp vitality may not be related only to pulpal diagnosis but also to the technical requirements of the treatment. Although very technically sensitive, it may be possible to treat the invaginated lumen exclusively, while preserving the vitality of the pulp. Necrotic cases may require a more aggressive approach to achieve a favorable prognosis. PMID:28042276

  13. Den-site characteristics of black bears in Rocky Mountain National Park, Colorado

    USGS Publications Warehouse

    Baldwin, R.A.; Bender, L.C.

    2008-01-01

    We compared historic (1985-1992) and contemporary (2003-2006) black bear (Ursus americanus) den locations in Rocky Mountain National Park (RMNP), Colorado, USA, for habitat and physiographic attributes of den sites and used maximum entropy modeling to determine which factors were most influential in predicting den-site locations. We observed variability in the relationship between den locations and distance to trails and elevation over rime. Locations of historic den sites were most associated with slope, elevation, and covertype, whereas contemporary sites were associated with slope, distance to roads, aspect, and canopy height. Although relationships to covariates differed between historic and contemporary periods, preferred den-site characteristics consistently included steep slopes and factors associated with greater snow depth. Distribution of den locations shifted toward areas closer to human developments, indicating little negative influence of this factor on den-site selection by black bears in RMNP.

  14. Coaxially electrospun PVDF-Teflon AF and Teflon AF-PVDF core-sheath nanofiber mats with superhydrophobic properties.

    PubMed

    Muthiah, Palanikkumaran; Hsu, Shu-Hau; Sigmund, Wolfgang

    2010-08-03

    This work reports the coaxial electrospinning of poly(vinylidene fluoride) (PVDF)-Teflon amorphous fluoropolymer (AF) and Teflon AF-PVDF core-sheath nanofiber mats yielding superhydrophobic properties. The coaxial electrospinning configuration allows for the electrospinning of Teflon AF, a nonelectrospinnable polymer, with the help of an electrospinnable PVDF polymer. PVDF-Teflon AF and Teflon AF-PVDF core-sheath fibers have been found to a have mean fiber diameter ranging from 400 nm to less than 100 nm. TEM micrographs exhibit a typical core-sheath fiber structure for these fibers, where the sheath fiber coats the core fiber almost thoroughly. Water contact angle measurements by sessile drop method on these core-sheath nanofiber mats exhibited superhydrophobic characteristics with contact angles close to or higher than 150 degrees. Surprisingly, PVDF-Teflon AF and Teflon AF-PVDF nanofiber mat surface properties were dominated by the fiber dimensions and less influenced by the type of sheath polymer. This suggests that highly fluorinated polymer Teflon AF does not advance the hydrophobicity beyond what surface physics and slightly fluorinated polymer PVDF can achieve. It is concluded that PVDF-Teflon AF and Teflon AF-PVDF core-sheath electrospun nanofiber mats may be used in lithium (Li)-air batteries.

  15. Selection of den sites by black bears in the southern Appalachians

    USGS Publications Warehouse

    Reynolds-Hogland, M. J.; Mitchell, M.S.; Powell, R.A.; Brown, D.C.

    2007-01-01

    We evaluated selection of den sites by American black bears (Ursus americanus) in the Pisgah Bear Sanctuary, western North Carolina, by comparing characteristics of dens at 53 den sites with availability of habitat characteristics in annual home ranges of bears and in the study area. We also tested whether den-site selection differed by sex, age, and reproductive status of bears. In addition, we evaluated whether the den component of an existing habitat model for black bears predicted where bears would select den sites. We found bears selected den sites far from gravel roads, on steep slopes, and at high elevations relative to what was available in both annual home ranges and in the study area. Den-site selection did not differ by sex or age, but it differed by reproductive status. Adult females with cubs preferred to den in areas that were relatively far from gravel roads, but adult females without cubs did not. The habitat model overestimated the value of areas near gravel roads, underestimated the value of moderately steep areas, and did not include elevation as a predictor variable. Our results highlight the importance of evaluating den selection in terms of both use and availability of den characteristics. ?? 2007 American Society of Mammalogists.

  16. A female black bear denning habitat model using a geographic information system

    USGS Publications Warehouse

    Clark, J.D.; Hayes, S.G.; Pledger, J.M.

    1998-01-01

    We used the Mahalanobis distance statistic and a raster geographic information system (GIS) to model potential black bear (Ursus americanus) denning habitat in the Ouachita Mountains of Arkansas. The Mahalanobis distance statistic was used to represent the standard squared distance between sample variates in the GIS database (forest cover type, elevation, slope, aspect, distance to streams, distance to roads, and forest cover richness) and variates at known bear dens. Two models were developed: a generalized model for all den locations and another specific to dens in rock cavities. Differences between habitat at den sites and habitat across the study area were represented in 2 new GIS themes as Mahalanobis distance values. Cells similar to the mean vector derived from the known dens had low Mahalanobis distance values, and dissimilar cells had high values. The reliability of the predictive model was tested by overlaying den locations collected subsequent to original model development on the resultant den habitat themes. Although the generalized model demonstrated poor reliability, the model specific to rock dens had good reliability. Bears were more likely to choose rock den locations with low Mahalanobis distance values and less likely to choose those with high values. The model can be used to plan the timing and extent of management actions (e.g., road building, prescribed fire, timber harvest) most appropriate for those sites with high or low denning potential. 

  17. Raccoon (Procyon lotor) diurnal den use within an intensively managed forest in central West Virginia

    USGS Publications Warehouse

    Owen, Sheldon F.; Berl, Jacob L.; Edwards, John W.; Ford, W. Mark; Wood, Petra Bohall

    2015-01-01

    Intensive forest management may influence the availability of suitable den sites for large den-seeking species, such as Procyon lotor (Raccoon). As part of a Raccoon ecology study on an industrial forest in the Allegheny Mountains of central West Virginia, we radio-tracked 32 Raccoons to 175 diurnal den sites to determine relative use of dens that included cavity trees, rock dens, log piles, slash piles, and exposed limbs. Patterns of den use significantly differed between sexes and among seasons. Overall, we recorded 58 cavity dens in 12 tree species with 7 maternal dens found in 5 tree species. Raccoons selected larger-diameter den trees than available cavity trees and non-cavity trees. Because the abundance of suitable tree cavities is known to influence Raccoon densities and recruitment at fine spatial scales and female Raccoons in this study used tree cavities as maternal den sites, the continued harvest of large-diameter trees (i.e., those capable of developing den cavities) without replacement may impact Raccoon recruitment within intensively managed forests throughout the central Appalachians.

  18. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 14 2013-01-01 2013-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  19. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  20. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 14 2014-01-01 2014-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  1. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  2. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  3. Part III: AFS - A Secure Distributed File System

    SciTech Connect

    Wachsmann, A.; /SLAC

    2005-06-29

    AFS is a secure distributed global file system providing location independence, scalability and transparent migration capabilities for data. AFS works across a multitude of Unix and non-Unix operating systems and is used at many large sites in production for many years. AFS still provides unique features that are not available with other distributed file systems even though AFS is almost 20 years old. This age might make it less appealing to some but with IBM making AFS available as open-source in 2000, new interest in use and development was sparked. When talking about AFS, people often mention other file systems as potential alternatives. Coda (http://www.coda.cs.cmu.edu/) with its disconnected mode will always be a research project and never have production quality. Intermezzo (http://www.inter-mezzo.org/) is now in the Linux kernel but not available for any other operating systems. NFSv4 (http://www.nfsv4.org/) which picked up many ideas from AFS and Coda is not mature enough yet to be used in serious production mode. This article presents the rich features of AFS and invites readers to play with it.

  4. DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex

    PubMed Central

    Mück, Fabian; Bracharz, Silvia; Marschalek, Rolf

    2016-01-01

    AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of “super elongation complexes” (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex. DDX6 is an evolutionarily conserved member of the DEAD-box RNA helicase family that is known to control miRNA and mRNA biology (translation, storage and degradation). Overexpressed DDX6 is associated with different cancer types and with c-Myc protein overexpression. We could demonstrate that DDX6 binds to 7SK snRNA and causes the release and transfer of P-TEFb to the AF4/AF4N SEC. DDX6 also binds stably to AF4 and AF4N as demonstrated by GST pull-down and co-immunoprecipitation experiments. As a consequence, overexpression of either AF4/AF4N or DDX6 resulted in a strong increase of mRNA production (5-6 fold), while their simultaneous expression increased the cellular mRNA production by 11-fold. Conversely, the corresponding knockdown of DDX6 decreased mRNA production by 70%. In conclusion, AF4/AF4N and DDX6 represent key molecules for the elongation process of gene transcription and a model will be proposed for the hand-over process of P-TEFb to SECs. PMID:27679741

  5. Compliance Testing of the Clear AFS Power Plant, Coal-Fired Boiler 1 Clear AFS, Alaska

    DTIC Science & Technology

    1989-10-01

    Background On 3 February 1987 Clear AFS requested a permit modification to allow limited burning of waste oil for their power plant shown in Figure 1...The Alaska DEC rescindel Permit to Operate No. 8331-AA003 and issued Permit No. 8731-AA004 (Appendix B) allowing the burning of waste oil. As a...below. 1. Visible Emissions (18 AAC 50.050(a)) Visible emissions, excluding condensed water vapor from an industrial process or fuel burning

  6. Landward and eastward shift of Alaskan polar bear denning associated with recent sea ice changes

    USGS Publications Warehouse

    Fischbach, A.S.; Amstrup, Steven C.; Douglas, D.C.

    2007-01-01

    Polar bears (Ursus maritimus) in the northern Alaska region den in coastal areas and on offshore drifting ice. We evaluated changes in the distribution of polar bear maternal dens between 1985 and 2005, using satellite telemetry. We determined the distribution of maternal dens occupied by 89 satellite collared female polar bears between 137°W and 167°W longitude. The proportion of dens on pack ice declined from 62% in 1985–1994 to 37% in 1998–2004 (P = 0.044) and among pack ice dens fewer occurred in the western Beaufort Sea after 1998. We evaluated whether hunting, attraction to bowhead whale remains, or changes in sea ice could explain changes in den distribution. We concluded that denning distribution changed in response to reductions in stable old ice, increases in unconsolidated ice, and lengthening of the melt season. In consort, these changes have likely reduced the availability and quality of pack ice denning habitat. Further declines in sea ice availability are predicted. Therefore, we expect the proportion of polar bears denning in coastal areas will continue to increase, until such time as the autumn ice retreats far enough from shore that it precludes offshore pregnant females from reaching the Alaska coast in advance of denning.

  7. Structure and Functional Studies of DEN-2 Virus Genome.

    DTIC Science & Technology

    1982-09-01

    Structure and Functional Studies on Dengue -2 Progress Report Virus Genome 1 Mar 82 - I Sep 82 6. PERFORMING ORO. REPORT NUMBER 7. AUTHOR(e) 8. CONTRACT OR...Identify by block number) Complementdry DNA synthesis of Dengue -2 RNA by avian reverse transcriptase in vitro. The size of the DNA copy of Dengue RNA is in...Unannounced 0 Justification ............ By........... Di.A b-Aio: i Availability Codes S Avail and (or 2 Abstract 1. Dengue -2 RNA (DEN-2 RNA) was extracted

  8. Nonlinear generalization of Den Hartog's equal-peak method

    NASA Astrophysics Data System (ADS)

    Habib, G.; Detroux, T.; Viguié, R.; Kerschen, G.

    2015-02-01

    This study addresses the mitigation of a nonlinear resonance of a mechanical system. In view of the narrow bandwidth of the classical linear tuned vibration absorber, a nonlinear absorber, termed the nonlinear tuned vibration absorber (NLTVA), is introduced in this paper. An unconventional aspect of the NLTVA is that the mathematical form of its restoring force is tailored according to the nonlinear restoring force of the primary system. The NLTVA parameters are then determined using a nonlinear generalization of Den Hartog's equal-peak method. The mitigation of the resonant vibrations of a Duffing oscillator is considered to illustrate the proposed developments.

  9. Einsteins Spuren in den Archiven der Wissenschaft: Physikgeschichte

    NASA Astrophysics Data System (ADS)

    Marx, Werner

    2005-07-01

    Die Erwähnungen und Zitierungen von Einsteins Arbeiten dokumentieren lediglich den quantifizierbaren Anteil von Einsteins Beitrag zur Physik. Gleichwohl belegen sie die außergewöhnliche Resonanz und Langzeitwirkung seiner Arbeiten. Die Häufigkeit der Zitierungen entspricht nicht der allgemeinen Einschätzung ihrer Bedeutung. Insbesondere die Pionierarbeiten werden inzwischen als bekannt vorausgesetzt und nicht mehr explizit zitiert. Interessanterweise ist seine nach 1945 meist zitierte Arbeit nicht eine der Pionierarbeiten zur Quantenphysik oder Relativitätstheorie, sondern jene aus dem Jahr 1935 zum berühmten Einstein-Podolsky-Rosen-Paradoxon.

  10. An Implicit LU/AF FDTD Method

    NASA Technical Reports Server (NTRS)

    Beggs, John H.; Briley, W. Roger

    2001-01-01

    There has been some recent work to develop two and three-dimensional alternating direction implicit (ADI) FDTD schemes. These ADI schemes are based upon the original ADI concept developed by Peaceman and Rachford and Douglas and Gunn, which is a popular solution method in Computational Fluid Dynamics (CFD). These ADI schemes work well and they require solution of a tridiagonal system of equations. A new approach proposed in this paper applies a LU/AF approximate factorization technique from CFD to Maxwell s equations in flux conservative form for one space dimension. The result is a scheme that will retain its unconditional stability in three space dimensions, but does not require the solution of tridiagonal systems. The theory for this new algorithm is outlined in a one-dimensional context for clarity. An extension to two and threedimensional cases is discussed. Results of Fourier analysis are discussed for both stability and dispersion/damping properties of the algorithm. Results are presented for a one-dimensional model problem, and the explicit FDTD algorithm is chosen as a convenient reference for comparison.

  11. Tin City AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-04-01

    GL&bAL CLIMATOLOGY 9 RA14CH T AC NG VERSUS Vi’SIBILITY A .FAT"E S[ PfIC /mAC I .17 TI CITY AFS AK 73-74,77-81 T 1b. 3 19.5 17.S 19.5 19.5...2. GOVT ACCESSION NO. 3 RECIPIENT’S CATALOG NUMBER USAFETAC/DS 83017 4. TITLE (d SubtII-)Reised Uniform Summary of Surface 5 TYPE OF REPORT & PERIOD...WINDS PART 0 CEILING VERSUS VISIBILITY PART F STATION PRESSURE SKYCOVER SEA LEVEL PRESSURE STANDARD 3 -HOUR GROUPS All su-nseri- requiring diurnal

  12. Indian Mountain AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-06-01

    31 8... . 1B b w., B. 0- r] N I o N.. Ob.. M.., N.. .1 N.-. it% To’p.Wo.- R. .1.__-___ 0 F 322 F *67 F *73 F 60S F *93 F To. 4 .. P , PSYCHROMETRIC...Psychrometrl- summary Surfoc, Worlds Extreme temperature Ceiling versus vis:boloi-; Helative Humidity -Climatological data (over) 20 ABSTRACT ’C- P ,, -1...uSAFETAC A2 4EATR SERVICE/MAC WEATHER CONDITIONS 70173C INDIAN MOUNTAIN AFS AK 73-8? P PEOCENTAGE FREQUENCY OF OCCURRENCE OF WEATHER CONDITIONS FROP HOURLY

  13. Post-den emergence behavior of polar bears (Ursus maritimus) in Northern Alaska

    USGS Publications Warehouse

    Smith, T.S.; Partridge, Steven T.; Amstrup, Steven C.; Schliebe, S.

    2007-01-01

    We observed polar bear (Ursus maritimus) maternity den sites on Alaska’s North Slope in March 2002 and 2003 in an effort to describe bears’ post-den emergence behavior. During 40 sessions spanning 459 h, we observed 8 adults and 14 dependent cubs outside dens for 37.5 h (8.2% of total observation time). There was no significant difference between den emergence dates in 2002 (mean = 15 Mar ± 4.1 d) and 2003 (mean = 21 Mar ± 2.1 d). Following initial den breakout, polar bears remained at their den sites for 1.5 to 14 days (mean = 8.1 ± 5.1 d). The average length of stay in dens between emergent periods was significantly shorter in 2002 (1.79 h) than in 2003 (4.82 h). While outside, adult bears were inactive 49.5% of the time, whereas cubs were inactive 13.4% of the time. We found no significant relationships between den emergence activity and weather. Adult polar bears at den sites subjected to industrial activity exhibited significantly fewer bouts of vigilance than denned bears in undisturbed areas (t = -5.5164, df = 4, p= 0.00). However, the duration of vigilance behaviors at sites near industrial activity was not significantly shorter than at the other sites studied (t = -1.8902, df = 4, p = 0.07). Results for these bears were within the range of findings in other studies of denned polar bears.

  14. Kin selection in den sharing develops under limited availability of tree hollows for a forest marsupial

    PubMed Central

    Banks, Sam C.; Lindenmayer, David B.; McBurney, Lachlan; Blair, David; Knight, Emma J.; Blyton, Michaela D. J.

    2011-01-01

    Animal social behaviour is not static with regard to environmental change. Flexibility in cooperative resource use may be an important response to resource decline, mediating the impacts of resource availability on fitness and demography. In forest ecosystems, hollow trees are key den resources for many species, but are declining worldwide owing to forestry. Altered patterns of den sharing may mediate the effects of the decline of this resource. We studied den-sharing interactions among hollow-dependent Australian mountain brushtail possums to investigate how spatial variation in hollow tree availability affects resource sharing and kin selection. Under reduced den availability, individuals used fewer dens and shared them less often. This suggests increased territoriality in the presence of resource competition. Further, there was a switch from kin avoidance to kin preference with decreasing hollow tree availability. This was driven primarily by a change in den sharing among siblings. The inclusive fitness benefits of den sharing with kin are likely to increase under resource-limiting conditions, but are potentially outweighed by the benefits of associating with non-relatives (avoidance of inbreeding or pathogen transmission) where dens are abundant. We discuss how predictions from social evolutionary theory can contribute to understanding animal responses to landscape change. PMID:21288953

  15. Polar bear maternal den habitat in the Arctic National Wildlife Refuge, Alaska

    USGS Publications Warehouse

    Durner, George M.; Amstrup, Steven C.; Ambrosius, Ken J.

    2006-01-01

    Polar bears (Ursus maritimus) give birth during mid-winter in dens of ice and snow. Denning polar bears subjected to human disturbances may abandon dens before their altricial young can survive the rigors of the Arctic winter. Because the Arctic coastal plain of Alaska is an area of high petroleum potential and contains existing and planned oil field developments, the distribution of polar bear dens on the plain is of interest to land managers. Therefore, as part of a study of denning habitats along the entire Arctic coast of Alaska, we examined high-resolution aerial photographs (n = 1655) of the 7994 km2 coastal plain included in the Arctic National Wildlife Refuge (ANWR) and mapped 3621 km of bank habitat suitable for denning by polar bears. Such habitats were distributed uniformly and comprised 0.29% (23.2 km2) of the coastal plain between the Canning River and the Canadian border. Ground-truth sampling suggested that we had correctly identified 91.5% of bank denning habitats on the ANWR coastal plain. Knowledge of the distribution of these habitats will help facilitate informed management of human activities and minimize disruption of polar bears in maternal dens.

  16. Den site activity patterns of adult male and female swift foxes, Vulpes velox, in Northwestern Texas

    USGS Publications Warehouse

    Lemons, P.R.; Ballard, W.B.; Sullivan, R.M.; Sovada, M.A.

    2003-01-01

    Activity of Swift Foxes (Vulpes velox) at den sites was studied in northwestern Texas during pup rearing seasons in 2000 and 2001 to determine role of males in parental care. Twenty-four percent of radio-collared females with a potential to breed successfully raised pups to eight weeks of age. We intensively monitored presence and absence of male and female Swift Foxes at two den sites each year. Females were present >2.6 times more at den sites than males during the pup rearing season. Female and male Swift Foxes largely stayed at dens during diurnal hours and were active away from dens during nocturnal and crepuscular hours. Females and males spent 12.4% and 3.0% more time at dens before pups emerged, than after pups emerged, respectively. Following depredation of one male parent, the female spent 29% less time at the den site. Decrease in time spent at the den by the female following loss of her mate suggested that loss of one parent might severely impact recruitment of Swift Foxes. Our observations indicated that intense Coyote (Canis latrans) depredation may severely impact pup-rearing success as well as the parental care within Swift Fox family groups.

  17. The Dens: A Review of its Diverse Nomenclature and a Recommended Simplified Terminology.

    PubMed

    Johal, Jaspreet; Fisahn, Christian; Burgess, Brittni; Loukas, Marios; Chapman, Jens; Oskouian, Rod J; Tubbs, R Shane

    2017-01-17

    Pathology of the dens, such as fractures, demands precise terminology so that communication between physicians are succinct, diagnoses are accurate, and treatment strategies exact. This review aims to summarize the various terms used to describe the parts of the dens and recommend the ideal terminology. Using standard search engines, English language publications were searched for the many terms used to describe parts of the dens. A multitude of terms was identified with many demonstrating overlaps. Terms identified included apex, tip, apicodental, subdental, dentocentral and odontocentral junctions, peg, waist, base, neck, shaft, shoulder, and stem. Exact terminology is necessary when diagnosing or treating patients with pathology of or near the dens. The authors suggest simplified terminology for describing the parts of the dens that can be used in the future in order to be unequivocal and to avoid confusion when classifying and communicating fractures through its parts.

  18. The Dens: A Review of its Diverse Nomenclature and a Recommended Simplified Terminology

    PubMed Central

    Johal, Jaspreet; Burgess, Brittni; Loukas, Marios; Chapman, Jens; Oskouian, Rod J; Tubbs, R. Shane

    2017-01-01

    Pathology of the dens, such as fractures, demands precise terminology so that communication between physicians are succinct, diagnoses are accurate, and treatment strategies exact. This review aims to summarize the various terms used to describe the parts of the dens and recommend the ideal terminology. Using standard search engines, English language publications were searched for the many terms used to describe parts of the dens. A multitude of terms was identified with many demonstrating overlaps. Terms identified included apex, tip, apicodental, subdental, dentocentral and odontocentral junctions, peg, waist, base, neck, shaft, shoulder, and stem. Exact terminology is necessary when diagnosing or treating patients with pathology of or near the dens. The authors suggest simplified terminology for describing the parts of the dens that can be used in the future in order to be unequivocal and to avoid confusion when classifying and communicating fractures through its parts. PMID:28229029

  19. Habitat, soils, and den use of San Joaquin kit fox (Vulpes velox macrotis) at Camp Roberts Army National Guard Training Site, California

    SciTech Connect

    Reese, E.A.; Standley, W.G.; Berry, W.H.

    1992-09-01

    Den use patterns, den characteristics, and effects of military training on dens were studied for San Joaquin kit foxes (Vulpes velox macrotis) at Camp Roberts Army National Guard Training Site, California.Ninety-four radiocollared kit foxes used 1059 dens and 334 buildings as shelter from December 1988, through September 1991. There were 1001 (95%) earthen dens, 57 (5%) culverts, and one den in a hollow log. Denentrance dimensions were measured for single entrance dens; the average height was 20 cm, and the average width was 21 cm. Most dens had two to five den entrances, and only 36% of dens found showed sign of fox activity. Dens were found at elevations between 161 and 351 m. The average slope of dens found on hillsides was 19 degrees, and most dens faced the western quadrant. Dens were found over much of the post exceptthe steep southwest portion. More kit fox dens were located in grassland and low to medium density oak woodlands than expected, and fewer dens were located in developed areas and medium to high density oak woodlands than expected. Denning range size was calculated for 16 foxes that were radiocollared at least one year and that were found using only earthen and culvert dens. The average denning range size was 171.0 [plus minus] 24.0 ha. There was no significant difference in male and female average denning range sizes. When buildings used as shelter were included in denning range sizes, there was no significant difference in average denning range size between developed and undeveloped areas. Foxes used 26 of 36 available soil series, and dens were not distributed proportionally among the 36 soil series. Kit fox dens were typically found in well drained soils. Few den entrances were destroyed by military training exercises.

  20. Habitat, soils, and den use of San Joaquin kit fox (Vulpes velox macrotis) at Camp Roberts Army National Guard Training Site, California

    SciTech Connect

    Reese, E.A.; Standley, W.G.; Berry, W.H.

    1992-09-01

    Den use patterns, den characteristics, and effects of military training on dens were studied for San Joaquin kit foxes (Vulpes velox macrotis) at Camp Roberts Army National Guard Training Site, California.Ninety-four radiocollared kit foxes used 1059 dens and 334 buildings as shelter from December 1988, through September 1991. There were 1001 (95%) earthen dens, 57 (5%) culverts, and one den in a hollow log. Denentrance dimensions were measured for single entrance dens; the average height was 20 cm, and the average width was 21 cm. Most dens had two to five den entrances, and only 36% of dens found showed sign of fox activity. Dens were found at elevations between 161 and 351 m. The average slope of dens found on hillsides was 19 degrees, and most dens faced the western quadrant. Dens were found over much of the post exceptthe steep southwest portion. More kit fox dens were located in grassland and low to medium density oak woodlands than expected, and fewer dens were located in developed areas and medium to high density oak woodlands than expected. Denning range size was calculated for 16 foxes that were radiocollared at least one year and that were found using only earthen and culvert dens. The average denning range size was 171.0 {plus_minus} 24.0 ha. There was no significant difference in male and female average denning range sizes. When buildings used as shelter were included in denning range sizes, there was no significant difference in average denning range size between developed and undeveloped areas. Foxes used 26 of 36 available soil series, and dens were not distributed proportionally among the 36 soil series. Kit fox dens were typically found in well drained soils. Few den entrances were destroyed by military training exercises.

  1. Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for the DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus in Fujian, China.

    PubMed

    Guo, Xiao-Xia; Li, Chun-Xiao; Zhang, Ying-Mei; Xing, Dan; Dong, Yan-De; Zhang, Heng-Duan; Qin, Cheng-Feng; Zhao, Tong-Yan

    2016-09-01

    Dengue is an acute, emerging, infectious disease transmitted by Aedes mosquitoes that has become a serious global public health problem. The DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus were originally isolated from the serum of a patient with dengue fever in Fujian Province, China, in 1999. Our data provide the first assessment of the vector competence of Aedes mosquitoes with respect to the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus. There were significant differences in the replication rates of these two viral strains in Aedes albopictus and Aedes aegypti (P<0.05); replication of the DEN2-FJ10 strain was greater in Ae. aegypti than in Ae. albopictus 5 days post infection whereas replication of the DEN2-FJ11 was greater in Ae. albopictus than in Ae. aegypti 7 days post infection. The replicative ability of the DEN2-FJ11 strain was greater than that of the DEN2-FJ10 strain in infected Ae. albopictus. In infected Ae. aegypti, rapid proliferation of the DEN2-FJ10 strain occurred earlier than in the DEN2-FJ11 strain. There were no significant differences in the midgut and salivary gland infection rates of Ae. albopictus and Ae. aegypti with respect to either viral strain. Although the DEN2-FJ10 and DEN2-FJ11 strains differ in their virulence to neonatal rats, there was no significant difference in the ability of either Ae. albopictus or Ae. aegypti to transmit the DEN2-FJ10 and DEN2-FJ10 strains of the dengue 2 virus (P>0.05). In summary, our results indicate that Ae. albopictus and Ae. aegypti mosquitoes are moderately competent vectors of the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus and provide the first evidence of the effect of these two viral strains on the vector competence of mosquitoes in China.

  2. Cape Newenham AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-04-01

    OBSERVATIONS) L P- 14 H~N A A-F S .~ 73-F2 ____ JA&,. ALL WI- LAt E -- .. - - 6 7 0 11 16 17 21 22 27 28- 33 34 *0 41 A7 48 5 .7 * . .3 .4 .4 . 1 . i E...PERCENTAGE FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 4LL . LAT -E- - 10 1 1 i 7 23 22 ’ 2 3 3 A 40 A 3 5 A7 A • ’ .. 5 .t",5...SCOTT A. APR 03 UNCLASSIFIED USAFETAC/DS-83/019 SBI-AD-EB50 397 F/6 4/2 NL SU 2. lii .0 EM *,*,- Ica L- 11111 1.25 s~w ,r- 1 . 11.6 I MiCRQ OPY

  3. Hibernacula and summer den sites of pine snakes (Pituophis melanoleucus) in the New Jersey pine barrens

    USGS Publications Warehouse

    Burger, J.; Zappalorti, R.T.; Gochfeld, M.; Boarman, W.I.; Caffrey, M.; Doig, V.; Garber, S.D.; Lauro, B.; Mikovsky, M.; Safina, C.; Saliva, Jorge

    1988-01-01

    We examined eight summer dens (used only in summer) and seven hibernacula (occupied both in winter and summer) of the snake Pituophis melanoleucus in the New Jersey Pine Barrens, comparing above ground characteristics of hibernacula and summer dens with characteristics at nearby random points. Temperatures at the soil surface and at 10 cm depth were significantly warmer, and there was less leaf cover around the random points compared to the entrances of the hibernacula and summer dens. Hibernacula had significantly more vegetation cover within 5 m, more leaf cover over the burrow entrance, and were closer to trees than were summer dens. Most hibernacula and summer dens were beside old fallen logs (73%), the entrance tunnels following decaying roots into the soil. Excavation of the hibernacula and summer dens indicated that most hibernacula appeared to be dug by the snakes and had an average of eight side chambers and 642 cm of tunnels, compared to less than one side chamber and 122 cm of tunnels for summer dens. Except for hatchlings, most snakes in hibernacula were located in individual chambers off the main tunnel; all snakes were at depths of 50-111 cm (X̄ = 79 cm). Pine snakes may select optimum hibernation sites which reduce winter mortality.

  4. Den Entry Behavior in Scandinavian Brown Bears: Implications for Preventing Human Injuries

    PubMed Central

    Sahlén, Veronica; Friebe, Andrea; Sæbø, Solve; Swenson, Jon E; Støen, Ole-Gunnar

    2015-01-01

    Encounters between Scandinavian brown bears (Ursus arctos) and humans that result in human injuries and fatalities typically coincide with den entry in October and November, and commonly occur near a den. Our aim was to determine when bears arrive at their dens, identify potential predictors of this event, document behavior and activity associated with this period, and attempt to explain the increased risk of bear-caused human injuries in this period. We analyzed global positioning system (GPS) location and activity data from brown bears in south-central Sweden, using generalized linear mixed models, statistical process control, and activity analyses. Bears arrived at their den sites between 6 October and 1 December. Timing varied by reproductive category, bear age, and year. Half of all bears significantly reduced their activity before arriving at the den area: on average 2,169 m away from the den and 1.8 days before arrival. The other half reduced their activity after arriving at the den area. The latter bears took longer time to reach hibernation activity levels, but we did not find a difference in the start date of hibernation between the 2 groups. Bears also appeared to be sensitive to disturbance in this period, with higher den abandonment rates than later in winter, particularly for males and for bears that had not visited their den sites previously. Den entry occurred from October to December, with high variability and poor predictability of its timing. Therefore, restricting hunting or other recreation activities to reduce risk of injury by bears and disturbing bears probably would be both impractical and ineffective. Our findings can be used to educate hunters about bear behavior at this time of year. Many people associate dens with an increased risk of a bear responding aggressively to disturbance to defend its den, but our results indicate that other behavioral, and possibly physiological, changes in this period also may be involved. © 2014 The

  5. AF-GEOSpace Version 2.5: Space Environment Software

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Hall, T.; Roth, C.; Ling, A.; Ginet, G. P.; Madden, D.

    2010-12-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed by the Space Weather Center of Excellence at AFRL. The software addresses a wide range of physical domains, e.g., solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. AF-GEOSpace has become a platform for developing and prototyping space weather visualization products. The new AF-GEOSpace Version 2.5 (release scheduled for 2010) expands on the content of Version 2.1 by including modules addressing the following new topics: (1) energetic proton maps for the South Atlantic Anomaly (from Ginet et al. [2007]), (2) GPS scintillation outage simulation tools, (3) magnetopause location determination (Shue et al. [1998]), (4) a plasmasphere model (Global Core Plasma Model, 2009 version based on Gallagher et al. [2000]), (5) a standard ionospheric model (International Reference Ionosphere 2007), (6) the CAMMICE/MICS model of inner magnetosphere plasma population (based on Roeder et al. [2005]), (7) magnetic field models (e.g., Tsyganenko and Sitnov [2005]), and (8) loading and displaying externally-produced 3D gridded data sets within AF-GEOSpace. Improvements to existing Version 2.1 capabilities include: (1) a 2005 update to the geomagnetic cutoff rigidity model of Smart and Shea [2003], (2) a 2005 update to the ionospheric scintillation Wide-Band Model (WBMOD) of Secan and Bussey [1994], and (3) improved magnetic field flux mapping options for the existing set of AF-GEOSpace radiation belt models. A basic review of these new AF-GEOSpace capabilities will be provided. To obtain a copy of the software, please contact the first author.

  6. GPIM AF-M315E Propulsion System

    NASA Technical Reports Server (NTRS)

    Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

    2014-01-01

    The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

  7. Inducing G2/M Cell Cycle Arrest and Apoptosis through Generation Reactive Oxygen Species (ROS)-Mediated Mitochondria Pathway in HT-29 Cells by Dentatin (DEN) and Dentatin Incorporated in Hydroxypropyl-β-Cyclodextrin (DEN-HPβCD)

    PubMed Central

    Ashwaq, Al-Abboodi Shakir; Al-Qubaisi, Mothanna Sadiq; Rasedee, Abdullah; Abdul, Ahmad Bustamam; Taufiq-Yap, Yun Hin; Yeap, Swee Keong

    2016-01-01

    Dentatin (DEN), purified from the roots of Clausena excavata Burm f., has poor aqueous solubility that reduces its therapeutic application. The aim of this study was to assess the effects of DEN-HPβCD (hydroxypropyl-β-cyclodextrin) complex as an anticancer agent in HT29 cancer cell line and compare with a crystal DEN in dimethyl sulfoxide (DMSO). The exposure of the cancer cells to DEN or DEN-HPβCD complex leads to cell growth inhibition as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To analyze the mechanism, in which DEN or DEN-HPβCD complex causes the death in human colon HT29 cancer cells, was evaluated by the enzyme-linked immunosorbent assay (ELIZA)-based assays for caspase-3, 8, 9, and reactive oxygen species (ROS). The findings showed that an anti-proliferative effect of DEN or DEN-HPβCD complex were via cell cycle arrest at the G2/M phase and eventually induced apoptosis through both mitochondrial and extrinsic pathways. The down-regulation of poly(ADP-ribose) polymerase (PARP) which leaded to apoptosis upon treatment, was investigated by Western-blotting. Hence, complexation between DEN and HPβCD did not diminish or eliminate the effective properties of DEN as anticancer agent. Therefore, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents in the future. PMID:27763535

  8. Nonsurgical endodontic management of dens invaginatus with open apex: A case report

    PubMed Central

    Rani, Nidhi; Sroa, Renu B

    2015-01-01

    Dens invaginatus is a rare malformation with a widely varied morphology. It typically affects permanent maxillary lateral incisors, central incisors, and premolars. This article demonstrates rapid management of type II dens invagination with open apex and large periradicular lesion using calcium hydroxide as intracanal medicament for 1-week followed by apical plug formation with mineral trioxide aggregate Plus and lateral condensation of Gutta-percha. At 24-month follow-up, the patient was asymptomatic and lesion was entirely resolved. PMID:26751206

  9. Sabiperones A-F, new diterpenoids from Juniperus sabina.

    PubMed

    Janar, Jenis; Nugroho, Alfarius Eko; Wong, Chin Piow; Hirasawa, Yusuke; Kaneda, Toshio; Shirota, Osamu; Morita, Hiroshi

    2012-01-01

    Six new diterpenoids, sabiperones A-F (1-6) have been isolated from the aerial part of Juniperus sabina. Their structures were elucidated by spectroscopic methods including 2D NMR techniques. Sabiperone F showed moderate cell growth inhibitory activities against five human cancer cell lines.

  10. Action of AF64A on rat brain muscarinic receptors

    SciTech Connect

    Eva, C.; Costa, E.

    1986-03-01

    ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased but its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.

  11. An Empirical Test of Oklahoma's A-F School Grades

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.; Ware, Jordan; Mwavita, Mwarumba; Barnes, Laura L.; Khojasteb, Jam

    2016-01-01

    Oklahoma is one of 16 states electing to use an A-F letter grade as an indicator of school quality. On the surface, letter grades are an attractive policy instrument for school improvement; they are seemingly clear, simple, and easy to interpret. Evidence, however, on the use of letter grades as an instrument to rank and improve schools is scant…

  12. Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)

    PubMed Central

    Steinberg, Benjamin A; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Gersh, Bernard J; Holmqvist, Fredrik; Hylek, Elaine; Kowey, Peter R; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Chang, Paul; Peterson, Eric D; Piccini, Jonathan P

    2015-01-01

    Background Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. Methods and Results We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Conclusions Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. Clinical Trial Registration URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. PMID:26370445

  13. Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens.

    PubMed

    Gharajehdaghipour, Tazarve; Roth, James D; Fafard, Paul M; Markham, John H

    2016-04-05

    Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ(15)N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra.

  14. Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens

    NASA Astrophysics Data System (ADS)

    Gharajehdaghipour, Tazarve; Roth, James D.; Fafard, Paul M.; Markham, John H.

    2016-04-01

    Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ15N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra.

  15. Arctic foxes as ecosystem engineers: increased soil nutrients lead to increased plant productivity on fox dens

    PubMed Central

    Gharajehdaghipour, Tazarve; Roth, James D.; Fafard, Paul M.; Markham, John H.

    2016-01-01

    Top predators can provide fundamental ecosystem services such as nutrient cycling, and their impact can be even greater in environments with low nutrients and productivity, such as Arctic tundra. We estimated the effects of Arctic fox (Vulpes lagopus) denning on soil nutrient dynamics and vegetation production near Churchill, Manitoba in June and August 2014. Soils from fox dens contained higher nutrient levels in June (71% more inorganic nitrogen, 1195% more extractable phosphorous) and in August (242% more inorganic nitrogen, 191% more extractable phosphorous) than adjacent control sites. Inorganic nitrogen levels decreased from June to August on both dens and controls, whereas extractable phosphorous increased. Pup production the previous year, which should enhance nutrient deposition (from urine, feces, and decomposing prey), did not affect soil nutrient concentrations, suggesting the impact of Arctic foxes persists >1 year. Dens supported 2.8 times greater vegetation biomass in August, but δ15N values in sea lyme grass (Leymus mollis) were unaffected by denning. By concentrating nutrients on dens Arctic foxes enhance nutrient cycling as an ecosystem service and thus engineer Arctic ecosystems on local scales. The enhanced productivity in patches on the landscape could subsequently affect plant diversity and the dispersion of herbivores on the tundra. PMID:27045973

  16. Remote identification of maternal polar bear (Ursus maritimus) denning habitat on the Colville River Delta, Alaska

    NASA Astrophysics Data System (ADS)

    Blank, Justin J.

    High resolution digital aerial photographs (1 foot pixel size) of the Colville River Delta, Alaska were examined in 3D, with the use of a digital photogrammetric workstation. Topographic features meeting the criteria required for adequate snow accumulation, and subsequent construction of terrestrial polar bear maternal dens, were identified and digitized into an ArcGIS line shapefile. Effectiveness, efficiency, and accuracy were improved when compared to previous polar bear denning habitat efforts which utilized contact photo prints and a pocket stereoscope in other geographic areas of northern Alaska. Accuracy of photograph interpretation was systematically evaluated visually from the air with the use of a helicopter and physically on the ground. Results show that the mapping efforts were successful in identifying den habitat 91.3% of the time. Knowledge denning habitat can improve and inform decision making by managers and regulators when considering travel and development in the study area. An understanding of polar bear denning habitat extent and location will be a crucial tool for planning activities within the study area in a way that minimizes conflicts with maternal dens.

  17. Extracting Uranium from Seawater: Promising AF Series Adsorbents

    SciTech Connect

    Das, S.; Oyola, Y.; Mayes, Richard T.; Janke, Chris J.; Kuo, L. -J.; Gill, G.; Wood, J. R.; Dai, S.

    2016-04-20

    A new family of high-surface-area polyethylene fiber adsorbents named the AF series was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series adsorbents were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/comonomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154-354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44 M KOH at 80 °C followed by screening at ORNL with sodium-based synthetic aqueous solution, spiked with 8 ppm uranium. The uranium adsorption capacity in simulated seawater screening ranged from 170 to 200 g-U/kg-ads irrespective of %DOG. A monomer/comonomer molar ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through column experiments to determine uranium loading capacity with varying KOH conditioning times at 80 °C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1 and 3 h of KOH conditioning at 80 °C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 1 to 3 h at 80 °C resulted in a 22-27% decrease in uranium adsorption capacity in seawater.

  18. Extracting uranium from seawater: Promising AF series adsorbents

    SciTech Connect

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.

  19. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGES

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; ...

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

  20. Despotism and risk of infanticide influence grizzly bear den-site selection.

    PubMed

    Libal, Nathan S; Belant, Jerrold L; Leopold, Bruce D; Wang, Guiming; Owen, Patricia A

    2011-01-01

    Given documented social dominance and intraspecific predation in bear populations, the ideal despotic distribution model and sex hypothesis of sexual segregation predict adult female grizzly bears (Ursus arctos) will avoid areas occupied by adult males to reduce risk of infanticide. Under ideal despotic distribution, juveniles should similarly avoid adult males to reduce predation risk. Den-site selection and use is an important component of grizzly bear ecology and may be influenced by multiple factors, including risk from conspecifics. To test the role of predation risk and the sex hypothesis of sexual segregation, we compared adult female (n = 142), adult male (n = 36), and juvenile (n = 35) den locations in Denali National Park and Preserve, Alaska, USA. We measured elevation, aspect, slope, and dominant land cover for each den site, and used maximum entropy modeling to determine which variables best predicted den sites. We identified the global model as the best-fitting model for adult female (area under curve (AUC) = 0.926) and elevation as the best predictive variable for adult male (AUC = 0.880) den sites. The model containing land cover and elevation best-predicted juvenile (AUC = 0.841) den sites. Adult females spatially segregated from adult males, with dens characterized by higher elevations (mean= 1,412 m, SE = 52) and steeper slopes (mean = 21.9°, SE = 1.1) than adult male (elevation: mean = 1,209 m, SE = 76; slope: mean = 15.6°, SE = 1.9) den sites. Juveniles used a broad range of landscape attributes but did not avoid adult male denning areas. Observed spatial segregation by adult females supports the sex hypothesis of sexual segregation and we suggest is a mechanism to reduce risk of infanticide. Den site selection of adult males is likely related to distribution of food resources during spring.

  1. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Aspergillus flavus AF36; exemption... FOOD Exemptions From Tolerances § 180.1206 Aspergillus flavus AF36; exemption from the requirement of a... pesticide Aspergillus flavus AF36 in or on cotton, gin byproducts; cotton, hulls; cotton, meal;...

  2. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  3. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  4. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  5. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  6. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  7. Embossed Teflon AF Laminate Membrane Microfluidic Diaphragm Valves

    NASA Technical Reports Server (NTRS)

    Willis, Peter; Hunt, Brian; White,Victor; Grunthaner, Frank

    2008-01-01

    A microfluidic system has been designed to survive spaceflight and to function autonomously on the Martian surface. It manipulates microscopic quantities of liquid water and performs chemical analyses on these samples to assay for the presence of molecules associated with past or present living processes. This technology lies at the core of the Urey Instrument, which is scheduled for inclusion on the Pasteur Payload of the ESA ExoMars rover mission in 2013. Fabrication processes have been developed to make the microfabricated Teflon-AF microfluidic diaphragm pumps capable of surviving extreme temperature excursions before and after exposure to liquid water. Two glass wafers are etched with features and a continuous Teflon membrane is sandwiched between them (see figure). Single valves are constructed using this geometry. The microfabricated devices are then post processed by heating the assembled device while applying pneumatic pressure to force the Teflon diaphragm against the valve seat while it is softened. After cooling the device, the embossed membrane retains this new shape. This solves previous problems with bubble introduction into the fluid flow where deformations of the membrane at the valve seat occurred during device bonding at elevated temperatures (100-150 C). The use of laminated membranes containing commercial Teflon AF 2400 sheet sandwiched between spun Teflon AF 1600 layers performed best, and were less gas permeable than Teflon AF 1600 membranes on their own. Spinning Teflon AF 1600 solution (6 percent in FLOURINERT(Registered TradeMark) FC40 solvent, 3M Company) at 500 rpm for 1.5 seconds, followed by 1,000 rpm for 3 seconds onto Borofloat glass wafers, results in a 10-micron-thick film of extremely smooth Teflon AF. This spinning process is repeated several times on flat, blank, glass wafers in order to gradually build a thick, smooth membrane. After running this process at least five times, the wafer and Teflon coating are heated under vacuum

  8. Heading for the hills: risk avoidance drives den site selection in African wild dogs.

    PubMed

    Jackson, Craig R; Power, R John; Groom, Rosemary J; Masenga, Emmanuel H; Mjingo, Ernest E; Fyumagwa, Robert D; Røskaft, Eivin; Davies-Mostert, Harriet

    2014-01-01

    Compared to their main competitors, African wild dogs (Lycaon pictus) have inferior competitive abilities and interspecific competition is a serious fitness-limiting factor. Lions (Panthera leo) are the dominant large carnivore in African savannah ecosystems and wild dogs avoid them both spatially and temporally. Wild dog young are particularly vulnerable and suffer high rates of mortality from lions. Since lions do not utilize all parts of the landscape with an equal intensity, spatial variation in lion densities can be exploited by wild dogs both during their general ranging behaviour, but more specifically when they are confined to a den with vulnerable young. Since patches of rugged terrain are associated with lower lion densities, we hypothesized that these comparatively safe habitats should be selected by wild dogs for denning. We investigated the relationship between the distribution of 100 wild dog den sites and the occurrence of rugged terrain in four wild dog populations located in Tanzania, Zimbabwe and South Africa. A terrain ruggedness index was derived from a 90 m digital elevation model and used to map terrain ruggedness at each site. We compared characteristics of actual and potential (random) den sites to determine how wild dogs select den sites. The distributions of wild dog dens were strongly associated with rugged terrain and wild dogs actively selected terrain that was more rugged than that available on average. The likelihood of encountering lions is reduced in these habitats, minimizing the risk to both adults and pups. Our findings have important implications for the conservation management of the species, especially when assessing habitat suitability for potential reintroductions. The simple technique used to assess terrain ruggedness may be useful to investigate habitat suitability, and even predict highly suitable denning areas, across large landscapes.

  9. Interaction between Subunits of Heterodimeric Splicing Factor U2AF Is Essential In Vivo

    PubMed Central

    Rudner, David Z.; Kanaar, Roland; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The heterodimeric pre-mRNA splicing factor, U2AF (U2 snRNP auxiliary factor), plays a critical role in 3′ splice site selection. Although the U2AF subunits associate in a tight complex, biochemical experiments designed to address the requirement for both subunits in splicing have yielded conflicting results. We have taken a genetic approach to assess the requirement for the Drosophila U2AF heterodimer in vivo. We developed a novel Escherichia coli copurification assay to map the domain on the Drosophila U2AF large subunit (dU2AF50) that interacts with the Drosophila small subunit (dU2AF38). A 28-amino-acid fragment on dU2AF50 that is both necessary and sufficient for interaction with dU2AF38 was identified. Using the copurification assay, we scanned this 28-amino-acid interaction domain for mutations that abrogate heterodimer formation. A collection of these dU2AF50 point mutants was then tested in vivo for genetic complementation of a recessive lethal dU2AF50 allele. A mutation that completely abolished interaction with dU2AF38 was incapable of complementation, whereas dU2AF50 mutations that did not effect heterodimer formation rescued the recessive lethal dU2AF50 allele. Analysis of heterodimer formation in embryo extracts derived from these interaction mutant lines revealed a perfect correlation between the efficiency of subunit association and the ability to complement the dU2AF50 recessive lethal allele. These data indicate that Drosophila U2AF heterodimer formation is essential for viability in vivo, consistent with a requirement for both subunits in splicing in vitro. PMID:9528748

  10. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    DTIC Science & Technology

    2015-10-01

    to U2AF1(WT). We validated several homologous dysregulated junctions (i.e., across species) in MDS patient bone marrow samples that have mutant ...U2AF1(S34F) versus U2AF1(WT). Together, these results suggest that mutant U2AF1 expression contributes to the altered hematopoiesis and pre-mRNA...whether the U2AF1(S34F) mutation alters hematopoiesis in vivo. We will inducibly express wild-type and S34F mutant (resulting from the most common

  11. Characterization of physically vapor deposited AF2400 thin films

    SciTech Connect

    Chow, R.; Spragge, M.K.; Loomis, G.E.; Rainer, F.; Ward, R.; Thomas, I.M.; Kozlowski, M.R.

    1993-11-01

    Anti-reflective coatings made with Teflon AF2400 had the highest damage thresholds recorded for physical vapor deposited coatings at the Lawrence Livermore National Laboratory damage facility. Physical vapor deposited layers of Teflon AF2400, a perfluorinated amorphous polymer, maintained the bulk optical properties of a high transmittance from 200 nm to 1600 nm, and a low refractive index. In addition, the refractive index can be intentionally reduced by control of two common deposition parameters, deposition rate and substrate temperature. Scanning electron microscopy and nuclear magnetic resonance observations indicated that morphological changes caused the variations in the refractive index rather than compositional changes. The coatings adhered to fused silica and silicon wafers under normal laboratory handling conditions.

  12. Gymnasterkoreaynes A-F, cytotoxic polyacetylenes from Gymnaster koraiensis.

    PubMed

    Jung, Hyun-Ju; Min, Byung-Sun; Park, Jin-Young; Kim, Young-Ho; Lee, Hyeong-Kyu; Bae, Ki-Hwan

    2002-06-01

    Six new polyacetylenes, gymnasterkoreaynes A-F (1-6), were isolated from the roots of Gymnaster koraiensis, together with 2,9,16-heptadecatrien-4,6-diyn-8-ol (7) and 1,9,16-heptadecatriene-4,6-diyn-3,8-diol (8), by bioassay-guided fractionation using the L1210 tumor cell line as a model for cytotoxicity. The structures of compounds 1-6 were established spectroscopically, which included 2D NMR experiments. Gymnasterkoreaynes A-F (1-6) are linear diacetylenes and are structurally related to falcarinol, panaxynol, panaxydiol, and panaxytriol. Of the compounds isolated, gymnasterkoreaynes B (2), C (3), F (6), and 1,9,16-heptadecatrien-4,6-diyn-3,8-diol (8) exhibited significant cytotoxicity against L1210 tumor cells with ED(50) values of 0.12-3.3 microg/mL.

  13. Improved AF Squadron Command Structure for Leadership, Accountability, and Efficiency

    DTIC Science & Technology

    2011-04-20

    of Defense respectively focus on span of control. The concept of span of control was developed in 1922 by Sir Ian Hamilton based on the assumption...For the AF, this means squadrons must be organized across a wing to minimize inconsistency within units as well as across them. A study by Dewar ... Dewar , Robert D., and Simet, Donald P. “A Level Specific Prediction of Spans of Control Examining the Effects of Size, Technology, and

  14. Adiabatic Compression Sensitivity of AF-M315E

    DTIC Science & Technology

    2015-07-01

    the development of green rocket propellants . The Air Force Research Laboratory’s (AFRL) monopropellant, AF-M315E, has been selected for...art rocket fuels and propellants . A known quantity of liquid propellant is placed in a metal U-tube and held isothermally in a preheated mixture of... Propellant Infusion Mission (GPIM) program. As the propulsion system developed by Aerojet- Rocketdyne for this propellant advances in maturity, studies

  15. Installation Restoration Program. Records Search, Newark AFS, Ohio

    DTIC Science & Technology

    1985-04-01

    plants. In this assignment and all that follow, a part of each was spent in conducting health and environment compliance inspections and audits at mili...OH 434&33 EiLO)( 2 bJATEP SYSTE-M, KTTC𔃻EN TAP, ’DATE: 76-P6-16*’.TI- E: 1304.1, APPEA0AfJCE OF SbmPLE CLEAR, TEA;:, 72 I PFE -ULTS OF ANALYS15 C T

  16. Genomic functions of U2AF in constitutive and regulated splicing.

    PubMed

    Wu, Tongbin; Fu, Xiang-Dong

    2015-01-01

    The U2AF heterodimer is generally accepted to play a vital role in defining functional 3' splice sites in pre-mRNA splicing. Given prevalent mutations in U2AF, particularly in the U2AF1 gene (which encodes for the U2AF35 subunit) in blood disorders and other human cancers, there are renewed interests in these classic splicing factors to further understand their regulatory functions in RNA metabolism in both physiological and disease settings. We recently reported that U2AF has a maximal capacity to directly bind ˜88% of functional 3' splice sites in the human genome and that numerous U2AF binding events also occur in various exonic and intronic locations, thus providing additional mechanisms for the regulation of alternative splicing besides their traditional role in titrating weak splice sites in the cell. These findings, coupled with the existence of multiple related proteins to both U2AF65 and U2AF35, beg a series of questions on the universal role of U2AF in functional 3' splice site definition, their binding specificities in vivo, potential mechanisms to bypass their requirement for certain intron removal events, contribution of splicing-independent functions of U2AF to important cellular functions, and the mechanism for U2AF mutations to invoke specific diseases in humans.

