Science.gov

Sample records for behandling af den

  1. The AFS Impact Study: Final Report. AFS Research Report 33.

    ERIC Educational Resources Information Center

    Hansel, Bettina

    The AFS Impact Study, initiated in 1977, is an attempt to document changes in learning and personal development associated with an intercultural "homestay" program. Completed in 1985, the study identifies several areas in which students show greater learning and educational growth than that shown by a group of students who had expressed interest…

  2. DEVILS DEN ROADLESS AREA, VERMONT.

    USGS Publications Warehouse

    Slack, John F.; Sabin, Andrew E.

    1984-01-01

    A mineral-resource survey was made of the Devils Den Roadless Area, Vermont, Geochemical sampling found traces of gold, copper, barium, lead, molybdenum, silver, tin, and thorium in rocks, stream sediments, and panned concentrates, but not in sufficient quantities to identify any resource potential. The only apparent resources are nonmetallic commodities including abundant rock suitable for crushihg, and very small deposits of sand and gravel and marble; these also occur outside the roadless area. The area was also evaluated for bedrock uranium and thorium deposits, but not anomalously high radioactive bedrock was found. A potential may exist for oil or natural gas at great depth, but this cannot be evaluated by the present study.

  3. Denning of grizzly bears in the Yellowstone National Park area

    USGS Publications Warehouse

    Judd, Steven L.; Knight, Richard R.; Blanchard, Bonnie M.

    1986-01-01

    Radiotelemetry was used to locate 101 grizzly bear (Ursus arctos) dens from 1975 to 1980; 35 dens were examined on the ground. Pregnant females denned in late October, and most other bears denned by mid-November. Duration of denning average 113, 132, and 170 days for males, females, and females with new cubs, respectively. Males emerged from mid-February to late March, followed by single females and females with yearlings and 2-year-olds. Females with new cubs emerged from early mid-April. Den sites were associated with moderate tree cover (26%-75% canopy cover) on 30°-60° slopes. Dens occurred on all aspects, although northerly exposures were most common. Grizzly bears usually dug new dens but occasionally used natural cavities or a den from a previous year. Males usually dug larger dens than females with young. Eight excavated and 2 natural dens of the 35 examined dens were used for more than 1 year.

  4. 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

  5. Dens invaginatus (dilated odontome) in mandibular canine

    PubMed Central

    Halawar, Sangamesh S; Satyakiran, GVV; Krishnanand, PS; Prashanth, R

    2014-01-01

    Dens invaginatus is a developmental malformation of teeth related to shape of the teeth. Affected teeth show a deep infolding of enamel and dentin starting from the tip of the cusps and may extend deep into the root. It results from the invagination of the enamel organ into the dental papilla before calcification has occurred. Teeth most affected are maxillary lateral incisors. The presence of dens invaginatus in mandibular canine is extremely rare. The tooth was symptomatic in that it was mobile and was oriented horizontally. This article presents a case of symptomatic dens invaginatus in mandibular canine. PMID:25364169

  6. 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

  7. 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.

  8. 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.

  9. 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. PMID:26135194

  10. Eaton AF5000+Genesis Communication Driver

    1995-05-25

    Communication driver allows the Genesis Control Series software to interact with Eaton AF5000+ frequency drives via RS-232 communications. All Eaton AF5000+ parameters that support communications are supported by the Genesis driver. Multidrop addressing to multiple units is available with the Genesis communication driver.

  11. [Dens invaginatus--a challenge in endodontics].

    PubMed

    De Moor, Roeland

    2005-01-01

    Dens invaginatus is a malformation of teeth probably due to infolding of the dental papilla during tooth development. A wide range of morphologic variations have been described. Both coronal and radicular invaginations have been demonstrated. Typical characteristics associated with the coronal invagination are the complex anatomy and the early pulp necrosis. The etiology, epidemiology, classification and therapeutic considerations are reviewed.

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

    MedlinePlus

    ... af Soomaali (Somali) Bilingual PDF Health Information Translations Tornadoes Sirens and Telephone Alerts - English Firimbiyada iyo Digniinaha telefonka - af Soomaali (Somali) PDF Healthy Roads Media Tornadoes - English Dabayl xoog badan (Ufo) - af Soomaali (Somali) ...

  13. 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.

  14. 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

  15. Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

    PubMed Central

    Choi, Eue-Keun; Park, Jae Hyung; Lee, Ji-Young; Nam, Chung Mo; Hwang, Min Ki; Uhm, Jae-Sun; Joung, Boyoung; Ko, Young-Guk; Lee, Moon-Hyoung; Lubitz, Steven A; Ellinor, Patrick T; Pak, Hui-Nam

    2015-01-01

    Background Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. Methods and Results We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10−16; PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10−11; ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10−14; KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. Conclusions SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation. PMID:26272656

  16. 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.

  17. Surgical Management of Periapical Lesion with Dens in Dente

    PubMed Central

    Jindal, MK; Asadullah, Md; Misra, SK

    2009-01-01

    The management of one case of dens in Dente (Dens invaginatus) in maxillary lateral incisor with history of trauma to maxillary central incisor with periradicular lesion is reported. The patient presented with pain and fracture of anterior tooth. Despite of complex anatomy and diagnosis of dens invaginatus, surgical root canal (Apicoectomy) was performed successfully. Further more essential clinical considerations and treatment options are suggested. Early diagnosis and management are important to avoid complications. PMID:25206098

  18. Entropy and time: A search for Denning's resting place

    NASA Astrophysics Data System (ADS)

    Beech, Martin

    2013-04-01

    The interminable scientific literature reveals William Frederick Denning (1848-1931) as one of the great practitioners of meteor astronomy: he wrote widely on the subject and dedicated innumerable hours to his observations. But who was Denning? What can we learn of his life, living and death. Glimpses of Denning the man do exist, but he is largely a man of translucency and unknowns. The journey recounted here reflects upon a recent search for Denning's final resting place, but, once again, it is found that time and circumstance have erased virtually all of the physical history.

  19. 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.

  20. 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.

  1. 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...

  2. View east along Wolf Den Road showing residences on the ...

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

    View east along Wolf Den Road showing residences on the north side of the road - Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

  3. View northwest along Wolf Den Road showing residences on the ...

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

    View northwest along Wolf Den Road showing residences on the north side of the road - Brooklyn Green, North Green, South Green, & West Green, parts of Brown Road, Canterbury Road (Route 169), Hartford Road (Route 6), Hyde Road, Pomfret Road (Route 169), Prince Hill Road, Providence Road (Route 6), Wauregan Road (Routes 169 & 205), & Wolf Den Road, Brooklyn, Windham County, CT

  4. 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.

  5. Dens evaginatus: case reports and review of the literature.

    PubMed

    Ponnambalam, Yoganathan; Love, Robert M

    2006-06-01

    Dens evaginatus is a developmental anomaly that produces a tubercle on the occlusal or palatal or lingual surfaces of teeth. The tubercle, which often contains pulp tissue, can cause occlusal interference, and pulpal pathology is a common sequel of attrition or fracture of the evagination. It affects a number of tooth types, but most commonly the premolar teeth of people of oriental ethnicity. Early diagnosis and management of dens evaginatus are important to maintain pulp vitality. This article describes three cases of dens evaginatus with different presentations. PMID:16773794

  6. MLL-AF6 fusion oncogene sequesters AF6 into the nucleus to trigger RAS activation in myeloid leukemia.

    PubMed

    Manara, Elena; Baron, Emma; Tregnago, Claudia; Aveic, Sanja; Bisio, Valeria; Bresolin, Silvia; Masetti, Riccardo; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

    2014-07-10

    A rare location, t(6;11)(q27;q23) (MLL-AF6), is associated with poor outcome in childhood acute myeloid leukemia (AML). The described mechanism by which MLL-AF6, through constitutive self-association and in cooperation with DOT-1L, activates aberrant gene expression does not explain the biological differences existing between t(6;11)-rearranged and other MLL-positive patients nor their different clinical outcome. Here, we show that AF6 is expressed in the cytoplasm of healthy bone marrow cells and controls rat sarcoma viral oncogene (RAS)-guanosine triphosphate (GTP) levels. By contrast, in MLL-AF6-rearranged cells, AF6 is found localized in the nucleus, leading to aberrant activation of RAS and of its downstream targets. Silencing MLL-AF6, we restored AF6 localization in the cytoplasm, thus mediating significant reduction of RAS-GTP levels and of cell clonogenic potential. The rescue of RAS-GTP levels after MLL-AF6 and AF6 co-silencing confirmed that MLL-AF6 oncoprotein potentiates the activity of the RAS pathway through retention of AF6 within the nucleus. Exposure of MLL-AF6-rearranged AML blasts to tipifarnib, a RAS inhibitor, leads to cell autophagy and apoptosis, thus supporting RAS targeting as a novel potential therapeutic strategy in patients carrying t(6;11). Altogether, these data point to a novel role of the MLL-AF6 chimera and show that its gene partner, AF6, is crucial in AML development.

  7. AfsR recruits RNA polymerase to the afsS promoter: a model for transcriptional activation by SARPs.

    PubMed

    Tanaka, Akiko; Takano, Yuji; Ohnishi, Yasuo; Horinouchi, Sueharu

    2007-06-01

    AfsR, a protein belonging to the Streptomyces antibiotic regulatory protein (SARP) family, is a global regulator of secondary metabolism in Streptomyces coelicolor A3(2). AfsR consists of three major functional domains: an N-terminal SARP domain, a central ATPase domain, and a C-terminal tetratrico peptide repeat (TPR) domain. Two truncated AfsR proteins, AfsRDeltaTPR containing the SARP and ATPase domains and AfsRDeltaC containing only the SARP domain, exhibited the same DNA-binding specificity as that of full-length AfsR. Two monomers bound cooperatively to a direct repeat located eight nucleotides 5' to the -10 element of the afsS promoter. Both truncated AfsR proteins, as well as full-length AfsR, were able to form ternary complexes with the afsS promoter and RNA polymerase (RNAP), although RNAP alone could not bind to the DNA. The DNA-(AfsRDeltaC)(2)-RNAP complex was capable of initiating afsS transcription in vitro, indicating that the ATPase and TPR domains are dispensable for the basic function of AfsR as a transcriptional activator. However, the ATPase domain was required to fully compensate for the defect in actinorhodin production in an afsR-disrupted mutant, suggesting that the ATPase domain exerts a regulatory function on the basic SARP domain. Deletion or addition of even a single nucleotide between the AfsR-binding site and the -10 element of the afsS promoter abolished afsS transcription both in vitro and in vivo, indicating that the recruitment of RNAP by AfsR to the correct location relative to the -10 element is critical for transcriptional activation. Since SARP-binding sites with similar direct repeats are located at the same position relative to the -10 element of their target promoters as is the afsS binding site, the SARP family members presumably activate transcription of their targets by recruiting RNAP to the promoter, where a ternary DNA-SARP-RNAP complex competent for transcriptional initiation is formed.

  8. 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.

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

    USGS Publications Warehouse

    Anthony, R.M.

    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 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.

  10. 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.

  11. Epidemiological and entomological surveillance of the co-circulation of DEN-1, DEN-2 and DEN-4 viruses in French Guiana.

    PubMed

    Fouque, Florence; Garinci, Romuald; Gaborit, Pascal

    2004-01-01

    We surveyed the disease epidemiology of dengue in French Guiana after the first dengue haemorrhagic fever epidemic from 1991 to 1993 and during an endemic period from 1993 to 1995. DEN-1, DEN-2 and DEN-4 viruses were isolated from patients and DEN-4 was also isolated from Aedes aegypti mosquitoes. Cases of dengue were reported from all over the country, not only from urban areas, but also from rural areas and isolated human settlements, indicating widespread circulation of the viruses. The mosquito vector A. aegypti was found in all inhabited areas of French Guiana and small outdoor containers were the most common breeding grounds. Some ecological features of A. aegypti, such as larvae breeding in Bromeliad plants in the rainforest, a non-exclusive anthropophily and a high vertical transmission rate for dengue viruses, indicate that A. aegypti can behave as a reservoir for dengue viruses in silent areas. Dengue viruses may survive at an endemic level and cause outbreaks when unknown conditions become more favourable. This finding adds to our knowledge of the natural history of dengue viruses in the Americas.

  12. [Progress in Teflon AF LWCC/LCW applications].

    PubMed

    Sun, Zhao-Hua; Zhou, Wen; Xu, Zhan-Tang; Ye, Hai-Bin; Yang, Chao-Yu; Lin, Jun-Fang; Hu, Shui-Bo; Yang, Yue-Zhong; Li, Cai; Cao, Wen-Xi

    2011-11-01

    Teflon AF is chemically very inert, quite physically and optically stable, a highly vapor-permeable polymer with optical transparency through much of the UV-Vis region and with an RI lower than that of water, so Teflon AF LWCC/LCW (Long path-length liquid waveguide capillary cell/liquid core waveguides) has been used with a range of different detection techniques, including absorbance spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and gas sensor. The present article describes the properties and the aspects of Teflon AF LWCC/LCW instrumentation and applications. And finally,the future prospect and outlook of Teflon AF LWCC/LCW is also discussed.

  13. AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

    PubMed Central

    Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

    2015-01-01

    AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

  14. AF-MSCs fate can be regulated by culture conditions

    PubMed Central

    Zagoura, D S; Trohatou, O; Bitsika, V; Makridakis, M; Pappa, K I; Vlahou, A; Roubelakis, M G; Anagnou, N P

    2013-01-01

    Human mesenchymal stem cells (hMSCs) represent a population of multipotent adherent cells able to differentiate into many lineages. In our previous studies, we isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF) and characterized them based on their phenotype, pluripotency and proteomic profile. In the present study, we investigated the plasticity of these cells based on their differentiation, dedifferentiation and transdifferentiation potential in vitro. To this end, adipocyte-like cells (AL cells) derived from AF-MSCs can regain, under certain culture conditions, a more primitive phenotype through the process of dedifferentiation. Dedifferentiated AL cells derived from AF-MSCs (DAF-MSCs), gradually lost the expression of adipogenic markers and obtained similar morphology and differentiation potential to AF-MSCs, together with regaining the pluripotency marker expression. Moreover, a comparative proteomic analysis of AF-MSCs, AL cells and DAF-MSCs revealed 31 differentially expressed proteins among the three cell populations. Proteins, such as vimentin, galectin-1 and prohibitin that have a significant role in stem cell regulatory mechanisms, were expressed in higher levels in AF-MSCs and DAF-MSCs compared with AL cells. We next investigated whether AL cells could transdifferentiate into hepatocyte-like cells (HL cells) directly or through a dedifferentiation step. AL cells were cultured in hepatogenic medium and 4 days later they obtained a phenotype similar to AF-MSCs, and were termed as transdifferentiated AF-MSCs (TRAF-MSCs). This finding, together with the increase in pluripotency marker expression, indicated the adaption of a more primitive phenotype before transdifferentiation. Additionally, we observed that AF-, DAF- and TRAF-MSCs displayed similar clonogenic potential, secretome and proteome profile. Considering the easy access to this fetal cell source, the plasticity of AF-MSCs and their potential to dedifferentiate and

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

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Ambrosius, K.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.

  16. 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.

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

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Fischbach, A.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.

  18. 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

  19. 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...

  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, 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...

  2. 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...

  3. 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...

  4. 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.

  5. Embedding Assessment for Learning (AfL) into Science

    ERIC Educational Resources Information Center

    Crossland, John

    2012-01-01

    Although the National Strategies for improving English schools no longer exist, the "Pedagogy and Practice" pack provides a valuable resource for producing an Assessment for Learning (AfL) framework that describes a hierarchy of skills for AfL. Based on the hierarchy, training took place in three North Yorkshire schools. To focus attention on the…

  6. 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

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

    PubMed

    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

  8. 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.

  9. Toward a petabyte-scale AFS service at CERN

    NASA Astrophysics Data System (ADS)

    van der Ster, Daniel; Moscicki, Jakub T.; Wiebalck, Arne

    2014-06-01

    AFS is a mature and reliable storage service at CERN, having worked for more than 20 years as the provider of Unix home directories and project areas. Recently, the AFS service has grown at unprecedented rates (200% in the past year); this growth was unlocked thanks to innovations in both the hardware and software components of our file servers. This work presents how AFS is used at CERN and how the service offering is evolving with the increasing storage needs of its local and remote user communities. In particular, we demonstrate the usage patterns for home directories, workspaces and project spaces, as well as show the daily work which is required to rebalance data and maintaining stability and performance. Finally, we highlight some recent changes and optimisations made to the AFS Service, thereby revealing how AFS can possibly operate at all while being subjected to frequent-almost DDOS-like-attacks from its users.

  10. 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

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

    PubMed

    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. 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.

  13. Grizzly bear denning chronology and movements in the Greater Yellowstone Ecosystem

    USGS Publications Warehouse

    Haroldson, Mark A.; Ternent, Mark A.; Gunther, Kerry A.; Schwartz, Charles C.