  17. Durable Superhydrophobic Surfaces via Spontaneous Wrinkling of Teflon AF.

    PubMed

    Scarratt, Liam R J; Hoatson, Ben S; Wood, Elliot S; Hawkett, Brian S; Neto, Chiara

    2016-03-01

    We report the fabrication of both single-scale and hierarchical superhydrophobic surfaces, created by exploiting the spontaneous wrinkling of a rigid Teflon AF film on two types of shrinkable plastic substrates. Sub-100 nm to micrometric wrinkles were reproducibly generated by this simple process, with remarkable control over the size and hierarchy. Hierarchical Teflon AF wrinkled surfaces showed extremely high water repellence (contact angle 172°) and very low contact angle hysteresis (2°), resulting in droplets rolling off the surface at tilt angles lower than 5°. The wrinkling process intimately binds the Teflon AF layer with its substrate, making these surfaces mechanically robust, as revealed by macroscale and nanoscale wear tests: hardness values were close to that of commercial optical lenses and aluminum films, resistance to scratch was comparable to commercial hydrophobic coatings, and damage by extensive sonication did not significantly affect water repellence. By this fabrication method the size of the wrinkles can be reproducibly tuned from the nanoscale to the microscale, across the whole surface in one step; the fabrication procedure is extremely rapid, requiring only 2 min of thermal annealing to produce the desired topography, and uses inexpensive materials. The very low roll-off angles achieved in the hierarchical surfaces offer a potentially up-scalable alternative as self-cleaning and drag-reducing coatings.

  18. Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

    PubMed Central

    Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

    2016-01-01

    We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

  19. Alternative splicing of U2AF1 reveals a shared repression mechanism for duplicated exons

    PubMed Central

    Kralovicova, Jana; Vorechovsky, Igor

    2017-01-01

    The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab. Each BP lacked canonical uridines at position -2 relative to the BP adenines, with efficient U2 base-pairing interactions predicted only for shifted registers reminiscent of programmed ribosomal frameshifting. The BP cluster was compensated by interactions involving unpaired cytosines in an upstream, EvoFold-predicted stem loop (termed ESL) that binds FUBP1/2. Exon Ab inclusion correlated with predicted free energies of mutant ESLs, suggesting that the ESL operates as a conserved rheostat between long inverted repeats upstream of each exon. The isoform-specific U2AF35 expression was U2AF65-dependent, required interactions between the U2AF-homology motif (UHM) and the α6 helix of U2AF35, and was fine-tuned by exon Ab/3 variants. Finally, we identify tandem homologous exons regulated by U2AF and show that their preferential responses to U2AF65-related proteins and SRSF3 are associated with unpaired pre-mRNA segments upstream of U2AF-repressed 3′ss. These results provide new insights into tissue-specific subfunctionalization of duplicated exons in vertebrate evolution and expand the repertoire of exon repression mechanisms that control alternative splicing. PMID:27566151

  20. Nonsurgical endodontic treatment of a maxillary lateral incisor with dens invaginatus type II: A case report

    PubMed Central

    Shadmehr, Elham; Kiaani, Sima; Mahdavian, Parinaz

    2015-01-01

    Dens invaginatus is a rare developmental anomaly of teeth with complex root canal system morphology. The present case describes a peg shape maxillary lateral incisor with dens invaginatus (Oehlers type II), necrotic pulp, and an associated large periradicular lesion. Nonsurgical endodontic treatment was performed with the aim of removing the blind sac with diamond bur under the use of operating surgical microscope. The root canal system was obturated with thermoplastic technique. Final restoration was done using composite. The 20-months clinical and radiological follow up revealed an asymptomatic tooth with healing of the periapical pathology; however, for complete healed periradicular lesion more follow up is needed. This case illustrated that a dens invaginatus malformed teeth with a large periradicular lesion can be managed successfully with nonsurgical root canal therapy (NSRCT). PMID:25878686

  1. The Chimeric Protein Domain III-Capsid of Dengue Virus Serotype 2 (DEN-2) Successfully Boosts Neutralizing Antibodies Generated in Monkeys upon Infection with DEN-2▿

    PubMed Central

    Valdés, Iris; Gil, Lázaro; Romero, Yaremis; Castro, Jorge; Puente, Pedro; Lazo, Laura; Marcos, Ernesto; Guzmán, María G.; Guillén, Gerardo; Hermida, Lisset

    2011-01-01

    Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time spacing. The present work deals with the evaluation of the heterologous prime-boost strategy combining a novel chimeric protein (domain III-capsid) of dengue virus serotype 2 (DEN-2) and the infective homologous virus in the same immunization schedule in monkeys. Primed monkeys received one dose of infective DEN-2 and were then vaccinated with the recombinant protein. We found that animals developed a neutralizing antibody response after the infective dose and were notably boosted with a second dose of the chimeric protein 3 months later. The neutralizing antibodies induced were long lasting, and animals also showed the ability to induce a specific cellular response 6 months after the booster dose. As a conclusion, we can state that the domain III region, when it is properly presented as a fusion protein to the immune system, is able to recall the neutralizing antibody response elicited following homologous virus infection in monkeys. Further prime-boost approaches can be performed in a condensed regime combining the chimeric domain III-capsid protein and candidate live attenuated vaccines against DEN-2. PMID:21209159

  2. Mapping polar bear maternal denning habitat in the National Petroleum Reserve -- Alaska with an IfSAR digital terrain model

    USGS Publications Warehouse

    Durner, George M.; Simac, Kristin; Amstrup, Steven C.

    2013-01-01

    The National Petroleum Reserve–Alaska (NPR-A) in northeastern Alaska provides winter maternal denning habitat for polar bears (Ursus maritimus) and also has high potential for recoverable hydrocarbons. Denning polar bears exposed to human activities may abandon their dens before their young are able to survive the severity of Arctic winter weather. To ensure that wintertime petroleum activities do not threaten polar bears, managers need to know the distribution of landscape features in which maternal dens are likely to occur. Here, we present a map of potential denning habitat within the NPR-A. We used a fine-grain digital elevation model derived from Interferometric Synthetic Aperture Radar (IfSAR) to generate a map of putative denning habitat. We then tested the map’s ability to identify polar bear denning habitat on the landscape. Our final map correctly identified 82% of denning habitat estimated to be within the NPR-A. Mapped denning habitat comprised 19.7 km2 (0.1% of the study area) and was widely dispersed. Though mapping denning habitat with IfSAR data was as effective as mapping with the photogrammetric methods used for other regions of the Alaskan Arctic coastal plain, the use of GIS to analyze IfSAR data allowed greater objectivity and flexibility with less manual labor. Analytical advantages and performance equivalent to that of manual cartographic methods suggest that the use of IfSAR data to identify polar bear maternal denning habitat is a better management tool in the NPR-A and wherever such data may be available.

  3. Identification of a dengue virus type 2 (DEN-2) serotype-specific B-cell epitope and detection of DEN-2-immunized animal serum samples using an epitope-based peptide antigen.

    PubMed

    Wu, Han-Chung; Jung, Mei-Ying; Chiu, Chien-Yu; Chao, Ting-Ting; Lai, Szu-Chia; Jan, Jia-Tsrong; Shaio, Men-Fang

    2003-10-01

    In this study, a serotype-specific monoclonal antibody (mAb), D(2) 16-1 (Ab4), against dengue virus type 2 (DEN-2) was generated. The specificity of Ab4, which recognized DEN-2 non-structural protein 1, was determined by ELISA, immunofluorescence and immunoblotting analyses. The serotype-specific B-cell epitope of Ab4 was identified further from a random phage-displayed peptide library; selected phage clones reacted specifically with Ab4 and did not react with other mAbs. Immunopositive phage clones displayed a consensus motif, His-Arg/Lys-Leu/Ile, and a synthetic peptide corresponding to the phage-displayed peptide bound specifically to Ab4. The His and Arg residues in this epitope were found to be crucial for peptide binding to Ab4 and binding activity decreased dramatically when these residues were changed to Leu. The epitope-based synthetic peptide not only identified serum samples from DEN-2-immunized mice and rabbits by ELISA but also differentiated clearly between serum samples from DEN-2- and Japanese encephalitis virus-immunized mice. This mAb and its epitope-based peptide antigen will be useful for serologic diagnosis of DEN-2 infection. Furthermore, DEN-2 epitope identification makes it feasible to dissect antibody responses to DEN and to address the role of antibodies in the pathogenesis of primary and secondary DEN-2 infections.

  4. AFS dynamics in a short-lived active region

    NASA Astrophysics Data System (ADS)

    Zuccarello, F.; Battiato, V.; Contarino, L.; Romano, P.; Spadaro, D.; Vlahos, L.

    2005-11-01

    In the framework of the study on active region emergence, we report the results obtained from the analysis of the short-lived (7 days) active region NOAA 10407. The data used were acquired during an observational campaign carried out with the THEMIS telescope in IPM mode in July 2003, coordinated with other ground- and space-based instruments (INAF-OACT, DOT, BBSO, MDI/SOHO, EIT/SOHO, TRACE). We determined the morphological and magnetic evolution of NOAA 10407, as well as the velocity fields associated with its magnetic structures. Within the limits imposed by the spatial and temporal resolution of the images analyzed, the first evidence of the active region formation is initially observed in the transition region and lower corona, and later on (i.e. after about 7 h) in the inner layers, as found in a previous analysis concerning a long-lived, recurrent active region. The results also indicate that the AFS formed in the active region shows typical upward motion at the AFS's tops and downward motion at the footpoints. The velocity values relevant to the upward motions decrease over the evolution of the region, similarly to the case of the recurrent active region, while we notice an increasing trend in the downflow velocity during the early phases of the time interval analyzed by THEMIS. On the other hand, the AFS preceding legs show a higher downflow than the following ones, a result in contrast with that found in the long-lived active region. The chromospheric area overhanging the sunspot umbra shows an upward motion of ˜ 2 km s-1, while that above the pores shows a downward motion of ~4 km s-1.

  5. Protective effects of guarana (Paullinia cupana Mart. var. Sorbilis) against DEN-induced DNA damage on mouse liver.

    PubMed

    Fukumasu, H; Avanzo, J L; Heidor, R; Silva, T C; Atroch, A; Moreno, F S; Dagli, M L Z

    2006-06-01

    Guarana (Paullinia cupana Mart. var. Sorbilis) is a plant originally from Brazil, which is rich in tannins. Some tannins are known to present protective effects against DNA damage. This study was performed to investigate the anti-genotoxic/cytotoxic properties of guarana in hepatocytes of mice injected with N-nitrosodiethylamine (DEN). The protective effect of guarana was evaluated both by comet assay and DNA smear fragmentation technique in two month-old female BALB/c mice. These were treated previously with 2.0 mg/g bw of guarana for 16 days and then injected with DEN (160 microg/g body weight) to induce DNA damage. The DEN-only treated group presented higher comet image length than the guarana plus DEN and untreated groups (116.06+/-5.0 microm, 104.09+/-3.3 microm and 93.28+/-14.4 microm, respectively; p<0.01). Guarana treatment presented a 52.54% reduction in comet image length when animals were exposed to DEN (p<0.05). DNA samples from the guarana plus DEN group clearly showed less EtBr fluorescence intensity when compared to the DEN-only group, reinforcing the comet assay data. These results show, for the first time, that guarana has a protective effect against DEN-induced DNA damage in mouse liver.

  6. The Advancing State of AF-M315E Technology

    NASA Technical Reports Server (NTRS)

    Masse, Robert; Spores, Ronald A.; McLean, Chris

    2014-01-01

    The culmination of twenty years of applied research in hydroxyl ammonium nitrate (HAN)-based monopropellants, the NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) will achieve the first on-orbit demonstration of an operational AF-M315E green propellant propulsion system by the end of 2015. Following an contextual overview of the completed flight design of the GPIM propellant storage and feed system, results of first operation of a flight-representative heavyweight 20-N engineering model thruster (to be conducted in mid-2014) are presented with performance comparisons to prior lab model (heavyweight) test articles.

  7. RX-26-AY/AF rifle bullet tests

    SciTech Connect

    Sharp, D.D.

    1980-11-01

    A series of rifle bullet tests was performed on two explosives, RX-26-AY and RX-26-AF, using the Pantex version of the Picatinny Arsenal Test (PA-2). With the exception of one test, both explosives displayed a relatively low sensitivity to bullet impact. However, a marked difference was noted in the average burn time duration between the two types of explosives being tested. A minor modification was made on the rifle barrel used at the test site in order to improve the sighting procedure.

  8. First evidence of gregarious denning in opossums (Didelphimorphia, Didelphidae), with notes on their social behaviour.

    PubMed

    Astúa, Diego; Carvalho, Rafael A; Maia, Paula F; Magalhães, Arthur R; Loretto, Diogo

    2015-06-01

    The Didelphidae are considered solitary opossums with few social interactions, usually limited to mating-related or mother-pouch young interactions. Anecdotal reports suggest that additional interactions occur, including den sharing by a few individuals, usually siblings. Here, we report novel observations that indicate opossums are more social than previously thought. These include nest sharing by males and females of Marmosa paraguayana, Gracilinanus microtarsus and Marmosops incanus prior to the onset of the breeding season and without signs of sexual activity; this is taken to indicate early pair-bonding matching and cooperative nest building. We also recorded den sharing among recently weaned siblings of Didelphis aurita and Caluromys philander. In addition, we observed 13 individuals of Didelphis albiventris representing three age classes resting without agonistic interactions in a communal den. These are the first reports of gregarious behaviour involving so many individuals, which are either unrelated or represent siblings from at least two litters, already weaned, sharing the same den with three adults. Sociality in opossums is probably more complex than previously established, and field experimental designs combining the use of artificial nests with camera traps or telemetry may help to gauge the frequency and extent of these phenomena.

  9. Surgical Orthodontic Treatment of an Impacted Canine in the Presence of Dens Invaginatus and Follicular Cyst

    PubMed Central

    Canevello, Carola; Laffi, Nicola

    2014-01-01

    Introduction. “Dens invaginatus” is a dental anomaly which originates from the invagination of the ameloblastic epithelium into the lingual surface of the dental crown during the odontogenesis. It can cause early pulpal necrosis, abscesses, retention or dislocation of contiguous elements, cysts, and internal resorptions. It normally affects the upper lateral incisors. In the following study the authors will discuss the etiology, the physiopathology, and the surgical-orthodontic management of a rare case of impacted canine associated with dens invaginatus and follicular cyst, with the aim of highlighting the importance of taking any therapeutic decision based on the data available in the literature. Case Report. The present study describes a combined surgical-orthodontic treatment of an impacted canine associated with a lateral incisor (2.2) suffering from type III dens invaginatus with radicular cyst, in a 15-year-old patient. Discussion. When treating a dens invaginatus there are different therapeutic solutions: they depend on the gravity of the anomaly and on the association with the retention of a permanent tooth. The aesthetic and functional restoration becomes extremely important when performing a surgical-orthodontic repositioning. PMID:24963421

  10. First evidence of gregarious denning in opossums (Didelphimorphia, Didelphidae), with notes on their social behaviour

    PubMed Central

    Astúa, Diego; Carvalho, Rafael A.; Maia, Paula F.; Magalhães, Arthur R.; Loretto, Diogo

    2015-01-01

    The Didelphidae are considered solitary opossums with few social interactions, usually limited to mating-related or mother–pouch young interactions. Anecdotal reports suggest that additional interactions occur, including den sharing by a few individuals, usually siblings. Here, we report novel observations that indicate opossums are more social than previously thought. These include nest sharing by males and females of Marmosa paraguayana, Gracilinanus microtarsus and Marmosops incanus prior to the onset of the breeding season and without signs of sexual activity; this is taken to indicate early pair-bonding matching and cooperative nest building. We also recorded den sharing among recently weaned siblings of Didelphis aurita and Caluromys philander. In addition, we observed 13 individuals of Didelphis albiventris representing three age classes resting without agonistic interactions in a communal den. These are the first reports of gregarious behaviour involving so many individuals, which are either unrelated or represent siblings from at least two litters, already weaned, sharing the same den with three adults. Sociality in opossums is probably more complex than previously established, and field experimental designs combining the use of artificial nests with camera traps or telemetry may help to gauge the frequency and extent of these phenomena. PMID:26085500

  11. DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions

    PubMed Central

    Arjunan, Selvam; Sastri, Narayan P.; Chandra, Nagasuma

    2016-01-01

    Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue–human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue–human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/). PMID:27618709

  12. First report of captive New Guinea dingo (Canis dingo hallstromi) den-digging and parental behavior.

    PubMed

    Koler-Matznick, Janice; Stinner, Mindy

    2011-01-01

    New Guinea dingoes (NGDs) (Canis dingo hallstromi; Troughton [1957] Proc Roy Soc new South Wells 1955-1956:93-94) have been kept in zoos since 1956. Almost nothing is known of their wild behavior. These observations of a captive pair are the first documentation of natal den-digging and parental behavior for this taxon. The main den, excavated near the top of a 1.5 m hill, consisted of a rounded chamber about 50.8 cm deep, with an entrance about 30.5 cm high and 40.6 cm wide. The dam frequently moved the pups from the natal den to secondary locations for short periods during the day and then back to the den, starting when the pups were 2 weeks old. When the pups were between 5 and 12 weeks of age, both parents regularly regurgitated for them. The sire expressed escalating threat behavior toward the male pup starting when the pup was 5 months old, and the female began threatening the female pups at about 6 months of age. Rejection of same-sex offspring is usual for captive NGDs as the next breeding season approaches.

  13. [Annual distribution and abundance of Ceratium dens (Peridinales: Ceratiaceae) in the Gulf of California, Mexico].

    PubMed

    Cortés Altamirano, R; Nuñez Pasten, A

    2000-01-01

    Ceratium dens distribution in the Gulf of California was studied based on three oceanographic campaigns, monthly abundance (1995-96) and during three red tide events in Mazatlán Bay. 52 phytoplankton samples with a Bongo net and 64 microns mesh light, during the year 120 water samples with a van Dorn bottle were collected in two sampling stations and from three red tide events. All samples were counted by the inverted-microscope method. The results showed that C. dens was present in the upper Gulf of California and surroundings of Cabo San Lucas. Two peaks were observed during spring and autumn in Mazatlán Bay during 1995-1996. The highest densities (20-360 cells.-l-1) were observed in coastal areas, whereas the lowest densities (1-14 cells.-l-1) were recorded in the open sea. During red tide events in 1985, 1989 and 1997, 144,000-256,000 cells.-l-1, 100,000-400,000 cells.-l-1, and 189,000-592,000 cells.ul-l was observed, respectively. During the red tide events C. dens varied, although sometimes was replaced by Skeletonema costatum or Pseudonitzchia spp and Ceratium furca. C. dens, seems to prefer areas with high productivity.

  14. "Where's the Bear? Over There!"--Creative Thinking and Imagination in Den Making

    ERIC Educational Resources Information Center

    Canning, Natalie

    2013-01-01

    This small scale research project examines opportunities for creative thinking and imagination through den making in a rural private day nursery with its own woodland area on the borders of England and Wales in the UK. The research is underpinned by sociocultural theory and is an ethnographic study of non-participant observations of children aged…

  15. Effect of age on respiratory carcinogenesis with diethyl-nitrosamine (DEN) in hamsters

    SciTech Connect

    Stinson, S.F.; Saffiotti, U.

    1986-03-01

    Groups of male and female Syrian golden hamsters were given 12 weekly s.c. injections of 10 mg/kg DEN beginning at 1 day (85 animals) or 8 weeks (70 animals) of age, and were held for lifetime observation. In hamsters receiving DEN from birth, the first respiratory tumors were observed at 15 experimental weeks; all animals were dead by 66 weeks with a 99% respiratory tumor incidence. Of these hamster, 87% developed carcinomas or adenomas in the nasal cavities, 75% papillomas of the trachea, larynx or extrapulmonary bronchi and 7% adenomas or adenocarcinomas of the peripheral lung. Hamsters given DEN from 8 weeks of age first showed respiratory tumors after 25 weeks with a 96% incidence by 62 weeks when all had died. Of these hamsters, 24% developed carcinomas or adenomas in the nasal cavities, 91% papillomas of the trachea, larynx or bronchi, and 9% adenomas or adenocarcinomas of the peripheral lung. In comparison, the nasal tumors in the first group were more anaplastic and invaded the brain more frequently than in the second. These results indicate that the nasal mucosa of newborns is more sensitive to carcinogenesis with DEN than is that of adults, while there appears to be little age-related susceptibility of the epithelium of the airways or lung. A serial sacrifice experiment is currently under way to study the cells of origin of the various tumors using immuno-histochemical and electron microscopic techniques.

  16. Sida rhombifolia ssp. retusa seed extract inhibits DEN induced murine hepatic preneoplasia and carbon tetrachloride hepatotoxicity.

    PubMed

    Poojari, Radhika; Gupta, Sanjay; Maru, Girish; Khade, Bharat; Bhagwat, Sanjay

    2009-01-01

    Sida rhombifolia ssp. retusa is a well established drug in the Ayurvedic system of medicine used for antirheumatism and antiasthmatism. Inhibitory effects of S. rhombifolia ssp. retusa seed extract on DEN induced hepatocellular preneoplastic foci and carbon tetrachloride (CCl4) induced hepatotoxicity was investigated in rats. Rats received DEN, 1ppm/g b.w. in drinking water for 6 weeks or CCl(4), 0.7 ml/kg i.p. once a week for 4 weeks and seed extract 50 mg, 100 mg/kg b.w. orally prior, during and after exposure to DEN/CCl4 for 20 or 5 weeks, respectively. Treatment with seed extract significantly inhibited the increase in DEN/CCl(4) induced activities of pre-cancerous marker enzymes; gamma-glutamyl transpeptidase, glutathione-S-transferase, hepatotoxicity marker enzymes; glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase as well as lipid peroxidase. Depleted glutathione, protein and albumin levels were restored. Also, histopathological and transmission electron microscopic studies showed prevention of cellular degenerative changes. The chemopreventive and hepatoprotective potentials of seed extract are due to free radical scavenging activity and restoration of cellular structural integrity.

  17. NMR study of the AF-SC-SC-AF phased transition in a pnictide superconductor LaFeAsO1-xHx

    NASA Astrophysics Data System (ADS)

    Fujiwara, Naoki; Sakurai, Ryosuke; Iimura, Soushi; Matsuishi, Satoru; Hosono, Hideo; Yamakawa, Youichi; Kontani, Hiroshi

    2014-03-01

    We have performed 75As and 1H NMR measurements in LaFeAsO1xHx, an isomorphic compound of LaFeAsO1xFx. LaFeAsO1xHx is an electron doped system, and O2- can be replaced with H- up to x = 0.5. LaFeAsO1xHx is known for having double superconducting (SC) domes on H doping. Recently, we discovered that a new antiferromagnetic (AF) phase follows the double SC domes on further H doping, forming a symmetric AF-SC-SC-AF phase alignment in the electronic phase diagram Unlike the AF ordering in the lightly H-doped regime, the AF ordering in the highly H-doped regime is attributed to the nesting between electron pockets. In the conference, we will show the data of both NMR spectra and the relaxation rate 1/T1 in the whole doping region. We will discuss the difference of electronic states between the lightly H-doped AF-SC phases and highly H-doped SC-AF phases. This work is supported by a Grant-in-Aid (Grant No. KAKENHI 23340101) from the Ministry of Education, Science, and Culture, Japan.

  18. Iron promotes DEN initiated GST-P foci in rat liver.

    PubMed

    Carthew, P; Nolan, B M; Smith, A G; Edwards, R E

    1997-03-01

    Diethylnitrosamine (DEN) was administered to rats as a single dose, which is known not to give rise to liver tumours without subsequent promotion. Iron dextran (Fe/Dex) was then administered parenterally to the animals, to induce iron overload. At 3 and 6 months after the final Fe/Dex treatments, livers were examined quantitatively for the numbers of the placental form of glutathione-S-transferase (GST-P) expressing foci, the area occupied by these foci and their size distribution. The results demonstrate that iron not only increased the number of foci after DEN initiation in the rat liver, but that the area occupied by these lesions increased significantly between 3 and 6 months after initiation. There is no evidence that iron increased the number of GST-P expressing foci present in rats not exposed to DEN. This indicates that iron did not act as an initiator in this rodent model of liver cancer. The increase in the area of the liver occupied by the foci in iron and DEN treated rats was due to an increase in the size of the foci, as well as to an increase in the number of foci. This is the first demonstration that iron can act as a promoter of DEN initiated hepatocytes. It also demonstrates that fibrogenesis is not an absolute requirement for the promotion, by iron, of liver foci in the rat, and that this could also be the case for iron overload in man. Iron may also act as a promoter of already initiated hepatocytes in the development of human liver cancer, as it does in the rat.

  19. AFS men and women differ most in their lifestyle choices

    USGS Publications Warehouse

    Connelly, N.A.; Brown, T.L.; Hardiman, J.M.

    2006-01-01

    The American Fisheries Society sponsored a survey to examine the career development choices of men and women and how they might differ by gender. A random sample of 700 men and 700 women was selected from the AFS membership database. The survey was mailed out in October 2004 and 991 questionnaires were returned for an adjusted response rate of 71%. Some differences exist between men and women in the areas of interest development, education, and employment, but the substantive differences occur in lifestyle choices. Women with a fisheries career are less likely to be married than men, even when age is controlled for, and women who are married are more likely to have dual-career considerations than their male counterparts. Among respondents without dependents in their home during their professional career, twice as many women as men think having children will adversely affect their career. For those with dependents, more than twice as many women as men said they had to put their career "on hold" because of their dependents. While AFS members do not represent all members of the fisheries profession, their experiences shed substantial light on the lifestyle choices likely faced by most members of the profession.

  20. Importance of Native Grassland Habitat for Den-Site Selection of Indian Foxes in a Fragmented Landscape

    PubMed Central

    Punjabi, Girish Arjun; Chellam, Ravi; Vanak, Abi Tamim

    2013-01-01

    Fragmentation of native habitats is now a ubiquitous phenomenon affecting wildlife at various scales. We examined selection of den-sites (n = 26) by Indian foxes (Vulpes bengalensis) in a highly modified short-grassland landscape in central India (Jan-May, 2010). At the scale of the home-range, defined by an 800 m circular buffer around den sites, we examined the effect of land-cover edges and roads on selection of sites for denning using a distance-based approach. At the smaller den-area scale, defined by a 25 m x 25 m plot around den and paired available sites, the effect of microhabitat characteristics was examined using discrete-choice models. Indian foxes selected den-sites closer to native grasslands (t = -9.57, P < 0.001) and roads (t = -2.04, P = 0.05) than random at the home-range scale. At the smaller scale, abundance of rodents and higher visibility increased the odds of selection of a site by eight and four times respectively, indicating resource availability and predator avoidance to be important considerations for foxes. Indian foxes largely chose to den in human-made structures, indicated by the proportion of dens found in earthen bunds (0.69) and boulder piles (0.27) in the study area. With agricultural expansion and human modification threatening native short-grassland habitats, their conservation and effective management in human-dominated landscapes will benefit the Indian fox. The presence of some human-made structures within native grasslands would also be beneficial for this den-dependent species. We suggest future studies examine the impact of fragmentation and connectivity of grasslands on survival and reproductive success of the Indian fox. PMID:24098494

  1. Importance of native grassland habitat for den-site selection of Indian foxes in a fragmented landscape.

    PubMed

    Punjabi, Girish Arjun; Chellam, Ravi; Vanak, Abi Tamim

    2013-01-01

    Fragmentation of native habitats is now a ubiquitous phenomenon affecting wildlife at various scales. We examined selection of den-sites (n = 26) by Indian foxes (Vulpes bengalensis) in a highly modified short-grassland landscape in central India (Jan-May, 2010). At the scale of the home-range, defined by an 800 m circular buffer around den sites, we examined the effect of land-cover edges and roads on selection of sites for denning using a distance-based approach. At the smaller den-area scale, defined by a 25 m x 25 m plot around den and paired available sites, the effect of microhabitat characteristics was examined using discrete-choice models. Indian foxes selected den-sites closer to native grasslands (t = -9.57, P < 0.001) and roads (t = -2.04, P = 0.05) than random at the home-range scale. At the smaller scale, abundance of rodents and higher visibility increased the odds of selection of a site by eight and four times respectively, indicating resource availability and predator avoidance to be important considerations for foxes. Indian foxes largely chose to den in human-made structures, indicated by the proportion of dens found in earthen bunds (0.69) and boulder piles (0.27) in the study area. With agricultural expansion and human modification threatening native short-grassland habitats, their conservation and effective management in human-dominated landscapes will benefit the Indian fox. The presence of some human-made structures within native grasslands would also be beneficial for this den-dependent species. We suggest future studies examine the impact of fragmentation and connectivity of grasslands on survival and reproductive success of the Indian fox.

  2. A Conditional Role of U2AF in Splicing of Introns with Unconventional Polypyrimidine Tracts▿ †

    PubMed Central

    Sridharan, Vinod; Singh, Ravinder

    2007-01-01

    Recognition of polypyrimidine (Py) tracts typically present between the branch point and the 3′ splice site by the large subunit of the essential splicing factor U2AF is a key early step in pre-mRNA splicing. Diverse intronic sequence arrangements exist, however, including 3′ splice sites lacking recognizable Py tracts, which raises the question of how general the requirement for U2AF is for various intron architectures. Our analysis of fission yeast introns in vivo has unexpectedly revealed that whereas introns lacking Py tracts altogether remain dependent on both subunits of U2AF, introns with long Py tracts, unconventionally positioned upstream of branch points, are unaffected by U2AF inactivation. Nevertheless, mutation of these Py tracts causes strong dependence on the large subunit U2AF59. We also find that Py tract diversity influences the requirement for the conserved C-terminal domain of U2AF59 (RNA recognition motif 3), which has been implicated in protein-protein interactions with other splicing factors. Together, these results suggest that in addition to Py tract binding by U2AF, supplementary mechanisms of U2AF recruitment and 3′ splice site identification exist to accommodate diverse intron architectures, which have gone unappreciated in biochemical studies of model pre-mRNAs. PMID:17709389

  3. Evaluation of the atoxigenic Aspergillus flavus strain AF36 in pistachio orchards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The atoxigenic strain Aspergillus flavus AF36, which has been extensively used as a biocontrol agent in commercial corn and cotton fields to reduce aflatoxin contamination, was applied in research pistachio orchards from 2002 to 2005 and in commercial pistachio orchards from 2008 to 2011. AF36 was a...

  4. HyDEn: a hybrid steganocryptographic approach for data encryption using randomized error-correcting DNA codes.

    PubMed

    Tulpan, Dan; Regoui, Chaouki; Durand, Guillaume; Belliveau, Luc; Léger, Serge

    2013-01-01

    This paper presents a novel hybrid DNA encryption (HyDEn) approach that uses randomized assignments of unique error-correcting DNA Hamming code words for single characters in the extended ASCII set. HyDEn relies on custom-built quaternary codes and a private key used in the randomized assignment of code words and the cyclic permutations applied on the encoded message. Along with its ability to detect and correct errors, HyDEn equals or outperforms existing cryptographic methods and represents a promising in silico DNA steganographic approach.

  5. HyDEn: A Hybrid Steganocryptographic Approach for Data Encryption Using Randomized Error-Correcting DNA Codes

    PubMed Central

    Regoui, Chaouki; Durand, Guillaume; Belliveau, Luc; Léger, Serge

    2013-01-01

    This paper presents a novel hybrid DNA encryption (HyDEn) approach that uses randomized assignments of unique error-correcting DNA Hamming code words for single characters in the extended ASCII set. HyDEn relies on custom-built quaternary codes and a private key used in the randomized assignment of code words and the cyclic permutations applied on the encoded message. Along with its ability to detect and correct errors, HyDEn equals or outperforms existing cryptographic methods and represents a promising in silico DNA steganographic approach. PMID:23984392

  6. Seladoeflavones A-F, six novel flavonoids from Selaginella doederleinii.

    PubMed

    Zou, ZhenXing; Xu, KangPing; Xu, PingSheng; Li, XiaoMin; Cheng, Fei; Li, Jing; Yu, Xia; Cao, DongSheng; Li, Dan; Zeng, Wei; Zhang, GuoGang; Tan, GuiShan

    2017-01-01

    Six new flavonoids, seladoeflavones A-F (1-6), were isolated from the whole herbs of Selaginella doederleinii, together with one known flavonoid (7). Their structures including absolute configuration were characterized on the basis of extensive spectroscopic methods including NMR, HRMS, and electronic circular dichroism (ECD). All compounds consist of an aryl substituent at the C-3' position of naringenin or apigenin skeletons, and compounds 1 and 6 were identified as R configurations, which are uncommonly encountered in nature. A possible biosynthetic pathway was postulated. In addition, bioassay of the isolates revealed that 5-7 exhibited moderate cytotoxicity against three human cancer cell lines NCI-H460, A549, and K562 in vitro with IC50 values ranging from 8.17 to 18.66μM.

  7. Optimised secure transmission through untrusted AF relays using link adaptation

    NASA Astrophysics Data System (ADS)

    Taki, Mehrdad; Sadeghi, Mohammad

    2016-05-01

    A new transmission scheme is presented for a two-hop relay network including two AF relays, considering physical layer security where relays are not able to detect signal with an acceptable bit error rate (BER) but the combined received signal is detected with an acceptable BER at the final receiver. It is assumed that there is no direct path between the transmitter and the receiver (relay network without diversity). Adaptive modulation and coding is utilised at the transmitter and transmission powers of the transmitter and of the relays are continuously adapted provisioning individual average power constraint for each node. Numerical evaluations show that an acceptable performance degradation is seen by the proposed secure relaying scheme compared to the optimum relay selection scheme without security constraint.

  8. Automation under suspicion--case flight AF-447 Air France.

    PubMed

    Martins, Edgard; Soares, Marcelo

    2012-01-01

    The probes allow the pilot to control the aircraft speed was essential to the balance of the flight. Opinions of experts who claim that "the design of the plane would have exercised a not inconsiderable role in the occurrence of a disaster." These messages revealed a series of important operating errors in a zone of turbulence, "making the plane uncontrollable, leading to a rapid depressurization device, according to these reports. A lawsuit in Toulouse and in Brazil aims to recognition of the liability of Air France and Airbus not insignificant role in the design and operation of the aircraft in the event of catastrophe. Opinions are taken from senior pilots that no commercial aviation training for certain situations abnormal flight that, if realized, could have influenced the pilots of the AF-447 to remove the plane's fatal dive show what experiments performed in simulators for military pilots, who are permanently subject to critical flight situations.

  9. The leukemogenic CALM/AF10 fusion protein alters the subcellular localization of the lymphoid regulator Ikaros.

    PubMed

    Greif, P A; Tizazu, B; Krause, A; Kremmer, E; Bohlander, S K

    2008-05-01

    The t(10;11)(p13;q14) translocation leads to the fusion of the CALM and AF10 genes. This translocation can be found as the sole cytogenetic abnormality in acute lymphoblastic leukemia, acute myeloid leukemia and in malignant lymphomas. The expression of CALM/AF10 in primary murine bone marrow cells results in the development of an aggressive leukemia in a murine bone marrow transplantation model. Using a yeast two-hybrid screen, we identified the lymphoid regulator Ikaros as an AF10 interacting protein. Interestingly, Ikaros is required for normal development of lymphocytes, and aberrant expression of Ikaros has been found in leukemia. In a murine model, the expression of a dominant negative isoform of Ikaros causes leukemias and lymphomas. The Ikaros interaction domain of AF10 was mapped to the leucine zipper domain of AF10, which is required for malignant transformation both by the CALM/AF10 and the MLL/AF10 fusion proteins. The interaction between AF10 and Ikaros was confirmed by GST pull down and co-immunoprecipitation. Coexpression of CALM/AF10 but not of AF10 alters the subcellular localization of Ikaros in murine fibroblasts. The transcriptional repressor activity of Ikaros is reduced by AF10. These results suggest that CALM/AF10 might interfere with normal Ikaros function, and thereby block lymphoid differentiation in CALM/AF10 positive leukemias.

  10. CheckDen, a program to compute quantum molecular properties on spatial grids.

    PubMed

    Pacios, Luis F; Fernandez, Alberto

    2009-09-01

    CheckDen, a program to compute quantum molecular properties on a variety of spatial grids is presented. The program reads as unique input wavefunction files written by standard quantum packages and calculates the electron density rho(r), promolecule and density difference function, gradient of rho(r), Laplacian of rho(r), information entropy, electrostatic potential, kinetic energy densities G(r) and K(r), electron localization function (ELF), and localized orbital locator (LOL) function. These properties can be calculated on a wide range of one-, two-, and three-dimensional grids that can be processed by widely used graphics programs to render high-resolution images. CheckDen offers also other options as extracting separate atom contributions to the property computed, converting grid output data into CUBE and OpenDX volumetric data formats, and perform arithmetic combinations with grid files in all the recognized formats.

  11. Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair.

    PubMed

    Castaño, Julio; Herrero, Ana B; Bursen, Aldeheid; González, Federico; Marschalek, Rolf; Gutiérrez, Norma C; Menendez, Pablo

    2016-05-24

    The most frequent rearrangement of the human MLL gene fuses MLL to AF4 resulting in high-risk infant B-cell acute lymphoblastic leukemia (B-ALL). MLL fusions are also hallmark oncogenic events in secondary acute myeloid leukemia. They are a direct consequence of mis-repaired DNA double strand breaks (DNA-DSBs) due to defects in the DNA damage response associated with exposure to topoisomerase-II poisons such as etoposide. It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. Conversely, the genome-wide mutational landscape in MLL-rearranged infant B-ALL has been reported silent. Thus, whether MLL fusions compromise the recognition and/or repair of DNA damage remains unanswered. Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. Repair kinetics of etoposide- and ionizing radiation-induced DSBs was identical in WT, MA4- and A4M-expressing cells, as revealed by flow cytometry, by immunoblot for γH2AX and by comet assay. Accordingly, no differences were observed between WT, MA4- and A4M-expressing cells in the presence of master proteins involved in non-homologous end-joining (NHEJ; i.e.KU86, KU70), alternative-NHEJ (Alt-NHEJ; i.e.LigIIIa, WRN and PARP1), and homologous recombination (HR, i.e.RAD51). Moreover, functional assays revealed identical NHEJ and HR efficiency irrespective of the genotype. Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. Collectively, expression of MA4 or A4M does neither influence DNA signaling nor DNA-DSB repair.

  12. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo

    PubMed Central

    Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Duncavage, Eric J.; Okeyo-Owuor, Theresa; Liu, Tuoen; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O’Laughlin, Michelle; Graubert, Timothy A.; Walter, Matthew J.

    2015-01-01

    SUMMARY Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently-mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in MDS patients. PMID:25965570

  13. Technische Systeme für den Herzersatz und die Herzunterstützung

    NASA Astrophysics Data System (ADS)

    Schöb, Reto; Loree, Howard M.

    Herzkrankheiten verursachen allein in den Vereinigten Staaten jährlich mehr als 700’000 Todesfälle. Ungefähr 3 Millionen Patienten in den U.S.A. leiden gemäss der American Heart Association (AHA) und dem National Heart, Lung and Blood Institute (NHLBI) an kongestivem Herzversagen (Congestive Heart Failure, CHF), welches eine chronische, sehr entkräftende und degenerative Krankheit ist: Das Herz ist dabei unfähig, hinreichend Blut zu den Organen des Körpers zu pumpen. Über 400’000 Fälle von CHF werden jedes Jahr diagnostiziert. Ähnliche Zahlen werden für Europa und Japan zusammen geschätzt. Basierend auf Daten vom AHA und NHLBI beträgt die fünfjährige Überlebensrate für CHF-Patienten lediglich etwa 50% [1]. 70’000-120’000 dieser Patienten könnten von einer Herzverpflanzung profitieren. 1999 wurden in den USA aber nur 2185 Herztransplantationen durchgeführt während die Warteliste über 4000 Patienten beträgt [2]. Ein akuter Mangel an Spenderherzen und die enormen Kosten (250’000-400’000 USD pro Patient) sind die begrenzenden Faktoren für Herztransplantationen [3]. Dies bedeutet, dass eine riesige Anzahl von Patienten durch ein zuverlässiges und verschleissfreies, nichtthrombotisches, total implantierbares, künstliches Herz gerettet werden könnten. Bis heute jedoch kein derartiges Implantat kommerziell verfügbar.

  14. Case study of total energy system, Sher-Den Mall, Sherman, Texas

    SciTech Connect

    Myrtetus, G.B.; Levey, M.D.

    1980-12-01

    The Sher-Den Mall shopping center receives all of its electricity and heating and cooling energy from a total energy plant located within the shopping center proper. Four engine-generator units are fueled primarily by natural gas, with some fuel oil use. The following are presented: initial corporate planning, investigation, and feasibility studies; a description of the total energy system; capital costs; plant operations, and revenue structure. Tables, figures, exhibits, and equipment specification lists are presented. (MHR)

  15. Computational anatomy of the dens axis evaluated by quantitative computed tomography: Implications for anterior screw fixation.

    PubMed

    Gehweiler, Dominic; Wähnert, Dirk; Meier, Norbert; Spruit, Maarten; Raschke, Michael Johannes; Richards, Robert Geoff; Noser, Hansrudi; Kamer, Lukas

    2017-01-05

    The surgical fracture fixation of the odontoid process (dens) of the second cervical vertebra (C2/axis) is a challenging procedure, particularly in elderly patients affected by bone loss, and includes screw positioning close to vital structures. The aim of this study was to provide an extended anatomical knowledge of C2, the bone mass distribution and bone loss, and to understand the implications for anterior screw fixation. One hundred and twenty standard clinical quantitative computed tomography (QCT) scans of the intact cervical spine from 60 female and 60 male European patients, aged 18-90 years, were used to compute a three-dimensional statistical model and an averaged bone mass model of C2. Shape and size variability was assessed via principal component analysis (PCA), bone mass distribution by thresholding and via virtual core drilling, and the screw placement via virtual positioning of screw templates. Principal component analysis (PCA) revealed a highly variable anatomy of the dens with size as the predominant variation according to the first principal component (PC) whereas shape changes were primarily described by the remaining PCs. The bone mass distribution demonstrated a characteristic 3D pattern, and remained unchanged in the presence of bone loss. Virtual screw positioning of two 3.5 mm dens screws with a 1 mm safety zone was possible in 81.7% in a standard, parallel position and in additional 15.8% in a twisted position. The approach permitted a more detailed anatomical assessment of the dens axis. Combined with a preoperative QCT it may further improve the diagnostic procedure of odontoid fractures. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  16. The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function.

    PubMed

    Jensen, Thomas; Elster, Lisbeth; Nielsen, Søren Møller; Poda, Suresh Babu; Loechel, Frosty; Volbracht, Christiane; Klewe, Ib Vestergaard; David, Laurent; Watson, Stephen P

    2014-11-15

    The identification of the novel and selective GPR3 inverse agonist AF64394, the first small molecule inhibitor of GPR3 receptor function, is described. Structure activity relationships and syntheses based around AF64394 are reported.

  17. ROK AFS, Kwandae-ri, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1968-04-15

    KlmANCAF RI KCREA/kC, AFS K-6 1-54 AL L STATION STATION NAME YEARS MONTH PERCEfNT G ’F C., YS , 1Th VPR IC Lc AT CSP-F PIC P H-C F FRCf. CAILY C4SV...DS 301 iq WTIONS Op THIS pOrn AM OIomr ATA PRrCESSIN;G C[ S!CN ETAC, LSAF SURFACE WINDS AS#-EVILLE9 N. C. 28E01 PERCENTAGE FREQUENCY OF WIND...NNW VAREIL F -3.4 7.4 5.4 .7 _ 1.0 TOTAL NUMBER OF OISERVATIONS 146 1210 WS j 0--S (0. SO) SSIeo.. KDSTIO,. oP TIN PORN AN O.S.OC. I [~. [ATA

  18. Catalogue of polar bear (Ursus maritimus) maternal den locations in the Beaufort Sea and neighboring regions, Alaska, 1910-2010

    USGS Publications Warehouse

    Durner, George M.; Fischbach, Anthony S.; Amstrup, Steven C.; Douglas, David C.

    2010-01-01

    This report presents data on the approximate locations and methods of discovery of 392 polar bear (Ursus maritimus) maternal dens found in the Beaufort Sea and neighboring regions between 1910 and 2010 that are archived by the U.S. Geological Survey, Alaska Science Center, Anchorage, Alaska. A description of data collection methods, biases associated with collection method, primary time periods, and spatial resolution are provided. Polar bears in the Beaufort Sea and nearby regions den on both the sea ice and on land. Standardized VHF surveys and satellite radio telemetry data provide a general understanding of where polar bears have denned in this region over the past 3 decades. Den observations made during other research activities and anecdotal reports from other government agencies, coastal residents, and industry personnel also are reported. Data on past polar bear maternal den locations are provided to inform the public and to provide information for natural resource agencies in planning activities to avoid or minimize interference with polar bear maternity dens.

  19. Assessment of adverse effects of neurotropic drugs in monkeys with the "drug effects on the nervous system" (DENS) scale.

    PubMed

    Uthayathas, Subramaniam; Shaffer, Christopher L; Menniti, Frank S; Schmidt, Christopher J; Papa, Stella M

    2013-04-30

    Research into therapeutics for neuropsychiatric disorders is increasingly focusing on drugs with new mechanisms of action, and such agents are often assessed in preclinical studies using nonhuman primates. However, researchers lack a standardised method to compare different drugs for common adverse effects on the nervous system. We have developed a new scale for this purpose, named "Drug Effects on the Nervous System" (DENS), and tested its utility in an analysis of the second-generation antipsychotic risperidone in monkeys. The behavioural effects of risperidone over a ten-fold clinically relevant exposure range were rated with the DENS scale and compared with a standard motor disability scale for primates. The ratings were correlated with projected D2 and 5-HT2A receptor occupancies over time. The DENS scale detected dose-dependent side effects of risperidone in addition to the motor effects detected with the motor disability scale, including cognitive, sensorimotor and autonomic functions. A consistent temporal association between the DENS scale changes and the projected D2 receptor occupancy was observed, and the DENS scale ratings demonstrated high inter-rater reliability. These results demonstrate the usefulness of the DENS scale as a highly sensitive, reliable and accurate method to identify common adverse effects of risperidone and potentially other neurotropics for translational studies in primates.

  20. Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF

    PubMed Central

    DeVore, Adam D.; Hellkamp, Anne S.; Becker, Richard C.; Berkowitz, Scott D.; Breithardt, Guenter; Hacke, Werner; Halperin, Jonathan L.; Hankey, Graeme J.; Mahaffey, Kenneth W.; Nessel, Christopher C.; Singer, Daniel E.; Fox, Keith A. A.; Patel, Manesh R.; Piccini, Jonathan P.

    2016-01-01

    Aims The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. Methods and results The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Conclusion Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. PMID:27174904

  1. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF)

    PubMed Central

    Hori, Juliana I.; Zamboni, Dario S.; Carrão, Daniel B.; Goldman, Gustavo Henrique; Berretta, Andresa A.

    2013-01-01

    Propolis extracts have gained the attention of consumers and researchers due to their unique chemical compositions and functional properties such as its anti-inflammatory activity. Recently, it was described a complex that is also important in inflammatory processes, named inflammasome. The inflammasomes are a large molecular platform formed in the cell cytosol in response to stress signals, toxins, and microbial infections. Once activated, the inflammasome induces caspase-1, which in turn induces the processing of inflammatory cytokines such as IL-1β and IL-18. So, to understand inflammasomes regulation becomes crucial to treat several disorders including autoinflammatory diseases. Since green propolis extracts are able to regulate inflammatory pathways, this work purpose was to investigate if this extract could also act on inflammasomes regulation. First, the extract was characterized and it demonstrated the presence of important compounds, especially Artepillin C. This extract was effective in reducing the IL-1β secretion in mouse macrophages and this reduction was correlated with a decrease in activation of the protease caspase-1. Furthermore, we found that the extract at a concentration of 30 μg/mL was not toxic to the cells even after a 18-hour treatment. Altogether, these data indicate that Brazilian green propolis (EPP-AF) extract has a role in regulating the inflammasomes. PMID:23690844

  2. Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Rasoanaivo, Philippe; Guéritte, Françoise; Litaudon, Marc

    2012-04-27

    In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM).

  3. Reconnaissance study of late quaternary faulting along cerro GoDen fault zone, western Puerto Rico

    USGS Publications Warehouse

    Mann, P.; Prentice, C.S.; Hippolyte, J.-C.; Grindlay, N.R.; Abrams, L.J.; Lao-Davila, D.

    2005-01-01

    The Cerro GoDen fault zone is associated with a curvilinear, continuous, and prominent topographic lineament in western Puerto Rico. The fault varies in strike from northwest to west. In its westernmost section, the fault is ???500 m south of an abrupt, curvilinear mountain front separating the 270- to 361-m-high La CaDena De San Francisco range from the Rio A??asco alluvial valley. The Quaternary fault of the A??asco Valley is in alignment with the bedrock fault mapped by D. McIntyre (1971) in the Central La Plata quadrangle sheet east of A??asco Valley. Previous workers have postulated that the Cerro GoDen fault zone continues southeast from the A??asco Valley and merges with the Great Southern Puerto Rico fault zone of south-central Puerto Rico. West of the A??asco Valley, the fault continues offshore into the Mona Passage (Caribbean Sea) where it is characterized by offsets of seafloor sediments estimated to be of late Quaternary age. Using both 1:18,500 scale air photographs taken in 1936 and 1:40,000 scale photographs taken by the U.S. Department of Agriculture in 1986, we iDentified geomorphic features suggestive of Quaternary fault movement in the A??asco Valley, including aligned and Deflected drainages, apparently offset terrace risers, and mountain-facing scarps. Many of these features suggest right-lateral displacement. Mapping of Paleogene bedrock units in the uplifted La CaDena range adjacent to the Cerro GoDen fault zone reveals the main tectonic events that have culminated in late Quaternary normal-oblique displacement across the Cerro GoDen fault. Cretaceous to Eocene rocks of the La CaDena range exhibit large folds with wavelengths of several kms. The orientation of folds and analysis of fault striations within the folds indicate that the folds formed by northeast-southwest shorTening in present-day geographic coordinates. The age of Deformation is well constrained as late Eocene-early Oligocene by an angular unconformity separating folDed, Deep

  4. Photoprotective implications of leaf variegation in E. dens-canis L. and P. officinalis L.

    PubMed

    Esteban, Raquel; Fernández-Marín, Beatriz; Becerril, José María; García-Plazaola, José Ignacio

    2008-08-25

    Variegated leaves occur rarely in nature, but there are some species, primarily in the forest understory, that possess this characteristic. We recently studied two variegated plants: Erytronium dens-canis L., which is characterised by a pattern of red patches and Pulmonaria officinalis L., with light green spots. These non-green areas could attenuate light reaching mesophyll cells with respect to green sections. The aim of the study was to verify whether such red and light green parts are more photoprotected than green ones and if this trait could be of adaptive value. Red patches in E. dens-canis were due to a single layer of red cells in the upper parenchyma, which accumulated anthocyanins. Light green spots in P. officinalis were caused by the presence of loosely arranged cells instead of a well-established layer of packed cells in the palisade parenchyma. Chlorophyll fluorescence imaging was performed under light treatment, showing a greater decrease of photochemical efficiency in red and light green patches than in green sections. Differences in the extent of photochemical efficiency among patches were not attributable to different activation of the xanthophyll cycle. These observations failed to confirm our initial hypothesis, but they questioned the physiological reason for this higher sensitivity in red and light green patches of photosynthetic tissues. Chlorophyll fluorescence imaging was therefore performed in the field. The same pattern of photochemical efficiency was maintained only in E. dens-canis. The current results demonstrate that in both species the benefits of variegation, if any, are different from enhanced photosynthetic performance.