    2002-01-01

    Den entrance and emergence dates of grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem are important to management agencies that wish to minimize impacts of human activities on bears. Current estimates for grizzly bear denning events use data that were collected from 1975–80. We update these estimates by including data obtained from 1981–99. We used aerial telemetry data to estimate week of den entry and emergence by determining the midpoint between the last known active date and the first known date denned, as well as the last known date denned and the first known active date. We also investigated post emergence movement patterns relative to den locations. Mean earliest and latest week of den entry and emergence were also determined. Den entry for females began during the fourth week in September, with 90% denned by the fourth week of November. Earliest den entry for males occurred during the second week of October, with 90% denned by the second week of December. Mean week of den entry for known pregnant females was earlier than males. Earliest week of den entry for known pregnant females was earlier than other females and males. Earliest den emergence for males occurred during the first week of February, with 90% of males out of dens by the fourth week of April. Earliest den emergence for females occurred during the third week of March; by the first week of May, 90% of females had emerged. Male bears emerged from dens earlier than females. Denning period differed among classes and averaged 171 days for females that emerged from dens with cubs, 151 days for other females, and 131 days for males. Known pregnant females tended to den at higher elevations and, following emergence, remained at higher elevation until late May. Females with cubs remained relatively close (<3 km) to den sites until the last 2 weeks in May. Timing of denning events was similar to previous estimates for this and other grizzly bear populations in the southern Rocky

  14. 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.

  15. Tuning the Music: Acoustic Force Spectroscopy (AFS) 2.0.

    PubMed

    Kamsma, Douwe; Creyghton, Ramon; Sitters, Gerrit; Wuite, Gijs J L; Peterman, Erwin J G

    2016-08-01

    AFS is a recently introduced high-throughput single-molecule technique that allows studying structural and mechanochemical properties of many biomolecules in parallel. To further improve the method, we developed a modelling tool to optimize the layer thicknesses, and a calibration method to experimentally validate the modelled force profiles. After optimization, we are able to apply 350pN on 4.5μm polystyrene beads, without the use of an amplifier, at the coverslip side of the AFS chip. Furthermore, we present the use of a transparent piezo to generate the acoustic force and we show that AFS can be combined with high-NA oil or water-immersion objectives. With this set of developments AFS will be applicable to a broad range of single-molecule experiments. PMID:27163865

  16. Non-Surgical Root Canal Treatment of Dens Invaginatus 3 in a Maxillary Lateral Incisor

    PubMed Central

    Moradi, Saeed; Donyavi, Zakyeh; Esmaealzade, Mohammad

    2008-01-01

    The aim of this case report was to describe the clinical management of an unusual dens invaginatus type 3. A case of dens invaginatus in a maxillary lateral incisor with a periapical lesion is reported. The patient presented with pain and localized swelling. Despite the complex anatomy and diagnosis of dens invaginatus, non-surgical root canal treatment was performed successfully. Key Learning Points: - Dens invaginatus may be presented in different forms, and the etiology of this phenomenon is not fully understood. - Due to abnormal anatomical configuration, dens invaginatus presents technical difficulties in its clinical management. - Non-surgical root canal treatment can be performed successfully. PMID:24171017

  17. Complex Transcriptional Control of the Antibiotic Regulator afsS in Streptomyces: PhoP and AfsR Are Overlapping, Competitive Activators▿

    PubMed Central

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F.

    2011-01-01

    The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the −35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named “superAfsR”). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity (“superPhoP”). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites. PMID:21378195

  18. Complex transcriptional control of the antibiotic regulator afsS in Streptomyces: PhoP and AfsR are overlapping, competitive activators.

    PubMed

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F

    2011-05-01

    The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the -35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named "superAfsR"). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity ("superPhoP"). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites.

  19. 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.

  20. 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.

  1. 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. 

  2. DNA sequencing using differential extension with nucleotide subsets (DENS).

    PubMed Central

    Raja, M C; Zevin-Sonkin, D; Shwartzburd, J; Rozovskaya, T A; Sobolev, I A; Chertkov, O; Ramanathan, V; Lvovsky, L; Ulanovsky, L E

    1997-01-01

    Here we describe template directed enzymatic synthesis of unique primers, avoiding the chemical synthesis step in primer walking. We have termed this conceptually new technique DENS (differential extension with nucleotide subsets). DENS works by selectively extending a short primer, making it a long one at the intended site only. The procedure starts with a limited initial extension of the primer (at 20-30 degrees C) in the presence of only two out of the four possible dNTPs. The primer is extended by 6-9 bases or longer at the intended priming site, which is deliberately selected, (as is the two-dNTP set), to maximize the extension length. The subsequent termination reaction at 60-65 degrees C then accepts the extended primer at the intended site, but not at alternative sites, where the initial extension (if any) is generally much shorter. DENS allows the use of primers as long as 8mers (degenerate in two positions) which prime much more strongly than modular primers involving 5-7mers and which (unlike the latter) can be used with thermostable polymerases, thus allowing cycle-sequencing with dye-terminators compatible with Taq DNA polymerase, as well as making double-stranded DNA sequencing more robust. PMID:9016632

  3. Effects of iron depletion on CALM-AF10 leukemias.

    PubMed

    Heath, Jessica L; Weiss, Joshua M; Lavau, Catherine P; Wechsler, Daniel S

    2014-12-01

    Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis. The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by clathrin-mediated endocytosis. CALM-AF10 leukemias harbor a single copy of the normal CALM gene and therefore may be more sensitive to the growth-inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that CALM heterozygous (CALM(HET)) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor levels and reduced growth rates. CALM(HET) hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity toward cultured CALM(HET)CALM-AF10 leukemia cells, and this effect was additive to that of chemotherapy. In mice transplanted with CALM(HET)CALM-AF10 leukemia, we found that dietary iron restriction reduced tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CALM(HET)CALM-AF10 leukemia. In summary, although CALM heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients.

  4. 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.

  5. 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.

  6. Teilchenphysik SESAME - Forschung für den Frieden

    NASA Astrophysics Data System (ADS)

    Schopper, Herwig

    2002-01-01

    Unter der Schirmherrschaft der UNESCO entsteht in den kommenden Jahren in Jordanien ein internationales Forschungszentrum, dessen wichtigste Forschungsanlage eine Quelle für Synchrotronstrahlung sein wird. Die SESAME (Synchrotron-Light for Experimental Science and Application in the Middle East) genannte Anlage soll auch dazu beitragen, Vertrauen und Toleranz zwischen Wissenschaftlern und Politikern aus verschiedenen Kulturkreisen und Traditionen zu fördern. Das europäische Teilchenlabor CERN diente hier in mancher Hinsicht als Vorbild. Technische Grundlage für SESAME wird das 1999 stillgelegte Berliner Synchrotron BESSY I sein.

  7. 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.

  8. afsS is a target of AfsR, a transcriptional factor with ATPase activity that globally controls secondary metabolism in Streptomyces coelicolor A3(2).

    PubMed

    Lee, Ping-Chin; Umeyama, Takashi; Horinouchi, Sueharu

    2002-03-01

    AfsR is a pleiotropic, global regulator that controls the production of actinorhodin, undecylprodigiosin and calcium-dependent antibiotic in Streptomyces coelicolor A3(2). AfsR, with 993 amino acids, is phosphorylated on serine and threonine residues by a protein serine/threonine kinase AfsK and contains an OmpR-like DNA-binding fold at its N-terminal portion and A- and B-type nucleotide-binding motifs in the middle of the protein. The DNA-binding domain, in-dependently of the nucleotide-binding domain, contributed the binding of AfsR to the upstream region of afsS that locates immediately 3' to afsR and encodes a 63-amino-acid protein. No transcription of afsS in the DeltaafsR background and restoration of afsS transcription by afsR on a plasmid in the same genetic background indicated that afsR served as a transcriptional activator for afsS. Interestingly, the AfsR binding site overlapped the promoter of afsS, as determined by DNase I protection assay and high-resolution S1 nuclease mapping. The nucleotide-binding domain contributed distinct ATPase and GTPase activity. The phosphorylation of AfsR by AfsK greatly enhanced the DNA-binding activity and modulated the ATPase activity. The DNA-binding ability of AfsR was independent of the ATPase activity. However, the ATPase activity was essential for transcriptional activation of afsS, probably because the energy available from ATP hydrolysis is required for the isomerization of the closed complex between AfsR and RNA polymerase to a transcriptionally competent open complex. Thus, AfsR turns out to be a unique transcriptional factor, in that it is modular, in which DNA-binding and ATPase activities are physically separable, and the two functions are modulated by phosphorylation on serine and threonine residues.

  9. 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…

  10. Ornicorrugatin, a new siderophore from Pseudomonas fluorescens AF76.

    PubMed

    Matthijs, Sandra; Budzikiewicz, Herbert; Schäfer, Mathias; Wathelet, Bernard; Cornelis, Pierre

    2008-01-01

    From a pyoverdin-negative mutant of Pseudomonas fluorescens AF76 a new lipopeptidic siderophore (ornicorrugatin) could be isolated. It is structurally related to the siderophore of Pseudomonas corrugata differing in the replacement of one Dab unit by Orn. PMID:18386480

  11. 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.

  12. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGESBeta

    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 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

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

    USGS Publications Warehouse

    Smith, T.S.; Partridge, S.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. 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;...

  15. Dens invaginatus in a geminated maxillary lateral incisor.

    PubMed

    Pallivathukal, Renjith George; Misra, Alok; Nagraj, Sumanth Kumbargere; Donald, Preethy Mary

    2015-01-01

    Dens invaginatus (DI) and gemination are two developmental abnormalities that are well reported in the dental literature, but their coexistence in a single tooth is rare. Such situations worsen the risk factors associated with these anomalies, and the treatment plan should be customised as they possess altered morphology and anatomy. A 19-year-old girl came for evaluation of a cracked tooth in the front region of the upper jaw. The tooth showed clinical features of gemination and radiographic features of DI, and was diagnosed as DI in geminated maxillary lateral incisor. The differential diagnoses based on clinical appearance without radiographic investigation may warrant the treatment approach if these two abnormalities coexist in a single tooth. The report also highlights the importance of three-dimensional imaging in diagnosis and treatment planning of teeth with altered pulp canal anatomy. There are few reported cases in the literature detailing the treatment options for these two anomalies occurring in the same tooth.

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

    USGS Publications Warehouse

    Durner, G.M.; Amstrup, Steven C.; Ambrosius, K.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.

  17. 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.

  18. Dens Invaginatus in Primary Maxillary Molar: A Rare Case Report and Review of Literature

    PubMed Central

    Bansal, Abhinav; Kulkarni, Vinaya Kumar; Dhar, Reema Sharma

    2012-01-01

    ABSTRACT Dens invaginatus is a rare developmental anomaly. It is unusual to find this anomaly in primary dentition. Diagnosis of this dens invaginatus is important due to possible pulpal involvement. Not only that, simultaneous presence of other dental anomaly may require long-term treatment planning. Dens invaginatus can be detected clinically in the tooth presenting unusual crown morphology or radiographically as radiopacity within tooth. This article describes one of the first case reports of dens invaginatus in primary maxillary second molar in a 5-year-old female patient. How to cite this article: Bansal AV, Bansal A, Kulkarni VK, Dhar RS. Dens Invaginatus in Primary Maxillary Molar: A Rare Case Report and Review of Literature. Int J Clin Pediatr Dent 2012;5(2):139-141. PMID:25206154

  19. 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

  20. Predominance of the DEN-3 genotype during the recent dengue outbreak in Bangladesh.

    PubMed

    Aziz, M M; Hasan, K N; Hasanat, M A; Siddiqui, M A; Salimullah, M; Chowdhury, A K; Ahmed, Moslehuddin; Alam, M N; Hassan, M S

    2002-03-01

    A recent outbreak of dengue in Bangladesh was marked by many fatal complications. As clinical virulence varies among the genotypes of dengue virus, a study was conducted to investigate the molecular genotypes of dengue in Bangladesh. Reverse transcription polymerase chain reaction was used to determine viral genotypes using oligonucleotide generic primers that produce a 511 bp product. The resulting product was typed by nested PCR with strain-specific primers, yielding 482 (DEN-1), 119 (DEN-2), 290 (DEN-3) and 392 (DEN-4), visualized on UV transilluminator after electrophoresis on 2% agarose gel stained with ethidium bromide. Of 45 clinically diagnosed dengue patients (mean age 28 years; male/female 30/15), 19 (42.2%) had detectable viral RNA in their blood. However, during the first 5 days of fever in 30 patients, the frequency was 60% (18/30), implying that the sooner serum is drawn after the fever, the greater the chances of detecting viral RNA. DEN-3 was detected in all except 2 patients who were infected with DEN-2. DEN-2 (two cases) and DEN-4 (one case) were present as co-infections with DEN-3. All of the patients presented with fever, anorexia and vomiting; many had headache and general body ache; a few had a rash. About a quarter had suffered episodes of bleeding, while ascites, pleural effusion and CNS symptoms were found in a few patients Patients positive for viral RNA were also positive for anti-dengue IgM (p=0.007) in subsequent sampling. The study suggests the predominance of DEN-3 infection with occasional co-infection with other types, during the recent outbreak of dengue in Bangladesh.

  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. 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. PMID:27260668

  3. 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.

  4. 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

  5. Identification and functional characterization of grass carp IL-17A/F1: An evaluation of the immunoregulatory role of teleost IL-17A/F1.

    PubMed

    Du, Linyong; Feng, Shiyu; Yin, Licheng; Wang, Xinyan; Zhang, Anying; Yang, Kun; Zhou, Hong

    2015-07-01

    In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act significant roles in eradicating extracellular pathogens. IL-17A and IL-17F homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions remain largely undefined. Here we identified and characterized grass carp IL-17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue distribution and inductive expression of gcIL-17A/F1 indicated its possible involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1) was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) mRNA expression in head kidney leukocytes. It is suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via NF-κB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and immunoneutralization of endogenous gcCXCL-8 could partially attenuate this stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also provided the basis for clarifying Th17 cells in teleost. PMID:25847875

  6. Radiographic Study of the Prevalence of Dens Invaginatus in a Sample Set of Turkish Dental Patients

    PubMed Central

    Çolak, Hakan; Tan, Enes; Aylıkçı, Bahadır Uğur; Uzgur, Recep; Turkal, Mustafa; Hamidi, Mehmet Mustafa

    2012-01-01

    Aim: The aim of this study was to determine the prevalence of dens invaginatus in a sample of Turkish dental patients. Materials and Methods: The sample included 6, 912 panoramic radiographs from different Turkish dental patients. The ages of the patients ranged from 18 to 50 years. A tooth was considered having dens invaginatus if an infolding of a radiopaque ribbon-like structure equal in density to enamel was seen extending from the cingulum into the root canal. Maxillary and mandibular teeth were evaluated on panoramic radiographs to determine the type of dens invaginatus using Oehlers’ classification. Results: The overall incidence of patients with dens invaginatus was 0.17%. Dens invaginatus were detected in 15 teeth of a total of 192 150 teeth to give a tooth prevalence of 0.008%. Maxillary lateral incisors were most commonly affected teeth in the mouth (80% of cases), followed by maxillary canine teeth (20% of cases). The bilateral incidence of a symmetrical distribution was 25%. Conclusion: The occurrence of dens invaginatus among this Turkish population was rare. Attention should be paid to the presence of dens invaginatus and the treatment problems associated with it. PMID:22919548

  7. Grizzly bear denning and potential conflict areas in the Greater Yellowstone Ecosystem

    USGS Publications Warehouse

    Podruzny, Shannon; Cherry, Steve; Schwartz, Charles C.; Landenburger, Lisa

    2002-01-01

    Increasing winter use of steep, high-elevation terrain by backcountry recreationists has elevated concern about disturbance of denning grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem (GYE). To help identify areas where such conflicts might occur, we developed a spatially explicit model to predict potential denning areas in the GYE. Using a scan area of 630 m around each location, we assigned site attributes to 344 den locations of radio-trackedg rizzly bears from 1975-99. Attributesi dentified as predictorsf or the analysis included elevation, slope, an index of solar radiation, and forest cover. We used the Mahalanobis distance statistic to model the similarity between sites used by denning bears and each cell in the data layers. We used the final Mahalanobis distance model to produce maps of the study area. Potential denning habitat, based upon the model, is abundantw ithin the GYE. Ourr esultsc an be used by land managementa gencies to identifyp otentialc onflict sites and minimize effects of regulated activities on denning grizzly bears. We illustrate how the Gallatin National Forest (GNF) used the model to examine the overlap between potential snowmobile use areas and potential denning habitat as part of a Biological Assessment submitted to the U.S. Fish and Wildlife Service.