  5. High-resolution micropatterned Teflon AF substrates for biocompatible nanofluidic devices.

    PubMed

    Czolkos, Ilja; Hakonen, Bodil; Orwar, Owe; Jesorka, Aldo

    2012-02-14

    We describe a general photolithography-based process for the microfabrication of surface-supported Teflon AF structures. Teflon AF patterns primarily benefit from superior optical properties such as very low autofluorescence and a low refractive index. The process ensures that the Teflon AF patterns remain strongly hydrophobic in order to allow rapid lipid monolayer spreading and generates a characteristic edge morphology which assists directed cell growth along the structured surfaces. We provide application examples, demonstrating the well-controlled mixing of lipid films on Teflon AF structures and showing how the patterned surfaces can be used as biocompatible growth-directing substrates for cell culture. Chinese hamster ovary (CHO) cells develop in a guided fashion along the sides of the microstructures, selectively avoiding to grow over the patterned areas.

  6. Adiabatic Compression Sensitivity of AF-M315E (Briefing Charts)

    DTIC Science & Technology

    2015-07-27

    dynamic response • Waterhammer effect Distribution A: Approved for public release; distribution unlimited Hydroxyethylhydrazinium Nitrate ...Hydroxylammonium Nitrate (HEHN) (HAN) [ ]-NO3 + [ ]HOCH2CH2N2H4 [ ]-+[ ]NH3OH NO3 AF-M315E

  7. Hubble constant from Pritchet and von den Bergh's nova distance to the Virgo cluster

    SciTech Connect

    Sandage, A.; Tammann, G.A.

    1988-05-01

    Two reasons are offered why the value for H(0) of 69 + or - 14 km/s/Mpc of Pritchet and van den Bergh (1987) is likely to be too high by about 20 percent even when their value of 6.8 + or - 0.4 for the M31-Virgo modulus difference is adopted. One reason concerns the free expansion velocity of the Virgo cluster core and the other concerns the apparent distance modulus of M31. Reasons for adopting a global H(0) value of 56 + or - 12 km/s/Mpc are discussed. 25 references.

  8. Air Sampling of Polychlorinated Dibenzodioxins, Polychlorinated Dibenzofurans, and Polychlorinated Biphenyls Arnold AFS, Tennessee.

    DTIC Science & Technology

    1987-01-01

    DIBENZOFURANS, AND POLYCHLORINATED BIPHENYLS ARNOLD AFS TN ISAAC ATKINS, JR., CAPTAIN, USAF, BSC January 1987 D I ~ELECTE FINAL REPORT 0Wfl D LU...NO 11. TITLE (Include Security ClassificatiOtl) Air Sampling of Polychlorinated Dibenzodioxins, Polychlorinated Dibenzofurans, and Polychlorinated ... Biphenyls at Arnold AFS TN (U) 12. PERSONAL AUTHOR(S) Captaiq Isaac Atkins, Jr. 13a. TYP OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month

  9. Services Officer Utilization Field (AFS 62XX and Equivalent-Grade Civilians).

    DTIC Science & Technology

    1986-06-01

    CHART le~ -- Sq ,.. O. pt’*. q UNITED STATES AIR FORCE cv, Lfl o D SERVICES OFFICER UTILIZATION FIELD (AFS 62XX AND EQUIVALENT-GRADE CIVILLANS) AFPT 90...Administration From January through Ma’ch 1985, job inventories were administered to all elicible AFSC 62XX nfficer: in the continental United States ... PUBLIC RELEASE: DISTRIBUTION UNLIMITED t, , . . . .. .. . . . . , . . . . . . , . _". ... , I! . . $ IJSTRIBIJTION FOR AFS( u-)XX OSR AND SUPPORTING

  10. AF-M315E Propulsion System Advances and Improvements

    NASA Technical Reports Server (NTRS)

    Masse, Robert K.; Allen, May; Driscoll, Elizabeth; Spores, Ronald A.; Arrington, Lynn A.; Schneider, Steven J.; Vasek, Thomas E.

    2016-01-01

    Even as for the GR-1 awaits its first on-orbit demonstration on the planned 2017 launch of NASA's Green Propulsion Infusion Mission (GPIM) program, ongoing efforts continue to advance the technical state-of-the-art through improvements in the performance, life capability, and affordability of both Aerojet Rocketdyne's 1-N-class GR-1 and 20-N-class GR-22 green monopropellant thrusters. Hot-fire testing of a design upgrade of the GR-22 thruster successfully demonstrated resolution of a life-limiting thermo-structural issue encountered during prototype testing on the GPIM program, yielding both an approximately 2x increase in demonstrating life capability, as well as fundamental insights relating to how ionic liquid thrusters operate, thruster scaling, and operational factors affecting catalyst bed life. Further, a number of producibility improvements, related to both materials and processes and promising up to 50% unit cost reduction, have been identified through a comprehensive Design for Manufacturing and Assembly (DFMA) assessment activity recently completed at Aerojet Rocketdyne. Focused specifically on the GR-1 but applicable to the common-core architecture of both thrusters, ongoing laboratory (heavyweight) thruster testing being conducted under a Space Act Agreement at NASA Glenn Research Center has already validated a number of these proposed manufacturability upgrades, additionally achieving a greater than 40% increase in thruster life. In parallel with technical advancements relevant to conventional large spacecraft, a joint effort between NASA and Aerojet Rocketdyne is underway to prepare 1-U CubeSat AF-M315E propulsion module for first flight demonstration in 2018.

  11. Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome

    PubMed Central

    Shirai, Cara Lunn; White, Brian S.; Tripathi, Manorama; Tapia, Roberto; Ley, James N.; Ndonwi, Matthew; Kim, Sanghyun; Shao, Jin; Carver, Alexa; Saez, Borja; Fulton, Robert S.; Fronick, Catrina; O'Laughlin, Michelle; Lagisetti, Chandraiah; Webb, Thomas R.; Graubert, Timothy A.; Walter, Matthew J.

    2017-01-01

    Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity to in vitro sudemycin treatment relative to controls. In vivo sudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouring U2AF1 mutations with pre-mRNA splicing modulators like sudemycins. PMID:28067246

  12. Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats.

    PubMed

    Yamada, Kazuo; Furukawa, Satoshi; Iwasaki, Tsuneo; Ichitani, Yukio

    2010-01-18

    Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxic derivative of choline that produces not only long-term presynaptic cholinergic deficits, but also various memory deficits in rats similar to some characteristics observed in Alzheimer's disease patients. This study investigated whether nicotine (NCT) administration attenuated spatial learning deficits induced by intracerebroventricular AF64A treatment. AF64A (6 nmol/6 microl)-or saline (SAL)-treated rats were trained in Morris water maze task. NCT (0.025-0.25mg/kg) was subcutaneously injected 5 min before the training every day. The results showed that moderate dose (0.10mg/kg) of NCT attenuated AF64A-induced prolongation of escape latency. Furthermore, NCT dose-dependently recovered the AF64A-induced decrease of time spent in the target quadrant in the probe test. These results suggest that NCT improves AF64A-induced spatial memory deficits, and thus it is a potential therapeutic agent for the treatment of memory deficits in dementia.

  13. Oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system.

    PubMed

    Meng, Yao; Jost, Carsten; Mumme, Jan; Wang, Kaijun; Linke, Bernd

    2016-07-01

    In order to investigate the oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39±0.27 and 0.99±0.38mg/L, respectively. pH was relatively stable around 7.11±0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85±7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity.

  14. Successful orthograde treatment of dens invaginatus Type 3 with a main C-shaped canal based on cone-beam computed tomography evaluation

    PubMed Central

    Solomonov, Michael; Itzhak, Joe Ben; Levin, Avi; Katzenell, Vered; Shemesh, Avi

    2016-01-01

    Dens invaginatus is a rare anatomic variation that is found primarily in maxillary lateral incisors. The management of dens invaginatus is challenging for clinicians; diagnosing the type of malformation, choosing the most appropriate treatment, and carrying out treatment are complicated by the intricate root system of these teeth. The following case report describes the diagnosis and treatment planning of dens invaginatus Type 3 after cone-beam computed tomography evaluation. PMID:27994325

  15. Insights from the Den: How Hibernating Bears May Help Us Understand and Treat Human Disease.

    PubMed

    Berg von Linde, Maria; Arevström, Lilith; Fröbert, Ole

    2015-10-01

    Hibernating brown bears (Ursus arctos) and black bears (Ursus americanus) spend half of the year in a physically inactive state inside their winter dens without food intake and defecating and no or little urination. Under similar extreme conditions, humans would suffer from loss of lean body mass, heart failure, thrombosis, azotemia, osteoporosis, and more. However, bears exit the den in the spring strong without organ injuries. Translational animal models are used in human medicine but traditional experimental animals have several shortcomings; thus, we believe that it is time to systematically explore new models. In this review paper, we describe physiological adaptations of hibernating bears and how similar adaptations in humans could theoretically alleviate medical conditions. The bear has solved most of the health challenges faced by humans, including heart and kidney disease, atherosclerosis and thrombosis, and muscle wasting and osteoporosis. Understanding and applying this library of information could lead to a number of major discoveries that could have implications for the understanding and treatment of human disease.

  16. Dens Axis Vertebroplasty Combined with C 3 Vertebral Body Arthroplasty. Case Study.

    PubMed

    Guzik, Grzegorz

    2015-01-01

    Spinal tumors are most commonly located in the thoracic and lumbar spine, less commonly in the cervical section of the spine. Diagnosis is usually late and surgery is not radical. Myeloma is one of the most frequent metastatic spinal tumors. Surgical treatment of osteolytic lesions in the spine involves posterior and anterior stabilization, full or partial tumorectomies as well as decompression of neural structures. Bone cement injection has been increasingly used in plastic surgery of vertebral bodies and is most frequently performed percutaneously in the thoracic and lumbar spine. Cervical vertebroplasty can be performed both percutaneously and after anterior exposure of the spine. The dens axis can also be approached transorally. The safest surgical technique seems to be the Southwick approach, which allows exposure of the spine at C2-Th2 and, if necessary, can be extended both proximally and distally. Cemented cervical vertebroplasty, especially dens axis vertebroplasty, shows good results, yet this technique has rarely been described in the literature. It has the advantage of early patient mobility and little limitation of motion of the spine. Cervical vertebroplasty can be successfully combined with other procedures utilizing the same surgical approach in a single-stage operation. Post-resection anterior stabilization of the cervical spine with plates and vertebral body prosthesis allows for good stability of the spine and makes it possible to restore the spinal axis and curvatures.

  17. Nonsurgical management of a dilacerated maxillary lateral incisor with type III dens invaginatus: a case report.

    PubMed

    Gound, Tom G; Maixner, David

    2004-06-01

    Type III dens invaginatus is a developmental anomaly characterized by an enamel-lined channel that originates on the coronal surface and passes apically through part or all of the root and exits into the periodontal ligament. In this case report, a 13-yr-old male had a Type III dens that exited at the midroot level of tooth #7. At that same level, the root dilacerated severely to the mesial, and a periradicular radiolucency was present on the distal. A 12-mm periodontal defect was present on tooth #6 and a sinus tract was present. All maxillary anterior teeth responded normally to pulp vitality testing, and no other abnormal probing depths were present. The channel opening in the crown was located, and the channel was negotiated, enlarged, and filled with calcium hydroxide. Thirteen weeks later, the probing was normal and the canal was obturated with gutta-percha and restored. Two- and 6-yr recalls showed complete healing of the bony defects and continued normal responses to vitality testing.

  18. Erythronium dens-canis L. (Liliaceae): an unusual case of change of leaf mottling.

    PubMed

    La Rocca, Nicoletta; Pupillo, Paolo; Puppi, Giovanna; Rascio, Nicoletta

    2014-01-01

    Erythronium dens-canis is an early-flowering understory lily of southern Europe with two leaves and a single flower, although a number of plants have only one leaf and do not flower. The leaves are mottled with silvery flecks and brown patches, that gradually vanish turning to a lively green color. The nature and function of this striking variegation pattern were investigated in differently colored leaf parts following the springtime color change. Tissue organization was examined by light and electron microscopy; photosynthetic pigments were analyzed by spectrophotometry and HPLC; chlorophyll fluorescence parameters were evaluated by MINI-PAM. The results showed that brown patches originated in vacuolar anthocyanins in the subepidermal cell layer while air spaces between the upper epidermis and underlying chlorenchyma resulted in silvery flecks. The two leaf areas did not differ in photosynthetic pigments, chloroplast organization and photosynthetic parameters (F(v)/F(m), NPQ, rETR). Greening of brown patches due to anthocyanin resorption was faster in non-flowering plants than in flowering ones, occurring only when young fruits were developing. Anthocyanin disappearance did not change the structural-functional features of photosynthetic tissues. As a whole the results suggest that the anthocyanin pigmentation of E. dens-canis leaves does not affect the photosynthetic light use and has no photoprotective function. It is proposed that the complex leaf color pattern may act as a camouflage to escape herbivores, while the reflective silvery spots may have a role in attracting pollinators of this early-flowering species.

  19. Management of Oehler's Type III Dens Invaginatus Using Cone Beam Computed Tomography

    PubMed Central

    Ranganathan, Jaya; Rangarajan Sundaresan, Mohan Kumar; Ramasamy, Srinivasan

    2016-01-01

    Dens Invaginatus is a dental malformation that poses diagnostic difficulties in the clinical context. This anomaly may increase the risk of pulp disease and can potentially complicate endodontic procedure due to the aberrant root canal anatomy. Compared to conventional radiographs, three-dimensional images obtained with Cone Beam Computed Tomography (CBCT) are invaluable in the diagnosis of the extent of this anomaly and in the appropriate treatment planning. Oehler's classification (1957) for Dens Invaginatus (DI) into three types depending on the depth of the invagination has been used for treatment planning. Of the three types Type III DI is characterized by infolding of the enamel into the tooth up to the root apex and is considered as the most severe variant of DI and hence the most challenging to treat endodontically, due to the morphological complexities. This report describes a case of Oehler's Type III DI in a necrotic permanent maxillary lateral incisor in which CBCT images played a key role in diagnosis and treatment planning. The case was managed successfully by a combination of nonsurgical and surgical endodontic therapy with orthograde and retrograde thermoplastic gutta percha obturation. PMID:27069697

  20. Characteristics of dens used by radiocollared San Joaquin kit fox, Vulpes macrotis mutica, Naval Petroleum Reserve No. 1, Kern County, California

    SciTech Connect

    Berry, W.H.; O'Farrell, T.P.; Kato, T.T.; McCue, P.M.

    1987-08-01

    A total of 946 dens used by radiocollared San Joaquin kit foxes, Vulpes macrotis mutica, were observed on Naval Petroleum Reserve No. 1 and surrounding lands in Kern County, California. Of these, 887 were typical subterranean dens located in 65 sections, and 59 were atypical dens in man-made structures located in 24 sections and in two pipe storage yards. Although the number of entrances to dens ranged between 1 and 17, most (90%) had six or fewer entrances and the average, which did not differ between developed and undeveloped habitats, was 3.4. Entrances were significantly higher than wide, and 53% had ramp-shaped dirt berms. Dens had an average slope angle of 16.1/sup 0/ and more were found on slopes than in flats. Fewer dens faced the northwest quadrant and more faced the southern quadrant than expected. Evidence of kit foxes (tracks, scats, or prey remains) was observed at 80% of the dens, but 11% were not associated with kit fox sign (matted vegetation or trails) even though they were occupied. Human disturbances, most frequently roads, were observed in the immediate vicinity of 78% of the dens. Most (93%) atypical dens were in metal pipes, three were in buried wooden culverts, and one was under a concrete slab. 27 refs., 7 figs., 10 tabs.

  1. Protective effect of Punica granatum peel and Vitis vinifera seeds on DEN-induced oxidative stress and hepatocellular damage in rats.

    PubMed

    Kumar, Ashok K; Vijayalakshmi, K

    2015-01-01

    This study was designed to find out the efficacy of ethanol extracts of Punica granatum peel and Vitis vinifera seeds on diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular damage in Wistar rats. Rats were divided into four groups. The first group served as normal control, and the second group received DEN at a dose of 200 mg/kg body weight by single intraperitoneal administration. The third one received DEN as in DEN-treated group and co-treated with 400 mg/kg P. granatum peel extract. The final group also received DEN and co-treated with 400 mg/kg V. vinifera seed extract. DEN administration to rats resulted in significantly elevated levels of serum SGPT, SGOT, ALP, and GGT which is indicative of hepatocellular damage. DEN-induced oxidative stress was confirmed by elevated levels of lipid peroxides and decreased activities of superoxide dismutase, catalase, and glutathione peroxidase in the serum and liver tissues. The status of non-enzymatic antioxidants like vitamin C, vitamin E, and reduced glutathione were also found to be decreased in serum and tissues of DEN-administered rats. Co-treatment with the P. granatum peel and V. vinifera seed extracts orally for 12 weeks significantly reversed the DEN-induced alterations in the serum and liver tissues.

  2. Recognition of the 3' splice site RNA by the U2AF heterodimer involves a dynamic population shift.

    PubMed

    Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R; Sattler, Michael; Lamb, Don C

    2016-11-15

    An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3' splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein-RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3' splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants.

  3. Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1

    PubMed Central

    Wu, J; Gustafsson, K L; Windahl, S H; Kim, S H; Katzenellenbogen, J A; Ohlsson, C; Lagerquist, M K

    2017-01-01

    Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-10) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-10 males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-10 mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis. PMID:28057769

  4. Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1.

    PubMed

    Farman, H H; Wu, J; Gustafsson, K L; Windahl, S H; Kim, S H; Katzenellenbogen, J A; Ohlsson, C; Lagerquist, M K

    2017-02-01

    Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-1(0)) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-1(0) males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-1(0) mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis.

  5. Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication.

    PubMed

    Suzuki, Youichi; Chin, Wei-Xin; Han, Qi'En; Ichiyama, Koji; Lee, Ching Hua; Eyo, Zhi Wen; Ebina, Hirotaka; Takahashi, Hirotaka; Takahashi, Chikako; Tan, Beng Hui; Hishiki, Takayuki; Ohba, Kenji; Matsuyama, Toshifumi; Koyanagi, Yoshio; Tan, Yee-Joo; Sawasaki, Tatsuya; Chu, Justin Jang Hann; Vasudevan, Subhash G; Sano, Kouichi; Yamamoto, Naoki

    2016-01-01

    Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells.

  6. Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication

    PubMed Central

    Ichiyama, Koji; Lee, Ching Hua; Eyo, Zhi Wen; Ebina, Hirotaka; Takahashi, Hirotaka; Takahashi, Chikako; Tan, Beng Hui; Hishiki, Takayuki; Ohba, Kenji; Matsuyama, Toshifumi; Koyanagi, Yoshio; Tan, Yee-Joo; Sawasaki, Tatsuya; Chu, Justin Jang Hann; Vasudevan, Subhash G.; Sano, Kouichi; Yamamoto, Naoki

    2016-01-01

    Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells. PMID:26735137

  7. Remote identification of potential polar bear maternal denning habitat in northern Alaska using airborne LiDAR

    NASA Astrophysics Data System (ADS)

    Jones, B. M.; Durner, G. M.; Stoker, J.; Shideler, R.; Perham, C.; Liston, G. E.

    2013-12-01

    Polar bear (Ursus maritimus) populations throughout the Arctic are being threatened by reductions in critical sea ice habitat. Throughout much of their range, polar bears give birth to their young in winter dens that are excavated in snowdrifts. New-born cubs, which are unable to survive exposure to Arctic winter weather, require 2-3 months of the relatively warm, stable, and undisturbed environment of the den for their growth. In the southern Beaufort Sea (BS), polar bears may den on the Alaskan Arctic Coastal Plain (ACP).The proportion of dens occurring on land has increased because of reductions in stable multi-year ice, increases in unconsolidated ice, and lengthening of the fall open-water period. Large portions of the ACP are currently being used for oil and gas activities and proposed projects will likely expand this footprint in the near future. Since petroleum exploration and development activities increase during winter there is the potential for human activities to disturb polar bears in maternal dens. Thus, maps showing the potential distribution of terrestrial denning habitat can help to mitigate negative interactions. Prior remote sensing efforts have consisted of manual interpretation of vertical aerial photography and automated classification of Interferometric Synthetic Aperture (IfSAR) derived digital terrain models (DTM) (5-m spatial resolution) focused on the identification of snowdrift forming landscape features. In this study, we assess the feasibility of airborne Light Detection and Ranging (LiDAR) data (2-m spatial resolution) for the automated classification of potential polar bear maternal denning habitat in a 1,400 km2 area on the central portion of the ACP. The study region spans the BS coast from the Prudhoe Bay oilfield in the west to near Point Thompson in the east and extends inland from 10 to 30 km. Approximately 800 km2 of the study area contains 19 known den locations, 51 field survey sites with information on bank height and

  8. The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors

    SciTech Connect

    Entzeroth, M.; Mayer, N. )

    1991-01-01

    The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-(2-(-(8-dipropylamino)methyl)-1-piperidinyl-ethyl-amino-carbonyl)-6H-pyrido (2,3-b) (1,4)benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of (3H)AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that (3H)AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations.

  9. [AF + BAF for treating effluent in the sewage plant of the resin and chemical industry park].

    PubMed

    Tu, Yong; Liu, Wei-Jing; Zhang, Yao-Hui; Xu, Jun; Tang, Min; Chen, Yong; Bai, Yong-Gang

    2014-06-01

    The anaerobic filter (AF) and biological aerated filter (BAF) were employed to treat the effluent in a sewage plant of the resin and chemical industry park. The ceramsite was used in BAF. In this study, the influent COD was 200-300 mg x L(-1) and the pilot model scale was 2-4 L x d(-1). According to the results, the AF-BAF treatment had a good effect on organic wastewater. When the AF HRT was 24 h and BAF was 12 h, the removal of COD reached 73.4%, and that of NH4(+)-N reached 93.8%. From gas chromatography-mass spectrometry (GC-MS) and three-dimensional fluorescence analysis, it was found that small organic molecules and microbial metabolites could be removed effectively. However, there was no obviously effect on the removal of saturated alkane and nitrogenous heterocyclic compounds. From the denature gradient gel electrophoresis (DGGE) spectra analysis, it was shown that there were more kinds of microorganism in the sludge of the AF than in the up-flow anaerobic sludge bed (UASB), which indicates that the AF-BAF system is more effective on treating effluent in a sewage plant of the resin and chemical industry park.

  10. A simple web-based tool to compare freshwater fish data collected using AFS standard methods

    USGS Publications Warehouse

    Bonar, Scott A.; Mercado-Silva, Norman; Rahr, Matt; Torrey, Yuta T.; Cate, Averill

    2016-01-01

    The American Fisheries Society (AFS) recently published Standard Methods for Sampling North American Freshwater Fishes. Enlisting the expertise of 284 scientists from 107 organizations throughout Canada, Mexico, and the United States, this text was developed to facilitate comparisons of fish data across regions or time. Here we describe a user-friendly web tool that automates among-sample comparisons in individual fish condition, population length-frequency distributions, and catch per unit effort (CPUE) data collected using AFS standard methods. Currently, the web tool (1) provides instantaneous summaries of almost 4,000 data sets of condition, length frequency, and CPUE of common freshwater fishes collected using standard gears in 43 states and provinces; (2) is easily appended with new standardized field data to update subsequent queries and summaries; (3) compares fish data from a particular water body with continent, ecoregion, and state data summaries; and (4) provides additional information about AFS standard fish sampling including benefits, ongoing validation studies, and opportunities to comment on specific methods. The web tool—programmed in a PHP-based Drupal framework—was supported by several AFS Sections, agencies, and universities and is freely available from the AFS website and fisheriesstandardsampling.org. With widespread use, the online tool could become an important resource for fisheries biologists.

  11. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    NASA Technical Reports Server (NTRS)

    Thakker, A. B.; Cowles, B. A.

    1983-01-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  12. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

  13. The Political Views of Students at the Universities of the Armed Forces in Comparison to Those of Students at Public Institutions (Die politischen Orientierungen der Studenten an den Universitaeten der Bundeswehr im Vergleich zu den Studenten an oeffentlichen Hochschulen)

    DTIC Science & Technology

    2001-12-01

    zu sein scheint" ( Noelle - Neumann , E. und Petersen, Th., S. 40).5 4 Gerade auch bei den rasant zunehmenden Aufgaben der Bundeswehr bei...Bonnemann A., Hoffmann-Broll U., 1999 Studentische Orientierungen zwischen akademischer und soldatischer Lebenswelt. Noelle - Neumann E., Petersen Th

  14. Diagnosis and Treatment of a Type III Dens Invagination Using Cone-Beam Computed Tomography

    PubMed Central

    Bahmani, Mohsen; Adl, Alireza; Javanmardi, Samane; Naghizadeh, Sina

    2016-01-01

    A 20-year-old man presented with the history of pain and swelling in the anterior maxillary segment. The periapical radiography was indicative of a dental anomaly in right maxillary lateral incisor. Due to the insufficient information from conventional radiography, cone-beam computed tomography (CBCT) was ordered. CBCT showed apical root resorption, large apical lucency and two separate canals with distinct apical foramen (Oehlers type III dens invagination). The CBCT image was used as a guide for dentine removal with an ultrasonic tip. Conventional root canal therapy was done using lateral compaction technique. One-and two-year follow-up radiographies revealed periapical repair and absence of symptoms. PMID:27790268

  15. Altered denA and anr gene expression in aminoglycoside adaptive resistance in Pseudomonas aeruginosa.

    PubMed

    Karlowsky, J A; Hoban, D J; Zelenitsky, S A; Zhanel, G G

    1997-09-01

    Adaptive resistance to aminoglycoside killing and cytoplasmic accumulation occurs in cultures of originally susceptible Pseudomonas aeruginosa following an initial incubation with aminoglycoside. Anaerobiosis has also been reported to reduce bacterial killing and limit cytoplasmic aminoglycoside accumulation. We hypothesized that a common mechanism may facilitate reduced bacterial killing and aminoglycoside accumulation in both cases. Northern blot analysis of P. aeruginosa adaptively resistant to gentamicin demonstrated increased mRNA levels of both denA (nitrite reductase), which facilitates terminal electron acceptance in the anaerobic respiratory pathway, and its regulatory protein, ANR, in the absence of promoter DNA sequence changes, when compared with controls. These observations suggested that P. aeruginosa may regulate the expression of genes in its anaerobic respiratory pathway in response to aminoglycosides and may explain, at least partially, P. aeruginosa adaptive resistance to aminoglycosides.

  16. [An alternative dorsal fusion technique after transoral dens resection in basilar impression with atlas assimilation].

    PubMed

    Kaden, B; Schramm, J; Koch, W; Solymosi, L

    1998-01-01

    Current therapy of basilar impression includes transoral dens resection. The essential disadvantage of this procedure is the instability of C1/C2 due to loss of the transverse ligament. We describe two patients in whom this instability was treated by modified screwing. Using MAGERL-screws between C0-C2 an interposition of an iliac graft between the occiput and the arc of C2 was made. Neurological symptoms improved in both patients postoperatively. In both cases stable fusion C0/C2 was achieved with an additional treatment with a HALO-fixateur for eight weeks. In our opinion the combined transoral/dorsal procedure is most suitable and efficient in treatment of basilar impressions. By this approach both, decompression of the myelon as well as stable fusion C0/C2, is achieved.

  17. Prenylation inhibitors stimulate both estrogen receptor α transcriptional activity through AF-1 and AF-2 and estrogen receptor β transcriptional activity

    PubMed Central

    Cestac, Philippe; Sarrabayrouse, Guillaume; Médale-Giamarchi, Claire; Rochaix, Philippe; Balaguer, Patrick; Favre, Gilles; Faye, Jean-Charles; Doisneau-Sixou, Sophie

    2005-01-01

    Introduction We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) α to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of a co-regulator complex. The present study investigates, in further detail, how prenylated proteins modulate the transcriptional activities mediated by ERα and by ERβ. Methods The ERE-β-globin-Luc-SV-Neo plasmid was either stably transfected into MCF-7 cells or HeLa cells (MELN cells and HELN cells, respectively) or transiently transfected into MCF-7 cells using polyethylenimine. Cells deprived of estradiol were analyzed for ERE-dependent luciferase activity 16 hours after estradiol stimulation and treatment with FTI-277 (a farnesyltransferase inhibitor) or with GGTI-298 (a geranylgeranyltransferase I inhibitor). In HELN cells, the effect of prenyltransferase inhibitors on luciferase activity was compared after transient transfection of plasmids coding either the full-length ERα, the full-length ERβ, the AF-1-deleted ERα or the AF-2-deleted ERα. The presence of ERα was then detected by immunocytochemistry in either the nuclei or the cytoplasms of MCF-7 cells. Finally, Clostridium botulinum C3 exoenzyme treatment was used to determine the involvement of Rho proteins in ERE-dependent luciferase activity. Results FTI-277 and GGTI-298 only stimulate ERE-dependent luciferase activity in stably transfected MCF-7 cells. They stimulate both ERα-mediated and ERβ-mediated ERE-dependent luciferase activity in HELN cells, in the presence of and in the absence of estradiol. The roles of both AF-1 and AF-2 are significant in this effect. Nuclear ERα is decreased in the presence of prenyltransferase inhibitors in MCF-7 cells, again in the presence of and in the absence of estradiol. By contrast, cytoplasmic ERα is mainly decreased after treatment with FTI

  18. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    PubMed Central

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  19. Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA

    PubMed Central

    Agrawal, Anant A.; McLaughlin, Krystle J.; Jenkins, Jermaine L.; Kielkopf, Clara L.

    2014-01-01

    Purine interruptions of polypyrimidine (Py) tract splice site signals contribute to human genetic diseases. The essential splicing factor U2AF65 normally recognizes a Py tract consensus sequence preceding the major class of 3′ splice sites. We found that neurofibromatosis- or retinitis pigmentosa-causing mutations in the 5′ regions of Py tracts severely reduce U2AF65 affinity. Conversely, we identified a preferred binding site of U2AF65 for purine substitutions in the 3′ regions of Py tracts. Based on a comparison of new U2AF65 structures bound to either A- or G-containing Py tracts with previously identified pyrimidine-containing structures, we expected to find that a D231V amino acid change in U2AF65 would specify U over other nucleotides. We found that the crystal structure of the U2AF65-D231V variant confirms favorable packing between the engineered valine and a target uracil base. The D231V amino acid change restores U2AF65 affinity for two mutated splice sites that cause human genetic diseases and successfully promotes splicing of a defective retinitis pigmentosa-causing transcript. We conclude that reduced U2AF65 binding is a molecular consequence of disease-relevant mutations, and that a structure-guided U2AF65 variant is capable of manipulating gene expression in eukaryotic cells. PMID:25422459

  20. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    PubMed

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.

  1. An Evaluation of the Impacts of AF-M315E Propulsion Systems for Varied Mission Applications

    NASA Technical Reports Server (NTRS)

    Deans, Matthew C.; Oleson, Steven R.; Fittje, James; Colozza, Anthony; Packard, Tom; Gyekenyesi, John; McLean, Christopher H.; Spores, Ronald A.

    2015-01-01

    The purpose of the AF-M315E COMPASS study is to identify near-term (3-5 years) and long term (5 years +) opportunities for infusion, specifically the thruster and associated component technologies being developed as part of the GPIM project. Develop design reference missions which show the advantages of the AF-M315E green propulsion system. Utilize a combination of past COMPASS designs and selected new designs to demonstrate AF-M315E advantages. Use the COMPASS process to show the puts and takes of using AF-M315E at the integrated system level.

  2. Acute non-ambulatory tetraparesis with absence of the dens in two large breed dogs: case reports with a radiographic study of relatives

    PubMed Central

    2013-01-01

    Background Non-ambulatory tetraparesis with an absence of the dens of C2 (axis) has not previously been reported in large breed dogs. An absence or hypoplasia of the dens has been reported in both small, medium and large breed dogs, but not in closely related animals. Methods Two young large-breed dogs (a German shepherd and a Standard poodle) both with an acute onset of non-ambulatory tetraparesis were subjected to physical, neurological and radiographic examinations. Both dogs were euthanased and submitted for postmortem examination within one week of onset of clinical signs. To investigate possible heritability of dens abnormalities, oblique radiographs of the cranial cervical vertebrae were taken of nine and eighteen dogs related to the German shepherd and the Standard poodle, respectively. Results Absence of the dens, atlantoaxial instability and extensive spinal cord injury was found in both case dogs. Radiographs revealed a normal dens in both parents and in the seven littermates of the German shepherd. An absence or hypoplasia of the dens was diagnosed in six relatives of the Standard poodle. Conclusions Atlantoaxial subluxation with cervical spinal cord injury should be considered as a differential diagnosis in non-ambulatory tetraparetic young large breed dogs. Absence of the dens and no history of external trauma increase the likelihood for this diagnosis. This study provides evidence to suggest that absence or hypoplasia of the dens is inherited in an autosomal way in Standard poodle dogs. PMID:23591104

  3. Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits

    PubMed Central

    Johnson, Barbara W.; Goodman, Christin H.; Jee, Youngmee; Featherstone, David A.

    2016-01-01

    Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JE Detect™ MAC-ELISA (JE Detect), a differential testing algorithm was developed in which samples tested by JE Detect with positive results were subsequently tested by the DEN Detect™ MAC-ELISA (DEN Detect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JE Detect and DEN Detect and were classified as JE− (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JE Detect and DEN Detect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF. PMID:26856911

  4. [Surgical treatment for third-grade fracture of the dens of the second cervical vertebra with transdental posterior subluxation].

    PubMed

    Dzukaev, D N; Dreval', O N; Sidorenko, V V; Siviakov, A A; Khoreva, N E

    2007-01-01

    The paper describes a case of successful treatment in a patient with third-grade fracture of the dens of the second cervical vertebra with transdental posterior subluxation. According to the treatment policy chosen, posterior upper cervical spine stabilization and anterior upper spinal cord decompression that was supplemented by anterior cervical spondylodesis were performed in the early period.

  5. Five root canals in peg lateral incisor with dens invaginatus: A case report with new nomenclature for the five canals

    PubMed Central

    Jaikailash, Shanmugam; Kavitha, Mahendran; Ranjani, Muthukrishnan Sudharshana; Saravanan, Balasubramaniam

    2014-01-01

    This case report describes endodontic treatment completed in a peg-shaped maxillary lateral incisor, with single root and five root canals of which, one is due to dens invaginatus. Cone beam computed tomogram scanning confirmed the unique morphology of the tooth. New nomenclature for the five canals is proposed. PMID:25125854

  6. Temperature controls seed germination and dormancy in the European woodland herbaceous perennial Erythronium dens-canis (Liliaceae).

    PubMed

    Mondoni, A; Rossi, G; Probert, R

    2012-05-01

    We examined the germination ecology and the temperature requirements for germination of Erythronium dens-canis, under both outdoor and laboratory conditions. E. dens-canis is a spring flowering woodland geophyte widely distributed across Europe. Germination phenology, including embryo development and radicle and cotyledon emergence, were investigated in a natural population growing in Northern Italy. Immediately after harvest, seeds of E. dens-canis were either sown on agar in the laboratory under simulated seasonal temperatures or placed in nylon mesh sachets and buried in the wild. Embryos, undifferentiated at the time of seed dispersal, grew during summer and autumn conditions in the laboratory and in the wild, culminating in radicle emergence in winter when temperatures fell to ≈ 5 °C. Emergence of cotyledons did not occur immediately after radicle emergence, but was delayed until the end of winter. Laboratory experiments showed that temperature is the main factor controlling dormancy and germination, with seeds becoming non-dormant only when given warmth, followed by cold stratification. Unlike seeds of E. dens-canis that germinate in winter, in other Erythronium species radicle emergence occurs in autumn, while in some it is delayed until seeds are transferred from winter to spring conditions. Our results suggest that there is genetic and environmental control of the expression of seed dormancy amongst Erythronium species, which is related to local climate.

  7. Distribution of dens used by radiocollared San Joaquin kit fox on Naval Petroleum Reserve No. 1, Kern County, California, 1980-1987

    SciTech Connect

    O'Farrell, T.P.; Tabor, S.P.; Kato, T.T.

    1987-09-01

    Locations of 945 dens used by radiocollared San Joaquin kit foxes (Vulpes macrotis mutica) on or adjacent to the US Department of Energy's Naval Petroleum Reserve No. 1 (NPR-1) in western Kern County, California between 1980-1987 were recorded on maps and stored within a computer-compatible data base. Most (516 of 887) typical subterranean dens of this endangered species were found in undeveloped portions of 65 sections, but most (41 of 58) atypical dens (dens in man-made structures) were found in developed portions of 26 sections. Program managers can plan construction, maintenance, and operational activities on NPR-1 in ways that avoid potential conflicts with the conservation of kit fox dens by using the section maps provided in this report or by accessing the computerized data base through the Endangered Species Contractor, EG and G Energy Measurements, Inc. 20 refs., 3 figs, 1 tab.

  8. 27. "SITE PLAN." Specifications No. OC15775, Drawing No. AF600915, sheet ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. "SITE PLAN." Specifications No. OC1-57-75, Drawing No. AF-60-09-15, sheet 1 of 96, D.O. Series No. AF 1394/20, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 5296 Rev. B, Date: 11/17/59. Site plan of 20,000-foot track, including construction phasing notes. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

  9. The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

    SciTech Connect

    Kim, Jeonghee; Chung, In Kwon

    2014-01-17

    Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure proper telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.

  10. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea

    PubMed Central

    dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  11. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification.

    PubMed

    Bueno, Clara; Montes, Rosa; Melen, Gustavo J; Ramos-Mejia, Verónica; Real, Pedro J; Ayllón, Verónica; Sanchez, Laura; Ligero, Gertrudis; Gutierrez-Aranda, Iván; Fernández, Agustín F; Fraga, Mario F; Moreno-Gimeno, Inmaculada; Burks, Deborah; Plaza-Calonge, María del Carmen; Rodríguez-Manzaneque, Juan C; Menendez, Pablo

    2012-06-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification.

  12. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification

    PubMed Central

    Bueno, Clara; Montes, Rosa; Melen, Gustavo J; Ramos-Mejia, Verónica; Real, Pedro J; Ayllón, Verónica; Sanchez, Laura; Ligero, Gertrudis; Gutierrez-Aranda, Iván; Fernández, Agustín F; Fraga, Mario F; Moreno-Gimeno, Inmaculada; Burks, Deborah; del Carmen Plaza-Calonge, María; Rodríguez-Manzaneque, Juan C; Menendez, Pablo

    2012-01-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification. PMID:22212479

  13. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2015-12-03

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1.

  14. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  15. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  16. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  17. Flow ozonolysis using a semipermeable Teflon AF-2400 membrane to effect gas-liquid contact.

    PubMed

    O'Brien, Matthew; Baxendale, Ian R; Ley, Steven V

    2010-04-02

    A flow-through chemistry apparatus has been developed which allows gases and liquids to contact via a semipermeable Teflon AF-2400 membrane. In this preliminary investigation, the concept was proven by application to the ozonolysis of a series of alkenes.

  18. Utilizing an Experiential Approach to Teacher Learning about AfL: A Consciousness Raising Opportunity

    ERIC Educational Resources Information Center

    Dixon, Helen; Hawe, Eleanor

    2016-01-01

    In this article we focus on how an experiential based approach to teacher learning about assessment for learning (AfL) provided opportunities for teachers to examine: their deep-seated beliefs about effective learning (and teaching); how these beliefs permeated their day-to-day actions and interactions with students, and the consequence of these…

  19. Fracture Mechanics Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, J. W.; Martinez, J.; McLean, C.

    2016-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant on orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent processing flaws will not cause failure during the design life of the tank. Material property inputs for this analysis require testing to determine the stress intensity factor for environment-assisted cracking (KEAC) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched, or SE(B), specimens representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to AF-M315E at 50 C for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor for environment-assisted cracking of the Ti 6Al-4V forged tank material was found to be at least 22 ksivin and at least 31 ksivin for the weld material when exposed to AF-M315E monopropellant.

  20. First report of an infant botulism case due to Clostridium botulinum type Af.

    PubMed

    de Jong, Laura I T; Fernández, Rafael A; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R; Dykes, Janet K; Lúquez, Carolina

    2015-02-01

    Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide.

  1. Genome Sequence of the Native Apiculate Wine Yeast Hanseniaspora vineae T02/19AF

    PubMed Central

    Giorello, Facundo M.; Berná, Luisa; Greif, Gonzalo; Camesasca, Laura; Salzman, Valentina; Medina, Karina; Robello, Carlos; Gaggero, Carina; Aguilar, Pablo S.

    2014-01-01

    The use of novel yeast strains for winemaking improves quality and provides variety including subtle characteristic differences in fine wines. Here we report the first genome of a yeast strain native to Uruguay, Hanseniaspora vineae T02/19AF, which has been shown to positively contribute to aroma and wine quality. PMID:24874663

  2. 28. Site Plan: AF Station P67, Fort Custer, Michigan, Plot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Site Plan: AF Station P-67, Fort Custer, Michigan, Plot Plan (to accompany FY 1956 project planning report), USACOE, 22 July 1954. - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  3. Mylar and Teflon-AF as cell culture substrates for studying endothelial cell adhesion.

    PubMed

    Anamelechi, Charles C; Truskey, George A; Reichert, W Monty

    2005-12-01

    The textured and opaque nature of Dacron and ePTFE has prevented the use of these fabrics in conventional cell culture techniques normally employed to optimize cell attachment and retention. This lack of optimization has led, in part, to the poor performance of endothelialization strategies for improving vascular graft patency. Here we show that thin, transparent films of Mylar and Teflon-AF are viable in vitro cell culture mimics of Dacron and ePTFE vascular graft materials, particularly for the study of protein mediated endothelial cell (EC) attachment, spreading and adhesion. Glass substrates were used as controls. X-ray photoelectron spectroscopy (XPS) and contact angle analysis showed that Mylar and Teflon-AF have surface chemistries that closely match Dacron and ePTFE. (125)I radiolabeling was used to quantify fibronectin (FN) adsorption, and FN and biotinylated-BSA "dual ligand" co-adsorption onto glass, Mylar and Teflon-AF substrates. Native human umbilical vein endothelial cells (HUVEC) and streptavidin-incubated biotinylated-HUVEC (SA-b-HUVEC) spreading was measured using phase contrast microscopy. Cell retention and adhesion was determined using phase contrast microscopy under laminar flow. All surfaces lacking protein pre-treatment, regardless of surface type, showed the lowest degree of cell spreading and retention. Dual ligand treated Mylar films showed significantly greater SA-b-HUVEC spreading up to 2 h, but were similar to HUVEC on FN treated Mylar at longer times; whereas SA-b-HUVEC spreading on dual ligand treated Teflon-AF was never significantly different from HUVEC on FN treated Teflon-AF at any time point. SA-b-HUVEC retention was significantly greater on dual ligand treated Mylar compared to HUVEC on FN treated Mylar over the entire range of shear stresses tested (3.54-28.3 dynes/cm(2)); whereas SA-b-HUVEC retention to dual ligand and HUVEC retention to FN treated Teflon-AF gave similar results at each shear stress, with only the mid

  4. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

  5. Low incidence of left atrial delayed enhancement with MRI in patients with AF: a single-centre experience

    PubMed Central

    Bois, John P; Glockner, James; Young, Phillip M; Foley, Thomas A; Sheldon, Seth; Newman, Darrell B; Lin, Grace; Packer, Douglas L; Brady, Peter A

    2017-01-01

    Background Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. One potential target for ablation is left atrial (LA) scar (LAS) regions that may be the substrate for re-entry within the atria, thereby sustaining AF. Identification of LAS through LA delayed gadolinium enhancement (LADE) with MRI has been proposed. Objectives We sought to evaluate LADE in patients referred for catheter ablation of AF. Methods Prospective analysis was conducted of consecutive patients who underwent pulmonary vein antrum isolation (PVAI) ablation for AF at a single institution. Patients underwent LADE with MRI to determine LAS regions before ablation. MRI data were analysed independently in accordance with prespecified institutional protocol by two staff cardiac radiologists to whom patient outcomes were masked, and reports of LADE were documented. Where no initial consensus occurred regarding delayed enhancement (DE), a third staff cardiac radiologist independently reviewed the case and had the deciding vote. Results Of the 149 consecutive patients (mean (SD) age, 59 (9) years), AF was persistent in 64 (43%) and paroxysmal in 85 (57%); 45 (30%) had prior ablation. Only five patients (3%) had identifiable DE in LA walls (persistent AF, n=1; paroxysmal AF, n=4). LADE was present in two (4%) of the 45 patients with previous left PVAI. The presence of LADE was not associated with a higher recurrence rate of AF. Conclusions In contrast to previous studies, the finding of DE within LA walls was uncommon and, when present, did not correlate with AF type or risk of AF recurrence. It therefore is of unclear clinical significance. PMID:28123766

  6. Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for DEN2-43 and New Guinea C virus strains of dengue 2 virus.

    PubMed

    Guo, Xiao-Xia; Zhu, Xiao-Juan; Li, Chun-Xiao; Dong, Yan-De; Zhang, Ying-Mei; Xing, Dan; Xue, Rui-De; Qin, Cheng-Feng; Zhao, Tong-Yan

    2013-12-01

    The vector competence of Aedes albopictus and Aedes aegypti with regard to DEN2-43 and New Guinea C (NGC) virus strains of Dengue 2 viruses was assessed and compared. The infection and dissemination rate and distribution of DEN2-43 antigens in orally infected Ae. albopictus was investigated using the reverse transcription polymerase chain reaction and an indirect immunofluorescence assay. To better understand the initial infection, dissemination and transmission of these viral strains in vector mosquitoes, Ae. albopoictus and Ae. aegypti were fed an artificial blood meal containing either the DEN2-43 or NGC strain. There was no significant difference in the infection and dissemination rates of DEN2-43 and NGC virus strains in Ae. albopictus, however, Ae. aegypti was more susceptible to infection by NGC than DEN2-43 vrius strain. Ae. albopictus mosquitoes infected with the NGC strain developed a higher percentage of midgut infections than those infected with the DEN2-43 strain (t=2.893, df=7, P=0.024). Approximately 26.7% of midgut samples were positive for the NGC antigen 5 days after infection, and 80% of mosquitoes had infected midgets after 15 days. The NGC antigen first became evident in mosquito salivary glands on Day 5, and 40% of mosquitoes had infected salivary by Day 9. In contrast, the DEN2-43 antigen first became evident in salivary glands on Day 7. The infection rate of NGC and DEN2-43 virus strains in salivary glands were similar. These results indicate that Ae. albopictus and Ae. aegypti are moderately competent vectors for the DEN2-43 virus, which could provide basic data for the epidemiology study of dengue fever in China.

  7. Equalization characteristics of an upflow sludge blanket-aerated biofilter (USB-AF) system.

    PubMed

    Jun, H B; Park, S M; Park, J K; Lee, S H

    2005-01-01

    Equalization characteristics of the upflow sludge blanket-aerated bio-filter (USB-AF) were investigated with the fluctuated raw domestic sewage. Recycle of nitrified effluent from AF to USB triggered the equalization characteristics of the sludge blanket on both soluble and particulate organic matter. Increment of EPS in sludge blanket by nitrate recycle was detected and removal of turbidity and particulates increased at higher recycle ratios by bio-flocculation. Increased TCOD removal in the USB was due to both denitrification of recycled nitrate and entrapment of the particulate organic matter in sludge blanket. Capture of both soluble and particulate organic matter increased sludge blanket layer in the USB, which improved the reactor performances and reduced the organic load on the subsequent AF. Overall TCOD and SS removal efficiencies were about 98% and 96%, respectively in the USB-AF system. Turbidity in the USB effluent was about 44, 20 and 5.5 NTU, at recycle ratios of 0, 100 and 200%, respectively. Particle counts in the range 2-4 microm in the USB effluent were higher than those in influent without nitrate recycle, while particle counts in the range of 0.5-15 microm in the USB effluent decreased 70% at recycle ratio of 200%. The major constituent of EPS extracted from anaerobic sludge was protein and total EPS increased from 109.1 to 165.7 mg/g-VSS with nitrate recycle of 100%. Removal efficiency and concentration of T-N in the UBS-AF effluent was over 70% and below 16 mg/L, respectively.

  8. Properties and transport behavior of perfluorotripentylamine (FC-70)-doped amorphous teflon AF 2400 films.

    PubMed

    Zhang, Hong; Hussam, Abul; Weber, Stephen G

    2010-12-22

    Teflon AF 2400 films are known to imbibe solvents, making films in the presence of solvents less fluorous than they might otherwise be. Herein, we demonstrate that doping films with perfluorotripentylamine (Fluorinert FC-70) maintains the fluorous nature of Teflon AF 2400 and improves transport selectivity for fluorine-containing organic compounds. Density measurements on the FC-70-doped films reveal that free volume decreases dramatically as the dopant concentration increases (0-12 wt %) and then increases to approach that of pure FC-70. Remarkably, films from 0 to 12 wt % FC-70 have the same w/v concentration of Teflon AF 2400, indicating that FC-70 fills the free volume of Teflon AF 2400. This is consistent with the observed increased storage modulus and significant decrease (compared to undoped films) of solute diffusion coefficients in the same range of FC-70 concentrations. In contrast, FC-70 at concentrations greater than 12 wt % dilutes Teflon AF 2400, leading to a decrease of storage modulus and dramatic increase in solute diffusion coefficients. Sorption of chloroform decreases from 11.8 g of chloroform/100 g of film (pure Teflon film) to 3.8 g of chloroform/100 g of film (27 wt % FC-70-doped Teflon film), less than the solubility of chloroform in pure FC-70 (4.06 g of chloroform/100 g of FC-70). Solute partition coefficients from chloroform to FC-70-doped films generally decrease with increased dopant concentration. However, within a series of toluenes and nitrobenzenes, selectivity for F-containing solutes over analogous H-containing solutes increases as dopant concentration increases if the substitution is on the aromatic ring but not if it is on the methyl group (toluene). Transport (partitioning × diffusion) rates, as they involve both thermodynamic and kinetic factors, are not simply related to composition.

  9. TYPE AF CERTIFICATE FOR TRANSPORTATION OF LOW ENRICHED URANIUM OXIDE (LEUO) FOR DISPOSAL

    SciTech Connect

    Opperman, E; Kenneth Yates, K

    2007-10-19

    Washington Savannah River Company (WSRC) operates the Savannah River Site (SRS) in Aiken, SC under contract with the U.S. Department of Energy (DOE). SRS had the need to ship 227 drums of low enriched uranium oxide (LEUO) to a disposal site. The LEUO had been packaged nearly 25 years ago in U.S. Department of Transportation (DOT) 17C 55-gallon drums and stored in a warehouse. Since the 235U enrichment was just above 1 percent by weight (wt%) the material did not qualify for the fissile material exceptions in 49 CFR 173.453, and therefore was categorized as 'fissile material' for shipping purposes. WSRC evaluated all existing Type AF packages and did not identify any feasible packaging. Applying for a new Type AF certificate of compliance was considered too costly for a one-time/one-way shipment for disposal. Down-blending the material with depleted uranium (to reduce enrichment below 1 wt% and enable shipment as low specific activity (LSA) radioactive material) was considered, but appropriate blending facilities do not exist at SRS. After reviewing all options, WSRC concluded that seeking a DOT Special Permit was the best option to enable shipment of the material for permanent disposal. WSRC submitted the Special Permit application to the DOT, and after one request-for-additional-information (RAI) the permit was considered acceptable. However, in an interesting development that resulted from the DOT Special Permit application process, it was determined that it was more appropriate for the DOE to issue a Type AF certificate [Ref. 1] for this shipping campaign. This paper will outline the DOT Special Permit application and Type AF considerations, and will discuss the issuance of the new DOE Type AF certificate of compliance.

  10. Dens evaginatus: review of the literature and report of several clinical cases.

    PubMed

    McCulloch, K J; Mills, C M; Greenfeld, R S; Coil, J M

    1998-02-01

    Dens evaginatus (DE) presents as an innocuous looking tubercle of enamel on the occlusal surface of a tooth, most commonly a bicuspid. Problems can arise when the tubercle is either worn, ground, or fractured off, resulting in pulpal exposure and possible loss of vitality of the tooth. Dentists who perform orthodontic treatment should be aware of this dental anomaly, which occurs in at least two per cent of the Asian and Native Indian populations. Bicuspid extraction cases should involve the extraction of the anomalous premolars rather than the normal ones. In addition, the dentist should be mindful of occlusal changes that may occur during treatment or occlusal equilibration, both of which can jeopardize the vitality of teeth with DE. Pulp capping or partial pulpotomy has been postulated to be one of the most reliable forms of vital tooth treatment when pulp exposure is encountered following the sterile removal of the tubercle. When pulp exposure is not encountered, preventive resin composite sealing of the dentin or class I amalgam cavity preparation seems to be the treatment of choice.

  11. Design und Analyse elektrisch kleiner Antennen für den Einsatz in UHF RFID Transpondern

    NASA Astrophysics Data System (ADS)

    Herschmann, R.; Camp, M.; Eul, H.

    2006-09-01

    RFID Systeme werden seit Anfang der neunziger Jahre mit stetig zunehmender Verbreitung im Bereich der automatischen Produktidentifikation, der Diebstahlsicherung (EAS, Electronic Article Surveillance) und für automatische Zutrittskontrollsysteme eingesetzt. Objekte werden hierzu mit einem Transponder ausgestattet, der aus einer Antenne und einem Chip auf einem Trägermaterial besteht. Von großem Interesse ist die Entwicklung und Optimierung von passiven Transpondern für den Einsatz in UHF RFID Systemen. Diese Transponder beziehen die Energie zum Betrieb des Chips aus dem elektromagnetischen Feld einer Schreib-Leseeinheit. Hierfür ist neben der Anpassung der Eingangsimpedanz der Antenne an die Chipimpedanz auch eine möglichst hohe Bandbreite der Antennen wünschenswert, um die Funktion des Transponders bei Schwankungen der Chipimpedanz und variablen Umgebungsparametern zu gewährleisten. Der aus Platzgründen notwendige Einsatz elektrisch kleiner Antennen bedingt eine möglichst optimale Ausnutzung der zur Verfügung stehenden Fläche auf dem Trägermaterial zur Aufnahme der Antenne. Die vorliegende Arbeit beschreibt ein Verfahren zur Analyse und Synthese neuartiger Antennendesigns auf der Basis parametrisierter meandrierter, spiralförmiger und logarithmisch periodischer Dipole.

  12. Recombinant soluble gp130 protein reduces DEN-induced primary hepatocellular carcinoma in mice

    PubMed Central

    Hong, Jing; Wang, Hang; Shen, Guoying; Lin, Da; Lin, Yanxue; Ye, Nanhui; Guo, Yashan; Li, Qiaoling; Ye, Nanhui; Deng, Chengjun; Meng, Chun

    2016-01-01

    IL-6 (interleukin 6) plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways. Soluble gp130 (sgp130) is known to be a natural inhibitor of the trans-signaling pathway. In the present study, our goal was to investigate whether recombinant sgp130 could suppress the initiation and progression of HCC in mouse models. Our results demonstrate that sgp130 induced an apoptosis of HepG2 cells and inhibited the clonogenicity of HepG2 in vitro. Moreover, the IL-6 trans-signaling pathway is significantly suppressed by sgp130 as reflected by the decrease in the level of STAT3 phosphorylation and other inflammatory factors both in vitro and in vivo. In the DEN-induced HCC mouse model, intravenous injection of sgp130 attenuated hepatic fibrosis at 16 weeks and reduced the initiation and progression of primary HCC at 36 weeks. Furthermore, our results also demonstrate that intravenous administration of sgp130 significantly suppressed the growth and metastasis of xenograft human HCC in NOD/SCID mice. PMID:27080032

  13. A comprehensive photometric study of dynamically evolved small van den Bergh-Hagen open clusters

    NASA Astrophysics Data System (ADS)

    Piatti, Andrés E.

    2016-12-01

    We present results from Johnson UBV, Kron-Cousins RI and Washington CT1T2 photometries for seven van den Bergh-Hagen (vdBH) open clusters, namely, vdBH 1, 10, 31, 72, 87, 92, and 118. The high-quality, multiband photometric data sets were used to trace the cluster stellar density radial profiles and to build colour-magnitude diagrams and colour-colour diagrams from which we estimated their structural parameters and fundamental astrophysical properties. The clusters in our sample cover a wide age range, from ˜60 Myr up to 2.8 Gyr, are of relatively small size (˜1-6 pc) and are placed at distances from the Sun which vary between 1.8 and 6.3 kpc, respectively. We also estimated lower limits for the cluster present-day masses as well as half-mass relaxation times (tr). The resulting values in combination with the structural parameter values suggest that the studied clusters are in advanced stages of their internal dynamical evolution (age/tr ˜ 20-320), possibly in the typical phase of those tidally filled with mass segregation in their core regions. Compared to open clusters in the solar neighbourhood, the seven vdBH clusters are within more massive (˜80-380 M⊙), with higher concentration parameter values (c ˜ 0.75-1.15) and dynamically evolved ones.

  14. Polar bear mother-offspring interactions in maternity dens in captivity.

    PubMed

    van Gessel, Chad

    2015-01-01

    Two female polar bears at Dierenrijk Zoo in the Netherlands were monitored at their maternity den one day before the birth of their cubs and three days postpartum. Each bear was monitored for 96 hr to document behaviour and vocalisations. The goal was to obtain insight into the differences between the mother that lost her litter and the other that successfully reared her cubs. Six groups of cub vocalisations were identified: Comfort, Discomfort, Distress, Nursing Attempts, Nursing, and No Vocalisation. Maternal vocalisations were split into three groups: Calm, Grooming, and Stress. Maternal behaviours were also split into three groups: Active, Rest, and Stress. The unsuccessful mother produced more stress vocalisations before and during the birth of her cub, whereas the successful mother appeared less stressed. Vocalisations indicate that the cub that died tried to nurse but was unsuccessful. The unsuccessful mother showed less stress as her cub got weaker and vocalised less. From this I suggest that maternal stress was a factor in cub mortality.

  15. A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

    PubMed Central

    Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

    2016-01-01

    A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

  16. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Accellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-09-01

    Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Li, Zhongyu CONTRACTING ORGANIZATION: Wake Forest...Gap Peripheral Nerve Injuries Using 5a. CONTRACT NUMBER Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5b. GRANT NUMBER...Major accomplishments this year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up

  17. An Observational, Prospective Survey Assessing the Control of Atrial Fibrillation in Asia Pacific: Rationale and Design of the RecordAF-AP Registry

    PubMed Central

    Amerena, John; Chen, Shih-Ann; Sriratanasathavorn, Charn; Cho, Jeong-Gwan; Dejia, Huang; Omar, Razali; Fat, Tse Hung; King, Anthony

    2011-01-01

    Background: The literature suggests that the prevalence of atrial fibrillation (AF) may be lower in Asian countries than in Western countries. Nevertheless, AF remains a significant public health problem in the region. The burden of AF, the experiences of previous trials and the lack of data on AF and its management in Asia Pacific highlight the need for a comprehensive prospective study of AF management. Methods: The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation Asia Pacific (RecordAF-AP) is a prospective, observational survey of the management of recently diagnosed AF patients with 1-year follow-up in 8 countries across Asia Pacific. Eligible patients presenting with AF, treated or not, will be included in the registry and data will be recorded prospectively during follow-up visits at 6 and 12 months. Results: RecordAF-AP will recruit more than 3000 patients. Study recruitment commenced in April 2009 and the final results anticipated at the end of 2011. Conclusions: RecordAF-AP will assess the real-life management of AF patients in Asia Pacific, including a comparison of clinical outcomes in rhythm versus rate control strategies, providing much needed insight into the costs, treatment choices and clinical outcomes of AF patients in this region. PMID:21344019

  18. Conservative management of dens evaginatus and attached supernumerary tooth/odontome in mandibular premolar with dual radiolucencies

    PubMed Central

    Shah, Naseem; Jadhav, Ganesh Ranganath; Mittal, Priya; Logani, Ajay

    2015-01-01

    Recently, an innovative, nonsurgical regenerative endodontic treatment protocol “SealBio” was introduced to manage mature nonvital permanent teeth with periapical lesions. This paper explains the management of an unusual case of dens evaginatus and an attached supernumerary tooth/an odontome associated with two distinct radiolucencies in a mandibular premolar with “SealBio” technique and discusses the various hypotheses on the pathogenesis of unusual malformation and associated pericervical cyst-like radiolucency in the involved tooth. PMID:26604586

  19. Regenerative Endodontic Treatment of an Infected Immature Dens Invaginatus with the Aid of Cone-Beam Computed Tomography

    PubMed Central

    Kaya-Büyükbayram, Işıl; Özalp, Şerife; Aydemir, Seda

    2014-01-01

    Dens invaginatus is a developmental anomaly that results in an enamel-lined cavity intruding into the crown or root before the mineralization phase. This report presents regenerative endodontic treatment of a necrotic immature tooth with Oehler's type III dens invaginatus of a nine-year-old female patient. A diagnosis of dens invaginatus (Oehler's type III) and a large periapical lesion was established with the aid of cone-beam computed tomography (CBCT). In the presented case contrary to the classic revascularization protocol, mechanical instrumentation was performed which apparently did not interfere with the regeneration process. After mechanical instrumentation of the invaginated canal by manual K-files, the invaginated canal space was disinfected by triple antibiotic paste followed by blood clot induction from the periapical tissues and the placement of mineral trioxide aggregate. At one-year follow-up, the tooth remained clinically asymptomatic. Radiographic examination revealed complete healing of the periapical lesion. At the 20-month follow-up, the radiographic examination also showed that the open apex was closed and the walls of the root canal were thickened. PMID:25530890

  20. Steppe lion remains imported by Ice Age spotted hyenas into the Late Pleistocene Perick Caves hyena den in northern Germany

    NASA Astrophysics Data System (ADS)

    Diedrich, Cajus G.

    2009-05-01

    Upper Pleistocene remains of the Ice Age steppe lion Panthera leo spelaea (Goldfuss, 1810) have been found in the Perick Caves, Sauerland Karst, NW Germany. Bones from many hyenas and their imported prey dating from the Lower to Middle Weichselian have also been recovered from the Perick Cave hyena den. These are commonly cracked or exhibit deep chew marks. The absence of lion cub bones, in contrast to hyena and cave bear cub remains in the Perick Caves, and other caves of northern Germany, excludes the possibility that P. leo spelaea used the cave for raising cubs. Only in the Wilhelms Cave was a single skeleton of a cub found in a hyena den. Evidence of the chewing, nibbling and cracking of lion bones and crania must have resulted from the importation and destruction of lion carcasses (4% of the prey fauna). Similar evidence was preserved at other hyena den caves and open air sites in Germany. The bone material from the Perick and other Central European caves points to antagonistic hyena and lion conflicts, similar to clashes of their modern African relatives.

  1. Identification and functional characterization of an afsR homolog regulatory gene from Streptomyces venezuelae ATCC 15439.

    PubMed

    Maharjan, Sushila; Oh, Tae-Jin; Lee, Hei Chan; Sohng, Jae Kyung

    2009-02-01

    Sequencing analysis of a 5-kb DNA fragment from Streptomyces venezuelae ATCC 15439 revealed the presence of one 3.1-kb open reading frame (ORF), designated afsRsv. The deduced product of afsR-sv (1,056 aa) was found to have high homology with the global regulatory protein AfsR. Homology-based analysis showed that afsR-sv represents a transcriptional activator belonging to the Streptomyces antibiotic regulatory protein (SARP) family that includes an Nterminal SARP domain containing a bacterial transcriptional activation domain (BTAD), an NB-ARC domain, and a Cterminal tetratricopeptide repeat domain. Gene expression analysis by reverse transcriptase PCR (RT-PCR) demonstrated the activation of transcription of genes belonging to pikromycin production, when afsR-sv was overexpressed in S. venezuelae. Heterologous expression of the afsR-sv in different Streptomyces strains resulted in increased production of the respective antibiotics, suggesting that afsR-sv is a positive regulator of antibiotics biosynthesis.

  2. Korrelationsstatistischer Vergleich zweier Schulleistungstests fur den Unterricht in Englisch an Hauptschulen (Comparison by Statistical Correlation of Two English Achievement Tests for Intermediate Schools)

    ERIC Educational Resources Information Center

    Koch, Holger; Scheibner-Herzig, Gudrun

    1971-01-01

    Expanded version of a lecture given at a meeting of the Teachers of Modern Languages in Colleges of Education (Tagung der Fachdidaktiker fur neuere Sprachen an den Padagogischen Hochschulen), October 1, 1970 in Luneburg, West Germany. (RS)

  3. [Co-infection by Chikungunya virus (CHIK-V) and dengue virus (DEN-V) during a recent outbreak in Cali, Colombia: Report of a fatal case].

    PubMed

    Rosso, Fernando; Pacheco, Robinson; Rodríguez, Sarita; Bautista, Diego

    2016-08-01

    The recent outbreaks of Chikungunya (CHIK-V) virus in endemic areas of dengue (DEN-V) could increase the risk of co-infection. CHIK infection has been considered not severe and with very unusual mortality, however DEN is associated with severe manifestations and increased mortality. Little is known about coinfection. It is possible that co-infection could generate severe cases. We present a case report of co-infection DEN-V -3 and CHIK-V in an elderly patient who developed acute renal failure, dengue shock syndrome (DSS), progresses to multiple organ failure and died. With the recent emergence of CHIK-V in Colombia, the possibility of co-infection with DEN-V should be suspected, especially in severe cases.

  4. Hot Isostatic Pressing/Heat Treatment of Cast Superalloy AF2-1DA, Radial Turbine Wheels.

    DTIC Science & Technology

    1980-06-01

    showing typical 19 shrinkage porosity Mag: 400X Etch: Electrolytic oxalic acid 10 Microstructure of HIPped AF2-1DA alloy 29 Mag: 400X Etch...Electrolytic oxalic acid 11 Microstructure of HIPped AF2-1DA alloy note 30 void formations form incipient melting after 2250OF hip Mag: 400X Etch: Electrolytic... oxalic acid V a.w LIST OF ILLUSTRATIONS (Continued) Figure Title Page 12 Microstructure of HIPped AF2-1DA showing effects 31 of solution heat

  5. Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

    PubMed Central

    Anastasio, Natascia; Ben-Omran, Tawfeg; Teebi, Ahmad; Ha, Kevin C.H.; Lalonde, Emilie; Ali, Rehab; Almureikhi, Mariam; Der Kaloustian, Vazken M.; Liu, Junhui; Rosenblatt, David S.; Majewski, Jacek; Jerome-Majewska, Loydie A.

    2010-01-01

    Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower lip. Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2.4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above. Sanger sequencing identified a missense change, c.773G>A (p.C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V443DfsX83), in two unrelated individuals. In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling. However, the function of SCARF2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes. PMID:20887961

  6. Mutations in SCARF2 are responsible for Van Den Ende-Gupta syndrome.

    PubMed

    Anastasio, Natascia; Ben-Omran, Tawfeg; Teebi, Ahmad; Ha, Kevin C H; Lalonde, Emilie; Ali, Rehab; Almureikhi, Mariam; Der Kaloustian, Vazken M; Liu, Junhui; Rosenblatt, David S; Majewski, Jacek; Jerome-Majewska, Loydie A

    2010-10-08

    Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower lip. Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2.4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above. Sanger sequencing identified a missense change, c.773G>A (p.C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V443DfsX83), in two unrelated individuals. In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling. However, the function of SCARF2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes.

  7. A Probabilistic Wake Vortex Lateral Transport Model Using Data from SFO and DEN

    NASA Technical Reports Server (NTRS)

    Mellman, George R.; Delisi, Donald P.

    2008-01-01

    In a previous report, we considered the behavior of the lateral position of vortices as a function of time after vortex formation for Out of Ground Effects (OGE) data for aircraft landing at San Francisco International Airport (SFO). We quantified the spread in lateral position as a function of time and examined how predictable lateral position is under a variety of assumptions. The combination of spread and predictability allowed us to derive probability distribution functions (PDFs) for lateral position given observed crosswind (CW) velocities. In this study, we examine the portability of these PDFs with respect to other landing sites. To this end, we consider OGE data obtained by the Federal Aviation Administration for landings at Denver International Airport (DEN) between 04/05/2006 and 06/03/2006. We consider vortices from both B733 (Boeing 737 models 200-500) and B757 (Boeing 757) aircraft. The data set contains 635 B733 landings and 506 B757 landings. The glide slope altitude for these measurements was 280 m, determined by the average initial vortex observation adjusted for a 3-second delay in the initial observation. The comparable SFO altitude was 158 m. We note that the principal mechanism for lateral transport in the OGE regime is advection by the ambient wind. This implies that a simple crosswind correction may be effective in explaining much of the variation in the lateral transport data. In this study, we again consider the use of ASOS data and average Lidar crosswind data over the vortex altitude range to predict vortex location as a function of time.

  8. ‘Neanderthal bone flutes’: simply products of Ice Age spotted hyena scavenging activities on cave bear cubs in European cave bear dens

    PubMed Central

    Diedrich, Cajus G.

    2015-01-01

    Punctured extinct cave bear femora were misidentified in southeastern Europe (Hungary/Slovenia) as ‘Palaeolithic bone flutes’ and the ‘oldest Neanderthal instruments’. These are not instruments, nor human made, but products of the most important cave bear scavengers of Europe, hyenas. Late Middle to Late Pleistocene (Mousterian to Gravettian) Ice Age spotted hyenas of Europe occupied mainly cave entrances as dens (communal/cub raising den types), but went deeper for scavenging into cave bear dens, or used in a few cases branches/diagonal shafts (i.e. prey storage den type). In most of those dens, about 20% of adult to 80% of bear cub remains have large carnivore damage. Hyenas left bones in repeating similar tooth mark and crush damage stages, demonstrating a butchering/bone cracking strategy. The femora of subadult cave bears are intermediate in damage patterns, compared to the adult ones, which were fully crushed to pieces. Hyenas produced round–oval puncture marks in cub femora only by the bone-crushing premolar teeth of both upper and lower jaw. The punctures/tooth impact marks are often present on both sides of the shaft of cave bear cub femora and are simply a result of non-breakage of the slightly calcified shaft compacta. All stages of femur puncturing to crushing are demonstrated herein, especially on a large cave bear population from a German cave bear den. PMID:26064624

  9. King Salmon, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-08-10

    1 .2 - i 121 1b 15 o -- 9 2.4 z 2 22 2 2 2fi 2 13 1ee (X) I me. O.. N.. o Nof " . Tom .eet W .. I T 0 F s 32P IN 67 P 3 FNP -93 P T...I w e Or ulb t...CLIMATOLOGY BRANCHT 2 AkETAHRSRVC/A PSYCHROMETRIC SUMMARY2 I ETE EVC /A 7 3260_ KING SALMON AFS AK 73-82 JAN STAT.Oft STATION NWAI villOAN *PAGE ? 1890...T,,.) .. ." " " , . - . . 1 i. . , ’. . ; : ; .-. A f;: ’ ,- ;. * GLr rA E LMTL~ T AC? PSYCHROMETRIC SUMMARYT2 FAH- EVC /A 7 3267 XING SALM4ON AFS

  10. Nanopatterning of mobile lipid monolayers on electron-beam-sculpted Teflon AF surfaces.

    PubMed

    Shaali, Mehrnaz; Lara-Avila, Samuel; Dommersnes, Paul; Ainla, Alar; Kubatkin, Sergey; Jesorka, Aldo

    2015-02-24

    Direct electron-beam lithography is used to fabricate nanostructured Teflon AF surfaces, which are utilized to pattern surface-supported monolayer phospholipid films with 50 nm lateral feature size. In comparison with unexposed Teflon AF coatings, e-beam-irradiated areas show reduced surface tension and surface potential. For phospholipid monolayer spreading experiments, these areas can be designed to function as barriers that enclose unexposed areas of nanometer dimensions and confine the lipid film within. We show that the effectiveness of the barrier is defined by pattern geometry and radiation dose. This surface preparation technique represents an efficient, yet simple, nanopatterning strategy supporting studies of lipid monolayer behavior in ultraconfined spaces. The generated structures are useful for imaging studies of biomimetic membranes and other specialized surface applications requiring spatially controlled formation of self-assembled, molecularly thin films on optically transparent patterned polymer surfaces with very low autofluorescence.

  11. Unciflavones A-F, six novel flavonoids from Selaginella uncinata (Desv.) Spring.

    PubMed

    Zou, Hui; Xu, Kang-Ping; Li, Fu-Shuang; Zou, Zhen-Xing; Liu, Rui; Liu, Rui-Huan; Li, Jing; Tan, Lei-Hong; Tan, Gui-Shan

    2014-12-01

    Six new flavonoids, unciflavones A-F (1-6), have been isolated from medicinal plant Selaginella uncinata (Desv.) Spring. Their structures were established on the basis of extensive NMR analysis including 1D NMR ((1)H, (13)C and DEPT) and 2D NMR (COSY, HSQC, HMBC) experiments as well as HRESIMS analysis. All compounds possess exceptional structural features with an aryl substituent at the C-8 position, which are uncommonly encountered in natural resources and firstly reported in genus Selaginella.

  12. Installation Restoration Program. Technical Support Document for Record of Decision, Cape Newenham, AFS.

    DTIC Science & Technology

    1988-01-18

    observed at any site. o No threatened or endangered species are known to use or exist on the installation. 0 No economically or commercially important ...which have the potential to exist in the environment at Cape Newenham AFS include many substances commonly used at LRRS installations. The most important ...Once adsorbed, PCBs 2-20 73/5/21 do not readily desorb. The implication is that PCBs will not leach or diffuse in soils; transport into the hydrosphere

  13. Oxytrofalcatins A-F, N-benzoylindole analogues from the roots of Oxytropis falcata (Leguminosae).

    PubMed

    Chen, Wen-Hao; Wu, Quan-Xiang; Wang, Rui; Shi, Yan-Ping

    2010-06-01

    Indole alkaloids, oxytrofalcatins A-F (1-6), together with five other known alkaloids (7-11), were isolated from the roots of Oxytropis falcata. Their structures were elucidated by comprehensive spectroscopic analyses, including using 1D and 2D NMR spectroscopy and mass spectrometry. This is the first report of N-benzoylindoles from a natural source. Compounds 1-6 lacked significant cytotoxicity against SGC-7901 and HL-60 tumor cell lines.

  14. Evolution of iron speciation during hydration of C{sub 4}AF

    SciTech Connect

    Rose, J.; El Mrabet, S.; Masion, A.; Moulin, I.; Briois, V.; Olivi, L.; Bottero, J.-Y.

    2006-07-01

    It is now well accepted and demonstrated that calcium silicate, calcium aluminate and calcium sulfo aluminate (ettringite, AFm) phases exhibit a good capability to fix metals and metalloids. Unfortunately the role of minor phases and especially calcium-ferric aluminate phase, shorthand C{sub 4}AF is not well defined. In other systems like in soils or sediments iron phases play a key role in the fixation of pollutant. In cement sorption isotherms, indicated that various metals can be retained by the C{sub 4}AF hydrated products. Therefore the capabilities of those phase to retain heavy metal should not be neglected. Previous investigations have shown that the minerals formed during the hydration of C{sub 4}AF are similar to those formed from C3A (pure tri-calcium aluminate) under comparable conditions. Nevertheless no investigation was conducted at the molecular level and there is still a controversy whether Fe substitutes for Al in the hydrated minerals in whole or in part, or if it forms FeOOH clusters scattered throughout the matrix. In this context we have conducted XAS experiments using synchrotron radiation. It was found that the hydration of C{sub 4}AF forms C{sub 3}AH{sub 6} (hydrogarnet) in which Fe randomly substitutes for Al as well as an amorphous FeOOH phase. Intermediate products like AFm (i.e., an ill organized lamellar phase) are also formed but rapidly evolve to C{sub 3}AH{sub 6}; iron does not seem to be incorporated in the AFm structure.

  15. AF-TRUST, Air Force Team for Research in Ubiquitous Secure Technology

    DTIC Science & Technology

    2010-07-26

    Live Streaming Systems. PhD. June 2008 • Jeffrey Hartline. Incremental Optimization, PhD, January 2008 AF-TRUST Final Performance Report...Against Intrusion in a Live Streaming Multicast System. Maya Haridasan, Robbert van Renesse. In Proceedings of the 6th IEEE International Conference...Walker White. In Proceedings of SIGMOD 2007 2008 Enforcing Fairness in a Live - Streaming System. Maya Haridasan, Ingrid Jansch-Porto, Kenneth Birman

  16. Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.

    PubMed

    Valerio, Daria G; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J; Huang, Chun-Hao; Lujambio, Amaia; Zheng, YuJun George; Zuber, Johannes; Pandita, Tej K; Lowe, Scott W; Armstrong, Scott A

    2017-02-15

    Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9-driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. Cancer Res; 77(7); 1-10. ©2017 AACR.

  17. Updated Reference Genome Sequence and Annotation of Mycobacterium bovis AF2122/97

    PubMed Central

    Farrell, Damien; Stuber, Tod P.; Schubert, Olga T.; Aebersold, Ruedi; Robbe-Austerman, Suelee

    2017-01-01

    ABSTRACT We report here an update to the reference genome sequence of the bovine tuberculosis bacillus Mycobacterium bovis AF2122/97, generated using an integrative multiomics approach. The update includes 42 new coding sequences (CDSs), 14 modified annotations, 26 single-nucleotide polymorphism (SNP) corrections, and disclosure that the RD900 locus, previously described as absent from the genome, is in fact present. PMID:28385856

  18. Air Traffic Control Radar Specialty AFS 303X1. Volume II.

    DTIC Science & Technology

    1981-05-01

    Surveillance Radars, and AN/ MPN -14H Mobile RAPCONs. Typical tasks performed by these incumbents when maintaining these radar systems include: perform PMIs on...document forms (AF Form 264) issue job control numbers maintain status boards, graphs, or charts maintain equipment status reports document equipment...related matters determine work priorities plan work assignments maintain training records, charts , or graphs These incumbents are the most senior of all

  19. ROCKET AF adds more concerns about Digoxin safety in patients with atrial fibrillation.

    PubMed

    ElMaghawry, Mohamed

    2015-01-01

    In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.(1) The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).(2) However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation. A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.(3) The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF.

  20. Fracture Growth Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, Jeffrey W.; Martinez, Jonathan; McLean, Christopher

    2015-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant in orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent flaws will not cause failure during the design life. Material property inputs for this analysis require testing to determine the stress intensity factor for environmentally-assisted cracking (K (sub EAC)) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched specimens SE(B) representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to the monopropellant at 50 degrees Centigrade for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor of the Ti 6Al-4V forged tank material when exposed to AF-M315E monopropellant was found to be at least 22.0 kilopounds per square inch. The stress intensity factor of the weld material was at least 31.3 kilopounds per square inch.

  1. [Improvement of natamycin production in an industrial strain by heterologous expression of the afsRS(cla) global regulatory genes].

    PubMed

    Tao, Zhengsheng; Wang, Yemin; Zheng, Hualiang; Tao, Meifeng

    2015-05-01

    The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.

  2. Meeting in Florida: Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

    EPA Science Inventory

    The study of nanomaterials in environmental systems requires robust and specific analytical methods. Analytical methods which discriminate based on particle size and molecular composition are not widely available. Asymmetric Flow Field-Flow Fractionation (AF4) is a separation...

  3. Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

    PubMed

    Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H

    2016-02-12

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

  4. UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

    SciTech Connect

    Stepanyuk, Galina A.; Serrano, Pedro; Peralta, Eigen; Farr, Carol L.; Axelrod, Herbert L.; Geralt, Michael; Das, Debanu; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Deacon, Ashley M.; Lesley, Scott A.; Elsliger, Marc-André; Godzik, Adam; Wilson, Ian A.; Wüthrich, Kurt; Salomon, Daniel R.; Williamson, James R.

    2016-03-24

    RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co-activator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein–protein interactions through a short tryptophan-containing peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39–U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemical shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35–U2AF65 and RBM39–SF3b155, the RBM39-UHM–U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM–ULM binding interface, providing a rationale for the known specificity of UHM–ULM interactions. This study therefore establishes a structural basis for specific UHM–ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.

  5. Microstructural basis for the effect of chromium on the strength and toughness of AF1410-based high performance steels

    NASA Astrophysics Data System (ADS)

    Ayer, Raghavan; Machmeier, P. M.

    1996-09-01

    The variation in strength and Charpy impact toughness as a function of tempering temperature in the range of 200 ‡C to 650 ‡C was investigated in AF 1410 and AF 1410 + 1 pct Cr steels produced in a laboratory-scale, and a commercially produced AerMet 100 steel. The tensile test results showed that AF 1410 + 1 pct Cr had lower strength compared to AF 1410, while AerMet 100 had the highest strength of the three steels examined. Transmission electron microscopy (TEM) studies demonstrated that the strength variations among the steels can be attributed to differences in the matrix/carbide coherency strain and the volume fraction of the strengthening M2C carbides. The toughness values of the three steels were comparable when tempered up to 424 ‡C. Tempering at and above 454 ‡C resulted in a relative enhancement of toughness in AF 1410 + 1 pct Cr steel compared to AF 1410. This toughening was attributed to the destabilization of cementite at lath and prior austenite boundaries and the formation of reverted austenite.

  6. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-02-27

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata.

  7. Structural Basis for Polypyrimidine Tract Recognition by the Essential Pre-mRNA Splicing Factor U2AF65

    SciTech Connect

    Sickmier,E.; Frato, K.; Shen, H.; Paranawithana, S.; Green, M.; Kielkopf, C.

    2006-01-01

    The essential pre-mRNA splicing factor, U2AF{sup 65}, guides the early stages of splice site choice by recognizing a polypyrimidine (Py)-tract consensus sequence near the 3'-splice site. Since Py-tracts are relatively poorly conserved in higher eukaryotes, U2AF{sup 65} is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py-tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF{sup 65} RNA binding domain bound to a Py-tract composed of seven uridines has been determined at 2.5Angstroms resolution. Specific hydrogen bonds between U2AF{sup 65} and the uracil bases provide an explanation for polyuridine recognition. Flexible sidechains and bound water molecules form the majority of the base contacts, and potentially could rearrange when the U2AF{sup 65} structure adapts to different Py-tract sequences. The energetic importance of conserved residues for Py-tract binding is established by analysis of site-directed mutant U2AF{sup 65} proteins using surface plasmon resonance.

  8. [Biomechanics of AF new 3-d pedical screw system and treatment of 31 patients with unstable thoracolumbar fracture].

    PubMed

    Zou, D; Hai, Y; Ma, H

    1995-04-01

    For anatomic reduction of the spinal frectures, the 3 dimensional multiple correction forces were needed. Several pedical screw systems were designed for reducion and fixation of the spinal fractures as the AO universal joint system and the RF angle screw system. Because of the contradiction of the universal joint and the fixed angle, a new generation of RF was designed and named AF (atlas fixator) system. This is a new concept of 3-D reduction, without complex structure as universal joint, but has truly 3-D adjustment that allowed to reduce the intra-canal compromise. It also provided rigid fixation to maintain the reduction. Comparison with CD, AO, Steffee, and RF, the AF was truly 3-D reduction in XTZ axis. It provided strong symmetric transmitter orthotic force to correct the deformity. 31 patients with unstable thoracolumbar fractures were treated with the new AF system. 17 had partial (15) or complete (2) neurologic deficits. The AF system provided accurate angle to restore the normal thoracic-lumbar lordosis and to maintain it. All patients had a anatomic reduction by AF system. The spinal canal area increased over 33% by CT scan (P < 0.01). All cases were followed up over 8 months. No one deteriorated neurologically after AF fixation.

  9. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  10. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

    PubMed Central

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G

    1993-01-01

    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 1. Figure 1. Figure 1. Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. PMID:8143597

  11. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

    PubMed

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G

    1993-12-01

    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Responsiveness of AF6, a new, short, validated, atrial fibrillation-specific questionnaire—symptomatic benefit of direct current cardioversion

    PubMed Central

    Härdén, Marie; Nyström, Britta; Bengtson, Ann; Medin, Jennie; Frison, Lars

    2010-01-01

    Objectives To measure the effects on symptoms of electrical cardioversion (DC) in patients with atrial fibrillation (AF) by means of a new, short, validated, AF-specific questionnaire, the AF6. Methods One hundred eleven patients (67 ± 12 years, 89 men) were screened before and 12 ± 3 days after DC using AF6, covering ‘breathing difficulties at rest’, ‘breathing difficulties on exertion’, ‘limitations in day-to-day life due to atrial fibrillation’, ‘feeling of discomfort due to atrial fibrillation’, ‘tiredness due to atrial fibrillation’, and ‘worry/anxiety due to atrial fibrillation’. A single global score was calculated. The Toronto AF Symptoms and Severity Check List (AFSS) and the generic SF-36 were also administered. Patients in sinus rhythm at 12 ± 3 days (n = 56) were defined as responders and patients in AF (n = 55) as non-responders. Results The mean single global score decreased in all patients (18 ± 12.4 to 13 ± 11.6, p < 0.0001) and in responders (22 ± 14 vs. 12 ± 12, p < 0.01) but not in non-responders (14 ± 9 vs. 14 ± 11, N.S). The AFSS frequency scores decreased from 14.5 ± 7.7 to 9.5 ± 7.8 in responders, p = 0.001, but not in non-responders. There was a strong correlation between changes in the AF6 and the SF-36 regarding four of the six items. Effect sizes of AF6 ranged from 0 to 0.52 in all patients, in responders from 0.10 to 0.85 and in non-responders from −0.23 to 0.34, the highest figures consistently referring to ‘tiredness due to atrial fibrillation’. Conclusions The symptom scores measured by AF6 decreased significantly, especially in responders. AF6 demonstrated adequate responsiveness to change, and effect sizes were mostly moderate, in responders moderate to high. PMID:20461545

  13. Differential modulation of plant immune responses by diverse members of the Pseudomonas savastanoi pv. savastanoi HopAF type III effector family.

    PubMed

    Castañeda-Ojeda, M Pilar; López-Solanilla, Emilia; Ramos, Cayo

    2016-04-26

    The Pseudomonas savastanoi pv. savastanoi NCPPB 3335 type III secretion system (T3SS) effector repertoire includes 33 candidates, seven of which translocate into host cells and interfere with plant defences. The present study was performed to investigate the co-existence of both plasmid- and chromosomal-encoded members of the HopAF effector family, HopAF1-1 and HopAF1-2, respectively, in the genome of NCPPB 3335. Here, we show that the HopAF1 paralogues are widely distributed in the Pseudomonas syringae complex, where HopAF1-1 is most similar to the homologues encoded by other P. syringae pathovars infecting woody hosts that belong to phylogroups 1 and 3. We show that the expression of both HopAF1-1 and HopAF-2 is transcriptionally dependent on HrpL and demonstrate their delivery into Nicotiana tabacum leaves. Although the heterologous delivery of either HopAF1-1 or HopAF1-2 significantly suppressed the production of defence-associated reactive oxygen species levels, only HopAF1-2 reduced the levels of callose deposition. Moreover, the expression of HopAF1-2 by functionally effectorless P. syringae pv. tomato DC3000D28E completely inhibited the hypersensitive response in tobacco and significantly increased the competitiveness of the strain in Nicotiana benthamiana. Despite their functional differences, subcellular localization studies reveal that green fluorescent protein (GFP) fusions to either HopAF1-1 or HopAF1-2 are targeted to the plasma membrane when they are expressed in plant cells, a process that is completely dependent on the integrity of their N-myristoylation motif. Our results further support the notion that highly similar T3SS effectors might differentially interact with diverse plant targets, even when they co-localize in the same cell compartment.

  14. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s disease

    PubMed Central

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A.; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M.; Medeiros, Rodrigo

    2015-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g., AF102B, AF267B, and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (phopho-ERK1/2, phospho-CREB). AF710B (1–30 µg/kg, po) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its anti-amnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice AF710B (10 µg/kg, ip/daily/2 months) – i) mitigated cognitive impairments in Morris water maze; ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1, M1 muscarinic (orthosteric, allosteric or bi-topic) or σ1/muscarinic agonists. These results highlight AF710B as a potential treatment for AD (e.g., improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies. PMID:26606130

  15. Geothermal Project Den Haag - 3-D models for temperature prediction and reservoir characterization

    NASA Astrophysics Data System (ADS)

    Mottaghy, D.; Pechnig, R.; Willemsen, G.; Simmelink, H. J.; Vandeweijer, V.

    2009-04-01

    In the framework of the "Den Haag Zuidwest" geothermal district heating system a deep geothermal installation is projected. The target horizon of the planned doublet is the "Delft sandstone" which has been extensively explored for oil- and gas reservoirs in the last century. In the target area, this upper Jurassic sandstone layer is found at a depth of about 2300 m with an average thickness of about 50 m. The study presented here focuses on the prediction of reservoir temperatures and production behavior which is crucial for planning a deep geothermal installation. In the first phase, the main objective was to find out whether there is a significant influence of the 3-dimensional structures of anticlines and synclines on the temperature field, which could cause formation temperatures deviating from the predicted extrapolated temperature data from oil and gas exploration wells. To this end a regional model was set up as a basis for steady state numerical simulations. Since representative input parameters are decisive for reliable model results, all available information was compiled: a) the subsurface geometry, depth and thickness of the stratigraphic layers known from seismic data sets 2) borehole geophysical data and c) geological and petrographical information from exploration wells. In addition 50 cuttings samples were taken from two selected key wells in order to provide direct information on thermal properties of the underlying strata. Thermal conductivity and rock matrix density were measured in the laboratory. These data were combined with a petrophysical log analysis (Gamma Ray, Sonic, Density and Resistivity), which resulted in continuous profiles of porosity, effective thermal conductivity and radiogenetic heat production. These profiles allowed to asses in detail the variability of the petrophysical properties with depth and to check for lateral changes between the wells. All this data entered the numerical simulations which were performed by a 3-D

  16. Monitoring of individual human exposure to aflatoxins (AF) and N-nitrosamines (NNO) by immunoassays

    SciTech Connect

    Wild, C.P.; Umbenhauer, D.; Chapot, B.; Montesano, R.

    1986-01-01

    Highly sensitive immunoassays have been used to quantitate aflatoxins (AF) and N-nitrosamines (NNO) in human body fluids and tissues, respectively. This approach was taken in order to quantitate environmental exposure to these agents at an individual level to facilitate the investigation of their role in the etiology of human cancer. In order to analyse AF in human urine, an immunopurification step has been developed by using AF-specific antibody bound to AH-Sepharose 4B gel in a small (4-ml gel volume) affinity column prior to enzyme-linked immunosorbent assay (ELISA). The ELISA can be used to quantitate aflatoxin B1 (AFB1) over the range 0.01 ng/ml to 10 ng/ml and the assay system has been validated by using human urine samples spiked with AFB1 over this concentration range. In addition, 29 urine samples from the Philippines have been analyzed and found to contain a range of levels from zero to 4.25 ng/ml AFB1 equivalent with a mean of 0.875 ng/ml. This compared with a mean of 0.066 ng/ml AFB1 equivalent in samples from France. Radioimmunoassay of O6-methyldeoxyguanosine (O6-medG) has been performed on human esophageal and cardiac stomach mucosal DNA from tissue samples obtained during surgery in Linxian County, People's Republic of China, an area of high risk for both esophageal and stomach cancer. Using the methodology described and having 1 mg of hydrolyzed DNA allows the detection of approximately 25 fmol O6medG per mg DNA.

  17. An Immature Type II Dens Invaginatus in a Mandibular Lateral Incisor with Talon's Cusp: A Clinical Dilemma to Confront

    PubMed Central

    Singal, Deepa; Giri, K. Y.; Keerthi, S. Sruthi

    2014-01-01

    Dens invaginatus (DI) is a malformation of teeth probably resulting from an infolding of the dental papilla during tooth development. DI is classified as type I, II, and III by Oehlers depending on the severity of malformation. The maxillary lateral incisor is the most commonly affected tooth. Structural defects do exist in the depth of the invagination pits, and as a consequence, the early development of caries and the subsequent necrosis of the dental pulp, as well as abscess and cyst formation are clinical implications associated with DI. Occasionally, we can see more than one developmental anomaly occurring in a single tooth. In such cases it becomes important to identify the anomalies and initiate a proper treatment plan for good prognosis. In this paper, an unusual case of DI which clinically presented as a huge talons cusp affecting a mandibular lateral incisor tooth is described. This case report illustrates grinding of the talons cusp followed by nonsurgical endodontic management of dens invaginatus type II with an immature apex and periapical lesions, in which Mineral Trioxide Aggregate (MTA) shows a complete periapical healing with bone formation at the site of the lesions. PMID:24660071

  18. Involvenflavones A-F, six new flavonoids with 3'-aryl substituent from Selaginella involven.

    PubMed

    Long, Hong-Ping; Zou, Hui; Li, Fu-Shuang; Li, Jing; Luo, Ping; Zou, Zhen-Xing; Hu, Chang-Ping; Xu, Kang-Ping; Tan, Gui-Shan

    2015-09-01

    Six new flavonoids, involvenflavones A-F (1-6), were isolated from Selaginella involven. Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3'-aryl substituent. This is the first report of the apigenin derivatives with 3'-aryl substituent from nature resources. These compounds also exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro.

  19. Fulda AAF, Germany. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1972-02-08

    SPEED (FROM HOURLY OBSERVATIONS) 355 Fi,&DA GERMiN ~IY 4AF b-~-Z______ STATON STATION MAN9 ICA.$ O.N ALL EATnE., 3" ,-.5 cuss NOUAS (L s 1 SPEEDN MEAN...30,1 33,1 3346 33,3 33 O 33, 34.7 1600 0 30,4 319,2 33,3 33,3 337. 239, 11000 1 4, 2 7,2 279 213 29,9 30.1 3,4 33.1 33.4 33,3 36 3,6 ’,>_20oo2. Zola

  20. Candenatenins A-F, phenolic compounds from the heartwood of Dalbergia candenatensis.

    PubMed

    Cheenpracha, Sarot; Karalai, Chatchanok; Ponglimanont, Chanita; Kanjana-Opas, Akkharawit

    2009-08-01

    Chemical investigation of the CH2Cl2 extract of the heartwood of Dalbergia candenatensis affored six new phenolic compounds, designated candenatenins A-F (1-6), as well as four known compounds, (2R,3R)-3,5-dihydroxy-7-methoxyflavanone (7), 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (8), nutiducol (9), and sophoraflavanone A (10). The structures of the new compounds were determined by 1D- and 2D-NMR spectroscopic studies as well as by MS analysis. The cytotoxic activities of the isolated compounds are also reported.

  1. Dover AFB Delaware. Revised Uniform Summary of Surface Weather Observations. Parts A-F

    DTIC Science & Technology

    1974-08-07

    SNOW X OF SMOKE DUST X OF OSS TOTALMONTH T. STORMS AD/OR RAIN &/fOR AND/OR HAIL IObs WITH FOG AND/ORt BOWIG AND/ORt WITH ORST NO. OF( ST )DRIZZLE DRIZZLE...OBSERVATIONS) 13707 DUVEF AF8 DELAWARE 4 Ago4 f!,SL 55 AR STATION STATION RA50 01055 MONTH ALL WEATHER ALL CLASS NOVAS ( ST .) ( CONDITION SPE MEAN (NT...DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 1.3707 )0VEIc AFB 0ELAwAIRE 43-46251-72 JAN4 ALL WEATHEV, 0600-0800 Cuss x05o5 ILL ST .) SIPEED i MEAN (KNTS

  2. A novel clinical multimodal multiphoton tomograph for AF, SHG, CARS imaging, and FLIM

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; König, Karsten

    2014-02-01

    We report on a flexible nonlinear medical tomograph with multiple miniaturized detectors for simultaneous acquisition of two-photon autofluorescence (AF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) images. The simultaneous visualization of the distribution of endogenous fluorophores NAD(P)H, melanin and elastin, SHG-active collagen and as well as non-fluorescent lipids within human skin in vivo is possible. Furthermore, fluorescence lifetime images (FLIM) can be generated using time-correlated single photon counting.

  3. miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.

    PubMed

    Kotani, Ai; Ha, Daon; Hsieh, James; Rao, Prakash K; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2009-11-05

    MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

  4. Acceleration of Regeneration of Large Gap-Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-10-01

    amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Thomas L. Smith, PhD CONTRACTING ORGANIZATION: Wake Forest University Health Sciences...Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5a. CONTRACT NUMBER W81XWH-13-1-0309 5b. GRANT NUMBER OR120157 5c...year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up to 72 hours after seeding. The

  5. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF'.

    PubMed

    Kirchhof, Paulus; Bax, Jeroen; Blomstrom-Lundquist, Carina; Calkins, Hugh; Camm, A John; Cappato, Ricardo; Cosio, Francisco; Crijns, Harry; Diener, Hans-Christian; Goette, Andreas; Israel, Carsten W; Kuck, Karl-Heinz; Lip, Gregory Y H; Nattel, Stanley; Page, Richard L; Ravens, Ursula; Schotten, Ulrich; Steinbeck, Gerhard; Vardas, Panos; Waldo, Albert; Wegscheider, Karl; Willems, Stephan; Breithardt, Günter

    2009-12-01

    Atrial fibrillation (AF) causes important mortality and morbidity on a population-level. So far, we do not have the means to prevent AF or AF-related complications adequately. Therefore, over 70 experts on atrial fibrillation convened for the 2nd AFNET/EHRA consensus conference to suggest directions for research to improve management of AF patients (Appendix 1). The group defined three main areas in need for research in AF: 1. better understanding of the mechanisms of AF; 2. Improving rhythm control monitoring and management; and 3. comprehensive cardiovascular risk management in AF patients. The group put forward the hypothesis that successful therapy of AF and its associated complications will require comprehensive therapy. This applies e.g. to the "old" debate of "rate versus rhythm control", since rhythm control is generally added to underlying (continued) rate control therapy, but also to the emerging debate of "antiarrhythmic drugs versus catheter ablation", of which both may be needed in most patients to maintain sinus rhythm, but also to therapy of conditions that predispose to AF and contribute to cardiovascular complications such as stroke, cognitive decline, heart failure, and acute coronary syndromes. We call for research initiatives aiming at a better understanding of the different causes of AF and its complications, and at development and validation of mechanism-based therapies. The future of AF therapy may require a combination of management of underlying and concomitant conditions, early and comprehensive rhythm control therapy, adequate control of ventricular rate and cardiac function, and continuous therapy to prevent AF-associated complications (e.g. antithrombotic therapy). The reasons for these suggestions are detailed in this paper.

  6. The splicing factor U2AF65 is functionally conserved in the thermotolerant deep-sea worm Alvinella pompejana.

    PubMed

    Henscheid, Kristy L; Shin, David S; Cary, S Craig; Berglund, J Andrew

    2005-03-10

    Due to their inherent stability, thermophilic bacteria and archaea serve as important resources for biochemical and biophysical analyses of many biological processes. Unfortunately, scientists characterizing eukaryote-specific processes, such as nuclear pre-mRNA splicing, are unable to take advantage of these sources of thermostable proteins. To identify and provide a source of thermostable eukaryotic proteins, we are characterizing splicing factors in the thermotolerant deep-sea vent polychaete, Alvinella pompejana. This worm, also known as the Pompeii worm, is found in the extreme environment of deep-sea hydrothermal vents, and is one of the most thermotolerant eukaryotic organisms known. We report on detailed analyses of U2AF65, the large subunit of the U2 small nuclear ribonucleoprotein auxiliary factor, an essential splicing factor important for intron definition and alternative splicing. The cloning and characterization of Pompeii U2AF65 show it is highly similar to human U2AF65 in sequence and function and is more thermostable than the human protein when bound to RNA in vitro. Notably, Pompeii U2AF65 can restore splicing in a human extract depleted of human U2AF. We also determine that the general splicing mechanisms and signal sequences are conserved in the Pompeii worm, an annelid which has previously been uncharacterized in terms of splicing factors and signals.

  7. Role of phosphorylated histone H3 serine 10 in DEN-induced deregulation of Pol III genes and cell proliferation and transformation

    PubMed Central

    Zhong, Shuping

    2013-01-01

    The products of Pol III genes (RNA polymerase III-dependent genes), such as tRNAs and 5S rRNA, are elevated in both transformed and tumor cells suggesting that they play a crucial role in tumorigenesis. An increase in Brf1 (TFIIIB-related factor 1), a subunit of TFIIIB, augments Pol III gene transcription and is sufficient for cell transformation and tumor formation. We have demonstrated that enhancement of Brf1 and Pol III gene expression is associated with the occurrences of hepatocellular carcinoma (HCC) in mice. This suggests that Brf1 may be a key molecule during HCC development. Diethylnitrosamine (DEN), a chemical carcinogen, has been used to induce HCC in rodents. To determine the role of Brf1 and the epigenetic-regulating events in cell proliferation and transformation, hepatocytes were treated with DEN. The results indicate that DEN increases proliferation and transformation of AML-12 cells. DEN enhanced Brf1 expression and tRNALeu and 5S rRNA transcription, as well as H3S10ph (phosphorylation of histone H3 serine 10). Interestingly, DEN-induced Pol III gene transcription and H3S10ph in tumor cells of liver are significantly higher than in non-tumor cells. Inhibition of H3S10ph by H3S10A attenuates the induction of Brf1 and Pol III genes. Further analysis indicates that H3S10ph occupies the promoters of Brf1 and Pol III genes to modulate their expression. Blocking H3S10ph represses cell proliferation and transformation. These results demonstrate that DEN induces H3S10ph, which mediate Brf1 expression, including but not limited Brf1-dependent genes, to upregulate Pol III gene transcription, resulting in an increase in cell proliferation and transformation. PMID:23774401

  8. Substrate specificity and gene expression of two Penicillium chrysogenum α-L-arabinofuranosidases (AFQ1 and AFS1) belonging to glycoside hydrolase families 51 and 54.

    PubMed

    Sakamoto, Tatsuji; Inui, Misako; Yasui, Kana; Hosokawa, Sachiko; Ihara, Hideshi

    2013-02-01

    We previously isolated two α-L-arabinofuranosidases (ABFs), termed AFQ1 and AFS1, from the culture filtrate of Penicillium chrysogenum 31B. afq1 and afs1 complementary DNAs encoding AFQ1 and AFS1 were isolated by in vitro cloning. The deduced amino acid sequences of AFQ1 and AFS1 are highly similar to those of Penicillium purpurogenum ABF 2 and ABF 1, respectively, which belong to glycoside hydrolase (GH) families 51 and 54, respectively. Pfam analysis revealed an "Alpha-L-AF_C" domain in AFQ1 and "ArabFuran-catal" and "AbfB" domains in AFS1. Semi-quantitative RT-PCR analysis indicated that the afq1 gene was constitutively expressed in P. chrysogenum 31B at a low level, although the expression was slightly induced with arabinose, arabinitol, arabinan, and arabinoxylan. In contrast, expression of the afs1 gene was strongly expressed by the above four carbohydrates and less strongly induced by galactan. Recombinant enzymes (rAFQ1 and rAFS1) expressed in Escherichia coli were active against both p-nitrophenyl α-L-arabinofuranoside and polysaccharides with different specificities. (1)H-NMR analysis revealed that rAFS1 degraded arabinofuranosyl side chains that were both singly and doubly linked to the backbones of arabinoxylan and L-arabinan. On the other hand, rAFQ1 preferentially released arabinose linked to C-3 of single-substituted xylose or arabinose residues in the two polysaccharides.