  8. Conservative Management of Type III Dens in Dente Using Cone Beam Computed Tomography

    PubMed Central

    Pradeep, K.; Charlie, M.; Kuttappa, M. A.; Rao, Prasana Kumar

    2012-01-01

    Dens in dente, also known as dens invaginatus, dilated composite odontoma, or deep foramen caecum, is a developmental malformation that usually affects maxillary incisor teeth, particularly lateral incisors. It may occur in teeth anywhere within the jaws, other locations are comparatively rare. It can occur within both the crown and the root, although crown invaginations are more common. The use of cone beam computed tomography (CBCT) is very helpful in endodontic diagnosis of complex anatomic variations. In this case we demonstrate the use of CBCT in the evaluation and endodontic management of a Type III dens in dente (Oehler's Type III). PMID:23029634

  9. Dens invagination: A review of literature and report of two cases

    PubMed Central

    Thakur, Seema; Thakur, Narbir S.; Bramta, Manmohan; Gupta, Mohit

    2014-01-01

    Dens invaginatus occurs as a result of the invagination of the enamel organ. These cases may present difficulties with respect to its diagnosis and treatment because of canal morphology. It frequently leads to caries, pulpal, and periodontal involvement with necrosis and loss of attachment. The knowledge of classification and anatomical variations of teeth with dens invaginatus are of great importance for correct treatment. This article presents two case reports of two different types of dens invaginatus along with profound review of the literature regarding etiology, epidemiology, and histology. It discusses clinical appearance and diagnosis, and it provides guidelines for decision-making and treatment of invaginated teeth. PMID:24678234

  10. 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

  11. Type III Dens Invaginatus with an Associated Cyst: A Case Report and Literature Review

    PubMed Central

    Thejokrishna, P

    2011-01-01

    Dens invaginatus (dens in dente) is a rare malformation with a widely varied morphology. An unusual presentation of a type III dens invaginatus affecting a conical shaped permanent lateral incisor in an 8-year-old female patient is reported. The presence of a pulp stone and a periapical radiolucency further added onto the complexity of the case. The etiology, pathophysiology, association with other dental anomalies as well as the challenges in management of this anomaly are discussed. An extensive literature review is also presented.

  12. 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

  13. Improvement and biological applications of fluorescent probes for zinc, ZnAFs.

    PubMed

    Hirano, Tomoya; Kikuchi, Kazuya; Urano, Yasuteru; Nagano, Tetsuo

    2002-06-12

    The development and cellular applications of novel fluorescent probes for Zn2+, ZnAF-1F, and ZnAF-2F are described. Fluorescein is used as a fluorophore of ZnAFs, because its excitation and emission wavelengths are in the visible range, which minimizes cell damage and autofluorescence by excitation light. N,N-Bis(2-pyridylmethyl)ethylenediamine, used as an acceptor for Zn2+, is attached directly to the benzoic acid moiety of fluorescein, resulting in very low quantum yields of 0.004 for ZnAF-1F and 0.006 for ZnAF-2F under physiological conditions (pH 7.4) due to the photoinduced electron-transfer mechanism. Upon the addition of Zn2+, the fluorescence intensity is quickly increased up to 69-fold for ZnAF-1F and 60-fold for ZnAF-2F. Apparent dissociation constants (K(d)) are in the nanomolar range, which affords sufficient sensitivity for biological applications. ZnAFs do not fluoresce in the presence of other biologically important cations such as Ca2+ and Mg2+, and are insensitive to change of pH. The complexes with Zn2+ of previously developed ZnAFs, ZnAF-1, and ZnAF-2 decrease in fluorescence intensity below pH 7.0 owing to protonation of the phenolic hydroxyl group of fluorescein, whose pKa value is 6.2. On the other hand, the Zn2+ complexes of ZnAF-1F and ZnAF-2F emit stable fluorescence around neutral and slightly acidic conditions because the pKa values are shifted to 4.9 by substitution of electron-withdrawing fluorine at the ortho position of the phenolic hydroxyl group. For application to living cells, the diacetyl derivative of ZnAF-2F, ZnAF-2F DA, was synthesized. ZnAF-2F DA can permeate through the cell membrane, and is hydrolyzed by esterase in the cytosol to yield ZnAF-2F, which is retained in the cells. Using ZnAF-2F DA, we could measure the changes of intracellular Zn2+ in cultured cells and hippocampal slices.

  14. Binding sites for two novel phosphoproteins, 3AF5 and 3AF3, are required for rbcS-3A expression.

    PubMed Central

    Sarokin, L P; Chua, N H

    1992-01-01

    Previous studies of boxes II (-151 to -138) and III (-125 to -114), binding sites for the nuclear factor GT-1 within the -166 deleted promoter of the ribulose-1,5-bisphosphate carboxylase-3A (rbcS-3A) gene, suggested that GT-1 might act in concert with an additional protein to confer light-responsive rbcS-3A expression. In this work, S1 analysis of RNA isolated from transgenic tobacco plants carrying mutant rbcS-3A constructs led to the identification of two short sequences located at the 5' and 3' ends of box III that are required for expression. These two sequences serve as binding sites for two novel proteins, 3AF5 and 3AF3. Gel shift studies using tetramerized binding sites for both 3AF5 and 3AF3 showed that complexes with faster mobilities were formed using nuclear extracts prepared from dark-adapted plants compared with those from light-grown tobacco plants. Phosphatase treatment of extracts from light-grown plants resulted in the formation of complexes with faster mobility. Although the binding of 3AF3 to its target site is dependent upon phosphorylation, the binding of 3AF5 does not appear to be affected by its phosphorylation state. These results suggest that the phosphorylated forms of both 3AF5 and 3AF3 are required for -166 rbcS-3A expression but that the mechanisms differ by which phosphorylation regulates the activities of 3AF5 and 3AF3. PMID:1498605

  15. Sex steroid and prolactin profiles in male American black bears (Ursus americanus) during denning.

    PubMed

    Tsubota, T; Garshelis, D L; Nelson, R A; Bahr, J M

    1999-01-01

    Serum sex steroid and prolactin profiles were examined in the male American black bear, Ursus americanus during denning. Sera collected in December and the following March from 8 denning male black bears in Minnesota, U.S.A. were assayed for testosterone, estradiol-17 beta and prolactin. Eight bears were confirmed to be the denning mode based on a serum urea to creatinine ratio less than 10. Serum testosterone concentrations tended to increase from December to the subsequent March whereas serum estradiol-17 beta concentrations tended to decrease during this period. There were few changes in serum prolactin concentrations between December and March. These findings suggest that spermatogenesis and testicular steroidogenesis initiated during denning may be influenced by changes in serum sex steroid concentrations in the American black bear. PMID:10027172

  16. 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.

  17. 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

  18. AF64A-induced brain damage and its relation to dementia.

    PubMed

    Hörtnagl, H

    1994-01-01

    Several data obtained in the AF64A-model are of particular relevance for our understanding of the pathogenesis and progression of Alzheimer's disease. The AF64A-induced withdrawal of cholinergic function in the rat hippocampus was associated with reversible functional changes in other neurotransmitters, including noradrenaline, serotonin, somatostatin and glutamate, thereby mimicking changes in Alzheimer's disease. Identical changes in markers for synaptic vesicles were found in Alzheimer's disease and AF64A-model. A study on the role of gender revealed a higher susceptibility to the neurotoxic action of AF64A in female rats. The cholinergic deficit was also responsible for a disinhibition of the negative feedback regulation of glucocorticoids. Increased exposure to glucocorticoids, however, enhanced the vulnerability of hippocampal cholinergic neurons to AF64A. These data indicate that the AF64A-induced cholinergic deficit in the rat brain represents a reliable tool to study several mechanisms possibly involved in Alzheimer's disease.

  19. 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

  20. 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.

  1. Characterization of Soil Organic Matter from African Dark Earth (AfDE) Soils

    NASA Astrophysics Data System (ADS)

    Plante, A. F.; Fujiu, M.; Ohno, T.; Solomon, D.; Lehmann, J.; Fraser, J. A.; Leach, M.; Fairhead, J.

    2014-12-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. While tropical soils are typically characterized by low soil organic matter (SOM) concentrations, African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils formed through an extant but ancient soil management system. The objective of this study was to characterize the organic matter accumulated in AfDE and contrast it with non-AfDE soils. Characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) resulted in substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant, but the fertility gains in AfDE are generated by labile, more rapidly cycling pools of SOM. As a result, we characterized hot water- and pyrophosphate-extractable pools of SOM using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FT-ICR-MS). EEM/PARAFAC data suggests that AfDE samples had a greater fraction of their DOM that was more humic-like than the paired non-AfDE samples. Similarly, FT-ICR-MS analyses of extracts suggest that differences among the sites analyzed were larger than between the paired AfDE and non-AfDE extracts. Overall, in spite of substantial differences in the composition of bulk SOM, the extractable fractions appear to be relatively similar between the AfDE and non-AfDE soils.

  2. MicroRNA-205 downregulates mixed-lineage-AF4 oncogene expression in acute lymphoblastic leukemia

    PubMed Central

    Dou, Liping; Li, Jingxin; Zheng, Dehua; Li, Yonghui; Gao, Xiaoning; Xu, Chengwang; Gao, Li; Wang, Lili; Yu, Li

    2013-01-01

    Myeloid/lymphoid or mixed-lineage AF4 acute lymphoblastic leukemia (MLL-AF4 ALL) is a pediatric leukemia that occurs rarely in adults. MLL-AF4 ALL is typically characterized by the presence of chromosomal translocation (t(4;1l)(q21;q23)), leading to expression of MLL-AF4 fusion protein. Although MLL-AF4 fusion protein triggers a molecular pathogenesis and hematological presentations that are unique to leukemias, the precise role of this oncogene in leukemogenesis remains unclear. Previous studies have indicated that microRNAs (miRs) might modulate the expression of MLL-AF4 ALL fusion protein, thereby suggesting the involvement of miR in progression or suppression of MLL-AF4 ALL. We have previously demonstrated that miR-205 negatively regulates transcription of an MLL-AF4 luciferase reporter. Here, we report that exogenous expression of miR-205 in MLL-AF4 human cell lines (RS4;11 and MV4-11) inversely regulates the expression of MLL-AF4 at both messenger RNA (mRNA) and protein level. Furthermore, miR-205 significantly induced apoptosis in MLL-AF4 cells as evidenced by Annex in V staining using fluorescence-activated cell sorting (FACS) analysis. The proliferative capacity of leukemic cells was suppressed by miR-205. The addition of an miR-205 inhibitor was able to restore the observed effects. In conclusion, these findings demonstrate that miR-205 may have potential value as a novel therapeutic agent in the treatment of MLL-AF4 ALL. PMID:24009426

  3. Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

    PubMed

    Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

    2000-11-01

    A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

  4. 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.

  5. Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952.

    PubMed

    Parajuli, Niranjan; Viet, Hung Trinh; Ishida, Kenji; Tong, Hang Thi; Lee, Hei Chan; Liou, Kwangkyoung; Sohng, Jae Kyung

    2005-01-01

    We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE* promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, gamma-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces.

  6. Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952.

    PubMed

    Parajuli, Niranjan; Viet, Hung Trinh; Ishida, Kenji; Tong, Hang Thi; Lee, Hei Chan; Liou, Kwangkyoung; Sohng, Jae Kyung

    2005-01-01

    We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE* promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, gamma-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces. PMID:15921897

  7. 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.

  8. Despotism and Risk of Infanticide Influence Grizzly Bear Den-Site Selection

    PubMed Central

    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 ( = 1,412 m, SE = 52) and steeper slopes ( = 21.9°, SE = 1.1) than adult male (elevation:  = 1,209 m, SE = 76; slope:  = 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. PMID:21935378

  9. 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.

  10. 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. PMID:21935378

  11. Heading for the Hills: Risk Avoidance Drives Den Site Selection in African Wild Dogs

    PubMed Central

    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. PMID:24918935

  12. Rac1 promotes diethylnitrosamine (DEN)-induced formation of liver tumors.

    PubMed

    Bopp, Anita; Wartlick, Friedrich; Henninger, Christian; Schwarz, Michael; Kaina, Bernd; Fritz, Gerhard

    2015-03-01

    To elucidate the function of the Ras-homologous GTPase Rac1 in hepatocarcinogenesis induced by diethylnitrosamine (DEN), mice lacking hepatic Rac1 expression were treated with DEN and compared to the wild-type (WT). Rac1 knock-out (KO) mice were found to have a lower tumor yield as compared to Rac1 proficient mice. The small-sized tumors formed in the absence of Rac1 lack an activated Ras/Raf/mitogen-activated protein kinase pathway, as indicated by the absence of p-ERK expression. Apparently, Rac1 is required for Ras-driven oncogenic pathways. Moreover, tumors in Rac1 deficient mice were glutamine synthase (GS) negative. They displayed a high number of p-H3-positive and cyclinB1 expressing cells, pointing to a defect in mitotic progression. To elucidate the influence of Rac1 on mechanisms of tumor initiation, acute DEN-induced hepatic stress responses were monitored. Rac1 deficiency caused fairly complex, partially time-dependent, alterations in both basal and/or DEN-induced messenger RNA (mRNA) and protein levels of susceptibility-related genes. Basal protein expression of DNA repair factors Brca1 and DNA repair protein RAD51 homolog (Rad51) and the cell cycle regulatory factor p27 was enhanced in the absence of Rac1. Following DEN treatment, p21 mRNA and protein expression was stimulated independent of the Rac1 status. Lack of Rac1 increased mechanisms of the DNA damage response (DDR), as shown by elevated protein levels of p-ATR, p-p53 and γH2AX 24h after DEN treatment. The data show that Rac1 is essential for DEN-stimulated hepatocarcinogenesis. We hypothesize that it promotes tumor initiation by counteracting the elimination of initiated cells and, moreover, alleviates the outgrowth of transformed cells. Hence, pharmacological targeting of Rac1 could be suitable for chemoprevention.

  13. 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. PMID:24918935

  14. 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.

  15. 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.

  16. Installation-restoration program. Records search, Newark AFS, Ohio

    SciTech Connect

    Not Available

    1985-04-01

    Since 1962, many hazardous and potentially hazardous wastes have been generated by industrial operations in Building 4 at Newark AFS. Dirty freon is recycled through a recovery still inside the building and reused. A beryllium dust collection system is located on the east side of Building 4. The collected dust is encapsulated in cement and sent off-station for disposal. Twelve hazardous materials storage or staging areas were identified. During interviews, it was determined that large quantities of dirty freon had been dumped along the entire perimeter fence line and in particular two specific locations. An additional spill site was located in the area at the north-east corner of Building 4 near the location of the virgin freon tanks. An unknown amount of spent battery acid and spent solvents were spilled in this area between 1962 and 1964.

  17. [HG-AFS determination of selenium in Moringa oleifera].

    PubMed

    Huang, Guo-qing; Xiao, Zi-jun

    2007-02-01

    The Se content in Moringa oleifera was studied by hydride generation atom fluorescence spectrometry (HG-AFS) with wet digestion. The effects of the way of digestion, the work condition of apparatus, the reaction medium and acidity, and the reducing agent and masking agent on the determination of Se were investigated. And the operating condition of apparatus was optimized. The results showed that the detection limit of Se in this method was 0.42 ng x mL(-1) in the linear ranger of 0-120 ng x mL(-1), the relative standard deviation was 3.53% (n = 11), and the recovery of the method was 95.2%-104.6%. It was showed that the method was very sensitive, simple, rapid and accurate.

  18. 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.

  19. 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...

  20. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2014-07-01 2014-07-01 false AF Form 813, Request for Environmental...

  1. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2012-07-01 2012-07-01 false AF Form 813, Request for Environmental...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental...

  5. AF Therapy Now and in the Future: Drugs, Biologicals, and Ablation

    PubMed Central

    Woods, Christopher E.; Olgin, Jeffrey

    2014-01-01

    Rationale Atrial fibrillation (AF) is a complex disease with multiple interrelating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is rapidly changing and improving. Objective The purpose of this review is to summarize current state-of-the-art diagnostic and therapeutic modalities for treatment of atrial fibrillation. The review focuses on reviewing treatment as it relates to the pathophysiological basis of disease and reviews pre-clinical and clinical evidence for potential new diagnostic and therapeutic modalities, including imaging, biomarkers, pharmacologic therapy as well as ablative strategies for AF. Conclusions Current ablation and drug therapy approaches to treating AF are largely based on treating the arrhythmia once the substrate occurs and is more effective in paroxysmal AF rather than persistent or permanent AF. However, there is much research aimed at prevention strategies, targeting AF substrate—so called upstream therapy. Improved diagnostics, using imaging, genetics and biomarkers are needed to better identify sub-types of AF based on underlying substrate/mechanism to allow more directed therapeutic approaches. In addition, novel anti-arrhythmics with more atrial specific effects may reduce limiting pro-arrhythmic side-effects. Advances in ablation therapy are aimed at improving technology to reduce procedure time and in mechanism targeted approaches. PMID:24763469

  6. Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer.

    PubMed

    Sun, Ting Ting; Wang, Yan; Cheng, Hong; Xiao, Hu Zhang; Xiang, Juan Juan; Zhang, Jie Ting; Yu, Siu Bun Sydney; Martin, Tracey Amanda; Ye, Lin; Tsang, Lai Ling; Jiang, Wen Guo; Xiaohua, Jiang; Chan, Hsiao Chang

    2014-03-01

    How mutations or dysfunction of CFTR may increase the risk of malignancies in various tissues remains an open question. Here we report the interaction between CFTR and an adherens junction molecule, AF-6/afadin, and its involvement in the development of colon cancer. We have found that CFTR and AF-6/afadin are co-localized at the cell-cell contacts and physically interact with each other in colon cancer cell lines. Knockdown of CFTR results in reduced epithelial tightness and enhanced malignancies, with increased degradation and reduced stability of AF-6/afadin protein. The enhanced invasive phenotype of CFTR-knockdown cells can be completely reversed by either AF-6/afadin over-expression or ERK inhibitor, indicating the involvement of AF-6/MAPK pathway. More interestingly, the expression levels of CFTR and AF-6/afadin are significantly downregulated in human colon cancer tissues and lower expression of CFTR and/or AF-6/afadin is correlated with poor prognosis of colon cancer patients. The present study has revealed a previously unrecognized interaction between CFTR and AF-6/afadin that is involved in the pathogenesis of colon cancer and indicated the potential of the two as novel markers of metastasis and prognostic predictors for human colon cancer.

  7. 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

  8. 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

  9. Dens invaginatus type II associated with an impacted mesiodens: a 3-year follow-up

    PubMed Central

    Nalawade, Triveni M; Pateel, Deepak; Mallikarjuna, Rachappa; Gunjal, Shilpa

    2013-01-01

    Dens invaginatus is a developmental anomaly resulting in a deepening or invagination of the enamel organ into the dental papilla prior to calcification of the dental tissues. The prevalence has been reported to vary from 0.04% to 10%. Dens invaginatus commonly affects lateral incisors and very rarely affects the mesiodens. This article presents a rare case of type II dens invaginatus affecting an impacted mesiodens in a 13-year-old boy and describes its gross and histological features. The associated tooth was dilated and showed invaginated enamel and dentin extending beyond the cement enamel junction. In this case, the clinical diagnosis was confirmed by histological evaluation of the internal morphology using a hard tissue microtome to section the tooth. PMID:23893282

  10. [Dens invaginatus. Review of the literature and diagnostic and therapeutic guidelines].

    PubMed

    Baumgart, Manuela; Hänni, Stefan; Suter, Beat; Schaffner, Markus; Lussi, Adrian

    2009-01-01

    Dens invaginatus is a clinically relevant malformation of teeth resulting from an infolding of enamel and dentine into the dental structure during tooth formation, hence the former denomination "dens in dente". The dens invaginatus shows multiple morphological variations of crown and root formation. This frequently leads to caries, pulpal and periodontal involvement with necrosis and loss of attachment. Therefore, early diagnosis and prevention are of utmost importance. Due to the complexity of the malformation, treatment options in former days were limited. This article presents a profound review of the literature regarding etiology, epidemiology and histology. It discusses clinical appearance and diagnosis and it provides guidelines for decision-making and treatment of invaginated teeth.

  11. 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.

  12. 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.

  13. Professional Development of Teachers--A Prerequisite for AfL to Be Successfully Implemented in the Classroom

    ERIC Educational Resources Information Center

    Smith, Kari

    2011-01-01

    A prerequisite for AfL to be successfully implemented in the classroom is the teachers' assessment practice. In many contexts, including the Norwegian, AfL has not been successfully dealt with during initial teacher education, and there is a need for qualified teachers to engage in professional development in AfL. This article first discusses…

  14. Critical behavior of a triangular lattice Ising AF/FM bilayer

    NASA Astrophysics Data System (ADS)

    Žukovič, M.; Bobák, A.

    2016-03-01

    We study a bilayer Ising spin system consisting of antiferromagnetic (AF) and ferromagnetic (FM) triangular planes, coupled by ferromagnetic exchange interaction, by standard Monte Carlo and parallel tempering methods. The AF/FM bilayer is found to display the critical behavior completely different from both the single FM and AF constituents as well as the FM/FM and AF/AF bilayers. Namely, by finite-size scaling (FSS) analysis we identify at the same temperature a standard Ising transition from the paramagnetic to FM state in the FM plane that induces a ferrimagnetic state with a finite net magnetic moment in the AF plane. At lower temperatures there is another phase transition, that takes place only in the AF plane, to different ferrimagnetic state with spins on two sublattices pointing parallel and on one sublattice antiparallel to the spins on the FM plane. FSS indicates that the corresponding critical exponents are close to the two-dimensional three-state ferromagnetic Potts model values.

  15. Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms

    PubMed Central

    Przychodzen, Bartlomiej; Jerez, Andres; Guinta, Kathryn; Sekeres, Mikkael A.; Padgett, Richard; Maciejewski, Jaroslaw P.

    2013-01-01

    Recently, recurrent mutations of spliceosomal genes were frequently identified in myeloid malignancies, as well as other types of cancers. One of these spliceosomal genes, U2AF1, was affected by canonical somatic mutations in aggressive type of myeloid malignancies. We hypothesized that U2AF1 mutations causes defects of splicing (missplicing) in specific genes and that such misspliced genes might be important in leukemogenesis. We analyzed RNA deep sequencing to compare splicing patterns of 201 837 exons between the cases with U2AF1 mutations (n = 6) and wild type (n = 14). We identified different alternative splicing patterns in 35 genes comparing cells with mutant and wild-type U2AF1. U2AF1 mutations are associated with abnormal splicing of genes involved in functionally important pathways, such as cell cycle progression and RNA processing. In addition, many of these genes are somatically mutated or deleted in various cancers. Of note is that the alternative splicing patterns associated with U2AF1 mutations were associated with specific sequence signals at the affected splice sites. These novel observations support the hypothesis that U2AF1 mutations play a significant role in myeloid leukemogenesis due to selective missplicing of tumor-associated genes. PMID:23775717

  16. 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

  17. 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.

  18. 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

  19. 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). PMID:22439591

  20. [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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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. PMID:21154450

  6. The Influence of the Outdoor Environment: Den-Making in Three Different Contexts

    ERIC Educational Resources Information Center

    Canning, Natalie

    2010-01-01

    This small-scale research examined den-making in three different settings in the UK. The research consisted of non-participant, narrative observations of children aged between 3- and 5-years and early years practitioners involved in supporting them in their play. Content analysis revealed common themes: the impact of the environment on the way…

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

    PubMed

    Karyala, Prashanthi; Metri, Rahul; Bathula, Christopher; Yelamanchi, Syam K; Sahoo, Lipika; Arjunan, Selvam; Sastri, Narayan P; Chandra, Nagasuma

    2016-09-01

    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

  8. 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.

  9. Cross-talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoRP transcription.

    PubMed

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Sola-Landa, Alberto; Martín, Juan F

    2009-04-01

    The regulatory proteins AfsR and PhoP control expression of the biosynthesis of actinorhodin and undecylprodigiosin in Streptomyces coelicolor. Electrophoretic mobility shift assays showed that PhoP(DBD) does not bind directly to the actII-ORF4, redD and atrA promoters, but it binds to the afsS promoter, in a region overlapping with the AfsR operator. DNase I footprinting studies revealed a PhoP protected region of 26 nt (PHO box; two direct repeats of 11 nt) that overlaps with the AfsR binding sequence. Binding experiments indicated a competition between AfsR and PhoP; increasing concentrations of PhoP(DBD) resulted in the disappearance of the AfsR-DNA complex. Expression studies using the reporter luxAB gene coupled to afsS promoter showed that PhoP downregulates afsS expression probably by a competition with the AfsR activator. Interestingly, AfsR binds to other PhoP-regulated promoters including those of pstS (a component of the phosphate transport system) and phoRP (encoding the two component system itself). Analysis of the AfsR-protected sequences in each of these promoters allowed us to distinguish the AfsR binding sequence from the overlapping PHO box. The reciprocal regulation of the phoRP promoter by AfsR and of afsS by PhoP suggests a fine interplay of these regulators on the control of secondary metabolism.

  10. Phosphorylation of AfsR by multiple serine/threonine kinases in Streptomyces coelicolor A3(2).

    PubMed

    Sawai, Reiko; Suzuki, Ayano; Takano, Yuji; Lee, Ping-Chin; Horinouchi, Sueharu

    2004-06-01

    AfsK, a protein serine/threonine kinase, autophosphorylates on serine and threonine residues and phosphorylates serine and threonine residues of AfsR, a transcriptional activator for afsS involved in secondary metabolism in Streptomyces coelicolor A3(2). pkaG encoding a 592-amino-acid protein and SCD10.09 (named afsL) encoding a 580-amino-acid protein, both of which encode an AfsK-like protein, were transcribed throughout growth. PkaG with a histidine-tag and the kinase catalytic domain of PkaG, produced in Escherichia coli, autophosphorylated dominantly on threonine and slightly on serine residues. In addition, these proteins phosphorylated AfsR on threonine and serine residues. The catalytic domain of AfsL also autophosphorylated and phosphorylated AfsR, on threonine and serine residues in both cases. AfsR was thus found to be phosphorylated by multiple kinases. Disruption of the chromosomal pkaG gene resulted in slightly reduced production of the pigmented antibiotic actinorhodin. These findings, together with the presence of about 40 AfsK homologues and at least five AfsR homologues in S. coelicolor A3(2), suggest that the regulatory networks via eukaryotic-type protein phosphorylation are more diverse and versatile than we have expected.

  11. Totally thorascopic surgical ablation of persistent AF and long-standing persistent atrial fibrillation using the "Dallas" lesion set.

    PubMed

    Edgerton, James R; Jackman, Warren M; Mahoney, Cecile; Mack, Michael J

    2009-12-01

    Minimally invasive surgery consisting of bipolar radiofrequency pulmonary vein (PV) isolation and limited ganglionated plexus ablation is effective in eliminating atrial fibrillation (AF) in patients with paroxysmal AF but is less effective in those with persistent AF or long-standing persistent AF. The purpose of this study was examine the results of minimally invasive surgery incorporating an additional set of radiofrequency ablation lines replicating a left-sided Cox maze III procedure. Thirty patients with persistent AF (n = 10) or long-standing persistent AF (n = 20) underwent minimally invasive surgery with an extended lesion set and PV isolation for a minimum follow-up of 6 months. Linear lesions were created at the roof line, at the anterior line, and between the roof line and the left atrial appendage. All patients underwent limited ganglionated plexus ablation and left atrial appendage excision as well as PV isolation verification. Block across the roof and anterior lines was confirmed in 29 (96.6%) of the 30 patients. Follow-up included 2-week event monitoring with auto-trigger in 21 patients, pacemaker interrogation in 8, and ECG in 1 who was in AF and refused longer-term monitoring. No operative mortality or major morbidity occurred. At 6 months, 24 (80%) of the 30 patients were free of AF: 15 (75%) with long-standing persistent AF and 9 (90%) with persistent AF. Among the six failures, burden of AF was low: one had 1 episode >15 seconds, two had 4 episodes, one had 6 episodes, one had >50 episodes, and one had AF on ECG and refused further monitoring. Early results of minimally invasive surgery with a new extended linear lesion set suggest increased efficacy over PV isolation and limited ganglionated plexus ablation in patients with persistent AF or long-standing persistent AF. PMID:19959146

  12. Effects of a novel cholinergic M1 agonist, AF102B, on ambulation and water drinking behavior in rats.

    PubMed

    Togashi, H; Matsumoto, M; Yoshioka, M; Saito, Y; Saito, H

    1991-01-01

    Effects of a novel M1 agonist, AF102B (cis-2-methylspiro(1,3-oxathiolane-5,3')quinuclidine HCl), on ambulation and water drinking behavior were examined using an Ambulo-Drinkometer. AF64A-treated rats, an animal model for senile dementia of the Alzheimer type (SDAT), and non-treated control rats were used. AF102B was administered orally via tap water at a concentration of 0.01% and 0.1% for an experimental therapeutic dose and a supramaximal dose, respectively. Four-week administration of 0.01% AF102B did not affect either ambulatory activity or water drinking activity in non-treated rats. Successive 0.1% AF102B administration for 4 weeks produced a significant decrease in drinking activity as compared with non-treated control rats. In AF64A-treated rats, AF102B did not change the cholinotoxin AF64A-induced high activity in ambulation. However, a decrease in water drinking activity was observed after 0.1% AF102B administration, as in non-treated rats. These results suggest that therapeutic dose of AF102B do not produce any changes in the spontaneous moter activity and water drinking behavior in normal rats or the animal model for SDAT. Several investigators reported that AF102B (FSK-508; cis-2-methylspiro (1,3-oxathiolane-5,3') quinuclidine HCl) had the property of a relatively specific muscarinic agonist of the M1-type This novel M1 agonist, AF102B, also exerted and ameliorating effect on experimental amnesia; in a T-maze, radial-arm maze task and passive avoidance tasks. AF102B improves the cognitive impairment in various animal models for memory disorders including senile dementia of the Alzheimer type (SDAT). Based on these observations, AF102B has been proposed for the treatment of SDAT.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.

    PubMed

    Baratti, C M; Opezzo, J W; Kopf, S R

    1993-07-01

    Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage. PMID:8216161

  14. Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.

    PubMed

    Baratti, C M; Opezzo, J W; Kopf, S R

    1993-07-01

    Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage.

  15. 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.

  16. 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. PMID:27372134

  17. 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

  18. AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease

    PubMed Central

    Haskin, Joseph; Szargel, Raymonde; Shani, Vered; Mekies, Lucy N.; Rott, Ruth; Lim, Grace G. Y.; Lim, Kah-Leong; Bandopadhyay, Rina; Wolosker, Herman; Engelender, Simone

    2013-01-01

    Parkin E3 ubiquitin-ligase activity and its role in mitochondria homeostasis are thought to play a role in Parkinson's disease (PD). We now report that AF-6 is a novel parkin interacting protein that modulates parkin ubiquitin-ligase activity and mitochondrial roles. Parkin interacts with the AF-6 PDZ region through its C-terminus. This leads to ubiquitination of cytosolic AF-6 and its degradation by the proteasome. On the other hand, endogenous AF-6 robustly increases parkin translocation and ubiquitin-ligase activity at the mitochondria. Mitochondrial AF-6 is not a parkin substrate, but rather co-localizes with parkin and enhances mitochondria degradation through PINK1/parkin-mediated mitophagy. On the other hand, several parkin and PINK1 juvenile disease-mutants are insensitive to AF-6 effects. AF-6 is present in Lewy bodies and its soluble levels are strikingly decreased in the caudate/putamen and substantia nigra of sporadic PD patients, suggesting that decreased AF-6 levels may contribute to the accumulation of dysfunctional mitochondria in the disease. The identification of AF-6 as a positive modulator of parkin translocation to the mitochondria sheds light on the mechanisms involved in PD and underscores AF-6 as a novel target for future therapeutics. PMID:23393160

  19. 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

  20. 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.

  1. Expression of the denV gene of coliphage T4 in UV-sensitive rad mutants of Saccharomyces cerevisiae

    SciTech Connect

    Valerie, K.; Fronko, G.; Henderson, E.E.; de Riel, J.K.

    1986-10-01

    A plasmid containing the denV gene from bacteriophage T4, under the control of the yeast alcohol dehydrogenase I (ADC1) promoter, conferred a substantial increase in UV resistance in the UV-sensitive Saccharomyces cerevisiae mutants rad1-2 and rad3-2. The UV resistance of the denV+ yeast cells was cell cycle dependent and correlated well with the level of the denV gene product as measured by immunoblotting and by a photoreversal assay for pyrimidine dimer-DNA glycosylase activity.

  2. 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. PMID:19447056

  3. A clinical report of Type III dens invaginatus: relevant aspects of a combined therapeutic approach.

    PubMed

    Silva E Souza, Patricia de Almeida Rodrigues; de Almeida, Bruno Vila Nova; Tartari, Talita; Alves, Ana Claudia Braga Amoras; Tuji, Farbicio Mesquita; Silva E Souza, Mario Honorato

    2013-01-01

    Dens invaginatus is a developmental abnormality that alters dental morphology; as a result, treating this condition is a challenge for endodontic practices. This article describes how a combination of nonsurgical and surgical therapies was utilized to treat a maxillary central incisor with Type III dens invaginatus and vital pulp. The treatment plan included using computed tomography (CT) for a detailed analysis of the dental anatomy and periapical area, endodontic and surgical procedures, and a 4-year follow-up period that included periodic clinical and radiographic examinations. The follow-up examinations revealed a regression of the apical lesion and no other signs or symptoms. Based on the present case report, the authors concluded that this combination of surgical and nonsurgical approaches was effective and that CT is a valuable auxiliary tool for the study of dental anatomy.

  4. 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.