  9. Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS domain on either the large or small Drosophila subunit is dispensable in vivo

    PubMed Central

    Rudner, David Z.; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The pre-mRNA splicing factor U2AF (U2 snRNP auxiliary factor) has an essential role in 3′ splice site selection. U2AF binds the intron pyrimidine tract between the branchpoint and the 3′ splice site and recruits U2 snRNP to the branch site at an early step in spliceosome assembly. Human U2AF is a heterodimer composed of large (hU2AF65) and small (hU2AF35) subunits. Both subunits contain a domain enriched in arginine–serine dipeptide repeats termed an RS domain. The two U2AF RS domains have been assigned essential and independent roles in spliceosome assembly in vitro—the hU2AF65 RS domain is required to target U2 snRNP to the branch site and the hU2AF35 RS domain is necessary for protein–protein interactions with constitutive and alternative splicing factors. We have investigated the functional requirements for the RS domains on the Drosophila U2AF homolog in vivo. In sharp contrast to its essential role in U2 snRNP recruitment in vitro, the RS domain on the Drosophila large subunit homolog (dU2AF50) was completely dispensable in vivo. Prompted by this unexpected result, we analyzed the RS domain on the Drosophila small subunit homolog (dU2AF38). Despite its requirement for enhancer-dependent splicing activity in vitro, the dU2AF38 RS domain was also inessential in vivo. Finally, we have tested whether the Drosophila U2AF heterodimer requires any RS domain. Flies mutant for both the small and large subunits could not be rescued by dU2AF50ΔRS and dU2AF38ΔRS transgenes. Therefore, in contrast to the separate roles assigned to the U2AF RS domains in vitro, our genetic data suggest that they may have redundant functions in vivo. PMID:9531538

  10. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection.

    PubMed

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-07-17

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes' status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors' detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability.

  11. Smyd2 is a Myc-regulated gene critical for MLL-AF9 induced leukemogenesis

    PubMed Central

    Bagislar, Sevgi; Sabò, Arianna; Kress, Theresia R.; Doni, Mirko; Nicoli, Paola; Campaner, Stefano; Amati, Bruno

    2016-01-01

    The Smyd2 protein (Set- and Mynd domain containing protein 2) is a methyl-transferase that can modify both histones and cytoplasmic proteins. Smyd2 is over-expressed in several cancer types and was shown to be limiting for tumor development in the pancreas. However, genetic evidence for a role of Smyd2 in other cancers or in mouse development was missing to date. Using germ line-deleted mouse strains, we now show that Smyd2 and the related protein Smyd3 are dispensable for normal development. Ablation of Smyd2 did not affect hematopoiesis, but retarded the development of leukemia promoted by MLL-AF9, a fusion oncogene associated with acute myeloid leukemia (AML) in humans. Smyd2-deleted leukemic cells showed a competitive disadvantage relative to wild-type cells, either in vitro or in vivo. The Smyd2 gene was directly activated by the oncogenic transcription factor Myc in either MLL9-AF9-induced leukemias, Myc-induced lymphomas, or fibroblasts. However, unlike leukemias, the development of lymphomas was not dependent upon Smyd2. Our data indicate that Smyd2 has a critical role downstream of Myc in AML. PMID:27655694

  12. Loss of Dnmt3b accelerates MLL-AF9 leukemia progression.

    PubMed

    Zheng, Y; Zhang, H; Wang, Y; Li, X; Lu, P; Dong, F; Pang, Y; Ma, S; Cheng, H; Hao, S; Tang, F; Yuan, W; Zhang, X; Cheng, T

    2016-12-01

    Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. Abnormal DNA methylation is involved in the initiation and progression of AML. The de novo methyltransferases Dnmt3a and Dnmt3b are responsible for the generation of genomic methylation patterns. While DNMT3A is frequently mutated in hematological malignancies, DNMT3B is rarely mutated. Although it has been previously reported that Dnmt3b functions as a tumor suppressor in a mouse model of Myc-induced lymphomagenesis, its function in AML is yet to be determined. In this study, we demonstrated that deletion of Dnmt3b accelerated the progression of MLL-AF9 leukemia by increasing stemness and enhancing cell cycle progression. Gene profiling analysis revealed upregulation of the oncogenic gene set and downregulation of the cell differentiation gene set. Furthermore, loss of Dnmt3b was able to synergize with Dnmt3a deficiency in leukemia development. Taken together, these results demonstrate that Dnmt3b plays a tumor suppressive role in MLL-AF9 AML progression, thereby providing new insights into the roles of DNA methylation in leukemia development.

  13. Intracardiac impedance response during acute AF internal cardioversion using novel rectilinear and capacitor-discharge waveforms.

    PubMed

    Rababah, A S; Walsh, S J; Manoharan, G; Walsh, P R; Escalona, O J

    2016-07-01

    Intracardiac impedance (ICI) is a major determinant of success during internal cardioversion of atrial fibrillation (AF). However, there have been few studies that have examined the dynamic behaviour of atrial impedance during internal cardioversion in relation to clinical outcome. In this study, voltage and current waveforms captured during internal cardioversion of acute AF in ovine models using novel radiofrequency (RF) generated low-tilt rectilinear and conventional capacitor-discharge based shock waveforms were retrospectively analysed using a digital signal processing algorithm to investigate the dynamic behaviour of atrial impedance during cardioversion. The algorithm was specifically designed to facilitate the simultaneous analysis of multiple impedance parameters, including: mean intracardiac impedance (Z M), intracardiac impedance variance (ICIV) and impedance amplitude spectrum area (IAMSA) for each cardioversion event. A significant reduction in ICI was observed when comparing two successive shocks of increasing energy where cardioversion outcome was successful. In addition, ICIV and IAMSA variables were found to inversely correlate to the magnitude of energy delivered; with a stronger correlation found to the former parameter. In conclusion, ICIV and IAMSA have been evidenced as two key dynamic intracardiac impedance variables that may prove useful in better understanding of the cardioversion process and that could potentially act as prognostic markers with respect to clinical outcome.

  14. Multiple-image-depth modeling for hotspot and AF printing detections

    NASA Astrophysics Data System (ADS)

    Tang, Y. P.; Chou, C. S.; Huang, W. C.; Liu, R. G.; Gau, T. S.

    2012-03-01

    Typical OPC models focus on predicting wafer contour or CD; therefore, the modeling approach emphasizes careful determination of feature and edge locations in the photo-resist (PR) as well as the exposure threshold, so that the 'cut' model image matches the wafer SEM contours or cut-line CDs most closely. This is an exquisite approach with regard to the contour-based OPC, for the model is calibrated directly from wafer CDs. However, for other applications such as hotspot detection or assist feature (AF) printing prediction that might occur at the top or the bottom of the PR, the typical OPC model approach may not be accurate enough. Usually, these kinds of phenomenon can only be properly described by rigorous simulation, which is very time-consuming and hence not suitable for OPC. In this paper, the approach of building the OPC model with multiple image depths will be discussed. This approach references the images at the bottom and/or the top of the PR. This way, the behavior of the images which are not shown at the normal image depth can be predicted more accurately without distorting the optical model. This compromised OPC modeling approach is beneficial for runtime reduction compared to the rigorous simulation, and for better accuracy compared to conventional model. The applications for AF printing and hotspot predictions using the multiple image depth approach will be demonstrated.

  15. Advanced Compatibility Characterization Of AF-M315E With Spacecraft Propulsion System Materials Project

    NASA Technical Reports Server (NTRS)

    McClure, Mark B.; Greene, Benjamin

    2014-01-01

    All spacecraft require propulsion systems for thrust and maneuvering. Propulsion systems can be chemical, nuclear, electrical, cold gas or combinations thereof. Chemical propulsion has proven to be the most reliable technology since the deployment of launch vehicles. Performance, storability, and handling are three important aspects of liquid chemical propulsion. Bipropellant systems require a fuel and an oxidizer for propulsion, but monopropellants only require a fuel and a catalyst for propulsion and are therefore simpler and lighter. Hydrazine is the state of the art propellant for monopropellant systems, but has drawbacks because it is highly hazardous to human health, which requires extensive care in handling, complex ground ops due to safety and environmental considerations, and lengthy turnaround times for reusable spacecraft. All users of hydrazine monopropellant must contend with these issues and their associated costs. The development of a new monopropellant, intended to replace hydrazine, has been in progress for years. This project will apply advanced techniques to characterize the engineering properties of materials used in AF-M315E propulsion systems after propellant exposure. AF-M315E monopropellant has been selected HQ's Green Propellant Infusion Mission (GPIM) to replace toxic hydrazine for improved performance and reduce safety and health issues that will shorten reusable spacecraft turn-around time. In addition, this project will fundamentally strengthen JSC's core competency to evaluate, use and infuse liquid propellant systems.

  16. Development of FDR-AF (Frictional Drag Reduction Anti-Fouling) Marine Coating

    NASA Astrophysics Data System (ADS)

    Lee, Inwon; Park, Hyun; Chun, Ho Hwan; GCRC-SOP Team

    2013-11-01

    In this study, a novel skin-friction reducing marine paint has been developed by mixing fine powder of PEO(PolyEthyleneOxide) with SPC (Self-Polishing Copolymer) AF (Anti-Fouling) paint. The PEO is well known as one of drag reducing agent to exhibit Toms effect, the attenuation of turbulent flows by long chain polymer molecules in the near wall region. The frictional drag reduction has been implemented by injecting such polymer solutions to liquid flows. However, the injection holes have been a significant obstacle to marine application. The present PEO-containing marine paint is proposed as an alternative to realize Toms effect without any hole on the ship surface. The erosion mechanism of SPC paint resin and the subsequent dissolution of PEO enable the controlled release of PEO solution from the coating. Various tests such as towing tank drag measurement of flat plate and turbulence measurement in circulating water tunnel demonstrated over 10% frictional drag reduction compared with conventional AF paint. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP(No. 2011-0030013).

  17. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection

    PubMed Central

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes’ status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors’ detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  18. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    SciTech Connect

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd; Schaefer, Tobias

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  19. A novel poly(3-hydroxybutyrate)-degrading Streptoverticillium kashmirense AF1 isolated from soil and purification of PHB-depolymerase.

    PubMed

    Shah, A A; Hasan, Fariha; Hameed, A; Ahmed, Safia

    2008-12-01

    A new bacterial strain, capable of degrading poly(3-hydroxybutyrate) (PHB) was isolated from soil. This organism, identified as Streptoverticillium kashmirense AF1, secreted PHB depolymerases both on solid as well as in liquid mineral salt medium containing poly(3-hydroxybutyrate) as sole carbon source. The optimum production of PHB depolymerase was observed at pH 8 and 7, at 45 degrees C, 1% substrate concentration and in the presence of lactose as an additional carbon source. The extracellular PHB depolymerase was purified by gel permeation chromatography using Sephadex G-75. The Streptoverticillium kashmirense AF1 produced two types of PHB depolymerases having molecular weights of about 37 and 45 kDa as determined by SDS-PAGE. The difference in dry cell mass and amount of CO2 evolved in the test and control calculated gravimetrically through Sturm test indicated the degradative capabilities of Streptoverticillium kashmirense AF1.

  20. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  1. A Comparison of Atrial Fibrillation Monitoring Strategies After Cryptogenic Stroke (from the Cryptogenic Stroke and Underlying AF Trial).

    PubMed

    Choe, William C; Passman, Rod S; Brachmann, Johannes; Morillo, Carlos A; Sanna, Tommaso; Bernstein, Richard A; Di Lazzaro, Vincenzo; Diener, Hans-Christoph; Rymer, Marilyn M; Beckers, Frank; Koehler, Jodi; Ziegler, Paul D

    2015-09-15

    Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke.

  2. USAF Bioenvironmental Noise Data Handbook. Volume 166. AF/M32T-1 Tester, Pressurized Cabin Leakage, Aircraft,

    DTIC Science & Technology

    1982-07-01

    OPERATOR NOISE MEASUREMENTS AF/M32T-1 Tester, Pressurized Cabin Leakage, Aircraft Tyndall AFB, 19 June 1980 NSN 4920-00- 347 -9455, Field * J108...a- a a o a af .4a a0 1 P ,? o4 o1 01 ao aD Nh s 1AA a ~ ~ a naaa .4 a aif CL O va I am wEj r .M PO -ODM.a)a D aa CDo NW)N 4 % ma a a. . 9 w ao N~ a I

  3. Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

    PubMed

    Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

    2016-01-01

    A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts.

  4. Magnetic nanoparticles are highly toxic to chloroquine-resistant Plasmodium falciparum, dengue virus (DEN-2), and their mosquito vectors.

    PubMed

    Murugan, Kadarkarai; Wei, Jiang; Alsalhi, Mohamad Saleh; Nicoletti, Marcello; Paulpandi, Manickam; Samidoss, Christina Mary; Dinesh, Devakumar; Chandramohan, Balamurugan; Paneerselvam, Chellasamy; Subramaniam, Jayapal; Vadivalagan, Chithravel; Wei, Hui; Amuthavalli, Pandiyan; Jaganathan, Anitha; Devanesan, Sandhanasamy; Higuchi, Akon; Kumar, Suresh; Aziz, Al Thabiani; Nataraj, Devaraj; Vaseeharan, Baskaralingam; Canale, Angelo; Benelli, Giovanni

    2017-02-01

    A main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. We investigated the toxicity of magnetic nanoparticles (MNP) produced by Magnetospirillum gryphiswaldense (strain MSR-1) on chloroquine-resistant (CQ-r) and sensitive (CQ-s) Plasmodium falciparum, dengue virus (DEN-2), and two of their main vectors, Anopheles stephensi and Aedes aegypti, respectively. MNP were studied by Fourier-transform infrared spectroscopy and transmission electron microscopy. They were toxic to larvae and pupae of An. stephensi, LC50 ranged from 2.563 ppm (1st instar larva) to 6.430 ppm (pupa), and Ae. aegypti, LC50 ranged from 3.231 ppm (1st instar larva) to 7.545 ppm (pupa). MNP IC50 on P. falciparum were 83.32 μg ml(-1) (CQ-s) and 87.47 μg ml(-1) (CQ-r). However, the in vivo efficacy of MNP on Plasmodium berghei was low if compared to CQ-based treatments. Moderate cytotoxicity was detected on Vero cells post-treatment with MNP doses lower than 4 μg ml(-1). MNP evaluated at 2-8 μg ml(-1) inhibited DEN-2 replication inhibiting the expression of the envelope (E) protein. In conclusion, our findings represent the first report about the use of MNP in medical and veterinary entomology, proposing them as suitable materials to develop reliable tools to combat mosquito-borne diseases.

  5. Fluorous Polymeric Membranes for Ionophore-Based Ion-Selective Potentiometry: How Inert is Teflon AF?

    PubMed Central

    Lai, Chun-Ze; Koseoglu, Secil S.; Lugert, Elizabeth C.; Boswell, Paul G.; Rábai, József; Lodge, Timothy P.; Bühlmann, Philippe

    2011-01-01

    Fluorous media are the least polar and polarizable condensed phases known. Their use as membrane materials considerably increases the selectivity and robustness of ion-selective electrodes (ISEs). In this research, a fluorous amorphous perfluoropolymer was used for the first time as a matrix for an ISE membrane. Electrodes for pH measurements with membranes composed of poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole]-co-poly(tetrafluoroethylene) (87% dioxole monomer content; known as Teflon AF2400) as polymer matrix, a linear perfluorooligoether as plasticizer, sodium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate providing for ionic sites, and bis[(perfluorooctyl)propyl]-2,2,2-trifluoroethylamine as H+-ionophore were investigated. All electrodes had excellent potentiometric selectivities, showed Nernstian responses to H+ over a wide pH range, exhibited enhanced mechanical stability and maintained their selectivity over at least four weeks. For membranes of low ionophore concentration, the polymer affected the sensor selectivity noticeably at polymer concentrations exceeding 15%. Also, the membrane resistance increased quite strongly at high polymer concentrations, which cannot be explained by the Mackie–Meares obstruction model. The selectivities and resistances depend on the polymer concentration because of a functional group associated with Teflon AF2400, with a concentration of one functional group per 854 monomer units of the polymer. In the fluorous environment of these membranes, this functional group binds to Na+, K+, Ca2+, and the unprotonated ionophore with binding constants of 103.5, 101.8, 106.8 and 104.4 M−1, respectively. Potentiometric and spectroscopic evidence indicates that these functional groups are COOH groups formed by the hydrolysis of carboxylic acid fluoride (COF) groups originally present in Teflon AF2400. The use of higher ionophore concentrations removes the undesirable effect of these COOH groups almost completely

  6. Protective Effect of Ethanolic Extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA Induced Liver Necrosis in Wistar Albino Rats

    PubMed Central

    2014-01-01

    This study is an attempt to evaluate the hepatoprotective activity of Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use of Tabernaemontana divaricata extract in the treatment of carcinogen induced hepatic necrosis. PMID:25136566

  7. Activation of Wnt signaling pathway by AF1q enriches stem-like population and enhance mammosphere formation of breast cells.

    PubMed

    Tse, Charlotte Olivia; Kim, Soojin; Park, Jino

    2017-03-18

    Wnt signaling pathway is believed to be responsible for control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state. Moreover, dysregulated Wnt signaling pathway is strongly associated with several diseases including cancer. Previously, we have shown that AF1q associates with a poor prognosis in leukemia, myelodysplastic syndromes, multiple myeloid, ovarian cancer, and breast cancer. Also, AF1q plays a pivotal role as an oncogene and metastasis enhancer in breast cancer via activation of Wnt signaling pathway. AF1q is highly expressed in stem cells, and this expression is diminished by differentiation. To understand the role of AF1q in stem-like population, we examined stem-like cells derived from breast cells which dysregulated Wnt signaling pathway by alteration of AF1q expression. The effect of Wnt signaling pathway by AF1q on EMT marker expression, stem cell marker expression, and sphere formation was determined. Activated Wnt signaling pathway by AF1q enriched stem-like population showed enhanced sphere formation ability. Interestingly, Wnt signaling pathway inhibitor, Quercetin, decreased the sphere formation in these cells. These results suggest that AF1q would have a role as an enhancer in generation of stem-like population through activation of Wnt signaling pathway.

  8. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  9. Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic differentiation in vitro and in vivo.

    PubMed

    Ma, Xiaorong; Zhang, Shengli; Zhou, Junmei; Chen, Baisong; Shang, Yafeng; Gao, Tongbing; Wang, Xue; Xie, Hua; Chen, Fang

    2012-08-01

    Stem cell-based therapy may be the most promising method to cure skeletal muscle degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the future. Human amniotic fluid is enriched with early-stage stem cells from developing fetuses and these cells have cardiomyogenic potential both in vitro and in vivo. In the present study, we investigated the characteristics of human amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry, immunofluorescence staining, reverse-transcription polymerase chain reaction, and osteogenic and adipogenic differentiation analysis. After confirming the stemness of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into skeletal myogenic cells in vitro and incorporate into regenerating skeletal muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'-deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells differentiated into skeletal myogenic cells, expressing skeletal myogenic cell-specific markers such as Desmin, Troponin I (Tn I) and α-Actinin. Four weeks after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated into myogenic precursor cells and fused with host myofibres. The findings that HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based therapy for skeletal muscle degenerative diseases.

  10. Evaluation of the Sustainability and Clinical Outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a Child Protection Center

    ERIC Educational Resources Information Center

    Kolko, David J.; Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for…

  11. Slurry sampling in serum blood for mercury determination by CV-AFS.

    PubMed

    Aranda, Pedro R; Gil, Raúl A; Moyano, Susana; De Vito, Irma; Martinez, Luis D

    2009-01-30

    The heavy metal mercury (Hg) is a neurotoxin known to have a serious health impact even at relatively low concentrations. A slurry method was developed for the sensitive and precise determination of mercury in human serum blood samples by cold vapor generation coupled to atomic fluorescence spectrometry (CV-AFS). All variables related to the slurry formation were studied. The optimal hydrochloric concentration and tin(II) chloride concentration for CV generation were evaluated. Calibration within the range 0.1-10 microg L(-1) Hg was performed with the standard addition method, and compared with an external calibration. Additionally, the reliability of the results obtained was evaluated by analyzing mercury in the same samples, but submitted to microwave-assisted digestion method. The limit of detection was calculated as 25 ng L(-1) and the relative standard deviation was 3.9% at levels around of 0.4 microg L(-1)Hg.

  12. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 μM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 μM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 μM.

  13. Adak NAS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-08-24

    operated by the U. S. Ser- vices aoi some foreig;n stations .silim, similar reporting prscticei. UiJesu otlherwise noted the Co ~luwilof suianries are...34 TRNSITERVEoRE .iF Oct 3.94 Longviev hAl Weather Sot available NA N/ N/A statin (Jo~Unit hAP & Navy) 2. 2 2/31/13 Ad~k(Joint’Unit) AF & Not available N/A I/A N/A...641214.15 2.18 cO 4 18.1 7.2 17. 9 .1.4421 FES 5 . 18.1 5.4 17.2 1 .5 19.1 17.4 L. 4 2.1 .1 76.Z IIG2 4 .7 _9.57) 1.97 MAN 5 5.5 19.5 13.3 1I.3 12. 9

  14. RAF Lakenheath, United Kingdom. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1988-02-01

    3: 1 ... . 2 . . jb -3VI SO I 7.27b 6 . ( 5.764 5.103 4.571 4.47 1 4.367 .47 5.244 b.712 7.717 7.3< 7 5.4.7 1333 osJ 915 a37 91 ’ɘ 911 645 0. 92’ 1...LA II WE17,rY uSAFLTAC fqL" LUlLy CFS[kVATO.V AIR .LA IHfP SERVICC/MAC STATIO, NUMPER: 75 3- STAIIOf, NAME : R AF LAKtNI-ATH L91[EU KINGf0CM L CIEC

  15. Hill AFB, Utah Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1984-09-01

    GLCqAL CLIMATOLOGY QRANCN b AX EAT,.C PSYCHROMETRIC SUMMARY AIP WE THER+ SEPICE /CPNIAC ?9 𔃿’ HILL AF- uT 14-81 ST" e~- STA?1010 1M1 VIA STN PAGE2 yeP...1 *, * 1-,* . 1 1 . I ! I i !9 -./ ., 1. 4 ,; ? , j : .. 7, dc L_ 1 I_ ’ I a AA I 6 if / "i - IT 𔃾 _ _"_ __. i ./ 2 . , 2 ., 921 ,- ’ 7 3 7.3...SEP. OCT NOV. DC ANNUAL MEAN ’’’ 7 *L 𔃾.3 23. .8 7.7 𔃽.3 4C.8 34.8 79.3 23.4 14.9 9.s SO 5D *143 7 4 7.128 7 . 94 6 .8g4 7.2;5 7 9 ;3 9.2 42 8 .632

  16. Palhicerines A-F, Lycopodium alkaloids from the club moss Palhinhaea cernua.

    PubMed

    Tang, Yu; Xiong, Juan; Zou, Yike; Zhang, Hai-Yan; Hu, Jin-Feng

    2016-11-01

    Four fawcettimine-type (palhicerines A-D, resp.) and two lycopodine-type (palhicerines E and F) Lycopodium alkaloids together with twenty known ones were isolated from the whole plant of Palhinhaea cernua. The structures and absolute configurations of the palhicerines A-F were determined by extensive spectroscopic methods, single-crystal X-ray diffraction analyses, chemical transformation, and electronic circular dichroism (ECD) calculations or induced electronic circular dichroism (IECD) spectra. Among the isolates, the new C/D-ring of the palhicerines A-C (trans-fused fawcettimine-type alkaloids) are rare, and each possesses a β-oriented C-16 methyl group and a distinctive tertiary methoxy group at C-13. Chemotaxonomy for differentiating species in the genus Palhinhaea is briefly discussed.

  17. Holloman AFB, New Mexico. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1982-04-12

    Information is provided: a. The min body of the sumary comslste of a bivariate percentage frequency distribution of wet-bulb depression in 17 classes...SERVICE/MAC C. 747320 HOLLOMAN AFS NM 68-70.7S-81 MAR STATION STATION WA&C VYZWS WONT" C PAGE 1 0 -MO. Temp. WET OUL11 TEMPEIATUIDE DEPRESSION (F) TOTAL...Tep. WET SUL& TEMPERATURE DEPRESSION (P) TOTAL TOTAL (F) 0 1-2 3-4 5-6 7-1 9.10 11-1213-14 15-16 17.18 19. 21.n23-24 25-262.029.20 -31 .L’W. S Ib Wt

  18. Extrasolar planets and brown dwarfs around AF-type stars. IX. The HARPS southern sample

    NASA Astrophysics Data System (ADS)

    Borgniet, S.; Lagrange, A.-M.; Meunier, N.; Galland, F.

    2017-03-01

    Context. Massive, main-sequence (MS) AF-type stars have so far remained unexplored in past radial velocities (RV) surveys due to their small number of spectral lines and high rotational velocities that prevent the classic RV computation method. Aims: Our aim is to search for giant planets (GPs) around AF MS stars, to get primary statistical information on their occurrence rate and to compare the results with evolved stars and lower-mass MS stars. Methods: We used the HARPS spectrograph located on the 3.6 m telescope at ESO La Silla Observatory to observe 108 AF MS stars with B-V in the range -0.04 to 0.58 and masses in the range 1.1 to 3.6 M⊙. We used our SAFIR software developed to compute the RV and other spectroscopic observables of these early-type stars. We characterized the detected companions as well as the intrinsic stellar variability. We computed the detection limits and used them as well as the detected companions to derive the first estimates of the close-in brown dwarf (BD) and GP frequencies around AF stars. Results: We report the detection of a mpsini = 4.51MJup planetary companion with an 826-day period to the F6V dwarf HD 111998. We also present new data on the two-planet system around the F6IV-V dwarf HD 60532. We also report the detections of 14 binaries with long-term RV trends and/or high-amplitude RV variations combined to a flat RV-bisector span diagram. We constrain the minimal masses and semi-major axes of these companions and check that these constraints are compatible with the stellar companions previously detected by direct imaging or astrometry for six of these targets. We get detection limits deep into the planetary domain with 70% of our targets showing detection limits between 0.1 and 10 MJup at all orbital periods in the 1- to 103-day range. We derive BD (13 ≤mpsini ≤ 80 MJup) occurrence rates in the 1- to 103-day period range of 2-2+5% and 2.6-2.6+6.7% for stars with M⋆ in the ranges 1.1 to 1.5 and 1.5 to 3 M

  19. Pope AFB, North Carolina Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1985-03-01

    OL.A IRE.IOA$ E0.T10S 01.S T 04. RtU ASP OOtE)U 6 *L’-AL .LI"!ATCL)GY i %A %Cm 2_T SURFACE WINDS .AT-Fd 1.RV1CL’?1AC PERCENTAGE FREQUENCY OF WIND...DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 72V~ -JP AF-!_~ _________ 7-L_________ tot ST A-T 0 k.I IsA .;T. A .L .LAT" E-’ •_ _-_ SPEED MEAN KNTS 1...0 , T ._ . _ * ,... . K . --- .. j , ,.. ’ . .. , m E¢ 800 1 ,00 2! 6100 9 . t 1200- ___? .. ..00 . . . : 100 2! goo EXAMPLE # 1 lHead ceiling

  20. RNA structure replaces the need for U2AF2 in splicing

    PubMed Central

    Lin, Chien-Ling; Taggart, Allison J.; Lim, Kian Huat; Cygan, Kamil J.; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G.

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes. PMID:26566657

  1. RNA structure replaces the need for U2AF2 in splicing.

    PubMed

    Lin, Chien-Ling; Taggart, Allison J; Lim, Kian Huat; Cygan, Kamil J; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.

  2. Taipei IAP, Taiwan. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1973-09-07

    t5LLA TwP r <,AT okES DFC F fk’ *J.Y SFRkv A C.. 4 66 T ’ " lrA.IPtl JAP TYA1xA 54-7, ’ AN FEB AR APR ~ A’ Wl -. A’ Af N NNC.A 5EA. 51-o1 5,4 58,9 64 77...C AC7-RESS Z2 REPORT ZA-E US~ t ~ ~ 7 Sep, 73 Air Weather Service (MAC) N~BR2 A Scott AFB IL 62225 4 M041TORINS A CN’.Y N AME 3 AUCAE3S,f :ie- floll t ...over) ’ T & report is sx-pat t sti~ calsmmr of surface weather observations for h,,jei IAP, Taiwan It contains the following parts: (A) Weather

  3. Hot-Fire Testing of a 1N AF-M315E Thruster

    NASA Technical Reports Server (NTRS)

    Burnside, Christopher G.; Pedersen, Kevin; Pierce, Charles W.

    2015-01-01

    This hot-fire test continues NASA investigation of green propellant technologies for future missions. To show the potential for green propellants to replace some hydrazine systems in future spacecraft, NASA Marshall Space Flight Center (MSFC) is continuing to embark on hot-fire test campaigns with various green propellant blends. NASA completed a hot-fire test of a 1N AF-M315E monopropellant thruster at the Marshall Space Flight Center in the small altitude test stand located in building 4205. The thruster is a ground test article used for basic performance determination and catalyst studies. The purpose of the hot-fire testing was for performance determination of a 1N size thruster and form a baseline from which to study catalyst performance and life with follow-on testing to be conducted at a later date. The thruster performed as expected. The result of the hot-fire testing are presented in this paper and presentation.

  4. AF printability check with a full-chip 3D resist profile model

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-En R.; Chang, Jason; Song, Hua; Shiely, James

    2013-09-01

    A single compact resist model capable of predicting 3D resist profile is strongly demanded for the advanced technology nodes to avoid the potential hotspots due to imperfect resist pattern shape and its lack of resistance in the subsequent etch process. In this work, we propose a resist 3D (R3D) compact model that takes acidz-diffusion effect into account. The chemical reaction between acid and base along z-direction is treated as second order effect that is absorbed into the anisotropic diffusion length as a fitting parameter. Meanwhile, the resist model in the x-y wafer plane is still kept in general by applying the compact solution of 2D reaction-diffusion equation. In order to have the 2D contour predictability at arbitrary resist height, calibration from entire 3D data (CDs at several heights) areconducted simultaneously witha single cost function so that the R3D compact model is described by a common set of resist free parameters and threshold for all resist heights. With the low energy approximation, the acid z-diffusion effect is equivalent to a z-diffused TCC that takes the form of linear combination of pure optical TCCs sampled at discrete image-depth which can be pre-calculated. With this benefit, the R3D compact model offers a more physical approach but adds no runtime concern on the OPC and verification applications. The predicted resist cross-section profiles from our test patterns are compared those computed with rigorous lithography simulator SLITHO and show very good matching results between them. The demonstration of the AF printability check from the predicted cross-section profile at AF indicates the success of our R3D compact model.

  5. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF

    PubMed Central

    Bassand, Jean-Pierre; Accetta, Gabriele; Camm, Alan John; Cools, Frank; Fitzmaurice, David A.; Fox, Keith A.A.; Goldhaber, Samuel Z.; Goto, Shinya; Haas, Sylvia; Hacke, Werner; Kayani, Gloria; Mantovani, Lorenzo G.; Misselwitz, Frank; ten Cate, Hugo; Turpie, Alexander G.G.; Verheugt, Freek W.A.; Kakkar, Ajay K.

    2016-01-01

    Aims The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. Methods and results GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. Conclusion The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier: NCT01090362. PMID:27357359

  6. Patterns of cellular immunity associated with experimental infection with rDEN2Δ30 (Tonga/74) supports its suitability as a human DENV challenge strain.

    PubMed

    Grifoni, Alba; Angelo, Michael; Sidney, John; Paul, Sinu; Peters, Bjoern; de Silva, Aruna D; Phillips, Elizabeth; Mallal, Simon; Diehl, Sean A; Botten, Jason; Boyson, Jonathan; Kirkpatrick, Beth D; Whitehead, Stephen S; Durbin, Anna P; Sette, Alessandro; Weiskopf, Daniela

    2017-02-01

    A deletion variant of the DENV2 Tonga/74 strain lacking 30 nucleotides from its 3' untranslated region (rDEN2Δ30) has previously been established for use in a controlled DENV human challenge model. To evaluate if this model is appropriate to derive correlates of protection for DENV vaccines based on cellular immunity, we wanted to compare how the cellular immune response to this challenge strain compares to the response induced by natural infection. To achieve this, we predicted HLA class I and class II restricted peptides from rDEN2Δ30 and used them, in an IFN-gamma ELISPOT assay, to interrogate CD8(+) and CD4(+) T cell responses in healthy volunteers infected with rDEN2Δ30. At the level of CD8 responses, vigorous ex vivo responses were detected in approximately 80% of donors. These responses were similar in terms of magnitude and numbers of epitopes recognized to previously reported responses observed in PBMC from donors from DENV hyper-endemic regions. The similarity extended to the immunodominance hierarchy of the DENV nonstructural proteins NS3, NS5, and NS1 being dominant in both donor cohorts. At the CD4 level, responses were less vigorous compared to natural DENV infection, and were more focused on nonstructural proteins. The epitopes recognized following rDEN2Δ30 infection and natural infection were largely overlapping for both CD8 (100%) and CD4 (85%) responses. Finally, rDEN2Δ30 induced stronger CD8 responses compared to other more attenuated DENV isolates.

  7. Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

    ERIC Educational Resources Information Center

    Hermansen, Hege; Nerland, Monika

    2014-01-01

    In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

  8. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

    PubMed

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

    2016-10-04

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

  9. Distribution of muscarinic receptor subtypes in rat brain as determined in binding studies with AF-DX 116 and pirenzepine

    SciTech Connect

    Giraldo, E.; Hammer, R.; Ladinsky, H.

    1987-03-02

    In vitro competition binding experiments with the selective muscarinic antagonists AF-DX 116 and pirenzepine (PZ) vs /sup 3/H-N-methylscopolamine as radioligand revealed a characteristic distribution of muscarinic receptor subtypes in different regions of rat brain. Based on nonlinear least squares analysis, the binding data were compatible with the presence of three different subtypes: the M/sub 1/ receptor (high affinity for PZ), the cardiac M/sub 2/ receptor (high affinity for AF-DX 116) and the glandular M/sub 2/ receptor (low affinity for PZ and AF-DX 116). The highest proportion of M/sub 1/ receptors was found in the hippocampus, while the cerebellum and the hypothalamus were the regions with the largest fraction of the cardiac M/sub 2/ and glandular M/sub 2/ receptors, respectively. In certain brain areas, depending on the relative proportions of the subtypes, flat binding curves were seen for AF-DX 116 and PZ. Based on these data, an approximate distribution pattern of the subtypes in the various brain regions is presented. 19 references, 1 figure, 2 tables.

  10. Rhein-Main Apt, Germany/Franfurt. Revised Uniform Summary of Surface Weather Observations. Parts A-F

    DTIC Science & Technology

    1977-08-01

    DATA PROCESSING BRANCH usAF E’ C CEILING, VERSUS VISIBILITY AIR WEATHER SERVICE/MAC 0 RHEINMAIN APT GERMANY/FRAtKFURT...SERVICE/MAC RHEINMAIN APT GENMANY/FRANKFURT 67-7o OEZ U. PERCENTAGE FREQUENCY OF OCCURRENCE 0000-.)200 , (FROM HOURLY OBSERVATIONS) o , - VISIBILITY

  11. Determining Aqueous Fullerene Particle Size Distributions by Asymmetric Flow Field-Flow Fractionation (AF4) without Surfactants

    EPA Science Inventory

    To determine the behavior of nanoparticles in environmental systems, methods must be developed to measure nanoparticle size. Asymmetric Flow Field Flow Fractionation (AF4) is an aqueous compatible size separation technique which is able to separate particles from 1 nm to 10 µm in...

  12. The Implementation of Collaborative Learning Using AfL through Giving Feedback Strategy for Improving Students’ Attention to Mathematics Lesson

    NASA Astrophysics Data System (ADS)

    Kurniasih, R.; Sujadi, I.; Pramesti, G.

    2016-02-01

    This research aims to describe the process of implementation collaborative learning with AfL through giving feedback strategy for improving students’ attention to mathematics lesson. Data which is collected in this research are students’ attention towards learning and students’ achievement. The result of this research showed that the learning steps by using collaborative learning with AfL through giving feedback strategy which can improve students’ attention are: 1) pre activity: the teacher delivers the purpose of the learning, successful criteria, apperception, and motivation. 2) main activity: the teacher gives the background of learning activity, explains learning materials at a glance, divides students discuss, the teacher observes and guides students to the problem solving, present their discussion result, gives feedback, the students do AfL problem and the answer is collected and result will be given before next meeting. 3) post activity: the teacher with students concludes the material. Test result, the percentage of students who complete the examination in the second cycle is 77.27%. Based on those results can be concluded that the implementation of collaborative learning using AfL through giving feedback can improve students’ attention towards learning and students’ achievement of XI IPA Students MA Al-Islam Jamsaren Surakarta academic year 2013/2014.

  13. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis

    PubMed Central

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy te; Basso, Giuseppe

    2016-01-01

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations. PMID:27698462

  14. Ultrasound body composition traits response to an endotoxin challenge in Brahman heifers supplemented with Omnigen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the body composition traits response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183 ± 5 kg) from the Texas AgriLife Research Center in Overton, TX, were separat...

  15. Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

    PubMed

    Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

    2014-08-01

    Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.

  16. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  17. Modulation of the metabolic response to an endotoxin challenge in Brahman heifers through OmniGen-AF supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the metabolic response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton, TX, were separated into 2...

  18. Complementary DNA cloning, sequence analysis, and tissue transcription profile of a novel U2AF2 gene from the Chinese Banna mini-pig inbred line.

    PubMed

    Wang, S Y; Huo, J L; Miao, Y W; Cheng, W M; Zeng, Y Z

    2013-04-02

    U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an important gene for pre-messenger RNA splicing in higher eukaryotes. In this study, the Banna mini-pig inbred line (BMI) U2AF2 coding sequence (CDS) was cloned, sequenced, and characterized. The U2AF2 complete CDS was amplified using the reverse transcription-polymerase chain reaction (RT-PCR) technique based on the conserved sequence information of cattle and known highly homologous swine expressed sequence tags. This novel gene was deposited into the National Center for Biotechnology Information database (Accession No. JQ839267). Sequence analysis revealed that the BMI U2AF2 coding sequence consisted of 1416 bp and encoded 471 amino acids with a molecular weight of 53.12 kDa. The protein sequence has high sequence homology with U2AF65 of 6 species - Homo sapiens (100%), Equus caballus (100%), Canis lupus (100%), Macaca mulatta (99.8%), Bos taurus (74.4%), and Mus musculus (74.4%). The phylogenetic tree analysis revealed that BMI U2AF65 has a closer genetic relationship with B. taurus U2AF65 than with U2AF65 of E. caballus, C. lupus, M. mulatta, H. sapiens, and M. musculus. RT-PCR analysis showed that BMI U2AF2 was most highly expressed in the brain; moderately expressed in the spleen, lung, muscle, and skin; and weakly expressed in the liver, kidney, and ovary. Its expression was nearly silent in the spinal cord, nerve fiber, heart, stomach, pancreas, and intestine. Three microRNA target sites were predicted in the CDS of BMI U2AF2 messenger RNA. Our results establish a foundation for further insight into this swine gene.

  19. Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2014-01-01

    Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

  20. The Elongation Complex Components BRD4 and MLLT3/AF9 Are Transcriptional Coactivators of Nuclear Retinoid Receptors

    PubMed Central

    Flajollet, Sébastien; Rachez, Christophe; Ploton, Maheul; Schulz, Céline; Gallais, Rozenn; Métivier, Raphaël; Pawlak, Michal; Leray, Aymeric; Issulahi, Al Amine; Héliot, Laurent; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

    2013-01-01

    Nuclear all-trans retinoic acid receptors (RARs) initiate early transcriptional events which engage pluripotent cells to differentiate into specific lineages. RAR-controlled transactivation depends mostly on agonist-induced structural transitions in RAR C-terminus (AF-2), thus bridging coactivators or corepressors to chromatin, hence controlling preinitiation complex assembly. However, the contribution of other domains of RAR to its overall transcriptional activity remains poorly defined. A proteomic characterization of nuclear proteins interacting with RAR regions distinct from the AF-2 revealed unsuspected functional properties of the RAR N-terminus. Indeed, mass spectrometry fingerprinting identified the Bromodomain-containing protein 4 (BRD4) and ALL1-fused gene from chromosome 9 (AF9/MLLT3), known to associate with and regulates the activity of Positive Transcription Elongation Factor b (P-TEFb), as novel RAR coactivators. In addition to promoter sequences, RAR binds to genomic, transcribed regions of retinoid-regulated genes, in association with RNA polymerase II and as a function of P-TEFb activity. Knockdown of either AF9 or BRD4 expression affected differentially the neural differentiation of stem cell-like P19 cells. Clusters of retinoid-regulated genes were selectively dependent on BRD4 and/or AF9 expression, which correlated with RAR association to transcribed regions. Thus RAR establishes physical and functional links with components of the elongation complex, enabling the rapid retinoid-induced induction of genes required for neuronal differentiation. Our data thereby extends the previously known RAR interactome from classical transcriptional modulators to components of the elongation machinery, and unravel a functional role of RAR in transcriptional elongation. PMID:23762261

  1. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4–MLL Fusion Protein

    PubMed Central

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-01-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4–MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4–MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4–MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4–MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4–MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  2. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications.

  3. Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C

    PubMed Central

    Sabry, Dina; Elamir, Azza; Mahmoud, Rania Hosny; Abdelaziz, Ahmed Ali; Fathy, Wael

    2017-01-01

    Background The current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients. Methods Thirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR. Results Our study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed. Conclusion LncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C. PMID:28392862

  4. Accounting for model error in air quality forecasts: an application of 4DEnVar to the assimilation of atmospheric composition using QG-Chem 1.0

    NASA Astrophysics Data System (ADS)

    Emili, Emanuele; Gürol, Selime; Cariolle, Daniel

    2016-11-01

    Model errors play a significant role in air quality forecasts. Accounting for them in the data assimilation (DA) procedures is decisive to obtain improved forecasts. We address this issue using a reduced-order coupled chemistry-meteorology model based on quasi-geostrophic dynamics and a detailed tropospheric chemistry mechanism, which we name QG-Chem. This model has been coupled to the software library for the data assimilation Object Oriented Prediction System (OOPS) and used to assess the potential of the 4DEnVar algorithm for air quality analyses and forecasts. The assets of 4DEnVar include the possibility to deal with multivariate aspects of atmospheric chemistry and to account for model errors of a generic type. A simple diagnostic procedure for detecting model errors is proposed, based on the 4DEnVar analysis and one additional model forecast. A large number of idealized data assimilation experiments are shown for several chemical species of relevance for air quality forecasts (O3, NOx, CO and CO2) with very different atmospheric lifetimes and chemical couplings. Experiments are done both under a perfect model hypothesis and including model error through perturbation of surface chemical emissions. Some key elements of the 4DEnVar algorithm such as the ensemble size and localization are also discussed. A comparison with results of 3D-Var, widely used in operational centers, shows that, for some species, analysis and next-day forecast errors can be halved when model error is taken into account. This result was obtained using a small ensemble size, which remains affordable for most operational centers. We conclude that 4DEnVar has a promising potential for operational air quality models. We finally highlight areas that deserve further research for applying 4DEnVar to large-scale chemistry models, i.e., localization techniques, propagation of analysis covariance between DA cycles and treatment for chemical nonlinearities. QG-Chem can provide a useful tool in this

  5. Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

    PubMed Central

    Nicolas, Valérie

    2014-01-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of d-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  6. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs

    PubMed Central

    Jenkins, Jermaine L.; Agrawal, Anant A.; Gupta, Ankit; Green, Michael R.; Kielkopf, Clara L.

    2013-01-01

    Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF65 is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3′ splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF65 recognizes degenerate Py tracts, we determined six crystal structures of human U2AF65 bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF65 bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF65 for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF65 conformations. Our results highlight both local and global conformational selection as a means for universal 3′ splice site recognition by U2AF65. PMID:23376934

  7. Flavonoid-enriched apple fraction AF4 induces cell cycle arrest, DNA topoisomerase II inhibition, and apoptosis in human liver cancer HepG2 cells.

    PubMed

    Sudan, Sudhanshu; Rupasinghe, H P Vasantha

    2014-01-01

    Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer.

  8. [Presence of the dinoflagellates Ceratium dens, C. fusus and C. furca (Gonyaulacales: Ceratiaceae) in Golfo de Nicoya, Costa Rica].

    PubMed

    Vargas-Montero, Maribelle; Freer, Enrique

    2004-09-01

    Harmful Algae Blooms (HAB) are a frequent phenomenon in the Gulf of Nicoya, Costa Rica, as in other parts of the world. The morphology and physiology of these microalgae are important because HAB species have adaptive characteristics. The production of high concentrations of paralytic toxins by Ceratium dinoflagellates has only been documented at the experimental level. However, this genus has been associated with the mortality of aquatic organisms, including oyster and shrimp larva, and fish, and with decreased water quality. Recently, fishermen reported massive mortality of encaged fish near Tortuga Island (Gulf of Nicoya). Samples were taken from an algal bloom that had produced an orange coloration and had a strong foul-smelling odor. Ultrastructural details were examined with scanning electron microscopy. The dinoflagellates Ceratium dens, C. furca and C. fusus were found in samples taken at the surface. The cell count revealed four million cells of this genus per liter. The morphological variability of these species is high; therefore electron microscopy is an useful tool in the ultrastructural study of these organisms. This is the first time that three Ceratium species are reported concurrently producing harmful blooms in Costa Rica.

  9. Hepatocyte-specific Smad7 deletion accelerates DEN-induced HCC via activation of STAT3 signaling in mice

    PubMed Central

    Feng, T; Dzieran, J; Yuan, X; Dropmann, A; Maass, T; Teufel, A; Marhenke, S; Gaiser, T; Rückert, F; Kleiter, I; Kanzler, S; Ebert, M P; Vogel, A; ten Dijke, P; Dooley, S; Meindl-Beinker, N M

    2017-01-01

    TGF-β signaling in liver cells has variant roles in the dynamics of liver diseases, including hepatocellular carcinoma (HCC). We previously found a correlation of high levels of the important endogenous negative TGF-β signaling regulator SMAD7 with better clinical outcome in HCC patients. However, the underlying tumor-suppressive molecular mechanisms are still unclear. Here, we show that conditional (TTR-Cre) hepatocyte-specific SMAD7 knockout (KO) mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine (DEN) challenge, verifying SMAD7 as a tumor suppressor in HCC. In line with our findings in patients, Smad7 levels in both tumor tissue as well as surrounding tissue show a significant inverse correlation with tumor numbers. SMAD7 KO mice presented with increased pSMAD2/3 levels and decreased apoptosis in the tumor tissue. Higher tumor incidence was accompanied by reduced P21 and upregulated c-MYC expression in the tumors. Activation of signal transducer and activator of transcription factor 3 signaling was found in Smad7-deficient mouse tumors and in patients with low tumoral SMAD7 expression as compared with surrounding tissue. Together, our results provide new mechanistic insights into the tumor-suppressive functions of SMAD7 in hepatocarcinogenesis. PMID:28134936

  10. Biological evidence of an oviposition-deterring pheromone inLobesia botrana Den. et Schiff. (Lepidoptera, Tortricidae).

    PubMed

    Gabel, B; Thiéry, D

    1992-03-01

    Females of the European grapevine moth (Lobesia botrana Den. et Schiff.) usually deposit isolated eggs on flowers and berries of the grapevine (Vitis vinifera L.). We have investigated whether an epideictic pheromone could be present on the egg surface to explain this spacing behavior. About 21,000 eggs ofL. botrana were washed in cold methanol, and the biological activity was tested in a two-choice bioassay offering treated and nontreated areas. Different dilutions of the extract were tested in methanol, which was inactive alone. At the dose of four egg equivalents per microliter of extract, the number of eggs laid by theL. botrana females was reduced by as much as 57% on the treated areas compared to nontreated areas. A longer-term suppression of oviposition (at least 24 hr) following an exposure to the extract occurred for two doses (0.6 and 4.0 eggs/μl) of egg extract. Our results strongly suggest the occurrence of an oviposition-deterring pheromone (ODP) on the eggs ofL. botrana. The ecological value of these results is discussed.

  11. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

    PubMed

    Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

    2014-06-01

    Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

  12. Insecticidal activity of Vip3Aa, Vip3Ad, Vip3Ae, and Vip3Af from Bacillus thuringiensis against lepidopteran corn pests.

    PubMed

    Hernández-Martínez, Patricia; Hernández-Rodríguez, Carmen Sara; Rie, Jeroen Van; Escriche, Baltasar; Ferré, Juan

    2013-05-01

    Vip3Aa, Vip3Ad, Vip3Ae, and Vip3Af proteins from Bacillus thuringiensis were tested for their toxicity against Spodoptera frugiperda and Agrotis ipsilon. Vip3Ad was non-toxic to the two species. Vip3Ae and Vip3Af were significantly more toxic than Vip3Aa against S. frugiperda, both as protoxins and as toxins. Against A. ipsilon, Vip3Ae protoxin was more toxic than Vip3Aa and Vip3Af protoxins. Purification by metal-chelate affinity chromatography significantly affected Vip3Ae toxicity against the two insect species.

  13. "Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

    NASA Astrophysics Data System (ADS)

    Lowsky, Martin

    Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

  14. A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4Δ30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers.

    PubMed

    Pierce, Kristen K; Whitehead, Stephen S; Kirkpatrick, Beth D; Grier, Palmtama L; Jarvis, Adrienne; Kenney, Heather; Carmolli, Marya P; Reynolds, Cynthia; Tibery, Cecilia M; Lovchik, Janece; Janiak, Anna; Luke, Catherine J; Durbin, Anna P; Pletnev, Alexander G

    2017-01-01

    West Nile virus (WNV) is a major cause of mosquito-borne illness in the United States. Human disease ranges from mild febrile illness to severe fatal neurologic infection. Adults aged >60 years are more susceptible to neuroinvasive disease accompanied by a high mortality rate or long-lasting neurologic sequelae. A chimeric live attenuated West Nile virus vaccine, rWN/DEN4Δ30, was shown to be safe and immunogenic in healthy adults aged 18-50 years. This study evaluated rWN/DEN4Δ30 in flavivirus-naive adults aged 50-65 years and found it to be safe and immunogenic. Outbreaks of WNV infection tend to be unpredictable, and a safe and effective vaccine will be an important public health tool.

  15. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.

    PubMed Central

    Durand, B; Saunders, M; Gaudon, C; Roy, B; Losson, R; Chambon, P

    1994-01-01

    A motif essential for the transcriptional activation function 2 (AF-2) present in the E region of retinoic acid receptor (RAR) alpha and 9-cis retinoic acid receptor (RXR) alpha has been characterized as an amphipathic alpha-helix whose main features are conserved between transcriptionally active members of the nuclear receptor superfamily. This conserved motif, which can activate autonomously in the absence of ligand in animal and yeast cells, can be swapped between nuclear receptors without affecting the ligand dependency for activation of transcription, thus indicating that a ligand-dependent conformational change is necessary to reveal the AF-2 activation potential within the E region of the nuclear receptor. Interestingly, we show that the precise nature of the direct repeat response element to which RAR/RXR heterodimers are bound can affect the activity of the AF-2s of the heterodimeric partners, as well as the relative efficiency with which all-trans and 9-cis retinoic acids activate the RAR partner. Images PMID:7957103

  16. Perturbative magnetoresistance technique used to investigate FM/AF coupled bilayers

    NASA Astrophysics Data System (ADS)

    Oliveira, Alexandre; da Costa, Ricardo; Melo, Abner; Chesman, Carlos

    2014-03-01

    In this study we introduced modifications to a collinear four probe magnetoresistance set-up in order to measure magnetic properties that can only be sensed by techniques based on magnetization perturbation. In addition to the applied DC magnetic field (Hdc) , in magnetoresistance experiments, a small and quasi-static alternating magnetic field (hac, less than 10 Oe and around 800 Hz) is applied perpendicularly, both parallel to the sample plane. Due to Zeeman interaction, hac drives sample magnetization to oscillate slightly around its equilibrium position. Although we apply only DC current (few mA), the detected voltage carries DC and AC components. The DC voltage component provides information on magnetoresistance (MR) and the AC component is called perturbative magnetoresistance (PMR). We successfully demonstrated that the PMR signal is proportional to the first derivative of resistance with respect to hac. Using this technique and a phenomenological model that takes into account the relevant free energy terms of FM/AF coupled bilayers, we were able to study reversible and irreversible magnetization rotation processes in these magnetic systems. With respect to magnetic anisotropy, we investigated rotatable anisotropy, proposed by McMichael et al and Geshev et al. Financial support: CNPq, FAPERN and CAPES (Brazilian agencies).