  5. A clinical report of Type III dens invaginatus: relevant aspects of a combined therapeutic approach.

    PubMed

    Silva E Souza, Patricia de Almeida Rodrigues; de Almeida, Bruno Vila Nova; Tartari, Talita; Alves, Ana Claudia Braga Amoras; Tuji, Farbicio Mesquita; Silva E Souza, Mario Honorato

    2013-01-01

    Dens invaginatus is a developmental abnormality that alters dental morphology; as a result, treating this condition is a challenge for endodontic practices. This article describes how a combination of nonsurgical and surgical therapies was utilized to treat a maxillary central incisor with Type III dens invaginatus and vital pulp. The treatment plan included using computed tomography (CT) for a detailed analysis of the dental anatomy and periapical area, endodontic and surgical procedures, and a 4-year follow-up period that included periodic clinical and radiographic examinations. The follow-up examinations revealed a regression of the apical lesion and no other signs or symptoms. Based on the present case report, the authors concluded that this combination of surgical and nonsurgical approaches was effective and that CT is a valuable auxiliary tool for the study of dental anatomy. PMID:23302365

  6. Rückwärtsintegration - Zu den Verhältnissen Gymnasium, Hochschule und Arbeitswelt

    NASA Astrophysics Data System (ADS)

    Schmid, Gerhard; Heppner, Winfried; Focht, Eva

    In seiner 2007 erschienen Sammlung von Vorträgen und Essays beschäftigt sich Wolfgang Frühwald, mit der Frage "Wieviel Wissen brauchen wir?“ [1] Die Kernproblematik moderner Wissenschaft und Forschung sieht der Autor, emeritierter Ordinarius für Neuere Deutsche Literaturwissenschaft und von 1992 bis 1997 Präsident der Deutschen Forschungsgemeinschaft, einerseits in der zunehmenden Spezialisierung der Wissenschaftsbereiche, andererseits in der Gefahr der Abkoppelung der Naturwissenschaften von den Geisteswissenschaften. Wiederholt plädiert er dafür, über der rasanten Entwicklung beispielsweise in der Biologie und Physik, die historische, gesellschaftliche und besonders die ethische Dimension der Forschung nicht zu übersehen und fordert eine übergeordnete Theorie der Wissenschaft, die nur im Dialog zwischen den einzelnen Fachgebieten zu entwickeln sei.

  7. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. 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. PMID:24551202

  15. Neuronal and microvascular alterations induced by the cholinergic toxin AF64A in the rat retina.

    PubMed

    Gómez-Ramos, P; Galea, E; Estrada, C

    1990-06-18

    The choline analogue ethylcholine mustard aziridinium ion (AF64A) produces both neuronal and non-neuronal alterations in the rat retina. The possible involvement of the retinal capillaries in the origin of the apparently non-specific lesions has been investigated. Two hours after a single intraocular injection of 5 nmol AF64A, ultrastructural alterations were observed in neurons of the inner nuclear layer and the ganglion cell layer, where cholinergic cells are located. One week later, the number of cholinergic neurons, identified by choline acetyltransferase immunohistochemistry, was decreased to 65% of control, the neurons located in the inner nuclear layer being more sensitive than those in the ganglion cell layer. The same dose of AF64A also induced ultrastructural changes in retinal capillaries, which showed a significant increase in the number of pinocytotic vesicles and microvilli in the endothelial cells, 2-5 h after the toxin administration. One day later, arterioles and capillaries presented contracted profiles and the lumen was occasionally lost. The sensitivity of endothelial cells to the toxic effects of AF64A may be explained by the presence in the cerebral endothelium of a choline transport mechanism with an affinity close to that of cerebral synaptosomes. In vitro, both neuronal and endothelial choline uptake systems were equally sensitive to the toxin inhibitory effect. The early and severe vascular alterations induced in the retinal microvessels by AF64A may produce changes in blood perfusion and capillary permeability that could account for the apparently non-specific histological damage.

  16. Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR)

    PubMed Central

    Weber, Axel; Taube, Sylvia; Starke, Sven; Bergmann, Eckhard; Christiansen, Nina Merete; Christiansen, Holger

    2011-01-01

    Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 106 to 8 × 106 control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas. PMID:21293059

  17. Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR).

    PubMed

    Weber, Axel; Taube, Sylvia; Starke, Sven; Bergmann, Eckhard; Christiansen, Nina Merete; Christiansen, Holger

    2011-02-01

    Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 10(6) to 8 × 10(6) control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas.

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

    SciTech Connect

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

    1983-04-01

    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.

  19. 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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26079538

  1. 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

  2. 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.

  3. Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

    PubMed

    Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

    2016-04-01

    Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. PMID:26921542

  4. Modeling spall in HY100, HY130, and AF1410 steels

    NASA Astrophysics Data System (ADS)

    Garrett, R. K.; Rajendran, A. M.; Last, H. R.

    1996-05-01

    A comparison spall analysis between three matensitic steels: HY100, HY130, and AF1410 is presented Metallurgical observations on the fracture surfaces of uniaxial tensile specimens as well as the spalled target plates confirmed the nucleation, growth, and coalescence of microvoids in these steels. The threshold stress for void nucleation in these steels were determined from the spall analysis using the EPIC finite element code. According to the model, the spall nucleation occurred at higher stress levels in AF1410 compared to HY100 and HY130. A complete set of material model constants has been determined for these three steels.

  5. 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

  6. 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.

  7. 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

  8. (/sup 3/H)AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart

    SciTech Connect

    Wang, J.X.; Roeske, W.R.; Gulya, K.; Wang, W.; Yamamura, H.I.

    1987-10-05

    The in vitro binding properties of the novel muscarinic antagonist (/sup 3/H)AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of (/sup 3/H)AF-DX 116 binding were rapid at 25/sup 0/C but 20-40 times slower at 0-4/sup 0/C. Kinetic dissociation constants (K/sub d/s) were estimated to be 31.8 nM and 30.9 nM at 25/sup 0/C; 23.1 nM and 22.9 nM at 0-4/sup 0/C for the cerebral cortex and heart, respectively. In saturation studies, (/sup 3/H)AF-DX 116 labeled 29% of the total (/sup 3/H)(-)QNB binding sites in the cerebral cortical membranes and 87% in the cardiac membranes, with K/sub d/ values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited (/sup 3/H)AF-DX 116 binding in a rank order of potency of atropine > dexetimide > AF-DX 116 > PZ > levetimide in both tissues. Except for PZ/(/sup 3/H)AF-DX 116 and AF-DX 116/(/sup 3/H)AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. 19 references, 2 figures, 4 tables.

  9. 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.

  10. Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

    PubMed

    Rao, Qi; Guo, Wenbin; Chen, Xinhua

    2015-05-01

    A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi. PMID:25394604

  11. Genome Sequence of Anoxybacillus thermarum AF/04T, Isolated from the Euganean Hot Springs in Abano Terme, Italy.

    PubMed

    Poli, Annarita; Nicolaus, Barbara; Chan, Kok-Gan; Kahar, Ummirul Mukminin; Chan, Chia Sing; Goh, Kian Mau

    2015-05-21

    Anoxybacillus thermarum AF/04(T) was isolated from the Euganean hot springs in Abano Terme, Italy. The present work reports a high-quality draft genome sequence of strain AF/04(T). This work also provides useful insights into glycoside hydrolases, glycoside transferases, and sugar transporters that may be involved in cellular carbohydrate metabolism.

  12. 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

  13. Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis.

    PubMed

    Kakeda, M; Schlapbach, Christoph; Danelon, G; Tang, M M; Cecchinato, V; Yawalkar, N; Uguccioni, M

    2014-12-01

    Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) are rare pustular skin disorders with systemic involvement. IL-17A/F is a proinflammatory cytokine involved in various neutrophilic inflammatory disorders. Here we show that IL-17A/F is highly expressed by innate immune cells such as neutrophils and mast cells in both AGEP and GPP.

  14. Bilateral dens invaginatus in the mandibular premolars – Diagnosis and treatment

    PubMed Central

    Kharangate, Nupur; Figueiredo, Nigel R.; Fernandes, Marina; Lambor, Rajan

    2015-01-01

    Dens invaginatus (DI) is a developmental anomaly that results from an infolding of the dental papilla during tooth development and simulates the appearance of a tooth within another tooth. It shows a wide spectrum of variations in morphology and usually affects the maxillary lateral incisors. This study presents an unusual case of an Oehlers’ Type I DI involving the bilateral mandibular first and second premolars, which presented as an incidental radiographic finding in the first premolars and was associated with a periapical lesion in the second premolars which was successfully treated using nonsurgical endodontics. PMID:26321850

  15. Geochemical survey of the Devil's Den Roadless Area, Rutland and Windsor counties, Vermont

    USGS Publications Warehouse

    Slack, J.F.; Atelsek, P.J.; Grosz, A.E.

    1985-01-01

    The Devils Den area is named for a large undercut cliff (Dale, 1915, p. 21) developed in Precambrian basement rocks. This undercut cliff forms a broad natural cave immediately west of and below Forest Service Road 10, at the head of Mt. Tabor Brook. Another much smaller cave is present in dolomite of probable Paleozoic (Early Cambrian) age on the east side of the same road. This smaller cave apparently is of artificial origin, having been made during early mining of the dolomite (Dale, 1915, p. 21). This man-made cave is the only evidence of previous mining activity within the study area.

  16. AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2).

    PubMed

    Horinouchi, Sueharu

    2003-08-01

    The genome sequence of Streptomyces coelicolor A3(2) has revealed the presence of about 40 protein serine/threonine or tyrosine kinases. AfsK, which is able to phosphorylate AfsR, a transcriptional activator with ATPase activity, represents the first instance in which a bacterial Hanks-type protein kinase phosphorylates a specific protein and exerts biologically important functions. The AfsK-AfsR system in S. coelicolor A3(2) globally controls secondary metabolism. The signal transduction pathway so far demonstrated or suggested is as follows: AfsK loosely attached to the membrane autophosphorylates threonine and serine residues, perhaps on sensing some external stimulus, and enhances its kinase activity. The kinase activity is modulated by KbpA, an AfsK-binding protein, by means of protein-protein interactions. The activated AfsK phosphorylates threonine and serine residues of AfsR in the cytoplasm, by which the DNA-binding activity of AfsR is greatly enhanced. In addition to AfsK, other kinases-including PkaG and AfsL-also phosphorylate AfsR, suggesting that AfsR serves as an integrator of multiple signals sensed by these kinases. The phosphorylated AfsR binds the promoter of afsS, which encodes a protein of 63 amino acids, and forms a closed complex with RNA polymerase. The closed complex is then converted to a transcriptionally active open complex by the energy available from ATP hydrolysis by AfsR. AfsS induced in this way activates transcription of pathway-specific transcriptional activators, such as actII-ORF4 for actinorhodin production and redD for undecylprodigiosin, in an as yet unknown manner.

  17. Unusual hydrogen bonding patterns in AF (aminofluorene) and AAF (acetylaminofluorene) modified DNA

    SciTech Connect

    Broyde, S.; Hingerty, B.E.; Shapiro, R.; Norman, D.

    1989-01-01

    New structures are presented for AF and AAF modified DNAs that place the carcinogen in the minor groove of a B-DNA helix. These structures employ non-Watson-Crick base pairing schemes with syn guanine at the modification site. 32 refs., 9 figs.

  18. 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.

  19. K-theory of the chair tiling via AF-algebras

    NASA Astrophysics Data System (ADS)

    Julien, Antoine; Savinien, Jean

    2016-08-01

    We compute the K-theory groups of the groupoid C∗-algebra of the chair tiling, using a new method. We use exact sequences of Putnam to compute these groups from the K-theory groups of the AF-algebras of the substitution and the induced lower dimensional substitutions on edges and vertices.

  20. 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,...

  1. 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,...

  2. 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,...

  3. 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.

  4. Developing an Assessment for Learning (AfL) Culture in School: The Voice of the Principals

    ERIC Educational Resources Information Center

    Smith, Kari; Engelsen, Knut Steinar

    2013-01-01

    This study reflects the voice of school leaders (principals) in a Norwegian school development project focusing on assessment for learning (AfL). The central role of the principal in school improvement is well documented, however, less is written about how the principals themselves see their roles. The voices presented belong to two experienced…

  5. Acutangulosides A-F, monodesmosidic saponins from the bark of Barringtonia acutangula.

    PubMed

    Mills, Clive; Carroll, Anthony R; Quinn, Ronald J

    2005-03-01

    Nine triterpene saponins, acutangulosides A-F (2-7), and acutanguloside D-F methyl esters (5a-7a) and a single triterpene aglycone (1) were isolated from a water extract of the bark of Barringtonia acutangula. Their structures were assigned on the basis of spectroscopic data. PMID:15787427

  6. 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

  7. 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. PMID:26927796

  8. 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.

  9. 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.

  10. 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.

  11. 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. PMID:25304489

  12. 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.

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

    PubMed

    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

  14. 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

  15. Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Yuvaraj, Sambandam; Parthasarathy, Chandrakesan

    2010-03-01

    Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9.

  16. 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.

  17. Structure of a Complex between Nedd8 and the Ulp/Senp Protease Family Member Den1

    SciTech Connect

    Reverter, David; Wu, Kenneth; Erdene, Tudeviin Gan; Pan, Zhen-Qiang; Wilkinson, Keith D.; Lima, Christopher D.

    2010-07-20

    The Nedd8 conjugation pathway is conserved from yeast to humans and is essential in many organisms. Nedd8 is conjugated to cullin proteins in a process that alters SCF E3 ubiquitin ligase activity, and it is presumed that Nedd8 deconjugation would reverse these effects. We now report the X-ray structures of the human Nedd8-specific protease, Den1, in a complex with the inhibitor Nedd8 aldehyde, thus revealing a model for the tetrahedral transition state intermediate generated during proteolysis. Although Den1 is closely related to the SUMO-specific protease family (Ulp/Senp family), structural analysis of the interface suggests determinants involved in Nedd8 selectivity by Den1 over other ubiquitin-like family members and suggests how the Ulp/Senp architecture has been modified to interact with different ubiquitin-like modifiers.

  18. 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. PMID:26735137

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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. PMID:24291157

  5. Jaspolides A-F, six new isomalabricane-type terpenoids from the sponge Jaspis sp.

    PubMed

    Tang, Shengan; Pei, Yuehu; Fu, Hongzheng; Deng, Zhiwei; Li, Jun; Proksch, Peter; Lin, Wenhan

    2006-01-01

    A chemical investigation of Jaspis sp., the marine sponge collected from the South China Sea led to the isolation of six new isomalabaricane-type compounds, jaspolides A-F (1-6). The structures of those compounds were elucidated by extensive spectroscopic methods. The structure-types of 1 to 6 could be classified into triterpenes (1, 2), sesterterpene (6), diterpenes (3, 4), and nortriterpene (5). The biogenetic transformation of the isolated compounds was also speculated.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. The distribution of DEN infected people in Dushan and Xingyi area of Yunnan-Guizhou Plateau, China.

    PubMed

    Liu, Wei; Zuo, Li; Zhou, Yongbing

    2006-12-01

    The dengue viruses (DEN, genus Flavivirus, family Flaviviridae) are mosquito borne and have caused 100 million cases of dengue fever each year in most tropical and subtropical areas of the world. However, in the southwest area of Yunnan-Guizhou Plateau, China, the previous work demonstrated that different geographic strains of Aedes albopictus were susceptible to dengue virus. In this study, we collected 456 sera samples from patients with fever and 994 sera samples from healthy population in Dushan and Xingyi area of Yunnan-Guizhou Plateau, China. All sera samples were tested for dengue IgG by enzyme-linked immunosorbent assay (ELISA). Patients' sera samples were tested for dengue IgM and DEN antigen was checked in the sera of 6 from 456 samples with which C6/36 cell inoculated by IFA. The results indicate that these patients with fever were infected with DEN-2 and suggest that DEN infection had existed in Dushan and Xingyi area of Yunnan-Guizhou Plateau, China.

  11. 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...

  12. [3H]AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart.

    PubMed

    Wang, J X; Roeske, W R; Gulya, K; Wang, W; Yamamura, H I

    1987-10-01

    The in vitro binding properties of the novel muscarinic antagonist [3H]AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of [3H]AF-DX 116 binding were rapid at 25 degrees C (2.74 and 2.70 X 10(7) min-1 M-1 for K+1; 0.87 and 0.93 min-1 for k-1) but 20-40 times slower at 0-4 degrees C (0.13 and 0.096 X 10(7) min-1 M-1 for k+1; 0.031 and 0.022 min-1 for k-1 in cerebral cortical and cardiac membranes, respectively). Kinetic dissociation constants (Kds) were estimated to be 31.8 nM and 30.9 nM at 25 degrees C; 23.1 nM and 0-4 degrees C for the cerebral cortex and heart, respectively. In saturation studies, [3H]AF-DX 116 labeled 29 percent of the total [3H](-)QNB binding sites in the cerebral cortical membranes and 87 percent in the cardiac membranes, with Kd values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited [3H]AF-DX 116 binding in a rank order of potency of atropine greater than dexetimide greater than AF-DX 116 greater than PZ greater than levetimide in both tissues. Except for PZ/[3H]AF-DX 116 and AF-DX 116/[3H]AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. Carbachol and oxotremorine produced shallow inhibition curves against [3H]AF-DX 116 binding in both tissues. Regional distribution studies with [3H](-)QNB, [3H]PZ and [3H]AF-DX 116 showed that most of the muscarinic receptors in the cerebral cortex, hippocampus, nucleus accumbens and corpus striatum are of the M1 subtype while those in the brainstem, cerebellum and other lower brain regions are of the M2 subtype. These results indicate that [3H]AF-DX 116 is a useful probe for the study of heterogeneity of muscarinic cholinergic receptors. PMID:3657382

  13. Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia.

    PubMed

    Bizarro, Susana; Cerveira, Nuno; Correia, Cecília; Lisboa, Susana; Peixoto, Ana; Norton, Lucília; Teixeira, Manuel R

    2007-10-01

    The t(4;11)(q21;q23) involving the genes MLL and AF4 (alias for AFF1) is detected in 50-70% of infant leukemia. We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia. Direct sequence analysis of the reverse transcriptase-polymerase chain reaction product showed an in-frame fusion between MLL exon 9 and AF4 exon 6. We further demonstrated that the genomic breakpoints were located 1,553 bp downstream of MLL exon 9 and 1,239 bp upstream of AF4 exon 6. Four Alu repeats were detected in MLL intron 9 and two Alu repeats and one LINE1 repetitive element were identified downstream of AF4 exon 5. Finally, a 9-bp polypurine (A) tract and an 8-bp polypyrimidine (T) tract were found flanking the translocation breakpoint. In summary, we have characterized at both the RNA and the DNA level a rare MLL-AF4 fusion variant that was presumably mediated by Alu repeats or polypurine and polypyrimidine tracts located in the vicinity of genomic breakpoints. PMID:17889710

  14. Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway.

    PubMed

    Feng, W; Webb, P; Nguyen, P; Liu, X; Li, J; Karin, M; Kushner, P J

    2001-01-01

    Estrogen receptor (ER) is activated either by ligand or by signals from tyrosine kinase-linked cell surface receptors. We investigated whether the nonreceptor Src tyrosine kinase could affect ER activity. Expression of constitutively active Src or stimulation of the endogenous Src/JNK pathway enhances transcriptional activation by the estrogen-ER complex and strongly stimulates the otherwise weak activation by the unliganded ER and the tamoxifen-ER complex. Src affects ER activation function 1 (AF-1), and not ER AF-2, and does so through its tyrosine kinase activity. This effect of Src is mediated partly through a Raf/mitogen-activated ERK kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) signaling cascade and partly through a MEKK/JNKK/JNK cascade. Although, as previously shown, Src action through activated ERK stimulates AF-1 by phosphorylation at S118, Src action through activated JNK neither leads to phosphorylation of S118 nor requires S118 for its action. We therefore suggest that the Src/JNK pathway enhances AF-1 activity by modification of ER AF-1-associated proteins. Src potentiates activation functions in CREB-binding protein (CBP) and glucocorticoid receptor interacting protein 1 (GRIP1), and we discuss the possibility that the Src/JNK pathway enhances the activity of these coactivators, which are known to mediate AF-1 action. PMID:11145737

  15. 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

  16. 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

    2016-01-01

    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

  17. 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

  18. S-adenosyl-L-methionine activates actinorhodin biosynthesis by increasing autophosphorylation of the Ser/Thr protein kinase AfsK in Streptomyces coelicolor A3(2).

    PubMed

    Jin, Ying-Yu; Cheng, Jinhua; Yang, Seung Hwan; Meng, Lingzhu; Palaniyandi, Sasikumar Arunachalam; Zhao, Xin-Qing; Suh, Joo-Won

    2011-01-01

    S-Adenosyl-L-methionine (SAM) is one of the major methyl donors in all living organisms. The exogenous treatment with SAM leads to increased actinorhodin production in Streptomyces coelicolor A3(2). In this study, mutants from different stages of the AfsK-AfsR signal transduction cascade were used to test the possible target of SAM. SAM had no significant effect on actinorhodin production in afsK, afsR, afsS, or actII-open reading frame 4 (ORF4) mutant. This confirms that afsK plays a critical role in delivering the signal generated by exogenous SAM. The afsK-pHJL-KN mutant did not respond to SAM, suggesting the involvement of the C-terminal of AfsK in binding with SAM. SAM increased the in vitro autophosphorylation of kinase AfsK in a dose-dependent manner, and also abolished the effect of decreased actinorhodin production by a Ser/Thr kinase inhibitor, K252a. In sum, our results suggest that SAM activates actinorhodin biosynthesis in S. coelicolor M130 by increasing the phosphorylation of protein kinase AfsK.

  19. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Breithardt, Günter; Hankey, Graeme J.; Becker, Richard C.; Singer, Daniel E.; Halperin, Jonathan L.; Hacke, Werner; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2015-01-01

    Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized 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 (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

  20. Incomplete complementation of the DNA repair defect in cockayne syndrome cells by the denV gene from bacteriophage T4 suggests a deficiency in base excision repair.

    PubMed

    Francis, M A; Bagga, P S; Athwal, R S; Rainbow, A J

    1997-10-01

    Endonuclease V (denV) from bacteriophage T4 has been examined for its ability to complement the repair defect in Cockayne syndrome (CS) cells of complementation groups A and B. CS is an autosomal recessive disorder characterized by hypersensitivity to UV light and a defect in the preferential repair of UV-induced lesions in transcriptionally active DNA by the nucleotide excision repair (NER) pathway. The denV gene was introduced into non-transformed normal and CS fibroblasts transiently via a recombinant adenovirus (Ad) vector and into SV40-transformed normal and CS cells via a retroviral vector. Expression of denV in CS-A cells resulted in partial correction of the UV-sensitive phenotype in assays of gene-specific repair and cell viability, while correction of CS-B cells by expression of denV in the same assays was minimal or non-existent. In contrast, denV expression led to enhanced host cell reactivation (HCR) of viral DNA synthesis in both CS complementation groups to near normal levels. DenV is a glycosylase which is specific for cyclobutane-pyrimidine dimers (CPDs) but does not recognize other UV-induced lesions. Previous work has indicated that CS cells can efficiently repair all non-CPD UV-induced transcription blocking lesions (S.F. Barrett et al.. Mutation Res. 255 (1991) 281-291 [1]) and that denV incised lesions are believed to be processed via the base excision repair (BER) pathway. The inability of denV to complement the NER defect in CS cells to normal levels implies an impaired ability to process denV incised lesions by the BER pathway, and suggests a role for the CS genes, particularly the CS-B gene, in BER. PMID:9372849

  1. 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.

  2. 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.

  3. Quality control in boar semen production by use of the FACSCount AF system.

    PubMed

    Christensen, Preben; Knudsen, Dorte B; Wachmann, Henrik; Madsen, Mads T

    2004-10-01

    A simple and rapid flow cytometric method has recently been developed for simultaneous determination of sperm concentration and viability in semen from domestic animals. Use of SYBR-14 trade mark in combination with propidium iodide (PI) allows estimation of the proportion of live sperm (viability). An internal standard of fluorescent microspheres (beads) makes it possible to determine the sperm concentration during the same analysis. In the first experiment, the relationship between sperm viability and litter size was investigated. The second experiment explored whether a smaller variation in the number of motile sperm per insemination dose could be obtained using the FACSCount AF flow cytometer than using a spectrophotometer. Results in the first experiment show that sperm viability is closer related to litter size than is the traditionally used motility parameter. Although the flow cytometer is precise and objective, a limited effect on litter size should be anticipated if ejaculates are selected for insemination according to the percentage of viable sperm. However, the present trial used large insemination doses (2.3 x 10(9) motile sperm/dose) which partially compensate for the differences in motility and viability between boars and ejaculates. In the second experiment it was found that variation in the number of motile sperm per insemination dose could be reduced significantly if the FACSCount AF flow cytometer rather than the Corning 254 spectrophotometer was used for determination of sperm concentration in the raw semen. It is concluded that the FACSCount AF flow cytometer is a strong tool for improvement of the quality control in artificial insemination (AI) centres. PMID:15325548

  4. Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment.

    PubMed

    Cozzani, E; Basso, D; Cimmino, M A; Larosa, M; Burlando, M; Rongioletti, F; Drago, F; Parodi, A

    2016-08-01

    Granuloma annulare (GA) is a chronic, benign, and usually self-limiting cutaneous inflammatory disease, typically characterized by small, localized, skin-coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50-70% of localized GA cases are self-limiting and show spontaneous resolution after 1-2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low-dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA. PMID:27335228

  5. 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. PMID:26252623

  6. Dens invaginatus in ancient Chinese teeth of 2,000 years ago.

    PubMed

    Shi, Sasa; Duan, Xiaohong; Shao, Jinling; Duan, Qingbo; Peng, Shaobin

    2013-10-01

    Dens invaginatus (DI) is a developmental anomaly of teeth. Here we observed the characteristics of DI in 517 permanent teeth from 67 ancient Chinese people using micro-computed tomography (micro-CT) scanning techniques. The individuals were excavated from Shaanxi province of China and identified to be about 2,000 years old. Four DI categories are proposed to distinguish the different types of DI. The invaginated lingual fossa is classified into three classes. The overall prevalence of DI in 67 individuals was 31.34% (21 of 67). DI was found in 25 of 517 teeth (4.83%). All affected teeth were maxillary lateral incisors. The invaginated lingual fossa (Type I DI) occurred most frequently (84%), followed by radicular grooves (Type II; 16%), while Type III and Type IV were not found in the present study. Some of fossae correspond with radicular grooves (8 of 21; 3 located at mesial, 5 were distal). The bilateral incidence of DI was 19.05%. Comparing our results to those of a retrospective survey of DI from 1873 to present, we found a higher rate of DI in the excavated teeth of Chinese individuals 2,000 years ago. The use of the micro-CT technique and ethnic origin might have contributed to the higher incidence of DI.

  7. 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

  8. 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.

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

    NASA Astrophysics Data System (ADS)

    Piatti, Andrés E.

    2016-09-01

    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, multi-band photometric data sets were used to trace the cluster stellar density radial profiles and to build colour-magnitude diagrams (CMDs) and colour-colour (CC) 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 - 380M$⊙$), with higher concentration parameter values (c ˜ 0.75-1.15) and dynamically evolved ones.

  10. Adriaan van den Spiegel (1578-1625): anatomist, physician, and botanist.

    PubMed

    Ghosh, Sanjib Kumar; Sharma, Suranjali; Biswas, Sudipa; Chakraborty, Soumya

    2014-10-01

    Adriaan van den Spiegel (1578-1625) was a Flemish anatomist and physician. He was one of the most prominent anatomists at the University of Padua during the 17th century and became professor of anatomy and surgery there in 1619. He was privileged to have two of the most accomplished anatomists of that period, Fabricius ab Aquapendente and Iulius Casserius, as his teachers. His anatomical works were published after his death by his pupil Bucretius and his son-in-law Liberalis Crema, with illustrations procured from Casserius's unpublished anatomical atlas. He contributed significantly to establishing basic morphological facts about the developing embryo in his text De formato foetu liber singularis. In his book De humani corporis fabrica libri decem, Spiegel's lobe (caudate lobe) of the liver and the linea semilunaris (Spiegel's line) on the lateral side of the rectus abdominis muscle were described for the first time. Subsequently, Spigelian aponeurosis (between the lateral margin of the rectus abdominis and the linea semilunaris) and Spigelian hernia (lateral ventral hernia) were named after him. He was a renowned physician in his time and was the first to give a detailed description of malaria. He made significant contributions as a botanist: the genus Spigelia, which has six species, is named after him.

  11. An improved AFS phase for AdS3 string integrability

    NASA Astrophysics Data System (ADS)

    Abbott, Michael C.; Aniceto, Inês

    2015-04-01

    We propose a number of modifications to the classical term in the dressing phase for integrable strings in AdS3 ×S3 ×S3 ×S1, and check these against existing perturbative calculations, crossing symmetry, and the semiclassical limit of the Bethe equations. The principal change is that the phase for different masses should start with a term Q1Q2, like the one-loop AdS3 dressing phase, rather than Q2Q3 as for the original AdS5 AFS phase.

  12. The strainrange partitioning behavior of an advanced gas turbine disk alloy, AF2-1DA

    NASA Technical Reports Server (NTRS)

    Halford, G. R.; Nachtigall, A. J.

    1979-01-01

    The low-cycle, creep-fatigue characteristics of the advanced gas turbine disk alloy, AF2-1DA have been determined at 1400 F and are presented in terms of the method of strainrange partitioning (SRP). The mean stresses which develop in the PC and CP type SRP cycles at the lowest inelastic strainrange were observed to influence the cyclic lives to a greater extent than the creep effects and hence interfered with a conventional interpretation of the results by SRP. A procedure is proposed for dealing with the mean stress effects on life which is compatible with SRP.

  13. 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.

  14. 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

    2009-11-01

    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.

  15. van den Ende-Gupta syndrome of blepharophimosis, arachnodactyly, and congenital contractures: clinical delineation and recurrence in brothers.

    PubMed

    Schweitzer, Daniela N; Lachman, Ralph S; Pressman, Barry D; Graham, John M

    2003-04-30

    We describe two Hispanic brothers born to unrelated parents with van den Ende-Gupta syndrome (VDEGS), a distinctive combination of characteristic dysmorphic features, skeletal abnormalities, and cerebellar hyperplasia. This syndrome was previously delineated by van den Ende et al. [1992: Am J Med Genet 42:467-469] and Gupta et al. [1995: J Med Genet 32:809-812], with additional reports by Phadke et al. [1998: Am J Med Genet 77:16-18] and Bistritzer et al. [1993: Clin Genet 44:15-19]. This is the fifth report of VDEGS, which is characterized by blepharophimosis, narrow nose with hypoplastic alae nasi, hypoplastic maxilla, everted lower lip, slender and elongated hands and feet, arachnodactyly, self-limiting joint contractures, and distinctive skeletal findings. This report of affected siblings, and a previous report of double second cousins born to consanguineous parents [Bistritzer et al. [1993: Clin Genet 44:15-19

  16. CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation

    PubMed Central

    Fu, Ailing; Zhu, Huifeng; Ren, Qiao; Wang, Bochu; Xu, Xingran; Bai, Huiyuan; Dong, Cheng

    2016-01-01

    Melanoma is one of the most lethal forms of skin cancer due to its early metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein, is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44 alternative splicing in melanoma and its pathogenic contributions are so far poorly understood. Here, we investigated the expression level of CD44 in a large set of melanocytic lesions at different stages. We found that the expression of CD44v8-10 and a splicing factor, U2AF2, is significantly increased during melanoma progression, while CD82/KAI1, a tetraspanin family of tumor suppressor, is reduced in metastatic melanoma. CD44v8-10 and U2AF2 expressions which are negatively correlated with CD82 levels are dramatically elevated in primary melanoma compared with dysplastic nevi and further increased in metastatic melanoma. We also showed that patients with higher CD44v8-10 and U2AF2 expression levels tended to have shorter survival. By using both in vivo and in vitro assays, we demonstrated that CD82 inhibits the production of CD44v8-10 on melanoma. Mechanistically, U2AF2 is a downstream target of CD82 and in malignant melanoma facilitates CD44v8-10 alternative splicing. U2AF2-mediated CD44 isoform switch is required for melanoma migration in vitro and lung and liver metastasis in vivo. Notably, overexpression of CD82 suppresses U2AF2 activity by inducing U2AF2 ubiquitination. In addition, our data suggested that enhancement of melanoma migration by U2AF2-dependent CD44v8-10 splicing is mediated by Src/FAK/RhoA activation and formation of stress fibers as well as CD44-E-selectin binding reinforcement. These findings uncovered a hitherto unappreciated function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative splicing and cancer aggressiveness, with potential prognostic and therapeutic implications in melanoma. PMID:27041584

  17. 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

  18. An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal

    PubMed Central

    Agrawal, Anant A.; Salsi, Enea; Chatrikhi, Rakesh; Henderson, Steven; Jenkins, Jermaine L.; Green, Michael R.; Ermolenko, Dmitri N.; Kielkopf, Clara L.

    2016-01-01

    How the essential pre-mRNA splicing factor U2AF65 recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF65–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 and 1.5 Å. These structures together with RNA binding and splicing assays reveal unforeseen roles for U2AF65 inter-domain residues in recognizing a contiguous, nine-nucleotide Py tract. The U2AF65 linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3′ terminus and third nucleotide. Single-molecule FRET experiments suggest that conformational selection and induced fit of the U2AF65 RRMs are complementary mechanisms for Py-tract association. Altogether, these results advance the mechanistic understanding of molecular recognition for a major class of splice site signals. PMID:26952537

  19. Response of Nitrosospira sp. Strain AF-Like Ammonia Oxidizers to Changes in Temperature, Soil Moisture Content, and Fertilizer Concentration▿

    PubMed Central

    Avrahami, Sharon; Bohannan, Brendan J. M.