  17. Chemically peculiar A/F stars in open clusters of the Milky Way

    NASA Astrophysics Data System (ADS)

    Gebran, M.; Monier, R.

    2010-12-01

    Abundance anomalies have been determined at the surface of many field and open cluster A and F dwarfs. These abundance anomalies are most likely caused by microscopic diffusion at work within the stable envelopes of A stars. However diffusion can be counteracted by several other mixing processes such as convection, rotational mixing and mass loss. We present a short review of the surface abundance patterns of A/F stars in the Pleiades (100 Myr), Coma Berenices (450 Myr) and Hyades (650 Myr) open clusters. Real star-to-star variations of the abundances were found for several chemical elements in the A dwarfs in these clusters. The derived abundances are then compared to evolutionary models from the Montreal group. These comparisons strongly suggest the occurence of hydrodynamical processes at play within the radiative zones of these stars and hindering the effects of microscopic diffusion (mixing processes/mass loss). In the frame of Gaia mission, simulations are presented that predict the number of A stars and open clusters that Gaia will observe in the Galaxy.

  18. Performance Analysis of Beamforming in Fixed-gain AF Relay Networks with Asymmetric Correlated Fading Channels

    NASA Astrophysics Data System (ADS)

    Li, Min

    2014-07-01

    In this paper, the performance of beamforming (BF) for a dual-hop amplify-and-forward (AF) relay network, where the source and destination are each equipped with multiple antennas, is investigated. It is assumed that the source-relay and relay-destination channels experience mixed fading distributions, namely, correlated Nakagami-m/Rician and correlated Rician/Nakagami-m, respectively. By considering fixed-gain relaying, analytical expressions for outage probability (OP) and average symbol error rate (ASER) are derived in closed-form. Numerical results are presented to demonstrate the efficacy of our performance analysis, also illustrate the impact of channel correlation, fading severity, Rician factor and antenna configuration on the performance of the system. It is shown that the correlated Nakagami-m/Rician fading channel can achieve better performance than the correlated Rician/Nakagami-m fading channel with the increase of fading severity parameter, and the correlated Rician/Nakagami-m fading channel may outperform the correlated Nakagami-m/Rician fading channel by enlarging the Rician factor.

  19. Search for A-F Spectral type pulsating components in Algol-type eclipsing binary systems

    NASA Astrophysics Data System (ADS)

    Kim, S.-L.; Lee, J. W.; Kwon, S.-G.; Youn, J.-H.; Mkrtichian, D. E.; Kim, C.

    2003-07-01

    We present the results of a systematic search for pulsating components in Algol-type eclipsing binary systems. A total number of 14 eclipsing binaries with A-F spectral type primary components were observed for 22 nights. We confirmed small-amplitude oscillating features of a recently detected pulsator TW Dra, which has a pulsating period of 0.053 day and a semi-amplitude of about 5 mmag in B-passband. We discovered new pulsating components in two eclipsing binaries of RX Hya and AB Per. The primary component of RX Hya is pulsating with a dominant period of 0.052 day and a semi-amplitude of about 7 mmag. AB Per has also a pulsating component with a period of 0.196 day and a semi-amplitude of about 10 mmag in B-passband. We suggest that these two new pulsators are members of the newly introduced group of mass-accreting pulsating stars in semi-detached Algol-type eclipsing binary systems. Table 4 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/405/231

  20. INTERPRETATION OF AT-LINE SPECTRA FROM AFS-2 BATCH #3 FERROUS SULFAMATE TREATMENT

    SciTech Connect

    Kyser, E.; O'Rourke, P.

    2013-12-10

    Spectra from the “at-line” spectrometer were obtained during the ferrous sulfamate (FS) valence adjustment step of AFS-2 Batch #3 on 9/18/2013. These spectra were analyzed by mathematical principal component regression (PCR) techniques to evaluate the effectiveness of this treatment. Despite the complications from Pu(IV), we conclude that all Pu(VI) was consumed during the FS treatment, and that by the end of the treatment, about 85% was as Pu(IV) and about 15% was as Pu(III). Due to the concerns about the “odd” shape of the Pu(IV) peak and the possibility of this behavior being observed in the future, a follow-up sample was sent to SRNL to investigate this further. Analysis of this sample confirmed the previous results and concluded that it “odd” shape was due to an intermediate acid concentration. Since the spectral evidence shows complete reduction of Pu(VI) we conclude that it is appropriate to proceed with processing of this the batch of feed solution for HB-Line including the complexation of the fluoride with aluminum nitrate.

  1. Joint Source-Relay Design for Full-Duplex MIMO AF Relay Systems

    NASA Astrophysics Data System (ADS)

    Shi, Qingjiang; Hong, Mingyi; Gao, Xiqi; Song, Enbin; Cai, Yunlong; Xu, Weiqiang

    2016-12-01

    The performance of full-duplex (FD) relay systems can be greatly impacted by the self-interference (SI) at relays. By exploiting multi-antenna in FD relay systems, the spectral efficiency of FD relay systems can be enhanced through spatial SI mitigation. This paper studies joint source transmit beamforming and relay processing to achieve rate maximization for FD MIMO amplify-and-forward (AF) relay systems with consideration of relay processing delay. The problem is difficult to solve due mainly to the SI constraint induced by the relay processing delay. In this paper, we first present a sufficient condition under which the relay amplification matrix has rank one structure. Then, for the case of rank one amplification matrix, the rate maximization problem is equivalently simplified into an unconstrained problem which can be locally solved using gradient ascent method. Next, we propose a penalty-based algorithmic framework, called P-BSUM, for a class of constrained optimization problems which have difficult equality constraints in addition to some convex constraints. By rewriting the rate maximization problem with a set of auxiliary variables, we apply the P-BSUM algorithm to the rate maximization problem in the general case. Finally, numerical results validate the efficiency of the proposed algorithms and show that the joint source-relay design approach under the rank one assumption could be strictly suboptimal as compared to the P-BSUM-based joint source-relay design approach.

  2. Dover AFB, Delaware Revised Uniform Summary of Surface Weather Observations (RUSSWO) Parts A-F.

    DTIC Science & Technology

    1981-10-16

    90. 92. 93.8 94.4 94 7 9497 94o8 94.9 95.0 95.0 95.0 95.1 95.* >oo 11. 75.1 86, 91.2 93.6 94* 95.3 95.6 95.6 95.7 95.8 95.9 95.9 95.9 95, 9 95.9...BRANCH uI AUFTAC PSYCHROMETRIC SUMMARY ! A. EATHCR SERVICE/MAC 1 7 7 LOVER AF3 Or 70,73-81 FEE STATION STATION NAkE Ytms MONTe PAGE I nb ~iJ-CS( ~OtAS 4L...30 31(IN.H;) B AR OMET R I C P RE S S URE ( NB ) 100 150 600 650 900 950 1000 1050 (O1) II -I’ g 5 1 I I F P R E S 5 U R E A L T I T U D E (10 0 O’S FT

  3. High temperature dielectric properties of Apical, Kapton, Peek, Teflon AF, and Upilex polymers

    NASA Technical Reports Server (NTRS)

    Hammoud, A. N.; Baumann, E. D.; Overton, E.; Myers, I. T.; Suthar, J. L.; Khachen, W.; Laghari, J. R.

    1992-01-01

    Reliable lightweight systems capable of providing electrical power at the magawatt level are a requirement for future manned space exploration missions. This can be achieved by the development of high temperature insulating materials which are not only capable of surviving the hostile space environment but can contribute to reducing the mass and weight of the heat rejection system. In this work, Apical, Upilex, Kapton, Teflon AF, and Peek polymers are characterized for AC and DC dielectric breakdown in air and in silicone oil at temperatures up to 250 C. The materials are also tested in terms of their dielectric constant and dissipation factor at high temperatures with an electrical stress of 60 Hz, 200 V/mil present. The effects of thermal aging on the properties of the films are determined after 15 hours of exposure to 200 and 250 C, each. The results obtained are discussed and conclusions are made concerning the suitability of these dielectrics for use in capacitors and cable insulations in high temperature environments.

  4. Studying at the Universities of the Armed Forces: Comparative Results from the 1999 Student Questionnaire (Studieren an den UniBw: Vergleichende Ergebnisse aus der Studentenbefragung 1999)

    DTIC Science & Technology

    2002-12-01

    distanziert kollegial UniBw Miinchen: Auf den ersten Blick scheint das allgemeine Kommunikationsgeschehen in M • nchen im Prinzip dem an der Hamburger UniBw...Hochschulforschung m )chten wir an dieser Stelle danken fMr das Oberlassen des Frageinstrumen- tariums, das dem ZHQ zur Nutzung fu-r die eigene...gerweise war schon im Grandungskonzept der UniBw diesem Moment einer m ~glichst nahen, en- gen und transparenten Kommunikation besondere Beachtung

  5. AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription

    PubMed Central

    Okuda, Hiroshi; Kanai, Akinori; Ito, Shinji; Matsui, Hirotaka; Yokoyama, Akihiko

    2015-01-01

    Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL–AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL–AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation. PMID:26593443

  6. Tinian Island Nas, Mariana Islands. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1973-05-25

    unlimited distribution of this report to the public at large, or by DDC to the National Technical Information Service (NTIS). a technical report has be...OBSOLETE DATA PROCESSING RRANCH ETAC/USAF SURFACE WINDS 2 AIR WEATER SERVICE /MAC PERCENTAGE FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY... Service ( MAC ) REVISED UNIFORM SUMMARY OF SURF6CE WEATHER OBSERVATION5 TINIAN NAS MARIANA IS WBAN #41413 N 150 0 E 145 38 ELEV 250 FT WMO# PARTS A-F

  7. An Updated Version of the U.S. Air Force Multi-Attribute Task Battery (AF-MATB)

    DTIC Science & Technology

    2014-08-01

    assessing human performance in a controlled multitask environment. The most recent release of AF-MATB contains numerous improvements and additions...Strategic Behavior, MATB, Multitasking , Task Battery, Simulator, Multi-Attribute Task Battery, Automation 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...performance and multitasking strategy. As a result, a specific Information Throughput (IT) Mode was designed to customize the task to fit the Human

  8. Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide glucoside and γ-pyrone glucoside from Dianthus japonicus.

    PubMed

    Nakano, Takahiro; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2011-01-01

    From aerial parts of Dianthus japonicus, six new and seven known oleanane-type triterpene saponins were isolated. The structures of the new saponins, named dianthosaponins A-F, were elucidated by means of high resolution mass spectrometry, and extensive inspection of one- and two-dimensional NMR spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of anthranilic acid amide and a maltol glucoside were also isolated.

  9. Environmental Assessment for Clear AFS Grid Tie-in and Heat Plant, Clear Air Force Station, Alaska

    DTIC Science & Technology

    2013-07-01

    Alaska Administrative Code AAAQS Alaska ambient air quality standards ACM asbestos -containing material ADEC Alaska Department of Environmental...maintenance activities. While asbestos or lead based paint may be encountered during the expansion of the existing mechanical rooms and within the...AFS July 2013 13 products. All work would be done in compliance with Federal and State regulations as well as the OSHA Asbestos Standard (29 CFR

  10. Self-assembly of amphiphilic peptide (AF)6H5K15 derivatives: roles of hydrophilic and hydrophobic residues.

    PubMed

    Thota, Naresh; Jiang, Jianwen

    2014-03-13

    A molecular dynamics simulation study is reported to investigate the roles of hydrophilic and hydrophobic residues in the self-assembly of (AF)6H5K15 peptide derivatives. The peptide, as well as water and counterions, are represented by the MARTINI coarse-grained model. The assembly is observed to follow a three-step process: formation of small clusters, large clusters, and micelles. With increasing length of hydrophilic Lys residues in (AF)6H5Kn (n = 10, 15, 20, and 25), assembly capability is found to be reduced with the formation of smaller micelles or the presence of individual peptide chains. Upon replacing Ala by more hydrophobic Phe in AmFnH5K15 (m + n = 12), larger micelles are formed. With increasing length of hydrophobic Phe residues in FnH5K15 (n = 4, 8, 12, and 16), micelle size increases and the morphology shifts from spherical to fiber-like. The simulation study provides mechanistic insight into the crucial roles of hydrophilicity and hydrophobicity in the assembly of (AF)6H5K15 derivatives; it reveals that assembly capability is reduced by increasing hydrophilicity, whereas increasing hydrophobicity leads to morphology transition.

  11. A spent SRB used on STS-87 is lifted in a hoisting slip in Hangar AF at CCAS

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is lifted in a hoisting slip in the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  12. The SRB recovery ship Liberty Star reenters the Hangar AF area at CCAS with a spent SRB used on STS-

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Seen carrying a spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is the solid rocket booster recovery ship Liberty Star as it reenters the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  13. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

    PubMed

    Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

    2016-08-01

    Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.

  14. DensToolKit: A comprehensive open-source package for analyzing the electron density and its derivative scalar and vector fields

    NASA Astrophysics Data System (ADS)

    Solano-Altamirano, J. M.; Hernández-Pérez, Julio M.

    2015-11-01

    DensToolKit is a suite of cross-platform, optionally parallelized, programs for analyzing the molecular electron density (ρ) and several fields derived from it. Scalar and vector fields, such as the gradient of the electron density (∇ρ), electron localization function (ELF) and its gradient, localized orbital locator (LOL), region of slow electrons (RoSE), reduced density gradient, localized electrons detector (LED), information entropy, molecular electrostatic potential, kinetic energy densities K and G, among others, can be evaluated on zero, one, two, and three dimensional grids. The suite includes a program for searching critical points and bond paths of the electron density, under the framework of Quantum Theory of Atoms in Molecules. DensToolKit also evaluates the momentum space electron density on spatial grids, and the reduced density matrix of order one along lines joining two arbitrary atoms of a molecule. The source code is distributed under the GNU-GPLv3 license, and we release the code with the intent of establishing an open-source collaborative project. The style of DensToolKit's code follows some of the guidelines of an object-oriented program. This allows us to supply the user with a simple manner for easily implement new scalar or vector fields, provided they are derived from any of the fields already implemented in the code. In this paper, we present some of the most salient features of the programs contained in the suite, some examples of how to run them, and the mathematical definitions of the implemented fields along with hints of how we optimized their evaluation. We benchmarked our suite against both a freely-available program and a commercial package. Speed-ups of ˜2×, and up to 12× were obtained using a non-parallel compilation of DensToolKit for the evaluation of fields. DensToolKit takes similar times for finding critical points, compared to a commercial package. Finally, we present some perspectives for the future development and

  15. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

    PubMed

    Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes

    2016-05-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

  16. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes

    PubMed Central

    Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka

    2016-01-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID:27187611

  17. Stroke prevention in atrial fibrillation and ‘real world’ adherence to guidelines in the Balkan Region: The BALKAN-AF Survey

    PubMed Central

    Potpara, Tatjana S.; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S.; Polovina, Marija M.; Petranov, Stanislav L.; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y. H.; Potpara, Tatjana S.; Polovina, Marija; Milanov, Srdjan; Pavlovic, Marija; Petrovic, Marijana; Simovic, Stefan; Mitic, Gorana; Milanov, Marko; Savic, Jelena; Gnip, Sanja; Radovic, Pavica; Markovic, Snezana; Koncarevic, Ivana; Gavrilovic, Jelena; Acimovic, Tijana; Djikic, Dijana; Malic, Semir; Hodzic, Jusuf; Stojanovic, Milovan; Ilic, Marina Deljanin; Zlatar, Milan; Matic, Dragan; Lazic, Snezana; Peric, Vladan; Markovic, Sanja; Kovacevic, Snezana; Arandjelovic, Aleksandra; Asanin, Milika; Zdravkovic, Marija; Dan, Gheorghe-Andrei; Breha, Anca; Dan, Anca Rodica; Musetescu, Rodica; Popescu, Mircea Ioachim; Badila, Elisabeta; Georgescu, Catalina Arsenescu; Pop, Sorina; Popescu, Raluca; Neamtu, Simina; Oancea, Floriana; Trendafilova, Elina; Dimitrova, Elena; Goshev, Evgenii; Velichkova, Anna; Petranov, Stanislav; Kamenova, Delyana; Kamenova, Penka; Elefterova, Svetoslava; Shterev, Valentin; Zekova, Maria; Diukiandzhieva, Stela; Dimitrov, Boiko; Sotirov, Tihomir; Simeonova, Valentina; Drianovska, Dimitrina; Boiadzhieva, Liliya Ivanova Vasileva; Buchukova, Darina; Goda, Artan; Paparisto, Vilma; Gjergo, Hortensia; Mijo, Alma; Shirka, Ervina; Gjini, Viktor; Ekmekciu, Uliks; Refatllari, Ina; Kusljugic, Zumreta; Loncar, Daniela; Mrsic, Denis; Tulumovic, Hazim; Pojskic, Belma; Sijamija, Alma; Bijedic, Amira; Karamujic, Indira; Bijedic, Irma; Halilovic, Sanela; Sokolovic, Sekib; Manola, Sime; Zeljkovic, Ivan; Pavlovic, Nikola; Radeljic, Vjekoslav; Brusich, Sandro; Anic, Ante; Jeric, Melita; Pekic, Petar; Milas, Kresimir; Music, Ljilja; Bulatovic, Nebojsa; Nenezic, Ana; Asanovic, Dijana

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary ‘real-world’ AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the ‘truly low-risk’ patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  18. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice

    PubMed Central

    Börjesson, Anna E.; Farman, Helen H.; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K.; Windahl, Sara H.

    2016-01-01

    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  19. Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry

    PubMed Central

    Hamatani, Yasuhiro; Yamashita, Yugo; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru

    2015-01-01

    Background Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts. Methods The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. Results The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. Conclusions Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients. PMID:26540107

  20. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

    PubMed Central

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-01-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  1. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR).

    PubMed

    Weber, Axel; Taube, Sylvia; Zur Stadt, Udo; Horstmann, Martin; Krohn, Knut; Bradtke, Jutta; Teigler-Schlegel, Andrea; Leiblein, Sabine; Christiansen, Holger

    2012-11-09

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available.

  2. U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 3' End Formation.

    PubMed

    Park, Sung Mi; Ou, Jianhong; Chamberlain, Lynn; Simone, Tessa M; Yang, Huan; Virbasius, Ching-Man; Ali, Abdullah M; Zhu, Lihua Julie; Mukherjee, Siddhartha; Raza, Azra; Green, Michael R

    2016-05-19

    Recurrent mutations in the splicing factor U2AF35 are found in several cancers and myelodysplastic syndrome (MDS). How oncogenic U2AF35 mutants promote transformation remains to be determined. Here we derive cell lines transformed by the oncogenic U2AF35(S34F) mutant and identify aberrantly processed pre-mRNAs by deep sequencing. We find that in U2AF35(S34F)-transformed cells the autophagy-related factor 7 (Atg7) pre-mRNA is abnormally processed, which unexpectedly is not due to altered splicing but rather selection of a distal cleavage and polyadenylation (CP) site. This longer Atg7 mRNA is translated inefficiently, leading to decreased ATG7 levels and an autophagy defect that predisposes cells to secondary mutations, resulting in transformation. MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome. Collectively, our results reveal a basis for U2AF35(S34F) oncogenic activity.

  3. Letter to the Editor: H-1, C-13 and N-15 Assignments for the Archaeglobus fulgidis Protein AF2095.

    SciTech Connect

    Powers, Robert; Acton, Thomas; Chiang, Yiwen; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Ma, LiChung; Rost, Burkhard; Montelione, Gaetano

    2004-09-01

    The Human genome project promises to provide an unprecedented wealth of information on cell biology, development, evolution and physiology. Translating this immense increase in genomic information into advances in medicine and human health requires a concerted effort to explore and investigate the structure and molecular activity for the vast amount of proteins in the Human proteome that lack any such explicit experimental information. Structural genomics is providing a means to determine the molecular and cellular function of these proteins by characterizing the complete range of protein folds (Montelione, 2001). By annotating sequence information with a protein structure, it is sometimes possible to decipher the biochemical activity of hypothetical proteins from structural similarity and the conservation of spatial arrangement of active site residues. Homology can often be inferred by structural similarity even in the absence of recognizable sequence similarity, and can sometimes be used to identify functional relationships between distantly related proteins. Determining an experimental structure for each protein in a proteome is currently impractical because of the significant time commitment and resources required by X-ray and NMR. Therefore, the current paradigm of structural genomics is to determine a representative structure for each cluster of homologous protein domain sequences that lack similarity to a protein domain with a known structure. In this manner, comparative modeling using a single experimental structure can provide approximate but useful 3D structural information for an entire protein domain family. The Northeast Structural Genomics Consortium (NESG; www.nesg.org) is a pilot project funded by the National Institutes of Health Protein Structure Initiative, focusing on proteins from eukaryotic model organisms including humans. The thermophillic archaea Archaeglobus fulgidis AF2095 protein is an example of a protein of unknown biological function

  4. Paleoenvironmental and Human Behavioral Implications of the Boegoeberg 1 Late Pleistocene Hyena Den, Northern Cape Province, South Africa

    NASA Astrophysics Data System (ADS)

    Klein, Richard G.; Cruz-Uribe, Kathryn; Halkett, David; Hart, Tim; Parkington, John E.

    1999-11-01

    Boegoeberg 1 (BOG1) is located on the Atlantic coast of South Africa, 850 km north of Cape Town. The site is a shallow rock shelter in the side of a sand-choked gully that was emptied by diamond miners. Abundant coprolites, chewed bones, and partially digested bones implicate hyenas as the bone accumulators. The location of the site, quantity of bones, and composition of the fauna imply it was a brown hyena nursery den. The abundance of Cape fur seal bones shows that the hyenas had ready access to the coast. Radiocarbon dates place the site before 37,000 14C yr ago, while the large average size of the black-backed jackals and the presence of extralimital ungulates imply cool, moist conditions, probably during the early part of the last glaciation (isotope stage 4 or stage 3 before 37,000 14C yr ago) or perhaps during one of the cooler phases (isotope substages 5d or 5b) within the last interglaciation. Comparisons of the BOG1 seal bones to those from regional Middle Stone Age (MSA) and Later Stone Age (LSA) archeological sites suggest (1) that hyena and human seal accumulations can be distinguished by a tendency for vertebrae to be much more common in a hyena accumulation and (2) that hyena and LSA accumulations can be distinguished by a tendency for hyena-accumulated seals to represent a much wider range of individual seal ages. Differences in the way hyenas and people dismember, transport, and consume seal carcasses probably explain the contrast in skeletal part representation, while differences in season of occupation explain the contrast in seal age representation. Like modern brown hyenas, the BOG1 hyenas probably occupied the coast year-round, while the LSA people focused their coastal visits on the August-October interval when nine-to-eleven-month-old seals were abundant. The MSA sample from Klasies River Mouth Cave 1 resembles BOG1 in seal age composition, suggesting that unlike LSA people, MSA people obtained seals more or less throughout the year.

  5. Intranasal Administration of the Antisecretory Peptide AF-16 Reduces Edema and Improves Cognitive Function Following Diffuse Traumatic Brain Injury in the Rat

    PubMed Central

    Clausen, Fredrik; Hansson, Hans-Arne; Raud, Johan; Marklund, Niklas

    2017-01-01

    A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls. The rats survived for either 48 h or 15 days post-injury. At 48 h, the animals were tested in the Morris water maze (MWM) for memory function and their brains analyzed for cerebral edema. Here, mFPI-induced brain edema compared to sham or naïve controls that was significantly reduced by AF-16 treatment (p < 0.05) although MWM performance was not altered. In the 15-day survival groups, the MWM learning and memory abilities as well as histological changes were analyzed. AF-16-treated brain-injured animals shortened both MWM latency and swim path in the learning trials (p < 0.05) and improved probe trial performance compared to brain-injured controls treated with the inactive reference peptide. A modest decrease by AF-16 on TBI-induced changes in hippocampal glial acidic fibrillary protein (GFAP) staining (p = 0.11) was observed. AF-16 treatment did not alter any other immunohistochemical analyses (degenerating neurons, beta-amyloid precursor protein (β-APP), and Olig2). In conclusion, intranasal AF-16-attenuated brain edema and enhanced visuospatial learning and memory following diffuse TBI in the rat. Intranasal administration early post-injury of a promising neuroprotective substance offers a novel treatment approach for TBI. PMID:28261150

  6. Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

    PubMed

    Spencer, Ryan J; Amerena, John V

    2015-12-01

    Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

  7. Evaluation of the sustainability and clinical outcome of alternatives for families: A cognitive-behavioral therapy (AF-CBT) in a child protection center

    PubMed Central

    Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for child physical abuse and family aggression/conflict that was included in the National Child Traumatic Stress Network’s initial EBT dissemination efforts in 2002. Seven practitioners participated in a year-long Learning Collaborative in AF-CBT and in similar training programs for 4 other EBTs. The agency’s routine data collection system was used to document the clinical and adjustment outcomes of 52 families presenting with a physically abused child who received their services between 2 and 5 years after the AF-CBT training had ended. Measures of the use of all 5 EBTs documented their frequency, internal consistency, and intercorrelations. Controlling for the unique content of the other four EBTs, the amount of AF-CBT Abuse-specific content delivered was related to improvements on standardized parent rating scales (i.e., child externalizing behavior, anger, anxiety, social competence) and both parent and clinician ratings of the child’s adjustment at discharge (i.e., child more safe, less scared/sad, more appropriate with peers). The amount of AF-CBT General content was related to a few discharge ratings (better child prognosis, helpfulness to parents). These novel data provide suggestive evidence for the sustainability and clinical benefits of AF-CBT in an existing community clinic serving physically abused children and their families, and are discussed in the context of key developments in the treatment model and dissemination literature. PMID:21354619

  8. Green-synthesized silver nanoparticles as a novel control tool against dengue virus (DEN-2) and its primary vector Aedes aegypti.

    PubMed

    Sujitha, Vasu; Murugan, Kadarkarai; Paulpandi, Manickam; Panneerselvam, Chellasamy; Suresh, Udaiyan; Roni, Mathath; Nicoletti, Marcello; Higuchi, Akon; Madhiyazhagan, Pari; Subramaniam, Jayapal; Dinesh, Devakumar; Vadivalagan, Chithravel; Chandramohan, Balamurugan; Alarfaj, Abdullah A; Munusamy, Murugan A; Barnard, Donald R; Benelli, Giovanni

    2015-09-01

    Dengue is an arthropod-borne viral infection mainly vectored through the bite of Aedes mosquitoes. Recently, its transmission has strongly increased in urban and semi-urban areas of tropical and sub-tropical regions worldwide, becoming a major international public health concern. There is no specific treatment for dengue. Its prevention and control solely depends on effective vector control measures. In this study, we proposed the green-synthesis of silver nanoparticles (AgNP) as a novel and effective tool against the dengue serotype DEN-2 and its major vector Aedes aegypti. AgNP were synthesized using the Moringa oleifera seed extract as reducing and stabilizing agent. AgNP were characterized using a variety of biophysical methods including UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and sorted for size categories. AgNP showed in vitro antiviral activity against DEN-2 infecting vero cells. Viral titer was 7 log10 TCID50/ml in control (AgNP-free), while it dropped to 3.2 log10 TCID50/ml after a single treatment with 20 μl/ml of AgNP. After 6 h, DEN-2 yield was 5.8 log10 PFU/ml in the control, while it was 1.4 log10 PFU/ml post-treatment with AgNP (20 μl/ml). AgNP were highly effective against the dengue vector A. aegypti, with LC50 values ranging from 10.24 ppm (I instar larvae) to 21.17 ppm (pupae). Overall, this research highlighted the concrete potential of green-synthesized AgNP in the fight against dengue and its primary vector A. aegypti. Further research on structure-activity relationships of AgNP against other dengue serotypes is urgently required.

  9. Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

    PubMed Central

    Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

    2016-01-01

    Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

  10. Adsorption/desorption phenomena on pure and Teflon AF-coated titania surfaces studied by dynamic contact angle analysis.

    PubMed

    Rupp, F; Axmann, D; Ziegler, C; Geis-Gerstorfer, J

    2002-12-15

    As a result of inflammatory processes, plaque formation on dental titanium implants often leads to clinically pathogenic situations. This special biofilm formation on (bio)materials in contact with saliva is initiated by ionic and protein interactions. In this interfacial process, albumin becomes a main constituent of dental pellicle. Interfacial reactions change the surface characteristics. They determine the following steps of macromolecular adsorption and bacterial adhesion. This work focuses on the dynamic contact angle analysis (DCA), which is a tool for online measurements of dynamic changes of wettability without disturbing the interface during detection. Repeatability of the DCA method has been assessed according to the Bland and Altman method. The kinetics and equilibrium data of shifts in the wetting tension hysteresis indicate ionic influences at the titanium/bovine serum albumin (BSA) interface: the Ca-mediated increase of the BSA adsorption on titanium and the adsorption maximum at the isoelectric point (IEP) of BSA. Ti was surface modified by Teflon AF polymeric coatings. The result of the assessment gives reason to consider Teflon AF as a reference material for DCA repeatability studies. This surface modification caused drastic changes in the dynamic interfacial reactions. Shifts in the wetting tensions during DCA adsorption-desorption experiments clearly demonstrated the partially irreversible adsorption of BSA on Teflon AF. In contrast, reversible adsorption behavior was detected on pure Ti surfaces. These findings strengthen the hypothesis that the analysis of dynamic changes in wetting tension and wetting tension hysteresis is a sensitive analytical method for the detection of dynamic interfacial changes at biomaterial/biosystem interfaces during the initial steps of biofilm formation.

  11. Single-unit activity during natural vision: diversity, consistency, and spatial sensitivity among AF face patch neurons.

    PubMed

    McMahon, David B T; Russ, Brian E; Elnaiem, Heba D; Kurnikova, Anastasia I; Leopold, David A

    2015-04-08

    Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene.

  12. The ultraviolet-bright, slowly declining transient PS1-11af as a partial tidal disruption event

    SciTech Connect

    Chornock, R.; Berger, E.; Zauderer, B. A.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Kirshner, R. P.; Lunnan, R.; Marion, G. H.; Narayan, G.; Gezari, S.; Rest, A.; Riess, A. G.; Chomiuk, L.; Huber, M. E.; Lawrence, A.; and others

    2014-01-01

    We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ∼0.002 M {sub ☉}, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

  13. Progress Report on Activities in Support of Composite Repair Engineering Development Program Tasks AF, AH and AI

    DTIC Science & Technology

    2006-11-01

    Task AF Designation Aluminium Alloy Surface Preparation GBSP 7075T76UC Bare 7075-T76 Scotchbrite abrade, solvent clean, grit-blast, 1% aqueous epoxy...silane, BR-127 prime GBSNP 7075T76UC Bare 7075-T76 Scotchbrite abrade, solvent clean, grit-blast, 1% aqueous epoxy silane GBSP 7075T6C Clad 7075-T76...Cohesive Failure (%) Specimen 1 2 3 4 5 Average GBSP 7075T76UC 100 85 90 90 95 92.0 GBSNP 7075T76UC 94 94 98 100 100 97.2 GBSP 7075T6C 30 40 50 35 20 35

  14. U-Tapao RTNAS, Thailand. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1973-10-26

    to unlimited distribution of this report to the public at large, or by DTIC to the National Technical Information Service (NTIS). This technical...Force Environmental Technical App1. Center Scott AFB IL 62225 ,bs~yfR ffoFFICE NAME AND ADDRESS 12. REPORT DATE Air Weather Service (MAC) 3. 26 OCT... Service (MAC ) " REVISED NIFORM SUMMARY OF SURFACE WEA1HER OBSERVATIONS U-TAPAO RTNAS THAILAND WBAN* 41028 N 12 41 E 101 01 ELEV 69 FT VTLU WMO# PARTS A-F

  15. Volk FLD. Camp Douglas, Wisconsin. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1970-08-03

    REVISED’UNIFORWSUMMARY OF SURFACE WEATHER, OBSERVATION4S CAMP DOUGLAS WISCONSIN/VOLK FLO WSAN# 94930 N 43 56 W 90󈧔, ELEVi 925 FT. KVOK Wt ~O#I t PARTS A-F’ POR...Observations (RUSSW0)- Volk FLD,’ Camp Douglas , Wisconsin b PERORMINc ORG REPORT NUW ER 7. AUTHOR(o) CNTRACT OR GRANT HUMBER() 9, PERFORMING ORGANIZATION NAME...STATIONIFTI) KBAAOMEICR OAI 1 Volk Fld/Camp Douglas Wsconsin A Jur ,. Sep 66 N 43 56 W 90 16 925 Ancrold 13to19 1 No Change A Oct V Oct 68 No Change No

  16. Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293

    PubMed Central

    Kanhayuwa, Lakkhana; Coutts, Robert H. A.

    2016-01-01

    Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4–14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140–493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3’-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50–65% and 60–75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259–343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity. PMID:27736869

  17. AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

    SciTech Connect

    Crapse, K.; Rudisill, T.; O'Rourke, P.; Kyser, E.

    2014-07-02

    In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used for dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling

  18. Neuroprotective and Anti-Inflammatory Effects of the Flavonoid-Enriched Fraction AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury

    PubMed Central

    Keddy, Paul G. W.; Dunlop, Kate; Warford, Jordan; Samson, Michel L.; Jones, Quinton R. D.; Rupasinghe, H. P. Vasantha; Robertson, George S.

    2012-01-01

    We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling. PMID:23251498

  19. Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury.

    PubMed

    Keddy, Paul G W; Dunlop, Kate; Warford, Jordan; Samson, Michel L; Jones, Quinton R D; Rupasinghe, H P Vasantha; Robertson, George S

    2012-01-01

    We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling.

  20. Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2)

    PubMed Central

    Lian, Wei; Jayapal, Karthik P; Charaniya, Salim; Mehra, Sarika; Glod, Frank; Kyung, Yun-Seung; Sherman, David H; Hu, Wei-Shou

    2008-01-01

    Background A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. Overexpression of afsS in S. coelicolor and certain related species causes antibiotic stimulatory effects in the host organism. Although recent studies have uncovered some of the upstream events activating this gene, the mechanisms through which this signal is relayed downstream leading to the eventual induction of antibiotic pathways remain unclear. Results In this study, we employed whole-genome DNA microarrays and quantitative PCRs to examine the transcriptome of an afsS disruption mutant that is completely deficient in the production of actinorhodin, a major S. coelicolor antibiotic. The production of undecylprodigiosin, another prominent antibiotic, was, however, perturbed only marginally in the mutant. Principal component analysis of temporal gene expression profiles identified two major gene classes each exhibiting a distinct coordinate differential expression pattern. Surprisingly, nearly 70% of the >117 differentially expressed genes were conspicuously associated with nutrient starvation response, particularly those of phosphate, nitrogen and sulfate. Furthermore, expression profiles of some transcriptional regulators including at least two sigma factors were perturbed in the mutant. In almost every case, the effect of afsS disruption was not observed until the onset of stationary phase. Conclusion Our data suggests a comprehensive role for S. coelicolor AfsS as a master regulator of both antibiotic synthesis and nutritional stress response, reminiscent of alternative sigma factors found in several bacteria. PMID:18230178

  1. Comparison of the exact thermodynamics of the AF Blume-Emery-Grifiths and of the spin-1 ferromagnetic Ising models

    NASA Astrophysics Data System (ADS)

    Corrêa Silva, E. V.; Thomaz, M. T.

    2016-11-01

    We study in detail the thermodynamics of the anti-ferromagnetic Blume-Emery-Griffiths (AF BEG) model in the presence of a longitudinal magnetic field. Its thermodynamics is derived from the exact Helmholtz free energy (HFE) of the model, valid for T > 0. Numerical simulations of this model on a periodic space chain with 10 sites (N=10) yield the energy spectra of the model at K/J = 2 for D/J = 1 and D/J = 2, thus helping us compare, for a broad range of temperature, how some (per site) thermodynamic functions with the same value of K/J but distinct values of D/J behave, namely: the z-component of the magnetization, the specific heat and the entropy. These thermodynamic functions of the AF BEG model at K/|J| = 2 are compared to those of the spin-1 ferromagnetic Ising model with D/|J| > 1.5, for which the T=0 phase diagrams of both models are identical. This comparison is done in a large interval of temperature.

  2. Inhibitory and Apoptosis-Inducing Effects of Newcastle Disease Virus Strain AF2240 on Mammary Carcinoma Cell Line

    PubMed Central

    Keong, Yong Yoke; Othman, Fauziah

    2015-01-01

    Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner. PMID:25821783

  3. Comparison of the ferromagnetic Blume-Emery-Griffiths model and the AF spin-1 longitudinal Ising model at low temperature

    NASA Astrophysics Data System (ADS)

    Thomaz, M. T.; Corrêa Silva, E. V.

    2016-03-01

    We derive the exact Helmholtz free energy (HFE) of the standard and staggered one-dimensional Blume-Emery-Griffiths (BEG) model in the presence of an external longitudinal magnetic field. We discuss in detail the thermodynamic behavior of the ferromagnetic version of the model, which exhibits magnetic field-dependent plateaux in the z-component of its magnetization at low temperatures. We also study the behavior of its specific heat and entropy, both per site, at finite temperature. The degeneracy of the ground state, at T=0, along the lines that separate distinct phases in the phase diagram of the ferromagnetic BEG model is calculated, extending the study of the phase diagram of the spin-1 antiferromagnetic (AF) Ising model in S.M. de Souza and M.T. Thomaz, J. Magn. and Magn. Mater. 354 (2014) 205 [5]. We explore the implications of the equality of phase diagrams, at T=0, of the ferromagnetic BEG model with K/|J| = - 2 and of the spin-1 AF Ising model for D/|J| > 1/2.

  4. Linear quadratic game and non-cooperative predictive methods for potential application to modelling driver-AFS interactive steering control

    NASA Astrophysics Data System (ADS)

    Na, Xiaoxiang; Cole, David J.

    2013-02-01

    This paper is concerned with the modelling of strategic interactions between the human driver and the vehicle active front steering (AFS) controller in a path-following task where the two controllers hold different target paths. The work is aimed at extending the use of mathematical models in representing driver steering behaviour in complicated driving situations. Two game theoretic approaches, namely linear quadratic game and non-cooperative model predictive control (non-cooperative MPC), are used for developing the driver-AFS interactive steering control model. For each approach, the open-loop Nash steering control solution is derived; the influences of the path-following weights, preview and control horizons, driver time delay and arm neuromuscular system (NMS) dynamics are investigated, and the CPU time consumed is recorded. It is found that the two approaches give identical time histories as well as control gains, while the non-cooperative MPC method uses much less CPU time. Specifically, it is observed that the introduction of weight on the integral of vehicle lateral displacement error helps to eliminate the steady-state path-following error; the increase in preview horizon and NMS natural frequency and the decline in time delay and NMS damping ratio improve the path-following accuracy.

  5. Heterologous expression of metK1-sp and afsR-sp in Streptomyces venezuelae for the production of pikromycin.

    PubMed

    Maharjan, Sushila; Oh, Tae-Jin; Lee, Hei Chan; Sohng, Jae Kyung

    2008-09-01

    Two regulator genes, metK1-sp and afsR-sp, from Streptomyces peucetius ATCC 27952 were heterologously expressed in S. venezuelae ATCC 15439, to produce 14-membered pikromycin antibiotics. The production of pikromycin was increased by 1.6-fold and 2.6-fold by the expression of metK1-sp and afsR-sp, respectively. The overexpression of metK1-sp and afsR-sp in S. venezuelae stimulated the expression of the pathway-specific regulatory genes, pikD and ketosynthase, as demonstrated by RT-PCR. The elevated transcripts of the pikD and ketosynthase genes were consistent with the enhanced production of pikromycin.

  6. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.

    PubMed Central

    vom Baur, E; Zechel, C; Heery, D; Heine, M J; Garnier, J M; Vivat, V; Le Douarin, B; Gronemeyer, H; Chambon, P; Losson, R

    1996-01-01

    Using a yeast two-hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand- and AF-2 activating domain (AF-2 AD)-dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha-helix core of the AF-2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF-2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF-2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF-2 of nuclear receptors through different mechanisms. Images PMID:8598193

  7. Variation of B1 gene and AF146527 repeat element copy numbers according to Toxoplasma gondii strains assessed using real-time quantitative PCR.

    PubMed

    Costa, Jean-Marc; Bretagne, Stéphane

    2012-04-01

    Using the multicopy B1 gene and AF146527 element for the amplification of Toxoplasma gondii DNA raises the issue of reliable quantification for clinical diagnosis. We applied relative quantification to reference strains using the single-copy P30 gene as a reference. According to the parasite type, the copy numbers for the B1 gene and AF146527 element were found to be 5 to 12 and 4 to 8 times lower than the previous estimations of 35 and 230 copies, respectively.

  8. Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116

    SciTech Connect

    Bloom, J.W.; Halonen, M.; Seaver, N.A.; Yamamura, H.I.

    1987-07-27

    Recent studies have demonstrated that the majority of muscarinic receptors in rabbit peripheral lung homogenates bind pirenzepine with high affinity (putative M1 subtype). In experiments of AF-DX 116 inhibiting (TH)(-)quinuclidinyl benzilate or (TH)pirenzepine, the authors found similar inhibitory constants for AF-DX 116 binding in rat heart and rabbit peripheral lung that were 4-fold smaller (i.e. of higher affinity) than the inhibitory constant for rat cerebral cortex. This results demonstrates heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex. 20 references, 1 figure, 2 tables.

  9. A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells.

    PubMed

    Kotani, Ai; Ha, Daon; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2010-03-15

    MLL-AF4 acute lymphocytic leukemia has a poor prognosis, and the mechanisms by which these leukemias develop are not understood despite intensive research based on well-known concepts and methods. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate expression of target mRNA transcripts. We recently reported that ectopic expression of miR-128b together with miR-221, two of the miRNAs downregulated in MLL-AF4 ALL, restores glucocorticoid resistance through downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11). Here we report the identification of new mutations in miR-128b in RS4;11 cells, derived from MLL-AF4 ALL patient. One novel mutation significantly reduces the processing of miR-128b. Finally, this base change occurs in a primary MLL-AF4 ALL sample as an acquired mutation. These results demonstrate that the novel mutation in miR-128b in MLL-AF4 ALL alters the processing of miR-128b and that the resultant downregulation of mature miR-128b contributes to glucocorticoid resistance through the failure to downregulate the fusion oncogenes.

  10. Environmental Aging of Scotch-Weld(TradeMark) AF-555M Structural Adhesive in Composite to Composite Bonds

    NASA Technical Reports Server (NTRS)

    Hou, Tan-Hung; Miner, Gilda A.; Lowther, Sharon E.; Connell, John W.; Baughman, James M.

    2010-01-01

    Fiber reinforced resin matrix composites have found increased usage in recent years. Due to the lack of service history of these relatively new material systems, their long-term aging performance is not well established. In this study, adhesive bonds were prepared by the secondary bonding of Scotch-Weld(TradeMark) AF-555M between pre-cured adherends comprised of T800H/3900-2 uni-directional laminate. The adherends were co-cured with wet peel-ply for surface preparation. Each bond-line of single-lap-shear (SLS) specimen was measured to determine thickness and inspected visually for voids. A three-year environmental aging plan for the SLS specimens at 82 C and 85% relative humidity was initiated. SLS strengths were measured for both controls and aged specimens at room temperature and 82 C. The aging results of strength retention and failure modes to date are reported.

  11. Selenium species determination in selenium-enriched pumpkin (Cucurbita pepo L.) seeds by HPLC-UV-HG-AFS.

    PubMed

    Smrkolj, Polona; Stibilj, Vekoslava; Kreft, Ivan; Kapolna, Emese

    2005-12-01

    Pumpkins were treated by spraying the leaves in the flowering period with a water solution containing 1.5 mg Se per liter in the form of Na2SeO4. The average total selenium content of seeds was found to be 0.19 microg g(-1) in nontreated pumpkins and 1.1 microg g(-1) in exposed ones. For speciation analysis, enzymatic hydrolysis with different amounts of Protease XIV was carried out. Under optimal conditions of enzymatic hydrolysis, 90% of the total selenium was found in soluble forms. Separation of species was performed using HPLC on anion and cation exchange columns and for detection UVHG-AFS was applied. In enzymatic hydrolysis extracts, the main fraction of selenium was bound as selenomethionine (SeMet), representing on average of 81 +/- 8% of the total Se content in the sample.

  12. Rubusuaviins A-F, monomeric and oligomeric ellagitannins from Chinese sweet tea and their alpha-amylase inhibitory activity.

    PubMed

    Li, Haizhou; Tanaka, Takashi; Zhang, Ying-Jun; Yang, Chong-Ren; Kouno, Isao

    2007-09-01

    Six new ellagitannins herein, rubusuaviins A-F, were isolated from the aqueous acetone extract of Chinese sweet tea (Tien-cha, dried leaves of Rubus suavissimus S. LEE) together with seven known tannins. Rubusuaviin A was characterized as 1-O-galloyl-2,3-O-(S)-HHDP-4,6-O-(S)-sanguisorboyl-beta-D-glucopyranose. Rubusuaviins B, C, and E are dimeric, trimeric, and tetrameric ellagitannins, respectively, in which the sanguisorboyl groups were connected ellagitannin units. Rubusuaviins D and F were desgalloyl derivatives of rubusuaviins C and E, respectively. The inhibition of alpha-amylase activity by rubusuaviins and related ellagitannins was compared. Ellagitannins with beta-galloyl groups at the glucose C-1 positions showed stronger inhibition compared with the alpha-galloyl and desgalloyl compounds. The molecular weight of these compounds was not important for the inhibition of alpha-amylase activity.

  13. Overtreatment and undertreatment with anticoagulation in relation to cardioversion of atrial fibrillation (the RHYTHM-AF study).

    PubMed

    Lip, Gregory Y H; Gitt, Anselm K; Le Heuzey, Jean-Yves; Bash, Lori D; Morabito, Christopher J; Bernhardt, Alexandra A; Sisk, Christine McCrary; Chazelle, François; Crijns, Harry J

    2014-02-01

    Antithrombotic therapy is central to the management of atrial fibrillation. This analysis from the RHYTHM-atrial fibrillation (RHYTHM-AF) registry explored the appropriateness of antithrombotic therapy in relation to stroke risk and atrial fibrillation duration in patients with atrial fibrillation. RHYTHM-AF, a prospective multinational registry, enrolled consecutive adult patients with atrial fibrillation considered for cardioversion. We compared the type of antithrombotic therapy administered at the time of cardioversion and at discharge with stroke risk ("high stroke risk" defined by CHA2DS2-VASc >1) and duration of atrial fibrillation (≤48 vs >48 hours or unknown duration). Of 2,972 patients who were cardioverted (34.5% through pharmacologic cardioversion [PCV] and 65.5% through electrical cardioversion [ECV]), 65% were at high risk of stroke and 30% presented with atrial fibrillation of >48-hour or unknown duration. At the time of PCV and ECV, 36% (n = 242) and 84% (n = 1,075) of high-risk patients, respectively, were taking vitamin K antagonists or heparin. At discharge, these rates increased to 62% (n = 414) and 93% (n = 1,191), respectively. Of all low-stroke risk patients with short-duration atrial fibrillation undergoing PCV (n = 260) and ECV (n = 111), 7% (n = 17) and 30% (n = 33), respectively, were taking vitamin K antagonists or heparin at the time of cardioversion. At discharge, these rates increased to 19% (n = 50) and 40% (n = 44), respectively. In conclusion, ECV was frequently performed under appropriate antithrombotic therapy for most high-risk patients with atrial fibrillation, whereas PCV was frequently performed without appropriate antithrombotic therapy. To enhance pericardioversion stroke prevention, cardioversion algorithms should focus less on the type of conversion and more on stroke risk factors and atrial fibrillation duration.

  14. RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers

    PubMed Central

    2012-01-01

    Background Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. Methods/design RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. Discussion A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve

  15. Morphological and molecular investigations of a microsporidium infecting the European grape vine moth, Lobesia botrana Den. et Schiff., and its taxonomic determination as Cystosporogenes legeri nov. comb.

    PubMed

    Kleespies, Regina G; Vossbrinck, Charles R; Lange, Martin; Jehle, Johannes A

    2003-07-01

    We have isolated a microsporidium from a laboratory stock of the European grape vine moth, Lobesia botrana Den. et Schiff. (Lepidoptera, Tortricidae). Screening of this stock showed an infection rate of more than 90%, whereas field collected larvae from three different locations in Rhineland-Palatinate (Germany) did not demonstrate any signs of infection. Light and electron microscopic investigations of infected insects showed that gross pathology, morphology, and ultrastructure of the microsporidium are similar to those described earlier for Pleistophora legeri. Comparative phylogenetic analysis of the small subunit rDNA using maximum likelihood, maximum parsimony, and neighbour joining distance methods showed that our isolate was closely related to Cystosporogenes operophterae. Based on our morphological and molecular investigations we propose to rename this species Cystosporogenes legeri nov. comb.

  16. Transoral vertebral augmentation with polymethylmethacrylate in the treatment of a patient with a dens fracture nonunion and subarticular vertebral body fracture of C2.

    PubMed

    Beall, Douglas P; Stanfield, Matthew; Martin, Hal D; Stapp, Annette M

    2007-05-01

    The injection of polymethylmethacrylate (PMMA) is a minimally invasive, image-guided procedure used to treat vertebral fractures due to osteoporosis, metastatic lesions, multiple myeloma, and benign but destabilizing bone tumors. The injection of PMMA into the C2 vertebral body using the transoral technique has been reported in three separate patients for treatment of benign tumors (a vertebral hemangioma and an aneurysmal bone cyst) and for multiple myeloma in the third patient. Although the injection of PMMA into the vertebral body is most commonly performed to treat benign vertebral compression fractures, a transoral C2 approach has not been reported in the English literature as a treatment for a benign fracture of C2. We report the treatment of a fracture and nonunion of the base of the dens and a subarticular fracture of the vertebral body of C2 using a bilateral transoral approach.

  17. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.

    PubMed Central

    Le Douarin, B; Zechel, C; Garnier, J M; Lutz, Y; Tora, L; Pierrat, P; Heery, D; Gronemeyer, H; Chambon, P; Losson, R

    1995-01-01

    Nuclear receptors (NRs) bound to response elements mediate the effects of cognate ligands on gene expression. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through intermediary proteins/mediators. We have isolated a mouse nuclear protein, TIF1, which enhances RXR and RAR AF-2 in yeast and interacts in a ligand-dependent manner with several NRs in yeast and mammalian cells, as well as in vitro. Remarkably, these interactions require the amino acids constituting the AF-2 activating domain conserved in all active NRs. Moreover, the oestrogen receptor (ER) AF-2 antagonist hydroxytamoxifen cannot promote ER-TIF1 interaction. We propose that TIF1, which contains several conserved domains found in transcriptional regulatory proteins, is a mediator of ligand-dependent AF-2. Interestingly, the TIF1 N-terminal moiety is fused to B-raf in the mouse oncoprotein T18. Images PMID:7744009

  18. OmniGen-AF alters rectal temperature (RT) and leukocyte profiles in dairy cows exposed to heat stress (HS) following acute activation of the stress axis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in the response of OmniGen-AF (OG) supplemented dairy cows to a corticotropin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 162±1 days in milk)...

  19. Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal-Knorr pyrrole formation and gas concentration measurement by inline flow titration.

    PubMed

    Cranwell, Philippa B; O'Brien, Matthew; Browne, Duncan L; Koos, Peter; Polyzos, Anastasios; Peña-López, Miguel; Ley, Steven V

    2012-08-14

    Using a simple and accessible Teflon AF-2400 based tube-in-tube reactor, a series of pyrroles were synthesised in flow using the Paal-Knorr reaction of 1,4-diketones with gaseous ammonia. An inline flow titration technique allowed measurement of the ammonia concentration and its relationship to residence time and temperature.