    2007-01-01

    Very little is known regarding the ecology of Nitrosospira sp. strain AF-like bacteria, a unique group of ammonia oxidizers within the Betaproteobacteria. We studied the response of Nitrosospira sp. strain AF-like ammonia oxidizers to changing environmental conditions by applying molecular methods and physiological measurements to Californian grassland soil manipulated in the laboratory. This soil is naturally high in Nitrosospira sp. strain AF-like bacteria relative to the much-better-studied Nitrosospira multiformis-like ammonia-oxidizing bacteria. Increases in temperature, soil moisture, and fertilizer interacted to reduce the relative abundance of Nitrosospira sp. strain AF-like bacteria, although they remained numerically dominant. The overall abundance of ammonia-oxidizing bacteria increased with increasing soil moisture and decreased with increasing temperature. Potential nitrification activity was altered by interactions among temperature, soil moisture, and fertilizer, with activity tending to be higher when soil moisture and temperature were increased. The increase in potential nitrification activity with increased temperature was surprising, given that the overall abundance of ammonia-oxidizing bacteria decreased significantly under these conditions. This observation suggests that (i) Nitrosospira sp. strain AF-like bacteria may respond to increased temperature with an increase in activity, despite a decrease in abundance, or (ii) that potential nitrification activity in these soils may be due to organisms other than bacteria (e.g., archaeal ammonia oxidizers), at least under conditions of increased temperature. PMID:17158615

  20. Relationship between Af temperature and load changes in Ni-Ti orthodontic wire under different thermomechanical conditions.

    PubMed

    Kawashima, I; Ohno, H; Sachdeva, R

    1999-12-01

    Simple three point bending tests were performed on Ni-Ti wires with three different Af points (1 degree C, 13 degrees C and 34 degrees C) to clarify the relationship between Af temperature and load changes under constant deformation. Each wire was deformed at 37 degrees C and then thermal changes were imposed by temperatures of 2 degrees C or 60 degrees C. The load changes with thermal changes from 37 degrees C to 2 degrees C or 60 degrees C showed the same tendency on the wires with different Af points: In the loading stage, the load became lower than the initial level at 37 degrees C and in the unloading stage, the load became higher than the initial load. The largest load change in the unloading stage was measured with the 13 degrees C Af point wire. Care must be taken when handling Ni-Ti wire with an Af point of less than 1 degree C in order to prevent it from reaching the limit of critical stress of slip deformation when the temperature in the mouth rises to above 40 degrees C. PMID:10786161

  1. 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.

  2. Response of Nitrosospira sp. strain AF-like ammonia oxidizers to changes in temperature, soil moisture content, and fertilizer concentration.

    PubMed

    Avrahami, Sharon; Bohannan, Brendan J M

    2007-02-01

    Very little is known regarding the ecology of Nitrosospira sp. strain AF-like bacteria, a unique group of ammonia oxidizers within the Betaproteobacteria. We studied the response of Nitrosospira sp. strain AF-like ammonia oxidizers to changing environmental conditions by applying molecular methods and physiological measurements to Californian grassland soil manipulated in the laboratory. This soil is naturally high in Nitrosospira sp. strain AF-like bacteria relative to the much-better-studied Nitrosospira multiformis-like ammonia-oxidizing bacteria. Increases in temperature, soil moisture, and fertilizer interacted to reduce the relative abundance of Nitrosospira sp. strain AF-like bacteria, although they remained numerically dominant. The overall abundance of ammonia-oxidizing bacteria increased with increasing soil moisture and decreased with increasing temperature. Potential nitrification activity was altered by interactions among temperature, soil moisture, and fertilizer, with activity tending to be higher when soil moisture and temperature were increased. The increase in potential nitrification activity with increased temperature was surprising, given that the overall abundance of ammonia-oxidizing bacteria decreased significantly under these conditions. This observation suggests that (i) Nitrosospira sp. strain AF-like bacteria may respond to increased temperature with an increase in activity, despite a decrease in abundance, or (ii) that potential nitrification activity in these soils may be due to organisms other than bacteria (e.g., archaeal ammonia oxidizers), at least under conditions of increased temperature.

  3. 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

  4. 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.

  5. Methodik der Erfassung und Bewertung von Biodiversitätsschäden aus ökologischer Sicht

    NASA Astrophysics Data System (ADS)

    Wiegleb, Gerhard; Krawczynski, René; Wagner, Hans-Georg

    Mit der Verabschiedung des Umweltschadensgesetzes (USchadG) hat der Schutz der Biodiversität in Deutschland ein neues Stadium erreicht. Zum ersten Male wird selbst die Vermeidung und Restitution der nichtintendierten Schädigung der Biodiversität in Gestalt bestimmter Arten und Lebensräume in ein umfassendes Naturschutzkonzept einbezogen. Das USchadG geht damit über die bisherigen Ansätze zum Schutz der belebten Natur hinaus, da es gleichzeitig neben der Erhaltung eines als günstig erkannten Ist-Zustandes der Biodiversität der Vermeidung vorhersehbarer Schäden sowie auch der Restitution nach einem eingetretenen Schaden verpflichtet ist. Naturschutzsystematisch gehört es wegen der Betonung der Vermeidung und Sanierung zum Bereich des reaktiven Naturschutzes (Gefahrenabwehr und Gefahrenbeseitigung), dem auch die Eingriffsregelung des Bundesnaturschutzgesetzes (BNatSchG), die Umweltverträglichkeitsprüfung nach Umweltverträglichkeitsprüfungsgesetz (UVPG) sowie die FFH-Verträglichkeitsprüfung nach Fauna-Flora-Habitat-Richtlinie (FFH-RL) zuzurechnen sind. Stärker noch als in den genannten Regelungen tritt im USchadG das Verursacherprinzip gegenüber der allgemeinen Umweltvorsorge in den Vordergrund.

  6. 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

  7. 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. PMID:27328164

  8. 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).

  9. 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.

  10. 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)

  11. 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.

  12. 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.

  13. 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

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

    PubMed

    Diedrich, Cajus G

    2015-04-01

    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

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

    PubMed

    Diedrich, Cajus G

    2015-04-01

    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.

  16. ‘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

  17. 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

  18. Escherichia coli Strain RDEC-1 AF/R1 Endogenous Fimbrial Glycoconjugate Receptor Molecules in Rabbit Small Intestine

    PubMed Central

    Ryu, Hyoik; Kim, Young S.; Grange, Philippe A.; Cassels, Frederick J.

    2001-01-01

    Escherichia coli strain RDEC-1 causes a diarrheagenic infection in rabbits with AF/R1 fimbriae, which have been identified as an important colonization factor in RDEC-1 adherence leading to disease. The AF/R1-mediated RDEC-1 adherence model has been used as a model systems for E. coli diarrheal diseases. In this study, RDEC-1 adhered specifically to small intestinal brush borders, with both sialic acid and β-galactosyl residues apparently involved. The AF/R1-mediated adherence activity of [14C]-labeled RDEC-1 was analyzed quantitatively by using 24-well plates coated with purified brush borders and purified microvilli. Two microvillus membrane proteins (130 and 140 kDa) were individually isolated, and chicken antibody raised to each protein inhibited bacterial adherence. These same two proteins, previously shown to be recognized by AF/R1, were individually digested with trypsin, and the amino acid sequences of peptides were determined by reversed-phase capillary liquid chromatography-mass spectrometry tandem mass spectrometry (LC-MS). This LC-MS analysis indicated that these proteins are subunits of the rabbit sucrase-isomaltase protein (SI) complex. Guinea pig serum raised to purified rabbit SI complex inhibited bacterial adherence to microvilli. Additionally, as determined by high-performance thin-layer chromatography and autoradiography, RDEC-1 adhered selectively, via AF/R1 fimbriae, to a glycolipid tentatively identified as galactosylceramide (Galβ1-1Cer) in the lipid extract of rabbit small intestinal brush borders. RDEC-1 adherence to Galβ1-1Cer was partially inhibited in the presence of galactose. These combined results indicate that the endogenous receptor molecule for AF/R1 fimbriae of RDEC-1 is each individual component of the SI complex, although binding to glycolipid may be responsible for an additional adherence mechanism. PMID:11159950

  19. 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. PMID:26183793

  20. 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. PMID:26589820

  1. 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.

  2. The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

    PubMed Central

    Movérare-Skrtic, Sofia; Börjesson, Anna E.; Farman, Helen H.; Sjögren, Klara; Windahl, Sara H.; Lagerquist, Marie K.; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

    2014-01-01

    The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. PMID:24395795

  3. Fluorous polymeric membranes for ionophore-based ion-selective potentiometry: how inert is Teflon AF?

    PubMed

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

    2009-02-01

    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 4 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 10(3.5), 10(1.8), 10(6.8), and 10(4.4) 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

  4. Analyse de l'interface cuivre/Teflon AF1600 par spectroscopie des photoelectrons rayons x

    NASA Astrophysics Data System (ADS)

    Popovici, Dan

    The speed of electrical signals through the microelectronic multilevel interconnects depends of the delay time R x C. In order to improve the transmission speed of future microdevices, the microelectronics industry requires the use of metals having lower resistivities and insulators having lower permittivities. Copper and fluoropolymers are interesting candidates for the replacement of the presently used Al/polyimide technology. This thesis presents an X-ray photoelectron spectroscopy (XPS) analysis of the Cu/Teflon AF1600 interface, in order to have a better understanding of those interfacial interactions leading to improved adhesion. Several deposition methods, such as evaporation, sputtering and laser-induced chemical deposition were analyzed and compared. X-ray photoelectron spectroscopy (XPS) was used as the primary characterization technique of the different surfaces and interfaces. In the case of evaporation and sputtering, the loss of fluorine and oxygen atoms leads to graphitization and the crosslinking of carbon chains. The extent of damage caused by copper deposition is higher for sputter deposition because of the higher energies of the incidents atoms. This energy (two orders of magnitude higher than the energy involved in the evaporation) is also responsible for the total reaction of Cu with F and C. For the physical depositions (sputtering and evaporation), an angle-resolved XPS diffusion study showed the copper distribution as a function of depth. (i) For sputter deposition, this distribution is uniform. (ii) In the case of evaporation, we computed the concentration profile using the inverse Laplace transform. Several samples, annealed at different temperatures, were used to calculate the diffusion coefficients for the Cu/Teflon AF1600 interface. The study of interactions at the interface between Teflon AF1600 and copper deposited by different metallization techniques permitted us to elucidate some aspects related to the chemistry and structure of

  5. AF-GEOSpace Version 2.0: Space Environment Software Products for 2002

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Tautz, M.

    2002-05-01

    AF-GEOSpace Version 2.0 (release 2002 on WindowsNT/2000/XP) is a graphics-intensive software program developed by AFRL with space environment models and applications. It has grown steadily to become a development tool for automated space weather visualization products and helps with a variety of tasks: orbit specification for radiation hazard avoidance; satellite design assessment and post-event analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; and physics research and education. The object-oriented C++ code is divided into five module classes. Science Modules control science models to give output data on user-specified grids. Application Modules manipulate these data and provide orbit generation and magnetic field line tracing capabilities. Data Modules read and assist with the analysis of user-generated data sets. Graphics Modules enable the display of features such as plane slices, magnetic field lines, line plots, axes, the Earth, stars, and satellites. Worksheet Modules provide commonly requested coordinate transformations and calendar conversion tools. Common input data archive sets, application modules, and 1-, 2-, and 3-D visualization tools are provided to all models. The code documentation includes detailed examples with click-by-click instructions for investigating phenomena that have well known effects on communications and spacecraft systems. AF-GEOSpace Version 2.0 builds on the success of its predecessors. The first release (Version 1.21, 1996/IRIX on SGI) contained radiation belt particle flux and dose models derived from CRRES satellite data, an aurora model, an ionosphere model, and ionospheric HF ray tracing capabilities. Next (Version 1.4, 1999/IRIX on SGI) science modules were added related to cosmic rays and solar protons, low-Earth orbit radiation dosages, single event effects probability maps, ionospheric

  6. Structures, reactivities, and antibiotic properties of the marinopyrroles A-F.

    PubMed

    Hughes, Chambers C; Kauffman, Christopher A; Jensen, Paul R; Fenical, William

    2010-05-21

    Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A-F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3'-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A-E, is configurationally stable at room temperature. Moreover, the natural products are fashioned strictly in the M-configuration. The Paal-Knorr condensation was adapted for the synthesis of the 1,3'-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4',5,5'-tetrahalogenated core that characterizes this class of marine-derived metabolites.

  7. 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

  8. 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.

  9. 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.

  10. Fatigue life estimation program for Part 23 airplanes, `AFS.FOR`

    SciTech Connect

    Kaul, S.K.

    1993-12-31

    The purpose of this paper is to introduce to the general aviation industry a computer program which estimates the safe fatigue life of any Federal Aviation Regulation (FAR) Part 23 airplane. The algorithm uses the methodology (Miner`s Linear Cumulative Damage Theory) and the various data presented in the Federal Aviation Administration (FAA) Report No. AFS-120-73-2, dated May 1973. The program is written in FORTRAN 77 language and is executable on a desk top personal computer. The program prompts the user for the input data needed and provides a variety of options for its intended use. The program is envisaged to be released through issuance of a FAA report, which will contain the appropriate comments, instructions, warnings and limitations.

  11. Verbesinosides A-F, 15,27-cyclooleanane saponins from the American native plant Verbesina virginica.

    PubMed

    Xu, Wen-Hui; Jacob, Melissa R; Agarwal, Ameeta K; Clark, Alice M; Liang, Zong-Suo; Li, Xing-Cong

    2009-06-01

    Verbesinosides A-F (1-6), six new 15,27-cyclooleanane-type triterpenoid saponins carrying different aromatic acyl moieties on the aglycon, were isolated from the leaves and flowers of Verbesina virginica. Their structures were established by interpretation of spectroscopic data and chemical methods. The representative major saponin, verbesinoside A (1), has the structure 21-trimethoxybenzoyl 15alpha,27-cycloolean-12-en-3beta,21beta-diol-28-oic acid 3-O-beta-D-xylopyranosyl(1-->4)-beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranoside. This is the first report of triterpenoid saponins possessing the unique 15,27-cyclooleanane skeleton. The anisotropic effects of the aromatic acyl moieties on the triterpenoid skeleton are discussed.

  12. 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.

  13. 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…

  14. 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

  15. 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.

  16. Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

    NASA Astrophysics Data System (ADS)

    Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

    2014-05-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had

  17. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... by the recipient. (c) Characteristics indicating a plan is not a 10 or more employer plan—(1) In general. The presence of any of the characteristics described in paragraphs (c)(2) through (c)(6) of this... requirements of section 419A(f)(6) and this section, a plan having any of the following characteristics is...

  18. 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...

  19. 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.

  20. 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…

  1. 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

  2. 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.

  3. 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...

  4. Enhancement of the acute phase response to lipopolysaccharide in feedlot steers supplemented with OmniGen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of supplementing feedlot steers with OmniGen-AF on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 270 ± 5 kilograms body weight) were separated into two treatment groups (n=9/treatment): one group was fed a standard ...

  5. 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...

  6. 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...

  7. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2).

    PubMed

    Floriano, B; Bibb, M

    1996-07-01

    The N-terminal region of AfsR, a putative pleiotropic regulatory protein for antibiotic production in Streptomyces coelicolor A3(2), is homologous to RedD and Actil-ORF4, pathway-specific regulatory proteins required for the production of the antibiotics undecylprodigiosin (Red) and actinorhodin (Act), respectively. The recent identification of afsS, which lies immediately 3' of afsR and which stimulates antibiotic production when cloned at high copy number, questioned whether afsR was a pleiotropic regulatory gene. In this study we demonstrate that multiple copies of afsR can stimulate both Act and Red production and that, despite its homology, it cannot substitute for the pathway-specific regulatory genes. Moreover, an in-frame deletion that removed most of the afsR coding sequence resulted in loss of Act and Red production, and a marked reduction in the synthesis of the calcium-dependent antibiotic (CDA), but only under some (non-permissive) nutritional conditions. Although additional copies of afsR resulted in elevated levels of the actII-ORF4 and redD transcripts, transcription of the pathway-specific regulatory genes under non-permissive conditions was unaffected by deletion of afsR. While afsR may operate independently of the pathway-specific regulatory proteins to influence antibiotic production, the activity of ActII-ORF4 and of RedD under non-permissive conditions could depend on interaction with, or modification by, AfsR.