  20. The Mouse Murr1 Gene Is Imprinted in the Adult Brain, Presumably Due to Transcriptional Interference by the Antisense-Oriented U2af1-rs1 Gene

    PubMed Central

    Wang, Youdong; Joh, Keiichiro; Masuko, Sadahiko; Yatsuki, Hitomi; Soejima, Hidenobu; Nabetani, Akira; Beechey, Colin V.; Okinami, Satoshi; Mukai, Tsunehiro

    2004-01-01

    The mouse Murr1 gene contains an imprinted gene, U2af1-rs1, in its first intron. U2af1-rs1 shows paternal allele-specific expression and is transcribed in the direction opposite to that of the Murr1 gene. In contrast to a previous report of biallelic expression of Murr1 in neonatal mice, we have found that the maternal allele is expressed predominantly in the adult brain and also preferentially in other adult tissues. This maternal-predominant expression is not observed in embryonic and neonatal brains. In situ hybridization experiments that used the adult brain indicated that Murr1 gene was maternally expressed in neuronal cells in all regions of the brain. We analyzed the developmental change in the expression levels of both Murr1 and U2af1-rs1 in the brain and liver, and we propose that the maternal-predominant expression of Murr1 results from transcriptional interference of the gene by U2af1-rs1 through the Murr1 promoter region. PMID:14673161

  1. 26 CFR 1.468A-8T - Special transfers to qualified funds pursuant to section 468A(f) (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) General rule—(1) In general. Under section 468A(f), a taxpayer maintaining a qualified nuclear decommissioning fund with respect to a nuclear power plant may transfer cash or property into the fund (a special... pre-2005 nonqualifying amount of nuclear decommissioning costs with respect to the nuclear power...

  2. Inactive allele-specific methylation and chromatin structure of the imprinted gene U2af1-rs1 on mouse chromosome 11

    SciTech Connect

    Shibata, Hideo; Yoshino, Kiyoshi; Kamiya, Mamoru

    1996-07-01

    The imprinted U2Af1-rs1 gene that maps to mouse chromosome 11 is predominately expressed from the paternal allele. We examined the methylation of genomic sequences in and around the U2af1-rs1 locus to establish the extent of sequence modifications that accompanied the silencing of the maternal allele. The analysis of HapII or HhaI sites showed that the silent maternal allele was hypermethylated in a block of CpG sequences that covered more than 10 kb. By comparison, the expressed paternal allele was unmethylated from a CpG island upstream of the transcribed region through 2 kb. An analysis of DNaseI hypersensitivity of a putative promoter of U2af1-rs1 showed an open chromatin conformation only on the unmethylated, expressed paternal allele. These results suggest that allele-specific hypermethylation covering the gene and its upstream CpG island plays a role in maternal allele repression of U2af1-rs1, which is reflected in altered chromatin conformation of DNaseI hypersensitive sites. 9 refs., 2 figs.

  3. Factors Affecting Date of Implantation, Parturition, and Den Entry Estimated from Activity and Body Temperature in Free-Ranging Brown Bears

    PubMed Central

    Friebe, Andrea; Evans, Alina L.; Arnemo, Jon M.; Blanc, Stéphane; Brunberg, Sven; Fleissner, Günther; Swenson, Jon E.; Zedrosser, Andreas

    2014-01-01

    Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human. PMID:24988486

  4. Factors affecting date of implantation, parturition, and den entry estimated from activity and body temperature in free-ranging brown bears.

    PubMed

    Friebe, Andrea; Evans, Alina L; Arnemo, Jon M; Blanc, Stéphane; Brunberg, Sven; Fleissner, Günther; Swenson, Jon E; Zedrosser, Andreas

    2014-01-01

    Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human.

  5. BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway

    PubMed Central

    Hu, Jinquan; Yan, Qiang; Shi, Changgui; Tian, Ye; Cao, Peng; Yuan, Wen

    2017-01-01

    We previously showed that bone mesenchymal stem cells (BMSCs) inhibit interleukin-1 beta (IL-1β) induced degenerative effects in NP cells by their paracrine activity, but the anti-inflammatory and anti-apoptotic effect of BMSC paracrine activity and the relative signaling pathway were not further investigated in annulus fibrosus (AF) cells. In this study, AF cells were exposed to IL-1β, which was applied to mimic intervertebral disc degeneration (IDD) in vitro. Indirect co-culture with BMSCs in a transwell co-culture system reduced the activity of nuclear factor-κB-p65 (NF-κB-p65) through the restoration of its inhibitor IκBa. Real time polymerase chain reaction (PT-PCR) and Western blotting revealed that the up-regulation of MMP-3 and MMP-13 induced by IL-1β were impeded by BMSC co-culture, and the decrease in aggrecan, collagen I and TIMP-1 were reversed. An ELISA showed that the increased inflammatory factors, such as nitrite, prostaglandin E-2 (PGE-2), IL-6 and cyclooxygenase-2 (COX-2), were decreased by the BMSC co-culture. Furthermore, the apoptosis rate of AF cells were detected by flow cytometry, and the apoptosis-related proteins, such as Bax, Bcl-2 and caspase-3, were analyzed by Western blotting and ELISA. The changes in mitochondrial membrane potentials were also detected by confocal microscopy. The results showed that IL-1β induced apoptosis of AF cells was attenuated by co-culturing, which suppressed the functions of the mitochondria function. We suggest that BMSC paracrine activity has an anti-inflammation effect and anti-apoptotic effect on IDD, and it is mediated, at least in part, via the relative NF-κF and mitochondrial apoptotic pathways in AF cells. PMID:28123635

  6. Association of circulating factor seven activating protease (FSAP) and of oral Omega-3 fatty acids supplements with clinical outcome in patients with atrial fibrillation: the OMEGA-AF study.

    PubMed

    Parahuleva, Mariana S; Kanse, Sandip; Hölschermann, Hans; Zheleva, Kirila; Zandt, Daniel; Worsch, Michael; Parviz, Behnoush; Güttler, Norbert; Tillmanns, Harald; Böning, Andreas; Erdogan, Ali

    2014-04-01

    Factor VII Activating Protease (FSAP) activates factor VII (FVII) as well as pro-urokinase (uPA). Our goal was to evaluate the relation between plasma levels of FSAP and clinical instability in atrial fibrillation (AF) and possible effects of oral omega-3 fatty acids (FA) supplements. 101 patients with persistent AF were analyzed in the OMEGA-AF Study. Plasma FSAP levels were measured at baseline and after 12 weeks of treatment with omega-3 FA. The median FSAP antigen concentration, in contrast to FSAP activity, was higher in patients with persistent AF. The maintenance of SR after successful cardioversion (CV) did not lead to a normalization of FSAP concentration. Supplementation with omega-3 FA but not placebo significantly reduced elevated FSAP concentration. Furthermore, elevated FSAP levels did not indicate a significantly increased risk of recurrence of AF after electrical CV or cardiovascular clinical events during 1 year of follow-up. Plasma FSAP concentration was increased in patients with AF and may be involved in the pathogenesis of this condition. The possible effects of omega-3 FA on clinical AF potential could be linked with modulation of circulating FSAP levels.

  7. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    SciTech Connect

    Fujiki, Atsushi; Imamura, Toshihiko; Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya; Sugita, Kanji; Hosoi, Hajime

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  8. Discovery of a new species of hermit crab of the genus Pylopaguropsis Alcock, 1905 from the Caribbean: "den commensal" or "cleaner"? (Crustacea, Anomura, Paguridae).

    PubMed

    Lemaitre, Rafael

    2017-01-01

    A new secretive, yet brightly colored hermit crab species of the family Paguridae, Pylopaguropsis mollymulleraesp. n., is fully described based on specimens from the reefs of Bonaire, Lesser Antilles, southern Caribbean Sea. Populations of this new species were discovered and photographed in the Bonaire National Marine Park under a large coral ledge, at a depth of 13.7 m, living in crevices known by scuba divers to serve as den to a pair of "flaming reef lobsters" Enoplometopus antillensis, or a "broad banded moray" Channomuraena vittata. This new species is only the second species of Pylopaguropsis Alcock, 1905 known from the western Atlantic, the 20(th) named worldwide, and belongs in the teevana group of species of the genus. It is remarkably similar, and herein considered geminate, to the tropical eastern Pacific congener, Pylopaguropsis teevana (Boone, 1932), the two being characterized and uniquely different from all other species of the genus, by the striking and deeply excavated, scoop-like ventral surface of the chela of the right cheliped. Minor differences separate this new species from Pylopaguropsis teevana in the relative length of the antennal acicles (exceeding the corneas versus not exceeding the corneas in Pylopaguropsis teevana); dorsal armature of the right chela (smooth or with scattered minute tubercles versus with numerous small tubercles in Pylopaguropsis teevana); surface shape of the lateral face of the dactyl of right pereopod 3 (evenly convex versus flattened in Pylopaguropsis teevana); and coloration (red bright red stripes versus brown stripes in Pylopaguropsis teevana). The highly visible color pattern of bright red stripes on white background typical of decapods known to have cleaning symbioses with fish, dense setation on the flagella of the antennae, and preference for a crevicular habitat, combined with brief in situ nocturnal observations, suggests the possibility that Pylopaguropsis mollymullerae sp. n. engages in "cleaner

  9. Discovery of a new species of hermit crab of the genus Pylopaguropsis Alcock, 1905 from the Caribbean: “den commensal” or “cleaner”? (Crustacea, Anomura, Paguridae)

    PubMed Central

    Lemaitre, Rafael

    2017-01-01

    Abstract A new secretive, yet brightly colored hermit crab species of the family Paguridae, Pylopaguropsis mollymullerae sp. n., is fully described based on specimens from the reefs of Bonaire, Lesser Antilles, southern Caribbean Sea. Populations of this new species were discovered and photographed in the Bonaire National Marine Park under a large coral ledge, at a depth of 13.7 m, living in crevices known by scuba divers to serve as den to a pair of “flaming reef lobsters” Enoplometopus antillensis, or a “broad banded moray” Channomuraena vittata. This new species is only the second species of Pylopaguropsis Alcock, 1905 known from the western Atlantic, the 20th named worldwide, and belongs in the teevana group of species of the genus. It is remarkably similar, and herein considered geminate, to the tropical eastern Pacific congener, Pylopaguropsis teevana (Boone, 1932), the two being characterized and uniquely different from all other species of the genus, by the striking and deeply excavated, scoop-like ventral surface of the chela of the right cheliped. Minor differences separate this new species from Pylopaguropsis teevana in the relative length of the antennal acicles (exceeding the corneas versus not exceeding the corneas in Pylopaguropsis teevana); dorsal armature of the right chela (smooth or with scattered minute tubercles versus with numerous small tubercles in Pylopaguropsis teevana); surface shape of the lateral face of the dactyl of right pereopod 3 (evenly convex versus flattened in Pylopaguropsis teevana); and coloration (red bright red stripes versus brown stripes in Pylopaguropsis teevana). The highly visible color pattern of bright red stripes on white background typical of decapods known to have cleaning symbioses with fish, dense setation on the flagella of the antennae, and preference for a crevicular habitat, combined with brief in situ nocturnal observations, suggests the possibility that Pylopaguropsis mollymullerae sp. n. engages

  10. Enhanced removal of bisphenol-AF onto chitosan-modified zeolite by sodium cholate in aqueous solutions.

    PubMed

    Peng, Sha; Hao, Kunyan; Han, Feng; Tang, Zheng; Niu, Beibei; Zhang, Xu; Wang, Zhen; Hong, Song

    2015-10-05

    The removal of bisphenol-AF (BPAF) from aqueous solutions onto chitosan-modified zeolite (Ch-Z) in the absence and presence of sodium cholate (NaC) was investigated. It was found that NaC significantly increased the adsorption capacity of Ch-Z for BPAF. At an initial concentration of 100 μmol/L, the removal of BPAF by adsorption onto Ch-Z with NaC was more than ninefold higher than without NaC, and the maximum removal was achieved at a Ch-Z dosage of 1g/L with a NaC concentration of 1.68 mmol/L. Besides, batch studies were performed to evaluate the effects of various experimental parameters on the removal of BPAF. Kinetic studies and adsorption isotherms indicated that the adsorption process of BPAF onto Ch-Z with NaC could be expressed by a pseudo second-order model and the Freundlich isotherm model, respectively. For the enhanced removal, an interaction mechanism was proposed involving the co-effect of BPAF and NaC adsorbed onto Ch-Z.

  11. Stellar Kinematics and Metallicities in the Draco and Ursa Minor Dwarf Spheroidal Galaxies from WHT/AF2-WYFFOS

    NASA Astrophysics Data System (ADS)

    Jin, S.; Irwin, M.; Tolstoy, E.; Lewis, J.; Hartke, J.

    2016-10-01

    We present preliminary results from our chemo-dynamical survey of two Milky Way dwarf spheroidal (dSph) galaxies, Draco and Ursa Minor. The two galaxies have similar radial velocities and reside in close proximity in the outskirts of the Milky Way halo, yet exhibit noteworthy differences in their morphologies. We obtained spectroscopic data with AF2-WYFFOS on the WHT for several hundred red-giant-branch (RGB) candidates in each galaxy out to its tidal radius, from which we have identified approximately 100 velocity members in each system. Metallicities are determined for the individual RGB stars using the Ca II triplet lines. Whereas Ursa Minor shows an RGB population of well-mixed metallicities, a clear gradient is observed in Draco, in which the outer regions host stars of lower [Fe/H]. Such differences may be a reflection of their differing morphologies, with Ursa Minor having been tidally stirred to give rise to both its highly elongated shape and a more mixed [Fe/H] distribution.

  12. Grade-2 Teflon (AF1601) PCF for optical communication using 2D FDTD technique: a simplest design

    NASA Astrophysics Data System (ADS)

    Muduli, N.; Achary, J. S. N.; Padhy, Hemanta ku.

    2016-04-01

    A nonlinear ytterbium-doped rectangular proposed PCF structure of inner and outer cladding is used to analyze effective mode field area (Aeff), nonlinear coefficient (γ), dispersion (D), and confinement loss (CL) in a wide range of wavelength. The fabrication of PCF structure is due to different size doped air hole, pitch, and air hole diameter in a regular periodic geometrical array fashion. The various property of PCF structure such as mode field area, nonlinear coefficient, dispersion, and confinement loss are analyzed by implementing 2D FDTD technique. The above PCF property investigated using suitable parameters like Λ1, ?, ?, and ? in three different situations is discussed in simulation. The high nonlinear coefficient and dispersion property of PCF structure are tailored by setting the cladding parameter. However, highly nonlinear fibers with nonzero dispersion at the wavelength of 1.55 μm are very attractive for a range of optical communication application such as laser amplifier, pulse compression, wavelength conversion, all optical switching, and supercontinuum generation. So our newly proposed ytterbium-doped PCF seems to be most suitable exclusively for supercontinuum generation and nonlinear fiber optics. Finally, it is observed that ytterbium-doped Teflon (AF1601) PCF has more nonlinear coefficient (γ(λ) = 65.27 W-1 km-1) as compared to pure silica PCF (γ(λ) = 52 W-1 km-1) design to have same mode field area (Aeff) 1.7 μm2 at an operating wavelength of 1.55 μm.

  13. Determination of arsenic speciation in sulfidic waters by Ion Chromatography Hydride-Generation Atomic Fluorescence Spectrometry (IC-HG-AFS).

    PubMed

    Keller, Nicole S; Stefánsson, Andri; Sigfússon, Bergur

    2014-10-01

    A method for the analysis of arsenic species in aqueous sulfide samples is presented. The method uses an ion chromatography system connected with a Hydride-Generation Atomic Fluorescence Spectrometer (IC-HG-AFS). With this method inorganic As(III) and As(V) species in water samples can be analyzed, including arsenite (HnAs(III)O3(n-3)), thioarsenite (HnAs(III)S3(n-3)), arsenate (HnAs(V)O4(n-3)), monothioarsenate (HnAs(V)SO3(n-3)), dithioarsenate (HnAs(V)S2O2(n-3)), trithioarsenate (HnAs(V)S3O(n-3)) and tetrathioarsenate (HnAs(V)S4(n-3)). The peak identification and retention times were determined based on standard analysis of the various arsenic compounds. The analytical detection limit was ~1-3 µg L(-1) (LOD), depending on the quality of the baseline. This low detection limit makes this method also applicable to discriminate between waters meeting the drinking water standard of max. 10 µg L(-1) As, and waters that do not meet this standard. The new method was successfully applied for on-site determination of arsenic species in natural sulfidic waters, in which seven species were unambiguously identified.

  14. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer.

    PubMed Central

    Moghal, N; Neel, B G

    1995-01-01

    Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans-acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer. PMID:7791800

  15. The PDZ Protein Canoe/AF-6 Links Ras-MAPK, Notch and Wingless/Wnt Signaling Pathways by Directly Interacting with Ras, Notch and Dishevelled

    PubMed Central

    Carmena, Ana; Speicher, Stephan; Baylies, Mary

    2006-01-01

    Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification. PMID:17183697

  16. Asymmetric AB3 Miktoarm Star Polymers: Synthesis, Self-Assembly, and Study of Micelle Stability Using AF4 for Efficient Drug Delivery.

    PubMed

    Moquin, Alexandre; Sharma, Anjali; Cui, Yiming; Lau, Anthony; Maysinger, Dusica; Kakkar, Ashok

    2015-12-01

    A simple and versatile methodology, which employs a combination of ring-opening polymerization and alkyne-azide click chemistry to synthesize amphiphilic AB3 miktoarm stars, is reported. Their aqueous self-assembly behavior was studied using dynamic light scattering, fluorescence, and asymmetrical flow field-flow fractionation (AF4). AB3 miktoarm stars form micelles which incorporate curcumin with high efficiency, and significantly reduce the viability of glioblastoma cells in spheroids. We demonstrate that AF4 is an effective technique to determine the size distribution of self-assembled structures exposed to a biological medium. The ease, with which asymmetric AB3 miktoarm polymers are constructed, provides a platform that can be widely employed to deliver a variety of lipophilic drugs.

  17. Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12–15, 2009, Yaoundé, Cameroon

    PubMed Central

    Sirugo, Giorgio; Williams, Scott M.; Royal, Charmaine D. M.; Newport, Melanie J.; Hennig, Branwen J.; Mariani-Costantini, Renato; Buonaguro, Franco M.; Velez Edwards, Digna R.; Ibrahim, Muntaser; Soodyall, Himla; Wonkam, Ambroise; Ramesar, Raj; Rotimi, Charles N.

    2010-01-01

    The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States. PMID:20682860

  18. Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome

    PubMed Central

    Bedeschi, M.F.; Colombo, L.; Mari, F.; Hofmann, K.; Rauch, A.; Gentilin, B.; Renieri, A.; Clerici, D.

    2011-01-01

    Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation. PMID:22140376

  19. Effekt einer ad libitum verzehrten fettreduzierten Kost, reich an Obst, Gemüse und Milchprodukten auf den Blutdruck bei Borderline-Hypertonikern

    NASA Astrophysics Data System (ADS)

    Möseneder, Jutta M.

    2002-01-01

    In der randomisierten, multizentrischen DASH-Studie (Dietary Approaches to Stop Hy-pertension), die unter kontrollierten Bedingungen stattfand, führte eine fettreduzierte Mischkost, reich an Obst, Gemüse und Milchprodukten, bei Borderline-Hypertonikern zu einer signifikanten Blutdrucksenkung. Während der Studienphase wurden Körpermasse, Natrium-Aufnahme sowie Alkoholzufuhr aufgrund der bekannten Einflussnahme auf den Blutdruck konstant gehalten. In der eigenen Pilot-Studie sollte untersucht werden, ob das Ergebnis der DASH-Studie (i) mit deutschen Hypertonikern und (ii) unter habituellen Ernährungs- und Lebensbedingungen mit regelmäßig durchgeführter Ernährungsberatung und ad libitum Verzehr anstelle des streng kontrollierten Studienansatzes bestätigt werden kann. Eine Konstanz der Körpermasse, der Natrium-Urinausscheidung (unter diesem Studienansatz valider als die Aufnahme) und des Alkoholkonsums wurde vorausgesetzt. Die Studienpopulation setzte sich aus 53 übergewichtigen Probanden mit einer nicht medikamentös therapierten Borderline-Hypertonie und ohne Stoffwechselerkrankungen zusammen. Die Studienteilnehmer wurden randomisiert entweder der Idealgruppe mit einer fettarmen Kost reich an Milchprodukten, Obst und Gemüse (ähnlich der DASH-Idealgruppe) oder der Kontrollgruppe mit habitueller Ernährungsweise zugeteilt. Über einen Zeitraum von fünf Wochen wurde den Probanden etwa 50% ihres täglichen Lebensmittelbedarfes entsprechend ihrer Gruppenzugehörigkeit kostenfrei zur Verfügung gestellt. Gelegenheitsblutdruckmessungen und 24h-Blutdruckmessungen, Ernährungs- und Aktivitätsprotokolle, Blut- und Urinproben sowie anthropometrische Messungen wurden vor, während und fünf Wochen nach der Interventionsphase durchgeführt. Die Ergebnisse zeigen, dass in der Idealgruppe keine signifikante Blutdrucksenkung beobachtet werden konnte. Dies lässt sich durch die Tatsache erklären, dass die Lebens-mittel- und Nährstoffaufnahme der deutschen

  20. [Immunohistochemical Analysis of Krebs von den Lungen-6 (KL-6) Expression in Lung Tissue in Primary Lung Cancer Patients with High Serum KL-6 Levels].

    PubMed

    Yatsuyanagi, Eiji; Sato, Kazuhiro; Sato, Keisuke

    2015-09-01

    We investigated sialylated carbohydrate antigen( Krebs von den Lungen-6:KL-6) expression in lung tissue and correlation between the expression and serum KL-6 level in the patients with primary lung cancer. Thirty-four primary lung cancer patients with high serum KL-6 levels( >500 U/ml) were evaluated. A coexistence of interstitial pneumonia (IP) was histopathologically evaluated and an immunohistochemical staining using a mouse anti-human KL-6 antibody (mKL-6) was performed. A multiple regression analysis was also caluculated using a serum KL-6 level as a target variable and the histopathological and immunohistochemical factors (KL-6 expression in cancer tissue and IP tissue, coexistence of IP, tumor size, pathological staging) as descriptive variables. Twenty-two patients (64.7%) were histopathologically concomitant with IP. Cancer tissues were positively stained by mKL-6 in 32 patients (94.1%). Among them, 20 patients were concomitant with IP and all of their cancer tissues were more strongly stained by mKL-6 than IP tissues. Although considerable high rate of lung cancer patients might express the KL-6 in the cancer tissue, we could not reveal the relationship between the expression and serum KL-6 level by a multiple regression analysis. For revealing the mechanism of elevating serum KL-6 level in the patients with lung cancer, more detailed and powerful study is thought to be needed.

  1. Anti-influenza A virus activity of a new dihydrochalcone diglycoside isolated from the Egyptian seagrass Thalassodendron ciliatum (Forsk.) den Hartog.

    PubMed

    Mohammed, Magdy M D; Hamdy, Abdel-Hamid A; El-Fiky, Nabaweye M; Mettwally, Walaa S A; El-Beih, Ahmed A; Kobayashi, Nobuyuki

    2014-01-01

    One new dihydrochalcone diglycoside has been isolated from the EtOAc fraction of the Egyptian seagrass Thalassodendrin ciliatum (Forsk.) den Hartog, and was identified as 6'-O-rhamnosyl-(1‴ → 6″)-glucopyranosyl asebogenin for which a trivial name Thalassodendrone was established. Furthermore, five known phenolics were isolated and identified as asebotin, quercetin 3,7-diglucoside, protocatechuic acid, ferulic acid and p-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and high-resolution-mass spectrometer. High-resolution electrospray ionization mass spectra (HR-ESI-MS) were obtained using a JEOL JMS-T100TD spectrometer (JEOL Ltd., Tokyo, Japan). The anti-influenza A virus activity of the isolated new compound and asebotin was evaluated, and the obtained results revealed that the inhibition dose concentration of asebotin was more than that of Thalassodendrone with IC50 = 2.00 and 1.96 μg/mL, respectively, and with cytotoxic concentration (CC50) of 3.36 and 3.14 μg/mL, respectively.

  2. Differential predation by age and sex classes in blue wildebeest in Serengeti: study of a modern carnivore den in Olduvai Gorge (Tanzania).

    PubMed

    Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Martínez-Maza, Cayetana; Mabulla, Audax; Baquedano, Enrique

    2015-01-01

    Age and sex selection of prey is an aspect of predator ecology which has been extensively studied in both temperate and African ecosystems. This dimension, along with fecundity, survival rates of prey and mortality factors other than predation are important in laying down the population dynamics of prey and have important implications in the management of species. A carnivore den located in the short-grassland ecological unit of the Serengeti was studied. Sex- and age- class (using five age categories) of the wildebeest remains recovered were analyzed through horn morphology, biometrics of the bones and tooth wear patterns. We compared our results with previous studies from lion and hyaena kills through multivariate analyses. Seasonality of the accumulation was analyzed through tooth histology. PCA and CVA results show that age class selection by predators depends on season, habitat-type, and growth rate of the wildebeest population. Female-biased predation was found to contradict classical hypotheses based on territorial male behaviour. The lion and spotted hyaena showed strong selection on age classes, contrary to previous studies. Migratory wildebeest sex ratio is regulated through differential predation by seasons and female deaths in the wet season are a trade-off for population stability. These data are crucial for an effective management of the species and the new method created may be useful for different carnivore species and their prey.

  3. Differential Predation by Age and Sex Classes in Blue Wildebeest in Serengeti: Study of a Modern Carnivore Den in Olduvai Gorge (Tanzania)

    PubMed Central

    Arriaza, Mari Carmen; Domínguez-Rodrigo, Manuel; Martínez-Maza, Cayetana; Mabulla, Audax; Baquedano, Enrique

    2015-01-01

    Age and sex selection of prey is an aspect of predator ecology which has been extensively studied in both temperate and African ecosystems. This dimension, along with fecundity, survival rates of prey and mortality factors other than predation are important in laying down the population dynamics of prey and have important implications in the management of species. A carnivore den located in the short-grassland ecological unit of the Serengeti was studied. Sex- and age- class (using five age categories) of the wildebeest remains recovered were analyzed through horn morphology, biometrics of the bones and tooth wear patterns. We compared our results with previous studies from lion and hyaena kills through multivariate analyses. Seasonality of the accumulation was analyzed through tooth histology. PCA and CVA results show that age class selection by predators depends on season, habitat-type, and growth rate of the wildebeest population. Female-biased predation was found to contradict classical hypotheses based on territorial male behaviour. The lion and spotted hyaena showed strong selection on age classes, contrary to previous studies. Migratory wildebeest sex ratio is regulated through differential predation by seasons and female deaths in the wet season are a trade-off for population stability. These data are crucial for an effective management of the species and the new method created may be useful for different carnivore species and their prey. PMID:26017363

  4. Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study

    PubMed Central

    Cacciani, Francesca; Zaniboni, Massimiliano

    2015-01-01

    Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation GKr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in ICaL. Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies. PMID:26229960

  5. Muscleblind-like 1 activates insulin receptor exon 11 inclusion by enhancing U2AF65 binding and splicing of the upstream intron.

    PubMed

    Echeverria, Gloria V; Cooper, Thomas A

    2014-02-01

    Alternative splicing regulates developmentally and tissue-specific gene expression programs, disruption of which have been implicated in numerous diseases. Muscleblind-like 1 (MBNL1) regulates splicing transitions, which are disrupted on loss of MBNL1 function in myotonic dystrophy type 1 (DM1). One such event is MBNL1-mediated activation of insulin receptor exon 11 inclusion, which requires an intronic enhancer element downstream of exon 11. The mechanism of MBNL1-mediated activation of exon inclusion is unknown. We developed an in vitro splicing assay, which robustly recapitulates MBNL1-mediated splicing activation of insulin receptor exon 11 and found that MBNL1 activates removal of the intron upstream of exon 11 upon binding its functional response element in the downstream intron. MBNL1 enhances early spliceosome assembly as evidenced by enhanced complex A formation and binding of U2 small nuclear ribonucleoprotein auxiliary factor 65 kDa subunit (U2AF65) on the upstream intron. We demonstrated that neither the 5' splice site nor exon 11 sequences are required for MBNL1-activated U2AF65 binding. Interestingly, the 5' splice site is required for MBNL1-mediated activation of upstream intron removal, although MBNL1 has no effect on U1 snRNA recruitment. These results suggest that MBNL1 directly activates binding of U2AF65 to enhance upstream intron removal to ultimately activate alternative exon inclusion.

  6. Role of the essential yeast protein PSU1 in p6anscriptional enhancement by the ligand-dependent activation function AF-2 of nuclear receptors.

    PubMed Central

    Gaudon, C; Chambon, P; Losson, R

    1999-01-01

    Nuclear receptors (NRs) can function as ligandinducible transregulators in both mammalian and yeast cells, indicating that important features of transcriptional control have been conserved throughout evolution. We report here the isolation and characterization of an essential yeast protein of unknown function, PSU1, which exhibits properties expected for a co-activator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of NRs. PSU1 interacts in a ligand-dependent manner with the LBD of several NRs, including retinoic acid (RARalpha), retinoid X (RXRalpha), thyroid hormone (TRalpha), vitamin D3 (VDR) and oestrogen (ERalpha) receptors. Importantly, both in yeast and in vitro, these interactions require the integrity of the AF-2 activating domain. When tethered to a heterologous DNA-binding domain, PSU1 can activate transcription on its own. By using yeast reporter cells that express PSU1 conditionally, we show that PSU1 is required for transactivation by the AF-2 of ERalpha. Taken together these data suggest that in yeast, PSU1 is involved in ligand-dependent transactivation by NRs. Sequence analysis revealed that in addition to a highly conserved motif found in a family of MutT-related proteins, PSU1 contains several alpha-helical leucine-rich motifs sharing the consensus sequence LLxPhiL (x, any amino acid; Phi, hydrophobic amino acid) in regions that elicit either transactivation or NR-binding activity. PMID:10205176

  7. A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene.

    PubMed

    Cha, Yeseul; Lee, Sang Hoon; Jang, Su Kil; Guo, Haiyu; Ban, Young-Hwan; Park, Dongsun; Jang, Gwi Yeong; Yeon, Sungho; Lee, Jeong-Yong; Choi, Ehn-Kyoung; Joo, Seong Soo; Jeong, Heon-Sang; Kim, Yun-Bae

    2017-01-01

    This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction. The active peptide in SP-NN was identified as tyrosine-glycine with 238.1 of molecular weight. Male rats were orally administered with SP-NN (50 or 300mg/kg) and challenged with a cholinotoxin AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A induced astrocytic activation, resulting in impairment of learning and memory function. Treatment with SP-NN exerted recovering activities on acetylcholine depletion and brain injury, as well as cognitive deficit induced by AF64A. The results indicate that, in addition to a neuroprotective activity, the SP-NN preparation restores cognitive function of Alzheimer disease model rats by increasing the release of acetylcholine.

  8. Crystallization and preliminary X-ray analysis of a U2AF{sup 65} variant in complex with a polypyrimidine-tract analogue by use of protein engineering

    SciTech Connect

    Sickmier, E. Allen; Frato, Katherine E.; Kielkopf, Clara L.

    2006-05-01

    A complex of the essential splicing factor U2AF{sup 65} and a deoxyuridine oligonucleotide has been crystallized by modification of an interdomain linker. The large subunit of the essential pre-mRNA splicing factor U2 auxiliary factor (U2AF{sup 65}) binds the polypyrimidine tract near the 3′ splice site of pre-mRNA introns and directs the association of the U2 small nuclear ribonucleoprotein particle (U2 snRNP) of the spliceosome with the pre-mRNA. Protein engineering, in which the flexible linker region connecting tandem RNA-recognition motifs (RRMs) within the U2AF{sup 65} RNA-binding domain was partially deleted, allowed successful crystallization of the protein–nucleic acid complex. Cocrystals of a U2AF{sup 65} variant with a deoxyuridine dodecamer diffract X-rays to 2.9 Å resolution and contain one complex per asymmetric unit.

  9. Data assimilative twin-experiment in a high-resolution Bay of Biscay configuration: 4DEnOI based on stochastic modeling of the wind forcing

    NASA Astrophysics Data System (ADS)

    Vervatis, V.; Testut, C. E.; De Mey, P.; Ayoub, N.; Chanut, J.; Quattrocchi, G.

    2016-04-01

    A twin-experiment is carried out introducing elements of an Ensemble Kalman Filter (EnKF), to assess and correct ocean uncertainties in a high-resolution Bay of Biscay configuration. Initially, an ensemble of 102 members is performed by applying stochastic modeling of the wind forcing. The target of this step is to simulate the envelope of possible realizations and to explore the robustness of the method at building ensemble covariances. Our second step includes the integration of the ensemble-based error estimates into a data assimilative system adopting a 4D Ensemble Optimal Interpolation (4DEnOI) approach. In the twin-experiment context, synthetic observations are simulated from a perturbed member not used in the subsequent analyses, satisfying the condition of an unbiased probability distribution function against the ensemble by performing a rank histogram. We evaluate the assimilation performance on short-term predictability focusing on the ensemble size, the observational network, and the enrichment of the ensemble by inexpensive time-lagged techniques. The results show that variations in performance are linked to intrinsic oceanic processes, such as the spring shoaling of the thermocline, in combination with external forcing modulated by river runoffs and time-variable wind patterns, constantly reshaping the error regimes. Ensemble covariances are able to capture high-frequency processes associated with coastal density fronts, slope currents and upwelling events near the Armorican and Galician shelf break. Further improvement is gained when enriching model covariances by including pattern phase errors, with the help of time-neighbor states augmenting the ensemble spread.

  10. Clinical Characteristics, Management, and Control of Permanent vs. Nonpermanent Atrial Fibrillation: Insights from the RealiseAF Survey

    PubMed Central

    Murin, Jan; Naditch-Brûlé, Lisa; Brette, Sandrine; Chiang, Chern-En; O’Neill, James; Steg, P. Gabriel

    2014-01-01

    Background Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample. Methods and Results Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS2 score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS2 score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke. Conclusion Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart

  11. The Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open Label, Clinical Trial (Substrate Modification with Aggressive Blood Pressure Control: SMAC- AF).

    PubMed

    Parkash, Ratika; Wells, George A; Sapp, John L; Healey, Jeffrey S; Tardif, Jean-Claude; Greiss, Isabelle; Rivard, Léna; Roux, Jean-Francois; Gula, Lorne; Nault, Isabelle; Novak, Paul G; Birnie, David H; Ha, Andrew C; Wilton, Stephen B; Mangat, Iqwal; Gray, Christopher J; Gardner, Martin J; Tang, Anthony S L

    2017-02-22

    Background -Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF, however recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden. Methods -We randomly assigned 184 patients with AF and a BP greater than 130/80 mmHg to aggressive BP (target <120/80 mm Hg) or standard BP treatment (target <140/90 mmHg) prior to their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting greater than 30 seconds, determined 3 months beyond catheter ablation by a blinded endpoint evaluation. Results -The median follow-up was 14 months. At six months, the mean systolic BP in the aggressive BP treatment group was 123.2±13.2 versus 135.4±15.7mm Hg (p<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group, compared to 52 (61.2%) in the standard treatment group, (Hazard Ratio 0.94, 95% Confidence Interval 0.65-1.38, p=0.763). In the prespecified subgroup analysis of the influence of age, patients aged ≥ 61 years had a lower primary outcome event rate with aggressive BP (Hazard Ratio 0.58, 95% Confidence Interval (0.34, 0.97), p=0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%). Conclusions -In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF, but resulted in more hypotension. Clinical Trial Registration -Clinicaltrials.gov Identifier: NCT00438113.

  12. CDKN1A-mediated responsiveness of MLL-AF4-positive acute lymphoblastic leukemia to Aurora kinase-A inhibitors.

    PubMed

    Chen, Ya-Ping; Lin, Hui-Ju; Chen, Jiann-Shiuh; Tsai, Ming-Ying; Hsieh, Hsing-Pang; Chang, Jang-Yang; Chen, Nai-Feng; Chang, Kung-Chao; Huang, Wen-Tsung; Su, Wu-Chou; Yang, Shu-Ting; Chang, Wen-Chang; Hung, Liang-Yi; Chen, Tsai-Yun

    2014-08-01

    Overexpression of Aurora kinases is largely observed in many cancers, including hematologic malignancies. In this study, we investigated the effects and molecular mechanisms of Aurora kinase inhibitors in acute lymphoblastic leukemia (ALL). Western blot analysis showed that both Aurora-A and Aurora-B are overexpressed in ALL cell lines and primary ALL cells. Both VE-465 and VX-680 effectively inhibited Aurora kinase activities in nine ALL cell lines, which exhibited different susceptibilities to the inhibitors. Cells sensitive to Aurora kinase inhibitors underwent apoptosis at an IC50 of ∼10-30 nM and displayed a phenotype of Aurora-A inhibition, whereas cells resistant to Aurora kinase inhibitors (with an IC50 more than 10 μM) accumulated polyploidy, which may have resulted from Aurora-B inhibition. Drug susceptibility of ALL cell lines was not correlated with the expression level or activation status of Aurora kinases. Interestingly, RS4;11 and MV4;11 cells, which contain the MLL-AF4 gene, were both sensitive to Aurora kinase-A inhibitors treatment. Complementary DNA (cDNA) microarray analysis suggested that CDKN1A might govern the drug responsiveness of ALL cell lines in a TP53-independent manner. Most importantly, primary ALL cells with MLL-AF4 and CDKN1A expression were sensitive to Aurora kinase inhibitors. Our study suggests CDKN1A could be a potential biomarker in determining the drug responsiveness of Aurora kinase inhibitors in ALL, particularly in MLL-AF4-positive patients.

  13. Quality of Vitamin K Antagonist Control and 1-Year Outcomes in Patients with Atrial Fibrillation: A Global Perspective from the GARFIELD-AF Registry

    PubMed Central

    Haas, Sylvia; ten Cate, Hugo; Accetta, Gabriele; Angchaisuksiri, Pantep; Bassand, Jean-Pierre; Camm, A. John; Corbalan, Ramon; Darius, Harald; Fitzmaurice, David A.; Goldhaber, Samuel Z.; Goto, Shinya; Jacobson, Barry; Kayani, Gloria; Mantovani, Lorenzo G.; Misselwitz, Frank; Pieper, Karen; Schellong, Sebastian M.; Stepinska, Janina; Turpie, Alexander G. G.; van Eickels, Martin; Kakkar, Ajay K.

    2016-01-01

    Aims Vitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0–3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality. Methods and Results TTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027). Conclusion A large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes. Trial Registration Clinical

  14. Characterization of plasma-enhanced teflon AF for sensing benzene, toluene, and xylenes in water with near-IR surface plasmon resonance.

    PubMed

    Erickson, Tim A; Nijjar, Rajvir; Kipper, Matt J; Lear, Kevin L

    2014-02-01

    Near-IR surface plasmon resonance is used to characterize Teflon AF films for refractive index-based detection of the aromatic hydrocarbon contaminants benzene, toluene, and xylenes in water. The technique requires no sample preparation, and film sensitivity is found to be enhanced by oxygen plasma etching. A diffusion equation model is used to extract the diffusion and partition coefficients, which indicate film enrichment factors exceeding two orders of magnitude, permitting a limit of detection of 183, 105 and 55 ppb for benzene, toluene, and xylenes, respectively. The effect of other potential interfering contaminants is quantified.

  15. A novel minimally invasive, dorsolateral, tubular partial odontoidectomy and autologous bone augmentation to treat dens pseudarthrosis: cadaveric, 3D virtual simulation study and technical report.

    PubMed

    Archavlis, Eleftherios; Serrano, Lucas; Schwandt, Eike; Nimer, Amr; Molina-Fuentes, Moisés Felipe; Rahim, Tamim; Ackermann, Maximilian; Gutenberg, Angelika; Kantelhardt, Sven Rainer; Giese, Alf

    2017-02-01

    OBJECTIVE The goal of this study was to demonstrate the clinical and technical nuances of a minimally invasive, dorsolateral, tubular approach for partial odontoidectomy, autologous bone augmentation, and temporary C1-2 fixation to treat dens pseudarthrosis. METHODS A cadaveric feasibility study, a 3D virtual reality reconstruction study, and the subsequent application of this approach in 2 clinical cases are reported. Eight procedures were completed in 4 human cadavers. A minimally invasive, dorsolateral, tubular approach for odontoidectomy was performed with the aid of a tubular retraction system, using a posterolateral incision and an oblique approach angle. Fluoroscopy and postprocedural CT, using 3D volumetric averaging software, were used to evaluate the degree of bone removal of C1-2 lateral masses and the C-2 pars interarticularis. Two clinical cases were treated using the approach: a 23-year-old patient with an odontoid fracture and pseudarthrosis, and a 35-year-old patient with a history of failed conservative treatment for odontoid fracture. RESULTS At 8 cadaveric levels, the mean volumetric bone removal of the C1-2 lateral masses on 1 side was 3% ± 1%, and the mean resection of the pars interarticularis on 1 side was 2% ± 1%. The median angulation of the trajectory was 50°, and the median distance from the midline of the incision entry point on the skin surface was 67 mm. The authors measured the diameter of the working channel in relation to head positioning and assessed a greater working corridor of 12 ± 4 mm in 20° inclination, 15° contralateral rotation, and 5° lateral flexion to the contralateral side. There were no violations of the dura. The reliability of C-2 pedicle screws and C-1 lateral mass screws was 94% (15 of 16 screws) with a single lateral breach. The patients treated experienced excellent clinical outcomes. CONCLUSIONS A minimally invasive, dorsolateral, tubular odontoidectomy and autologous bone augmentation combined with C1

  16. Long-term Outcomes and Quality of Life of 186 Patients With Primary Parotid Carcinoma Treated With Surgery and Radiotherapy at the Daniel den Hoed Cancer Center

    SciTech Connect

    Al-Mamgani, Abrahim; Rooij, Peter van; Verduijn, Gerda M.; Meeuwis, Cees A.; Levendag, Peter C.

    2012-09-01

    Purpose: To assess the outcomes, toxicity, and quality of life (QOL) of patients with primary parotid carcinoma treated with surgery and postoperative radiotherapy at the Daniel den Hoed Cancer Center. Methods and Materials: Between 1995 and 2010, 186 patients with parotid carcinoma were treated with parotidectomy with or without neck dissection, followed by radiotherapy. Elective nodal irradiation (ENI) was applied to high-risk, node-negative disease. End points were locoregional control (LRC), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS), late toxicity, and QOL. Results: After a median follow-up of 58 months (range, 4-172 months), the 5-year Kaplan-Meier estimates for LRC, DFS, CSS, and OS were 89%, 83%, 80%, and 68%, respectively. Forty-five events were reported: 24 distant metastases (DM) and 21 locoregional failures (LRF). Event-free survival rates by histological types were 89%, 78%, 76%, 74%, and 70% for acinic cell, mucoepidermoid, adenoid cystic, adenocarcinoma, and squamous cell carcinoma, respectively. More LRF were reported in patients with squamous cell and high-grade mucoepidermoid carcinoma (21% and 19%, respectively) than in patients with other histological types (p = 0.04) and more DM in patients with adenoid cystic and adenocarcinoma (20% and 19%, respectively) than in patients with other types (p = 0.03). None of the high-risk node-negative patients who received ENI developed regional failure. On multivariate analysis, T stage, N stage, grade, and presence of perineural invasion and facial paralysis correlated significantly with DFS. The 5-year cumulative incidence of grade {>=}2 late toxicity was 8%. QOL scores deteriorate during and shortly after treatment but returned in almost all scales to baseline scores within 6 months. Conclusions: Of the entire group, surgery and postoperative radiotherapy resulted in excellent outcomes with minimal side effects and preservation of good QOL scores. However, in

  17. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    SciTech Connect

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E.

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  18. Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.

    PubMed

    Marechal, Damien; Lopes Pereira, Patricia; Duchon, Arnaud; Herault, Yann

    2015-01-01

    Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.

  19. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors.

    PubMed Central

    Henttu, P M; Kalkhoven, E; Parker, M G

    1997-01-01

    Hormone-dependent transcriptional activation by nuclear receptors depends on the presence of a conserved C-terminal amphipathic alpha-helix (helix 12) in the ligand-binding domain. Here we show that a lysine residue, which is conserved in most nuclear receptors in the predicted helix 3, is also required for estrogen-dependent transactivation. The replacement of lysine 366 with alanine appreciably reduced activation function 2 (AF-2) activity without affecting steroid- or DNA-binding activity in the mouse estrogen receptor. The mutation dramatically reduced the ability of the receptor to bind steroid receptor coactivator 1 (SRC-1) but had no effect on receptor-interacting protein 140 (RIP-140) binding, indicating that while their sites of interaction overlap, they are not entirely consistent and in keeping with the proposal that the recruitment of coactivators, such as SRC-1, is required for AF-2 activity. Although the function of RIP-140 remains to be established, RIP-140 appears to be capable of recruiting the basal transcription machinery, since overexpression of the protein markedly increased the transcriptional activity of the mutant receptor. Since the lysine residue is conserved, we propose that it is required, together with residues in helix 12, to form the surface by which members of the nuclear receptor family interact with coactivators. PMID:9121431

  20. A novel Pseudomonas aeruginosa bacteriophage, Ab31, a chimera formed from temperate phage PAJU2 and P. putida lytic phage AF: characteristics and mechanism of bacterial resistance.

    PubMed

    Latino, Libera; Essoh, Christiane; Blouin, Yann; Vu Thien, Hoang; Pourcel, Christine

    2014-01-01

    A novel temperate bacteriophage of Pseudomonas aeruginosa, phage vB_PaeP_Tr60_Ab31 (alias Ab31) is described. Its genome is composed of structural genes related to those of lytic P. putida phage AF, and regulatory genes similar to those of temperate phage PAJU2. The virion structure resembles that of phage AF and other lytic Podoviridae (S. enterica Epsilon 15 and E. coli phiv10) with similar tail spikes. Ab31 was able to infect P. aeruginosa strain PA14 and two genetically related strains called Tr60 and Tr162, out of 35 diverse strains from cystic fibrosis patients. Analysis of resistant host variants revealed different phenotypes, including induction of pigment and alginate overproduction. Whole genome sequencing of resistant variants highlighted the existence of a large deletion of 234 kbp in two strains, encompassing a cluster of genes required for the production of CupA fimbriae. Stable lysogens formed by Ab31 in strain Tr60, permitted the identification of the insertion site. During colonization of the lung in cystic fibrosis patients, P. aeruginosa adapts by modifying its genome. We suggest that bacteriophages such as Ab31 may play an important role in this adaptation by selecting for bacterial characteristics that favor persistence of bacteria in the lung.

  1. TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9.

    PubMed Central

    Cairns, B R; Henry, N L; Kornberg, R D

    1996-01-01

    The SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products are all required for proper transcriptional control of many genes in the yeast Saccharomyces cerevisiae. Genetic studies indicated that these gene products might form a multiprotein SWI/SNF complex important for chromatin transitions preceding transcription from RNA polymerase II promoters. Biochemical studies identified a SWI/SNF complex containing these and at least six additional polypeptides. Here we show that the 29-kDa component of the SWI/SNF complex is identical to TFG3/TAF30/ANC1. Thus, a component of the SWI/SNF complex is also a member of the TFIIF and TFIID transcription complexes. TFG3 interacted with the SNF5 component of the SWI/SNF complex in protein interaction blots. TFG3 is significantly similar to ENL and AF-9, two proteins implicated in human acute leukemia. These results suggest that ENL and AF-9 proteins interact with the SNF5 component of the human SWI/SNF complex and raise the possibility that the SWI/SNF complex is involved in acute leukemia. PMID:8668146

  2. Antimony speciation in soils: improving the detection limits using post-column pre-reduction hydride generation atomic fluorescence spectroscopy (HPLC/pre-reduction/HG-AFS).

    PubMed

    Quiroz, Waldo; Olivares, David; Bravo, Manuel; Feldmann, Jorg; Raab, Andrea

    2011-04-15

    HG-AFS is highly sensitive and low cost detection system and its use for antimony chemical speciation coupled to HPLC is gaining popularity. However speciation analysis in soils is strongly hampered because the most efficient extractant reported in the literature (oxalic acid) strongly inhibits the generation of SbH(3) by Sb(V), the major species in this kind of matrix, severely affecting its detection limits. The purpose of this research is to reduce the detection limit of Sb(V), by using a post column on-line reduction system with l-cysteine reagent (HPLC/pre-reduction/HG-AFS). The system was optimized by experimental design, optimum conditions found were 2% (w/v) and 10°C temperature coil. Detection limits of Sb(V) and Sb(III) in oxalic acid (0.25 mol L(-1)) were improved from 0.3 and 0.1 μg L(-1) to 0.07 and 0.07 μg L(-1), respectively. The methodology developed was applied to Chilean soils, where Sb(V) was the predominant species.

  3. Direct Competition between hnRNP C and U2AF65 Protects the Transcriptome from the Exonization of Alu Elements

    PubMed Central

    Zarnack, Kathi; König, Julian; Tajnik, Mojca; Martincorena, Iñigo; Eustermann, Sebastian; Stévant, Isabelle; Reyes, Alejandro; Anders, Simon; Luscombe, Nicholas M.; Ule, Jernej

    2013-01-01

    Summary There are ∼650,000 Alu elements in transcribed regions of the human genome. These elements contain cryptic splice sites, so they are in constant danger of aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about the molecular mechanisms preventing their inclusion. Here, we present a mechanism for protecting the human transcriptome from the aberrant exonization of transposable elements. Quantitative iCLIP data show that the RNA-binding protein hnRNP C competes with the splicing factor U2AF65 at many genuine and cryptic splice sites. Loss of hnRNP C leads to formation of previously suppressed Alu exons, which severely disrupt transcript function. Minigene experiments explain disease-associated mutations in Alu elements that hamper hnRNP C binding. Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease. PMID:23374342

  4. Dosage of the Abcg1-U2af1 Region Modifies Locomotor and Cognitive Deficits Observed in the Tc1 Mouse Model of Down Syndrome

    PubMed Central

    Marechal, Damien; Pereira, Patricia Lopes; Duchon, Arnaud; Herault, Yann

    2015-01-01

    Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features. PMID:25706610

  5. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

    PubMed

    Ten Cate, V; Ten Cate, H; Verheugt, F W A

    2016-10-01

    There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

  6. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  7. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

    PubMed

    Whisenant, Thomas C; Peralta, Eigen R; Aarreberg, Lauren D; Gao, Nina J; Head, Steven R; Ordoukhanian, Phillip; Williamson, Jamie R; Salomon, Daniel R

    2015-01-01

    Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA

  8. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

    PubMed Central

    Aarreberg, Lauren D.; Gao, Nina J.; Head, Steven R.; Ordoukhanian, Phillip; Williamson, Jamie R.; Salomon, Daniel R.

    2015-01-01

    Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly

  9. Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum.

    PubMed

    Brunger, Axel T; Das, Debanu; Deacon, Ashley M; Grant, Joanna; Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Levitt, Michael; Schröder, Gunnar F

    2012-04-01

    Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence.

  10. Brocazines A-F, Cytotoxic Bisthiodiketopiperazine Derivatives from Penicillium brocae MA-231, an Endophytic Fungus Derived from the Marine Mangrove Plant Avicennia marina.

    PubMed

    Meng, Ling-Hong; Li, Xiao-Ming; Lv, Cui-Ting; Huang, Cai-Guo; Wang, Bin-Gui

    2014-08-22

    Six new disulfide-bridged diketopiperazine derivatives, brocazines A-F (1-6), along with one known analogue (7), were isolated and identified from the cytotoxic extract of Penicillium brocae MA-231, a fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were established on the basis of detailed interpretation of NMR and mass spectroscopic data. X-ray crystallographic analysis confirmed the structure of 1 and established the structure and absolute configuration of 5, while the absolute configurations for compounds 1, 4, and 6 were deduced by comparison of the CD data with those of 5. Compounds 1, 2, 5, and 6 showed cytotoxic activities against several tumor cell lines.

  11. [Pehr af Bjerkén 1765-1818. Chief baber-surgeon at the Serafimer hospital. Physician to the king].

    PubMed

    Hallböök, Torgil

    2005-01-01

    Pehr af Bjerkén had his descent from a parish named Bjärka in western Sweden. His father was a medical doctor and assessor in Stockholm. At the age of sixteen Bjerkén began his studies in Uppsala. Later on he became a "chirurgiae studiosus" in Stockholm at the Serafimer hospital as a pupil of professor Olof Acrel. He defended a doctor's dissertation on "Febris puerperalis" in 1793. Thereafter Bjerkén went to London, where he spent three years. He was taken care of by mr Henry Cline and he met also John Hunter. After some time mr Cline made him a "House surgeon" at S:t Thomasis and Guys hospitals. He got good practice especially regarding the surgery of stones in the urinary bladder and in the surgery of the eye. During the stay he was appointed a member of the Medical Society of London. Back in Sweden Bjerkén practised the surgery with great success.and became physician in ordinary to the king. When in Februar 1808 the Russian tzar Alexander invaded Finland Bjerkén was appointed chief army surgeon in nothern Finland. During this war Bjerkén showed his courage on the battle fields operating and taking care of the wounded soldiers, also the enemies. Most wellknowned for us he became through a sentense in the poem "Döbeln at Juutas". In February 1809, when the Russian tzar had conquered all of Finland. Bjerkén resigned from the Finnish army. The first of June 1809 af Bjerkén was appointed to be head barber-surgeon (head surgeon) of the Serafimer hospital in Stockholm. He was then the most qualified surgeon in Sweden and was looked upon as the most important authority in surgery. Bjerkén was the first one to describe an operation and ligation of an aneurysm of the carotide artery. In 1812 he also published a ligation and resektion of a huge tongue reaching below the chin on a girl eleven years of age. Together with the description there was an engraving. This became the first illustrated publication in the proceedings of the Swedish Society of Medicine. He

  12. Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP.

    PubMed

    Tamura, Tomohide; Kiura, Katsuyuki; Seto, Takashi; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Murakami, Haruyasu; Kuriki, Hiroshi; Shimada, Tadashi; Tanaka, Tomohiro; Takeuchi, Kengo; Nishio, Makoto

    2017-03-15

    Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

  13. Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

    PubMed

    Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

    2015-11-01

    Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

  14. Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats.

    PubMed

    Ossowska, Krystyna; Wardas, Jadwiga; Berghauzen-Maciejewska, Klemencja; Głowacka, Urszula; Kuter, Katarzyna; Pilc, Andrzej; Zorn, Stevin H; Doller, Dario

    2014-08-01

    Harmaline induces tremor in animals resembling essential tremor which has been suggested to result from activation of the glutamatergic olivo-cerebellar projection. The aim of the present study was to examine the effects of systemic administration of Lu AF21934, a brain-penetrating positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu4), on the harmaline-induced tremor and other forms of motor activity in rats using fully automated Force Plate Actimeters. The influence of harmaline on the mGlu4 mRNA expression in the cerebellum and inferior olive was analysed by in situ hybridization. Harmaline at a dose of 15 mg/kg (ip) triggered tremor which was manifested by an increase in the power within 9-15 Hz band and in the tremor index (a difference in power between bands 9-15 Hz and 0-8 Hz). Harmaline induced a biphasic effect on mobility, initially inhibiting the exploratory locomotor activity of rats (0-30 min after administration), followed by an increase in their basic activity. Lu AF21934 (0.5-5 mg/kg sc) did not influence tremor but at doses of 0.5 and 2.5 mg/kg reversed harmaline-induced hyperactivity. MGlu4 mRNA expression was high in the cerebellar cortex and low in the inferior olive. Repeated harmaline (15 mg/kg ip once a day for 5 days] decreased mGlu4 mRNA in the cerebellum and inferior olive. The present study indicates that the mGlu4 stimulation counteracts hyperactivity induced by harmaline which suggests the involvement of cerebellar glutamatergic transmission in this process. In contrast, neuronal mechanisms involved in tremor seem to be insensitive to the stimulation of mGlu4.

  15. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  16. Helicobacter pylori infection related long noncoding RNA (lncRNA) AF147447 inhibits gastric cancer proliferation and invasion by targeting MUC2 and up-regulating miR-34c.

    PubMed

    Zhou, Xiaoying; Chen, Han; Zhu, Li; Hao, Bo; Zhang, Weifeng; Hua, Jie; Gu, Huiyuan; Jin, Wujuan; Zhang, Guoxin

    2016-12-13

    Long non-coding RNAs (lncRNAs) were shown to play critical roles in cancer biology. We investigated whether H. pylori infection could promote gastric cancer by regulating lncRNAs expression. Differentially expressed lncRNAs between H. pylori positive and negative tissues were identified by microarray and validated by qRT-PCR. Our results indicated that H. pylori positive tissues have a specific profile of lncRNAs. Cell biological assays with siRNA-mediated knockdown or lentivirus vector-mediated over-expression were performed to probe the functional relevance of the lncRNAs. We identified an lncRNA-AF147447 decreased expressed by H. pylori infection, which can inhibit GC proliferation and invasion in vitro and in vivo, act as a tumor suppressor in the development of H. pylori induced GC. LncRNA AF147447 could repress MUC2 expression by direct binding or increasing miR-34c expression. We also found that transcription factor E2F1 could be recruited to lncRNA AF147447 promoter by RNA immunoprecipatation and RNA pull down assays. These findings support a role of lncRNA AF147447 in tumor suppression. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by H. pylori infection and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of H. pylori-related gastric cancer.

  17. The dating of the ornithological section of Middendorff's Reise in den äussersten Norden und Osten Sibiriens, with comments on the nomenclature of Pallas's Bunting Emberiza pallasi Cabanis (Aves: Emberizidae).

    PubMed

    Mlíkovský, Jiří

    2014-05-14

    Middendorff's work on the Säugethiere, Vögel und Amphibien, published as part 2 of volume 2 of his Reise in den äussersten Norden und Osten Sibiriens, was variably dated from 1851, 1852 or 1853. I document that the work was published shortly before 15 December 1852 and I recommend using this date for the purposes of zoological nomenclature.Due to this, Emberiza polaris Middendorff, 1852 has precedence over Cynchramus pallasi Cabanis, 1853. This bunting species thus should be called Emberiza polaris and its four subspecies should be called Emberiza polaris polaris Middendorff, 1852, E. polaris minor Middendorff, 1852, E. polaris pallasi (Cabanis, 1853) and E. polaris lydiae Portenko, 1929. 

  18. Mutations in the Caenorhabditis elegans U2AF Large Subunit UAF-1 Alter the Choice of a 3′ Splice Site In Vivo

    PubMed Central

    Ma, Long; Horvitz, H. Robert

    2009-01-01

    The removal of introns from eukaryotic RNA transcripts requires the activities of five multi-component ribonucleoprotein complexes and numerous associated proteins. The lack of mutations affecting splicing factors essential for animal survival has limited the study of the in vivo regulation of splicing. From a screen for suppressors of the Caenorhabditis elegans unc-93(e1500) rubberband Unc phenotype, we identified mutations in genes that encode the C. elegans orthologs of two splicing factors, the U2AF large subunit (UAF-1) and SF1/BBP (SFA-1). The uaf-1(n4588) mutation resulted in temperature-sensitive lethality and caused the unc-93 RNA transcript to be spliced using a cryptic 3′ splice site generated by the unc-93(e1500) missense mutation. The sfa-1(n4562) mutation did not cause the utilization of this cryptic 3′ splice site. We isolated four uaf-1(n4588) intragenic suppressors that restored the viability of uaf-1 mutants at 25°C. These suppressors differentially affected the recognition of the cryptic 3′ splice site and implicated a small region of UAF-1 between the U2AF small subunit-interaction domain and the first RNA recognition motif in affecting the choice of 3′ splice site. We constructed a reporter for unc-93 splicing and using site-directed mutagenesis found that the position of the cryptic splice site affects its recognition. We also identified nucleotides of the endogenous 3′ splice site important for recognition by wild-type UAF-1. Our genetic and molecular analyses suggested that the phenotypic suppression of the unc-93(e1500) Unc phenotype by uaf-1(n4588) and sfa-1(n4562) was likely caused by altered splicing of an unknown gene. Our observations provide in vivo evidence that UAF-1 can act in regulating 3′ splice-site choice and establish a system that can be used to investigate the in vivo regulation of RNA splicing in C. elegans. PMID:19893607

  19. Effect of Brazilian propolis (AF-08) on genotoxicity, cytotoxicity and clonogenic death of Chinese hamster ovary (CHO-K1) cells irradiated with (60)Co gamma-radiation.

    PubMed

    Santos, Geyza Spigoti; Tsutsumi, Shigetoshi; Vieira, Daniel Perez; Bartolini, Paolo; Okazaki, Kayo

    2014-03-01

    The present study was conducted in order to evaluate the effect of Brazilian propolis (AF-08; 5, 10, 15, 30, 50, 100, and 200μg/mL) in protecting CHO-K1 cells against genotoxic and cytotoxic damage and clonogenic death induced by (60)Co gamma-radiation (1.0, 2.0, 4.0, and 6.0Gy). For this purpose, three interlinked endpoints were analyzed: induction of DNA damage by use of the micronucleus (MN) test (genotoxic damage), cell viability by means of the MTS assay, and differential staining (cytotoxic damage) and clonogenic death via the colony-formation test (cytotoxic damage). The MN test revealed that propolis alone (5-100μg/mL) was not genotoxic up to 100μg/mL and that 30μg/mL of propolis reduced the radiation-induced DNA damage (∼56% reduction, p<0.05), exhibiting a radio-protective effect on irradiated CHO-K1 cells. On the other hand, analysis of cytotoxicity showed that a concentration of 50μg/mL presented a significant proliferative effect (p<0.001) when associated with radiation, decreasing the percentage of necrotic cells (p<0.01). No mediated cytotoxic effect was found, but the concentration of 200μg/mL was toxic when analyzed at 24 and 48h via the differential staining technique, but not at 72h after irradiation, analyzed with the MTS assay. Differential staining also showed that necrosis was the main death modality in irradiated cells and that apoptosis was induced only at the toxic concentration of propolis (200μg/mL). Concerning the clonogenic capacity, a concentration of 50μg/mL also exhibited a significant stimulating effect on cell proliferation (p<0.001), in agreement with the data from differential staining. Taken together, these data suggest that the use of propolis AF-08 for the prevention of the adverse effects of ionizing radiation is promising. Nevertheless, additional investigations are necessary for a better understanding of potential applications of propolis to improve human health.

  20. Binding of hnRNP H and U2AF65 to Respective G-codes and a Poly-Uridine Tract Collaborate in the N50-5'ss Selection of the REST N Exon in H69 Cells

    PubMed Central

    Ortuño-Pineda, Carlos; Galindo-Rosales, José Manuel; Calderón-Salinas, José Victor; Villegas-Sepúlveda, Nicolás; Saucedo-Cárdenas, Odila; De Nova-Ocampo, Mónica; Valdés, Jesús

    2012-01-01

    The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3'ss, three alternative 5'ss (N4-, N50-, and N62-5'ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5'ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5'ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/β-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5'ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes. PMID:22792276

  1. Tribological characteristics of bisphenol AF bis(diphenyl phosphate) as an antiwear additive in polyalkylene glycol and polyurea grease for significantly improved lubrication

    NASA Astrophysics Data System (ADS)

    Zhu, Lili; Wu, Xinhu; Zhao, Gaiqing; Wang, Xiaobo

    2016-02-01

    A new antiwear additive of Bisphenol AF bis(diphenyl phosphate) (BAFDP) was synthesized and characterized. The tribological behaviors of the additive for polyalkylene glycol (PAG) and polyurea grease (PG) application in steel/steel contacts were evaluated on an Optimol SRV-IV oscillating reciprocating friction and wear tester at elevated temperature. The results revealed that BAFDP could drastically reduce friction and wear of sliding pairs in both PAG and also in PG at 100 °C. The tribological properties of BAFDP are superior to the normally used zinc dialkyldithiophosphate-based additive package (ZDDP) in PAG and PG. Moreover, BAFDP as additive for PAG and PG displays relatively significant tribological properties in temperature-ramp tests by performing well at 50-300 °C, indicating the excellent high temperature friction reduction and anti-wear capacity of BAFDP. XPS results showed that boundary lubrication films composed of Fe(OH)O, Fe3O4, FePO4, FeF2, FeF3, compounds containing the Psbnd O bonds, nitrogen oxide, and so forth, were formed on the worn surface, which contributed to excellent friction reduction and antiwear performance.

  2. Analysis of β-glucan molar mass from barley malt and brewer's spent grain with asymmetric flow field-flow fractionation (AF4) and their association to proteins.

    PubMed

    Zielke, Claudia; Teixeira, Cristina; Ding, Huihuang; Cui, Steve; Nyman, Margareta; Nilsson, Lars

    2017-02-10

    β-Glucan benefits are related with its molar mass and it would be of interest to better understand how this parameter can be changed by processing and variety for design of food with specific health effects. For this purpose, extracts from barley malts and brewers' spent grain, processed at different conditions, were analysed regarding β-glucan content, molar mass, and protein content. Molar mass distribution was assessed using asymmetric flow field-flow fractionation (AF4) with multiangle light scattering (MALS), differential refractive index (dRI) and fluorescence (FL) detection. β-Glucan was detected in a wide molar mass range, <2000 to approximately 6.7×10(6)g/mol. Differences in molar masses were more noticeable between barley varieties and steeping malting conditions than by mashing of malt. Barley products processed to preserve β-glucan contained more β-glucan of high molar mass with potential to shift the fermentation site to the distal colon. Enzymatic degradation of proteins indicated presence of aggregates containing β-glucan and protein.

  3. Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine.

    PubMed

    Chen, Xiaoyi; Clark, Jason; Wunderlich, Mark; Fan, Cuiqing; Davis, Ashley; Chen, Song; Guan, Jun-Lin; Mulloy, James C; Kumar, Ashish; Zheng, Yi

    2017-02-15

    Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo. Mechanistically, neither Atg5 nor Rb1cc1 disruption impairs endolysosome formation or survival signaling pathways. The autophagy inhibitor chloroquine shows autophagy-independent anti-leukemic effects in vitro but has no efficacy in vivo likely due to limited achievable drug efficacy in blood. Further, vesicular exocytosis appears to mediate chloroquine resistance in AML cells, and exocytotic inhibition significantly enhances the anti-leukemic effect of chloroquine. Thus, chloroquine can induce leukemia cell death in vitro in an autophagy-independent manner but with inadequate efficacy in vivo, and vesicular exocytosis is a possible mechanism of chloroquine resistance in MA9-AML. This study also reveals that autophagy-specific targeting is unlikely to benefit MA9-AML therapy.

  4. The Effects of Temperature, Humidity and Aircraft Fluid Exposure on T800H/3900-2 Composites Bonded with AF-555M Adhesive

    NASA Technical Reports Server (NTRS)

    Miner, Gilda A.; Hou, Tan-Hung; Lowther, Sharon E.; Thibeault, Sheila A.; Connell, John W.; Blasini, Sheila Roman

    2010-01-01

    Fiber reinforced resin matrix composites and structural adhesives have found increased usage on commercial and military aircraft in recent years. Due to the lack of service history of these relatively new material systems, their long-term aging performance has not been well established. In this study, single lap shear specimens (SLS) were fabricated by secondary bonding of Scotch-Weld(TradeMark) AF-555M between pre-cured adherends comprised of T800H/3900-2 uni-directional laminates. The adherends were co-cured with wet peel-ply for surface preparation. Each bond-line of the SLS specimen was measured to determine thickness and inspected visually using an optical microscope for voids. A three-year environmental aging plan for the SLS specimens at 82 C (180 F) and 85% relative humidity was initiated. SLS strengths were measured for both controls and aged specimens at room temperature and 82 C. The effect of this exposure on lap shear strength and failure modes to date is reported. In addition, the effects of water, saline water, deicing fluid, JP-5 jet fuel and hydraulic fluid on both the composite material and the adhesive bonds were investigated. The up to date results on the effects of these exposures will be discussed.

  5. Multi-pair two-way massive MIMO AF relaying with ZFR/ZFT beamforming and imperfect CSI over ricean fading channels

    NASA Astrophysics Data System (ADS)

    Xu, Kui; Sun, Xiaoli; Zhang, Dongmei

    2016-10-01

    This paper investigates the spectral and energy efficiencies of a multi-pair two-way amplify-and-forward (AF) relay system over Ricean fading channels, where multiple user-pairs exchange information within pair through a relay with very large number of antennas, while each user equipped with a single antenna. Firstly, beamforming matrixe of zero-forcing reception/zero-forcing transmission (ZFR/ZFT) with imperfect channel state information (CSI) at the relay is given. Then, the unified asymptotic signal-to-interference-plus-noise ratio (SINR) expressions with imperfect CSI are obtained analytically. Finally, two power scaling schemes are proposed and the asymptotic spectral and energy efficiencies based on the proposed power scaling schemes are derived and verified by the Monte-Carlo simulations. Theoretical analyses and simulation results show that with imperfect CSI, if the number of relay antennas grows asymptotically large, we need cut down the transmit power of each user and relay to different proportion when the Ricean K-factor is non-zero and zero (Rayleigh fading) in order to maintain a desirable rate.

  6. Morphometric evaluation of the Afşin-Elbistan lignite basin using kernel density estimation and Getis-Ord's statistics of DEM derived indices, SE Turkey

    NASA Astrophysics Data System (ADS)

    Sarp, Gulcan; Duzgun, Sebnem

    2015-11-01

    A morphometric analysis of river network, basins and relief using geomorphic indices and geostatistical analyses of Digital Elevation Model (DEM) are useful tools for discussing the morphometric evolution of the basin area. In this study, three different indices including valley floor width to height ratio (Vf), stream gradient (SL), and stream sinuosity were applied to Afşin-Elbistan lignite basin to test the imprints of tectonic activity. Perturbations of these indices are usually indicative of differences in the resistance of outcropping lithological units to erosion and active faulting. To map the clusters of high and low indices values, the Kernel density estimation (K) and the Getis-Ord Gi∗ statistics were applied to the DEM-derived indices. The K method and Gi∗ statistic highlighting hot spots and cold spots of the SL index, the stream sinuosity and the Vf index values helped to identify the relative tectonic activity of the basin area. The results indicated that the estimation by the K and Gi∗ including three conceptualization of spatial relationships (CSR) for hot spots (percent volume contours 50 and 95 categorized as high and low respectively) yielded almost similar results in regions of high tectonic activity and low tectonic activity. According to the K and Getis-Ord Gi∗ statistics, the northern, northwestern and southern parts of the basin indicates a high tectonic activity. On the other hand, low elevation plain in the central part of the basin area shows a relatively low tectonic activity.

  7. Application of a GIS-AF/RF model to assess the risk of herbicide leaching in a citrus-growing area of the Valencia Community, Spain.

    PubMed

    de Paz, José M; Rubio, José L

    2006-12-01

    We integrated an index-based attenuation factor/retardation factor (AF/RF) model into a GIS to evaluate the risk of leaching of the most frequently applied herbicides (glyphosate, diuron, diquat, bromacil, simazine, linuron, terbuthylazine, and terbumeton) used in citrus orchards of the Valencia Community, Spain. The GIS-model system was applied to a region of 33,800 ha located near Valencia City. The soil and climate data required by the model were stored in an Arc/Info GIS in which the model algorithms were integrated using the AML programming language. A graphical user interface was developed to facilitate the use of the GIS-model system. The resulting simulation maps indicate that terbumeton, bromacil, and simazine herbicides have the highest risk of leaching because of their high mobility and low K(oc) (32-158 mg l(-1)). The remaining herbicides are strongly adsorbed by clay particles and organic matter, thus minimising the risk of leaching through the soil profile and into groundwater. The obtained ranking of the leaching potential of analysed herbicides is as follows, from highest to lowest risk: terbumeton>bromacil>simazine>terbuthylazine>diuron>linuron>glyphosate>diquat.

  8. [Psychometric analysis of the AF5 multidimensional scale of self-concept in a sample of adolescents and adults in Catalonia].

    PubMed

    Malo Cerrato, Sara; Bataller Sallent, Sílvia; Casas Aznar, Ferran; Gras Pérez, Ma Eugenia; González Carrasco, Mònica

    2011-11-01

    The aim of this study is to carry out a psychometric study of the AF5 scale in a sample of 4.825 Catalan subjects from 11 to 63 years-old. They are students from secondary compulsory education (ESO), from high school, middle-level vocational training (CFGM) and from the university. Using a principal component analysis (PCA) the theoretical validity of the components is established and the reliability of the instrument is also analyzed. Differential analyses are performed by gender and normative group using a 2 x 6 factorial design. The normative group variable includes the different levels classified into 6 sub-groups: university, post-compulsory secondary education (high school and CFGM), 4th of ESO, 3rd of ESO, 2nd of ESO and 1st of ESO. The results indicate that the reliability of the Catalan version of the scale is similar to the original scale. The factorial structure also fits with the original model established beforehand. Significant differences by normative group in the four components of self-concept explored (social, family, academic/occupational and physical) are observed. By gender, significant differences appear in the component of physical self-concept, academic and social but not in the family component.

  9. First Article Noise Survey of the A/F32T-9 Large Turbo Fan Engine Enclosed Noise Suppressor System, Far-Field Noise, McConnell AFB, Kansas.

    DTIC Science & Technology

    1987-05-01

    Continue on reverse if necessary and identify by block number) ’FIELD GROUP SUB-GROUP A/F32T-9 Jet Engine Noise Engine Test Cell Noise Suppressor Noise T-9...energy reflected off of the surrounding buildings and the spurious and transient nature of aircraft operations noise from the flight line . It is...interfering noise from highly active flight line operations. F-4s and KC-135 flyovers were routine, as were helicopters. Noise from ground support equipment

  10. First article noise survey of the A/F32T-9 large turbo fan engine enclosed noise suppressor system, far-field noise, McConnell AFB, Kansas

    NASA Astrophysics Data System (ADS)

    Fairman, Terry M.

    1987-05-01

    This report presents the results of noise measurements made on the A/F32T-9 Large Turbo Fan Engine, Enclosed Noise Suppressor System, during First Article Tests at McConnell AFB, Kansas. Noise measurements obtained at 100 meters distance are summarized for the following engines: the J57-59W, TF33-P3, TF30-P7, F100, TF41-A1, J85-5, F101-GE-102, and the F109-CF-100.

  11. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

    PubMed Central

    Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

    1996-01-01

    The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

  12. Prevalence of cry2-type genes in Bacillus thuringiensis isolates recovered from diverse habitats in India and isolation of a novel cry2Af2 gene toxic to Helicoverpa armigera (cotton boll worm).

    PubMed

    Katara, Jawahar Lal; Kaur, Sarvjeet; Kumari, Gouthami Krishna; Singh, Nagendra Kumar

    2016-12-01

    Insecticidal cry and vip genes from Bacillus thuringiensis (Bt) have been used for control of lepidopteran insects in transgenic crops. However, novel genes are required for gene pyramiding to delay evolution of resistance to the currently deployed genes. Two PCR-based techniques were employed for screening of cry2-type genes in 129 Bt isolates from diverse habitats in India and 27 known Bt strains. cry2Ab-type genes were more prevalent than cry2Aa- and cry2Ac-type genes. Correlation between source of isolates and abundance of cry2-type genes was not observed. Full-length cry2A-type genes were amplified by PCR from 9 Bt isolates and 4 Bt strains. The genes from Bt isolates SK-758 from Sorghum grain dust and SK-793 from Chilli seeds warehouse, Andhra Pradesh, were cloned and sequenced. The gene from SK-758 (NCBI GenBank accession No. GQ866915) was novel, while that from SK-793 (NCBI GenBank accession No. GQ866914) was identical to the cry2Ab1 gene. The Bacillus thuringiensis Nomenclature Committee ( http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/toxins2.html ) named these genes cry2Af2 and cry2Ab16, respectively. The cry2Af2 gene was expressed in Escherichia coli and found to be toxic towards Helicoverpa armigera. The cry2Af2 gene will be useful for pyramiding in transgenic crops.

  13. Modifications on A-F hardening rule to assess ratcheting response of materials and its interaction with fatigue damage under uniaxial stress cycles

    NASA Astrophysics Data System (ADS)

    Ahmadzadehrishehri, Gholamreza

    Ratcheting deformation is accumulated progressively over three distinct stages in materials undergoing asymmetrical cyclic stresses. The present thesis evaluates the triphasic ratcheting response of materials from two stand points: (i) Mechanistic approach at which stages of ratcheting progress over stress cycles was related to mechanistic parameters such as stress level, lifespan, mechanical properties and the softening/hardening response of materials. Mechanistic approach formulated in this thesis was employed to assess ratcheting strain over triphasic stages in various steel and copper alloys under uniaxial stress cycles. Good agreements were achieved between the predicted ratcheting strain values based on the proposed formulation and those of experimentally reported. (ii) Kinematic hardening rule approach at which the hardening rule was characterized by the yield surface translation mechanism and the corresponding plastic modulus calculated based on the consistency condition. Various cyclic plasticity models were employed to assess ratcheting response of materials under different loading conditions. The Armstrong-Frederick (A-F) hardening rule was taken as the backbone of ratcheting analysis developed in this thesis mainly due to less complexity and number of coefficients in the hardening rule as compared with other earlier developed hardening rules in the literature. To predict triphasic ratcheting strain over stress cycles, the A-F hardening rule has been further developed by means of new strain rate coefficients gamma 2 and delta. These coefficients improved the hardening rule capability to calibrate and control the rate of ratcheting over its progressive stages. The modified hardening formulation holds the coefficients of the hardening rule to control stress-strain hysteresis loops generated over stress cycles during ratcheting process plus the ratcheting rates over stages I, II, and III. These coefficients were calibrated and defined based on the applied

  14. Fluence-to-dose conversion coefficients based on the posture modification of Adult Male (AM) and Adult Female (AF) reference phantoms of ICRP 110

    NASA Astrophysics Data System (ADS)

    Galeano, D. C.; Santos, W. S.; Alves, M. C.; Souza, D. N.; Carvalho, A. B.

    2016-04-01

    The aim of this work was to modify the standing posture of the anthropomorphic reference phantoms of ICRP publication 110, AM (Adult Male) and AF (Adult Female), to the sitting posture. The change of posture was performed using the Visual Monte Carlo software (VMC) to rotate the thigh region of the phantoms and position it between the region of the leg and trunk. Scion Image software was used to reconstruct and smooth the knee and hip contours of the phantoms in a sitting posture. For 3D visualization of phantoms, the VolView software was used. In the change of postures, the organ and tissue masses were preserved. The MCNPX was used to calculate the equivalent and effective dose conversion coefficients (CCs) per fluence for photons for six irradiation geometries suggested by ICRP publication 110 (AP, PA, RLAT, LLAT, ROT and ISO) and energy range 0.010-10 MeV. The results were compared between the standing and sitting postures, for both sexes, in order to evaluate the differences of scattering and absorption of radiation for different postures. Significant differences in the CCs for equivalent dose were observed in the gonads, colon, prostate, urinary bladder and uterus, which are present in the pelvic region, and in organs distributed throughout the body, such as the lymphatic nodes, muscle, skeleton and skin, for the phantoms of both sexes. CCs for effective dose showed significant differences of up to 16% in the AP irradiation geometry, 27% in the PA irradiation geometry and 13% in the ROT irradiation geometry. These results demonstrate the importance of using phantoms in different postures in order to obtain more precise conversion coefficients for a given exposure scenario.

  15. Anteaglonialides A-F and Palmarumycins CE(1)-CE(3) from Anteaglonium sp. FL0768, a Fungal Endophyte of the Spikemoss Selaginella arenicola.

    PubMed

    Xu, Ya-ming; Mafezoli, Jair; Oliveira, Maria C F; U'Ren, Jana M; Arnold, A Elizabeth; Gunatilaka, A A Leslie

    2015-11-25

    Anteaglonialides A-F (1-6), bearing a spiro[6-(tetrahydro-7-furanyl)cyclohexane-1,2'-naphtho[1,8-de][1,3]-dioxin]-10-one skeleton, three new spirobisnaphthalenes, palmarumycins CE1-CE3 (7-9), nine known palmarumycin analogues, palmarumycins CP5 (10), CP4a (11), CP3 (12), CP17 (13), CP2 (14), and CP1 (15), CJ-12,371 (16), 4-O-methyl CJ-12,371 (17), and CP4 (18), together with a possible artifact, 4a(5)-anhydropalmarumycin CE2 (8a), and four known metabolites, O-methylherbarin (19), herbarin (20), herbaridine B (21), and hyalopyrone (22), were encountered in a cytotoxic extract of a potato dextrose agar culture of Anteaglonium sp. FL0768, an endophytic fungus of the sand spikemoss, Selaginella arenicola. The planar structures and relative configurations of the new metabolites 1-9 were elucidated by analysis of extensive spectroscopic data, and the absolute configuration of 1 was determined by the modified Mosher's ester method. Application of the modified Mosher's ester method combined with the NOESY data resulted in revision of the absolute configuration previously proposed for 10. Co-occurrence of 1-6 and 7-18 in this fungus led to the proposal that the anteagloniolides may be biogenetically derived from palmarumycins. Among the metabolites encountered, anteaglonialide F (6) and known palmarumycins CP3 (12) and CP1 (15) exhibited strong cytotoxic activity against the human Ewing's sarcoma cell line CHP-100, with IC50 values of 1.4, 0.5, and 1.6 μM, respectively.

  16. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study)

    PubMed Central

    Takeuchi, K.; Togashi, Y.; Kamihara, Y.; Fukuyama, T.; Yoshioka, H.; Inoue, A.; Katsuki, H.; Kiura, K.; Nakagawa, K.; Seto, T.; Maemondo, M.; Hida, T.; Harada, M.; Ohe, Y.; Nogami, N.; Yamamoto, N.; Nishio, M.; Tamura, T.

    2016-01-01

    Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). PMID:26487585

  17. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial.

    PubMed

    Matsumoto, Masayasu; Hori, Masatsugu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-05-01

    The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

  18. Atrial Fibrillation (AF or AFib)

    MedlinePlus

    ... Giving for Heart.org Media for Heart.org Arrhythmia About Arrhythmia Why Arrhythmia Matters Understand Your Risk for Arrhythmia Symptoms, Diagnosis & Monitoring of Arrhythmia Prevention & Treatment of ...

  19. AFS Orientation Handbook. Volume IV.

    ERIC Educational Resources Information Center

    Zaremba, Mary Ann; And Others

    This handbook is intended for use by all who design, plan, and lead orientation and cross-cultural training sessions for American Field Service students, natural and host families, and volunteers. It features orientation and training resources originating in Venezuela, France, Italy, Denmark, Canada, Argentina, Japan, Portugal, Germany, and the…

  20. Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times

  1. Ostracoda (Crustacea) association and a new species (Dolerocypris anatolia nov. sp.) from the Pliocene-Pleistocene Afşin-Elbistan (Kahraman Maraş) Coal Basin of Turkey

    NASA Astrophysics Data System (ADS)

    Tunoǧlu, Cemal; Besbelli, Berk; Ertekin, İbrahim Kadri

    2012-04-01

    The Afşin-Elbistan Coal Basin, which is one of the largest and most important Pliocene-Pleistocene lignite basins of Turkey, is located in Eastern Anatolia. The basin was formed between two normal faults having NE-SW direction and these faults controlled both the sedimentation and the subsidence. The coal horizon of over 50 meters in thickness indicates the balance between the sedimentation and subsidence rates, and was preserved during peat deposition. Coals were generated in this extensive and shallow freshwater lake and evolved from the Pliocene to Pleistocene. Typical faunal and floral assemblages of this ancient Afşin-Elbistan freshwater lake are Ostracoda, Mollusca (Gastropoda and Pelecypoda), spore-pollen and Characeae (gyrogonites). Eleven Cypridoidea species were identified from the investigation area. Eight of them are already known (Candona neglecta Sars, Candona iliensis Mandelstam, Candona aff. candida (Müller), Pseudocandona compressa (Koch), Cyclocypris ovum (Jurine), Ilyocypris gibba (Ramdohr), Cypris pubera Müller, Heterocypris salina (Brady)), whereas three belong to open nomenclature — Candona sp. and Eucypris sp.; Dolerocypris anatolia nov. sp. is proposed as a new species. Dolerocypris Kaufmann is one of the largest genera among the freshwater Ostracoda. It has a very wide geographical distribution. Representatives of this genus are actively swimming species found in shallow zones of freshwater lakes and reported from small grassy water bodies with megascopic plants. Dolerocypris anatolia nov. sp. is recorded from core samples of the Pliocene-Pleistocene Afşin-Elbistan Coal Basin for the first time.

  2. Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

    PubMed

    Parra Lopez, Rafael; Nemes, Laszlo; Jimenez-Yuste, Victor; Rusen, Luminita; Cid, Ana R; Charnigo, Robert J; Baumann, James A; Smith, Lynne; Korth-Bradley, Joan M; Rendo, Pablo

    2015-10-01

    This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

  3. Preconcentration and speciation of ultra-trace Se (IV) and Se (VI) in environmental water samples with nano-sized TiO2 colloid and determination by HG-AFS.

    PubMed

    Fu, Jiaqi; Zhang, Xu; Qian, Shahua; Zhang, Lin

    2012-05-30

    A united method for speciation analysis of Se (IV) and Se (VI) in environmental water samples was developed using nano-sized TiO(2) colloid as adsorbent and hydride generation atomic fluorescence spectrometry (HG-AFS) as determination means. When the pH values of bulk solution were between 6.0 and 7.0, successful adsorption onto 1 mL nano-sized TiO(2) colloid (0.2%) was achieved for more than 97.0% of Se (IV) while Se (VI) barely got adsorbed. Therefore, the method made it possible to preconcentrate and determine Se (IV) and Se (VI) separately. The precipitated TiO(2) with concentrated selenium was directly converted to colloid without desorption. Selenium in the resulting colloid was then determined by HG-AFS. The detection limits (3σ) and relative standard deviations (R.S.D) of this method were 24 ng/L and 42 ng/L, 7.8% (n=6) and 7.0% (n=6) for Se (IV) and Se (VI), respectively. This simple, sensitive, and united method was successfully applied to the separation and speciation of ultra-trace Se (IV) and Se (VI) in environmental water samples.

  4. TEG-1 CD2BP2 regulates stem cell proliferation and sex determination in the C. elegans germ line and physically interacts with the UAF-1 U2AF65 splicing factor

    PubMed Central

    Wang, Chris; Wilson-Berry, Laura; Schedl, Tim; Hansen, Dave

    2012-01-01

    Background For a stem cell population to exist over an extended period, a balance must be maintained between self-renewing (proliferating) and differentiating daughter cells. Within the Caenorhabditis elegans germ line, this balance is controlled by a genetic regulatory pathway, which includes the canonical Notch signaling pathway. Results Genetic screens identified the gene teg-1 as being involved in regulating the proliferation vs. differentiation decision in the C. elegans germ line. Cloning of TEG-1 revealed that it is a homolog of mammalian CD2BP2, which has been implicated in a number of cellular processes, including in U4/U6.U5 tri-snRNP formation in the pre-mRNA splicing reaction. The position of teg-1 in the genetic pathway regulating the proliferation vs. differentiation decision, its single mutant phenotype, and its enrichment in nuclei, all suggest TEG-1 also functions as a splicing factor. TEG-1, as well as its human homolog, CD2BP2, directly bind to UAF-1 U2AF65, a component of the U2 auxiliary factor. Conclusions TEG-1 functions as a splicing factor and acts to regulate the proliferation vs. meiosis decision. The interaction of TEG-1 CD2BP2 with UAF-1 U2AF65, combined with its previously described function in U4/U6.U5 tri-snRNP, suggests that TEG-1 CD2BP2 functions in two distinct locations in the splicing cascade. PMID:22275078

  5. A comparative study on the effects of tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h-AF) and basic fibroblast growth factor (bFGF) on the chorioallantoic membrane of the chick embryo.

    PubMed

    Olivo, M; Bhardwaj, R; Schulze-Osthoff, K; Sorg, C; Jacob, H J; Flamme, I

    1992-09-01

    The chorioallantoic membrane (CAM) assay is a widely used bioassay for testing angiogenic activities. In the present study we compared the gross and micromorphological effects of three angiogenic factors applied in Elvax carriers on the CAM: Tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h-AF), and basic fibroblast growth factor (bFGF). Our question was whether the CAM responds to these factors which have very different actions with a stereotype or with a factor specific reaction. By microangiography and light microscopy, all positive reactions appeared as a spoke-wheel vascular pattern with a bundle of small capillary blood vessels in the center. These vessels were predominantly of a distended type in h-AF and TNF experiments, while narrower capillary vessels followed bFGF application. Chorioallantoic ectoderm and endoderm were thickened by cell accumulation and the mesenchymal stroma of the CAM was edematous and infiltrated with leucocytes in all three reactions. Additionally, bFGF experiments showed areas of densely arranged fibroblasts. Observations in vivo showed chorioallantoic tissue movements as a possible mechanism for the spokewheel vascular pattern. As compared with our results from studies of cytokinetics with bromodeoxyuridine, these current findings indicate that chemotaxis is responsible for the chorioallantoic angiogenic reaction rather than cellular proliferation.

  6. Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo

    PubMed Central

    Becerra, Soraya; Montes, Marta; Hernández-Munain, Cristina

    2015-01-01

    The first stable complex formed during the assembly of spliceosomes onto pre-mRNA substrates in mammals includes U1 snRNP, which recognizes the 5′ splice site, and the splicing factors SF1 and U2AF, which bind the branch point sequence, polypyrimidine tract, and 3′ splice site. The 5′ and 3′ splice site complexes are thought to be joined together by protein–protein interactions mediated by factors that ensure the fidelity of the initial splice site recognition. In this study, we identified and characterized PRPF40B, a putative mammalian ortholog of the U1 snRNP-associated yeast splicing factor Prp40. PRPF40B is highly enriched in speckles with a behavior similar to splicing factors. We demonstrated that PRPF40B interacts directly with SF1 and associates with U2AF65. Accordingly, PRPF40B colocalizes with these splicing factors in the cell nucleus. Splicing assays with reporter minigenes revealed that PRPF40B modulates alternative splice site selection. In the case of Fas regulation of alternative splicing, weak 5′ and 3′ splice sites and exonic sequences are required for PRPF40B function. Placing our data in a functional context, we also show that PRPF40B depletion increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate cell survival. PMID:25605964

  7. Astronomische Konzepte und Jenseitsvorstellungen in den Pyramidentexten.

    NASA Astrophysics Data System (ADS)

    Krauss, R.

    The Egyptian pyramid texts were first written down around 2300 B.C. They are based on the religious belief in a stellar hereafter and contain the astronomical knowledge of their authors. For example, the ecliptical belt was understood as a canal, on which moon and planets cruise; of the latter Mercury, Venus and Mars were identified. On the basis of their visibility in the course of a year the fixed stars were divided into two groups; a southern group with a period of invisibility and a northern group with continual visibility. The ecliptical "canal" was correctly identified as a division line between the two groups of fixed stars. The aim of this book is to bring these texts foreward to a better understanding of their astronomical background.

  8. Denning, William Frederick (1848-1931)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Possibly a journalist and certainly an amateur astronomer. Born in Redpost, Somerset, England. The spectacular meteor storm of 1866, and a fireball in 1869, focused his interest on meteor astronomy. In 1877 he demonstrated a steady night by night movement in the Perseid meteor radiant, which proved that meteors came from showers of dust distributed along the path of a comet. Had the distinction t...

  9. Understanding the effect of locked nucleic acid and 2'-O-methyl modification on the hybridization thermodynamics of a miRNA-mRNA pair in the presence and absence of AfPiwi protein.

    PubMed

    Kumar, Santosh; Mapa, Koyeli; Maiti, Souvik

    2014-03-18

    miRNAs are some of the key epigenetic regulators of gene expression. They act through hybridization with their target mRNA and modulate the level of respective proteins via different mechanisms. Various cancer conditions are known to be associated with up- and downregulation of the oncogenic and tumor suppressor miRNAs, respectively. The levels of aberrantly expressed oncogenic miRNAs can be downregulated in different ways. Similarly, restoration of tumor suppressor miRNAs to their normal levels can be achieved using miRNA mimics. However, the use of miRNA mimics is limited by their reduced biostability and function. We have studied the hybridization thermodynamics of the miRNA 26a (11-mer, including the seed sequence) guide strand with the mRNA (11-mer) target strand in the absence and presence of AfPiwi protein. We have also inserted locked nucleic acids (LNAs) and 2'-O-methyl-modified nucleotides into the guide strand, in a walk-through manner, to assess their effect on the binding efficiency between guide and target RNA. Insertion of LNA and 2'-O-methyl-modified nucleotides into the guide strand helped to strengthen the binding affinity irrespective of the position of insertion. However, in the presence of AfPiwi protein, these modifications reduced the binding affinity to different extents depending on the position of insertion. Insertion of a modification leads to an increase in the enthalpic contribution with an increased unfavorable entropic contribution, which negatively compensates for the higher favorable enthalpy.

  10. The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model.

    PubMed

    Lessing, Franziska; Kniemeyer, Olaf; Wozniok, Iwona; Loeffler, Juergen; Kurzai, Oliver; Haertl, Albert; Brakhage, Axel A

    2007-12-01

    Macrophages and neutrophils kill the airborne fungal pathogen Aspergillus fumigatus. The dependency of this killing process on reactive oxygen intermediates (ROI) has been strongly suggested. Therefore, we investigated the enzymatic ROI detoxifying system by proteome analysis of A. fumigatus challenged by H(2)O(2). Since many of the identified proteins and genes are apparently regulated by a putative Saccharomyces cerevisiae Yap1 homolog, the corresponding gene of A. fumigatus was identified and designated Afyap1. Nuclear localization of a functional AfYap1-eGFP fusion was stress dependent. Deletion of the Afyap1 gene led to drastically increased sensitivity of the deletion mutant against H(2)O(2) and menadione, but not against diamide and NO radicals. Proteome analysis of the DeltaAfyap1 mutant strain challenged with 2 mM H(2)O(2) indicated that 29 proteins are controlled directly or indirectly by AfYap1, including catalase 2. Despite its importance for defense against reactive agents, the Afyap1 deletion mutant did not show attenuated virulence in a murine model of Aspergillus infection. These data challenge the hypothesis that ROI such as superoxide anions and peroxides play a direct role in killing of A. fumigatus in an immunocompromised host. This conclusion was further supported by the finding that killing of A. fumigatus wild-type and DeltaAfyap1 mutant germlings by human neutrophilic granulocytes worked equally well irrespective of whether the ROI scavenger glutathione or an NADPH-oxidase inhibitor was added to the cells.

  11. Characterization and expression pattern of KIFC1-like kinesin gene in the testis of the Macrobrachium nipponense with discussion of its relationship with structure lamellar complex (LCx) and acroframosome (AFS).

    PubMed

    Wang, Yan-Ting; Mao, Huan; Hou, Cong-Cong; Sun, Xiao; Wang, Da-Hui; Zhou, Hong; Yang, Wan-Xi

    2012-07-01

    Spermiogenesis is a developmental process undergoing continuous differentiation to drive a diploid spermatogonium towards a haploid sperm cell. This striking transformation from spermatogonium to spermatozoa is made possible by the stage-specific adaption of cytoskeleton and associated molecular motor proteins. KIFC1 is a C-terminal kinesin motor found to boast essential roles in acrosome biogenesis and nuclear reshaping during spermiogenesis in rat. To explore its functions during the same process in Macrobrachium nipponense, we have cloned and sequenced the cDNA of a mammalian KIFC1 homologue (termed mn-KIFC1) from the total RNA of the testis. The 2,296 bp mn-KIFC1 cDNA contained a 87 bp 5' untranslated region, a 211 bp 3' untranslated region and a 1,998 bp open reading frame. Protein alignment demonstrated that mn-KIFC1 had 37.7, 58.7, 38.4, 37.2, 38.9 and 37.8% identity with its homologues in Salmo salar, Eriocheir sinensis, Homo sapiens, Mus musculus, Danio rerio and Xenopus laevis respectively. The phylogenetic tree revealed that mn-KIFC1 is most related to E. Sinensis KIFC1 among the examined species. Tissue expression analysis showed the presence of mn-KIFC1 in the testis, hepatopancreas, gill, muscle and heart. In situ hybridization showed that the mn-KIFC1 mRNA was localized at the periphery of the nuclear membrane and in the proacrosomal vesicle in early and middle spermatids. In late spermatids and spermatozoa, mn-KIFC1 was expressed in the acrosome and in the spike. In situ hybridization also indicated that KIFC1 works together with lamellar complex (LCx) and acroframosome (AFS) to drive acrosome formation and cellular transformation. LCx and AFS have both been previously proved to have essential roles during spermiogenesis in M. nipponense. In conclusion, the expression of mn-kifc1 at specific stages of spermiogenesis suggests a role in cellular transformations in M. nipponense.

  12. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

    PubMed Central

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

  13. Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae) Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member

    PubMed Central

    Augustinos, Antonios A.; Drosopoulou, Elena; Lanzavecchia, Silvia B.; Cladera, Jorge L.; Caceres, Carlos; Bourtzis, Kostas; Mavragani-Tsipidou, Penelope; Zacharopoulou, Antigone

    2016-01-01

    Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6) pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT) applications. PMID:27362546

  14. A fast method for bisphenol A and six analogues (S, F, Z, P, AF, AP) determination in urine samples based on dispersive liquid-liquid microextraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Rocha, Bruno Alves; da Costa, Bruno Ruiz Brandão; de Albuquerque, Nayara Cristina Perez; de Oliveira, Anderson Rodrigo Moraes; Souza, Juliana Maria Oliveira; Al-Tameemi, Maha; Campiglia, Andres Dobal; Barbosa, Fernando

    2016-07-01

    In this study, a novel method combining dispersive liquid-liquid microextraction (DLLME) and fast liquid chromatography coupled to mass spectrometry (LC-MS/MS) was developed and validated for the extraction and determination of bisphenol A (BPA) and six bisphenol analogues, namely bisphenol S (BPS), bisphenol F (BPF), bisphenol P (BPP), bisphenol Z (BPZ), bisphenol AP (BPAP) and bisphenol AF (BPAF) in human urine samples. Type and volume of extraction and disperser solvents, pH sample, ionic strength, and agitation were evaluated. The matrix-matched calibration curves of all analytes were linear with correlation coefficients higher than 0.99 in the range level of 0.5-20.0ngmL(-1). The relative standard deviation (RSD), precision, at three concentrations (1.0, 8.0 and 15.0ngmL(-1)) was lower than 15% with accuracy ranging from 90 to 112%. The biomonitoring capability of the new method was confirmed with the analysis of 50 human urine samples randomly collected from Brazilians. BPA was detected in 92% of the analyzed samples at concentrations ranging

  15. Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae) Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member.

    PubMed

    Gariou-Papalexiou, Angeliki; Giardini, María Cecilia; Augustinos, Antonios A; Drosopoulou, Elena; Lanzavecchia, Silvia B; Cladera, Jorge L; Caceres, Carlos; Bourtzis, Kostas; Mavragani-Tsipidou, Penelope; Zacharopoulou, Antigone

    2016-01-01

    Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6) pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT) applications.

  16. Selective and sensitive determination of As(III) and tAs in Chinese herbal medicine samples using L-cysteine modified carbon paste electrode-based electrolytic hydride generation and AFS analysis.

    PubMed

    Lu, Xiao-Ping; Yang, Xin-An; Liu, Lin; Hu, Hui-Hui; Zhang, Wang-Bing

    2017-04-01

    A novel non-chromatographic speciation technique for ultra-trace arsenite [As(III)] and total arsenic (tAs) in Chinese herbal medicine (CHM) is developed and validated by electrolytic hydride generation (EHG) coupled with atomic fluorescence spectrometry (AFS). The studies show that As(III) can be converted efficiently to AsH3 on an L-cysteine modified carbon paste electrode (CMCPE), which has never been reported before. Significantly, other arsenic species such as arsenate [As(V)], monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) do not form any or only less volatile hydrides at low applied current mode (<1.0 A). The results also demonstrate that L-cysteine and graphite powder play different roles in the electrolytic generation of AsH3. Comparing with the traditional graphite electrode, CMCPE has better stability, sensitivity and interference tolerance. Under the optimal conditions, the limit of detection (LOD) of tAs and As(III) for this method are 0.087µgL(-1) and 0.095µgL(-1) respectively. The accuracy of the method is verified through the analysis of reference materials (CRM 08231 and SRM1568a), and the proposed method has been applied satisfactorily to the determination of As(III) and tAs in several CHM samples.

  17. Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

    NASA Astrophysics Data System (ADS)

    Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

    2017-02-01

    Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

  18. Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI).

    PubMed

    Rigaux, G; Gheran, C V; Callewaert, M; Cadiou, C; Voicu, S N; Dinischiotu, A; Andry, M C; Vander Elst, L; Laurent, S; Muller, R N; Berquand, A; Molinari, M; Huclier-Markai, S; Chuburu, F

    2017-02-03

    Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

  19. Impact of gender on event rates at 1 year in patients with newly diagnosed non-valvular atrial fibrillation: contemporary perspective from the GARFIELD-AF registry

    PubMed Central

    Camm, A John; Accetta, Gabriele; Al Mahmeed, Wael; Ambrosio, Giuseppe; Goldhaber, Samuel Z; Haas, Sylvia; Jansky, Petr; Kayani, Gloria; Misselwitz, Frank; Oh, Seil; Oto, Ali; Raatikainen, Pekka; Steffel, Jan; van Eickels, Martin; Kakkar, Ajay K

    2017-01-01

    Objectives Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) explored the impact of gender, risk factors and anticoagulant (AC) treatment on 1-year outcomes in patients with non-valvular atrial fibrillation (NVAF). Design GARFIELD-AF is a prospective non-interventional registry. Setting Investigator sites (n=1048) are representative of the care settings/locations in each of the 35 countries. Participants Patients ≥18yrs with newly diagnosed (≤6 weeks' duration) NVAF and ≥1 investigator-determined stroke risk factors. Main outcome measures Event rates per 100 person-years were estimated from the Poisson model and HRs and 95% CIs calculated. Results Of 28 624 patients (women 44.4%; men 55.6%) enrolled, there were more elderly (≥75 years) women (46.9%) than men (30.4%). All-cause mortality rates per 100 person-years (95% CI) for women and men were 4.48 (4.12 to 4.87) and 4.04 (3.74 to 4.38), respectively, stroke/systemic embolism (SE) (1.62 (1.41 to 1.87) and 1.17 (1.01 to 1.36)) and major bleeding (0.93 (0.78 to 1.13) and 0.79 (0.66 to 0.95)). After adjustment for baseline risk factors in treated and untreated patients, HRs (95% CI) for women (relative to men) for stroke/SE rates were 1.3-fold higher in women (HR 1.30 (1.04 to 1.63)), and similar for major bleeding (1.13 (0.85 to 1.50)) and all-cause mortality (1.05 (0.92 to 1.19)). Antithrombotic treatment patterns in men and women were almost identical. 63.8% women and 62.9% men received AC± antiplatelets. Relative to no AC treatment, the reduction in stroke/SE rates with AC treatment was greater (p=0.01) in men (HR 0.45 (0.33 to 0.61)) than women 0.77 (0.57 to 1.03). All-cause mortality reduction with AC treatment was similar (women: 0.65 (0.54 to 0.77); men: 0.57 (0.48 to 0.68)). The risk of major bleeding when treated with AC versus no AC was 2.33 (1.41 to 3.84) in men and 1.86 (1.16 to 2.99) in women (p value=0.53). Conclusions Women have a higher risk of stroke/SE and

  20. IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial

    PubMed Central

    Shantsila, Eduard; Haynes, Ronnie; Fisher, James; Kirchhof, Paulus; Gill, Paramjit S; Lip, Gregory Y H

    2016-01-01

    Introduction Patients with atrial fibrillation frequently suffer from heart failure with preserved ejection fraction. At present there is no proven therapy to improve physical capacity and quality of life in participants with permanent atrial fibrillation with preserved left ventricular contractility. Objective The single-centre IMproved exercise tolerance In heart failure With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether treatment with spironolactone as compared with placebo improves exercise tolerance (cardiopulmonary exercise testing), quality of life and diastolic function in patients with permanent atrial fibrillation. Methods and analysis A total of 250 patients have been randomised in this double-blinded trial for 2-year treatment with 25 mg daily dose of spironolactone or matched placebo. Included participants are 50 years old or older, have permanent atrial fibrillation and ejection fraction >55%. Exclusion criteria include contraindications to spironolactone, poorly controlled hypertension and presence of severe comorbidities with life expectancy <2 years. The primary outcome is improvement in exercise tolerance at 2 years and key secondary outcomes include quality of life (assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with Heart Failure (MLWHF) questionnaires), diastolic function and all-cause hospitalisation. Ethics and dissemination The study has been approved by the National Research and Ethics Committee West Midlands—Coventry and Warwickshire (REC reference number 14/WM/1211). The results of the trial will be published in an international peer-reviewed journal. Trial registration numbers EudraCT2014-003702-33; NCT02673463; Pre-results. PMID:27707827