  8. Implementation of AF-CBT by community practitioners serving child welfare and mental health: a randomized trial.

    PubMed

    Kolko, David J; Baumann, Barbara L; Herschell, Amy D; Hart, Jonathan A; Holden, Elizabeth A; Wisniewski, Stephen R

    2012-02-01

    The Partnerships for Families project is a randomized clinical trial designed to evaluate the implementation of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT), an evidence-based treatment for family conflict, coercion, and aggression, including child physical abuse. To evaluate the effectiveness of a training program in this model, 182 community practitioners from 10 agencies were randomized to receive AF-CBT training (n = 90) using a learning community model (workshops, consultation visits) or Training as Usual (TAU; n = 92) which provided trainings per agency routine. Practitioners completed self-report measures at four time points (0, 6, 12, and 18 months following baseline). Of those assigned to AF-CBT, 89% participated in at least one training activity and 68% met a "training completion" definition. A total of 80 (44%) practitioners were still active clinicians in the study by 18-month assessment in that they had not met our staff turnover or study withdrawal criteria. Using an intent-to-train design, hierarchical linear modeling analyses revealed significantly greater initial improvements for those in the AF-CBT training condition (vs. TAU condition) in CBT-related knowledge and use of AF-CBT teaching processes, abuse-specific skills, and general psychological skills. In addition, practitioners in both groups reported significantly more negative perceptions of organizational climate through the intervention phase. These significant, albeit modest, findings are discussed in the context of treatment training, research, and work force issues as they relate to the diverse backgrounds, settings, and populations served by community practitioners.

  9. 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

  10. 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

  11. Predicting movements of female polar bears between summer sea ice foraging habitats and terrestrial denning habitats of Alaska in the 21st century: Proposed methodology and pilot assessment

    USGS Publications Warehouse

    Bergen, Scott; Durner, George M.; Douglas, David C.; Amstrup, Steven C.

    2007-01-01

    Polar bears (Ursus maritimus) require the relative warmth and stability afforded by snow dens for successful reproduction. Pregnant bears must travel from foraging habitats on the sea ice to land in autumn to establish winter dens. Data of sea ice extent and composition from satellite-acquired passive microwave (PMW) imagery show a reduction in summer sea ice extent throughout the Arctic from 1979-2006. Additionally, General Circulation Models (GCM) predict that Arctic sea ice extent will continue to diminish throughout the 21st century. Greater energetic demands will be placed on pregnant polar bears in the future if they travel greater distances from summer forage habitats to traditional denning habitats on land. We developed an approach for estimating how much these distances may change by modeling autumn movement paths of polar bears using the observational PMW record of sea ice distribution and sea ice projections of 5 GCMs during the 21st century. Over the 1979-2006 PMW record, polar bears returning to Alaska to den have experienced an annual increase in travel of > 6 km/year—an increase of >168 km over the 28 year period. Based on GCM sea ice projections during 2001-2060, the average increase in the distance required to reach traditional Alaskan denning regions was estimated to increase > 16 km/year. Distances traveled, and therefore, energetic demands, will likely vary among the different circumpolar sub-populations of polar bears.

  12. 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

  13. Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.

    PubMed

    Niederhoffer, Karen Y; Fahiminiya, Somayyeh; Eydoux, Patrice; Mawson, John; Nishimura, Gen; Jerome-Majewska, Loydie A; Patel, Millan S

    2016-09-01

    Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc. PMID:27375131

  14. 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. PMID:25256427

  15. Overlapping binding of PhoP and AfsR to the promoter region of glnR in Streptomyces coelicolor.

    PubMed

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F

    2012-10-12

    Growth of soil bacteria is often limited by the availability of essential nutrients such as carbon, nitrogen and phosphate. The reaction to a specific nutrient starvation triggers interconnected responses to equilibrate the metabolism. It is known that PhoP (response regulator involved in phosphate control) specifically binds to several promoters of genes involved in nitrogen metabolism which are also regulated by GlnR (regulator involved in nitrogen control). In this article we report a novel cross-talk between GlnR and the SARP-like regulator, AfsR. AfsR binds to some PhoP-regulated promoters including those of afsS (a small regulatory protein of secondary metabolism), pstS (a component of the phosphate transport system) and phoRP (encoding the two component system itself). We have characterized the regulation exerted upon the nitrogen regulator glnR gene by AfsR, using EMSA and DNase I footprinting assays as well as in vivo expression studies with ΔphoP, ΔafsR and ΔafsR-ΔphoP mutants. Both PhoP and AfsR proteins are able to bind to overlapping regions within the glnR promoter producing different effects. This work demonstrates a cross-talk of three different regulators of both primary and secondary metabolism.

  16. 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.

  17. 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. PMID:24687081

  18. Penarines A-F, (nor-)sesquiterpene carboxylic acids from Hygrophorus penarius (Basidiomycetes).

    PubMed

    Otto, Alexander; Porzel, Andrea; Schmidt, Jürgen; Wessjohann, Ludger; Arnold, Norbert

    2014-12-01

    Five sesquiterpene carboxylic acids (1-5) and one nor-sesquiterpene carboxylic acid (6) of the very rare ventricosane type, named penarines A-F, were isolated from fruiting bodies of the basidiomycete Hygrophorus penarius (Hygrophoraceae). This is the first report of (nor)-sesquiterpenes isolated from basidiocarps of the family Hygrophoraceae. Their structures were elucidated on the basis of extensive 1D ((1)H, (13)C) and 2D (HSQC, HMBC, COSY, ROESY) NMR spectroscopic analyses as well as high-resolution mass spectrometry studies. Additionally, the only known member of this rare type of sesquiterpenes, ventricos-7(13)-ene (7), could be identified via headspace GC-MS analysis in a fruiting body of H. penarius. Compounds 1-6 were devoid of remarkable antifungal activity against Cladosporium cucumerinum. Additionally, the cytotoxic activities of compounds 1 and 2 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29 showing no significant cytotoxic activity.

  19. 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).

  20. The Detection of a Light Echo from Type Ia SN 2007af in NGC 5584

    NASA Astrophysics Data System (ADS)

    Drozdov, Dina; Leising, M. D.; Milne, P.; Riess, A. G.

    2013-06-01

    We report the discovery of a light echo (LE) at t ~1000 days past maximum from the normal Type Ia supernova (SNe Ia) SN 2007af in the spiral galaxy NGC 5584. The presence of a LE is supported by photometric data and analysis of the images acquired during the Cepheid campaign using the Hubble Space Telescope (HST) Wide Field Camera 3 (Riess et al. 2011). The F350 and F555 images show a distinct ring-like structure with an additional central source. The images, taken months apart, show an evolution of the ring structure, which is consistent with a growing light echo in time. We find an angular radius of the outer echo to be ~0.29'' - 0.36''. Using the Cepheid distance to NGC 5584 of 24 Mpc, we find the dust illuminated by the light echo to be at a distance ~800 pc from the supernova. This rare discovery adds to the select few light echoes found in Type Ia SNe: SN 1572, SN 1991T, SN 1995E, SN 1998bu, and SN 2006X. Light echoes are powerful tools that probe the environment around supernovae, determine dust properties and characteristics, and could provide constraints on the progenitors, which are not fully understood for SN Ia.

  1. 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.

  2. 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.

  3. Detection of a Light Echo from the Otherwise Normal SN 2007af

    NASA Astrophysics Data System (ADS)

    Drozdov, D.; Leising, M. D.; Milne, P. A.; Pearcy, J.; Riess, A. G.; Macri, L. M.; Bryngelson, G. L.; Garnavich, P. M.

    2015-05-01

    We present the discovery of a light echo from SN 2007af, a normal Type Ia supernova (SN Ia) in NGC 5584. Hubble Space Telescope images taken three years post explosion reveal two separate echoes: an outer echo and an extended central region, which we propose to be an inner echo for which details are unresolved. Multiple images were obtained in the F160W, F350LP, F555W, and F814W using the Wide Field Camera 3. If the outer echo is produced by an interstellar dust sheet perpendicular to the line of sight, it is located ∼800 pc in front of the SN. The dust for the inner echo is 0.45 pc \\lt d\\lt 90 pc away from the SN. The inner echo color is consistent with typical interstellar dust wavelength-dependent scattering cross-sections, while the outer echo is redder than predicted. Both dust sheets, if in the foreground, are optically thin for scattering, and the outer echo sheet thickness is consistent with the inferred extinction from peak brightness. Whether the inner echo is from interstellar or circumstellar dust is ambiguous. Overall, the echo characteristics are quite similar to previously observed SN Ia echoes.

  4. 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

  5. Purification, crystallization and preliminary crystallographic analysis of the non-Pfam protein AF1514 from Archeoglobus fulgidus DSM 4304

    SciTech Connect

    Bahti, Pazilat; Chen, Shunmei; Li, Yang; Shaw, Neil; Zhang, Xuejun; Zhang, Min; Cheng, Chongyun; Song, Gaojie; Yin, Jie; Zhang, Hua; Che, Dongsheng; Abbas, Abdulla; Xu, Hao; Wang, Bi-Cheng; Liu, Zhi-Jie

    2008-02-01

    A non-Pfam protein, AF1514, from A. fulgidus has been crystallized. A 10.5 kDa non-Pfam hypothetical protein, AF1514, from the hyperthermophilic archaeon Archeoglobus fulgidus has been overexpressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The crystals diffracted X-rays to 2.09 Å resolution and a data set was collected at 100 K using Cu Kα radiation from a rotating-anode X-ray source. The crystals belong to space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 49.27, c = 106.61 Å. The calculated Matthews coefficient was 3.16 Å{sup 3} Da{sup −1}, suggesting the presence of one molecule in the asymmetric unit.

  6. Human PSENEN and U2AF1L4 genes are concertedly regulated by a genuine bidirectional promoter.

    PubMed

    Didych, D A; Shamsutdinov, M F; Smirnov, N A; Akopov, S B; Monastyrskaya, G S; Uspenskaya, N Y; Nikolaev, L G; Sverdlov, E D

    2013-02-15

    Head-to-head genes with a short distance between their transcription start sites may constitute up to 10% of all genes in the genomes of various species. It was hypothesized that this intergenic space may represent bidirectional promoters which are able to initiate transcription of both genes, but the true bidirectionality was proved only for a few of them. We present experimental evidence that, according to several criteria, a 269 bp region located between the PSENEN and U2AF1L4 human genes is a genuine bidirectional promoter regulating a concerted divergent transcription of these genes. Concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity. PMID:23246698

  7. AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription.

    PubMed

    Okuda, Hiroshi; Kanai, Akinori; Ito, Shinji; Matsui, Hirotaka; Yokoyama, Akihiko

    2015-11-23

    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.

  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. Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death.

    PubMed

    Hinterleitner, C; Huelsenbeck, J; Henninger, C; Wartlick, F; Schorr, A; Kaina, B; Fritz, G

    2013-08-01

    We investigated the relevance of signaling mechanisms regulated by the Ras-homologous GTPase Rac1 for survival of acute myeloid leukemia (AML) cells harbouring the MLL-AF9 oncogene due to t(9;11)(p21;q23) translocation. Monocytic MLL-AF9 expressing cells (MM6, THP-1) were hypersensitive to both small-molecule inhibitors targeting Rac1 (EHT 1864, NSC 23766) (IC50EHT ~12.5 μM) and lipid lowering drugs (lovastatin, atorvastatin) (IC50Lova ~7.5 μM) as compared to acute myelocytic leukemia (NOMO-1, HL60) and T cell leukemia (Jurkat) cells (IC50EHT >30 μM; IC50Lova >25 μM). Hypersensitivity of monocytic cells following Rac1 inhibition resulted from caspase-driven apoptosis as shown by profound activation of caspase-8,-9,-7,-3 and substantial (~90 %) decrease in protein expression of pro-survival factors (survivin, XIAP, p-Akt). Apoptotic death was preceded by S139-posphorylation of histone H2AX (γH2AX), a prototypical surrogate marker of DNA double-strand breaks (DSBs). Taken together, abrogation of Rac1 signaling causes DSBs in acute monocytic leukemia cells harbouring the MLL-AF9 oncogene, which, together with downregulation of survivin, XIAP and p-Akt, results in massive induction of caspase-driven apoptotic death. Apparently, Rac1 signaling is required for maintaining genetic stability and maintaining survival in specific subtypes of AML. Hence, targeting of Rac1 is considered a promising novel strategy to induce lethality in MLL-AF9 expressing AML. PMID:23624644

  10. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  11. 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. PMID:27071942

  12. 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.

  13. The M2 selective antagonist AF-DX 116 shows high affinity for muscarine receptors in bovine tracheal membranes.

    PubMed

    Roffel, A F; in't Hout, W G; de Zeeuw, R A; Zaagsma, J

    1987-05-01

    We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using 3H-dexetimide/pirenzepine and 3H-dexetimide/AF-DX 116 competition studies. Pirenzepine exhibited low (M2) affinity binding to both preparations; Kd was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (Kd = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (Kd = 40.7 nM) to 74% of the receptors and with low (M3) affinity (Kd = 2.26 microM) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M2 (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M3 (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors. PMID:3614390

  14. 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.

  15. 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.

  16. The role for estrogen receptor-alpha and prolactin receptor in sex-dependent DEN-induced liver tumorigenesis

    PubMed Central

    Bigsby, Robert M.; Caperell-Grant, Andrea

    2011-01-01

    Mice treated neonatally with diethylnitrosamine (DEN) develop liver tumors in a male-dominant manner, reflecting the male bias in human hepatocellular carcinoma. Evidence suggests that estrogen, androgen, prolactin (PRL) and growth hormone (GH) modify liver tumorigenesis. We determined the roles of estrogen receptor-α (ERα) and prolactin receptor (PRLR) using receptor null mice, ERαKO (C57Bl/6J) and PRLR-KO (129Ola-X-C57BL/6), in the neonatal-DEN model of liver tumorigenesis. In both mouse strains, females had reduced tumorigenesis compared with males (P < 0.01), regardless of ERα or PRLR status. Tumorigenesis was not affected by ovariectomy in C57Bl/6J mice but it was increased by ovariectomy in the mixed strain, 129Ola-X-C57BL/6, regardless of PRLR status. ERαKO males had 47% fewer tumors than ERα wild-type males (P < 0.01). On the other hand, estradiol treatment protected against tumorigenesis in males only in the presence of ERα. As evidenced by liver gene expression, lack of ERα did not alter the pattern of GH secretion in males but resulted in the male GH pattern in females. These observations indicate that ERα is not required for lower tumorigenesis in females, but it is required for the protective effects of exogenously delivered estradiol. Unexpectedly, the results indicate that ERα plays a role in promotion of liver tumors in males. In addition, it can be concluded that sex differences in liver tumorigenesis cannot be explained by the sexually dimorphic pattern of GH secretion. The results also rule out PRL as the mediator of the protective effect of the ovaries. PMID:21606321

  17. 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

  18. 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

  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. Endodontic treatment of a maxillary lateral incisor presenting dens invaginatus and transposition to the region of the canine--case report.

    PubMed

    Pécora, J D; Saquy, P C; de Souza, J E; Sousa Neto, M D

    1991-01-01

    Endodontic treatment was performed in a maxillary lateral incisor presenting two different types of anomalies: dens invaginatus and transposition to the region of the canine. The two transposed teeth were subsequently restored with light-cured composite, bringing dental esthetics to normal in a single session.

  1. 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

  2. Comment to the Article by van Arensbergen and van den Besselaar "The Selection of Scientific Talent in the Allocation of Research Grants"

    ERIC Educational Resources Information Center

    Maessen, K. M. H.

    2012-01-01

    The article entitled "The selection of scientific talent in the allocation of research grants" by van Arensbergen and van den Besselaar published in "Higher Education Policy" 25/3 (2012) is based on research that both researchers carried out on behalf of The Netherlands Organisation for Scientific Research. In this comment, we want to address…

  3. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF.

    PubMed

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-10-01

    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

  4. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    PubMed

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota.

  5. 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

  6. Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity.

    PubMed

    Li, Ming; Yang, Yunjia; Yang, Yi; Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  7. Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Tanaka, Masaru; Bagosi, Zsolt; Jászberényi, Miklós

    2014-11-01

    Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice.

  8. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    PubMed

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota. PMID:26957022

  9. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)

    PubMed Central

    2012-01-01

    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. PMID:23210797

  10. 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

  11. 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.

  12. Evaluation of the sustainability and clinical outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a child protection center.

    PubMed

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

    2011-02-01

    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.

  13. 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

  14. Single-Unit Activity during Natural Vision: Diversity, Consistency, and Spatial Sensitivity among AF Face Patch Neurons

    PubMed Central

    Russ, Brian E.; Elnaiem, Heba D.; Kurnikova, Anastasia I.; Leopold, David A.

    2015-01-01

    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. PMID:25855170

  15. 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.

  16. Photometric Properties for Selected Algol-type Binaries. VIII. The Triple Systems DI Peg and AF Gem Revisited

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui; Yang, Ying; Li, Shu-Zheng

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are fp = 78.2(± 0.4)% for DI Peg, and fp = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O-C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P 3 = 54.6(± 0.5) yr and P 4 = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M in = 0.095 M ⊙ and M out = 0.170 M ⊙, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  17. The Ultraviolet-bright, Slowly Declining Transient PS1-11af as a Partial Tidal Disruption Event

    NASA Astrophysics Data System (ADS)

    Chornock, R.; Berger, E.; Gezari, S.; Zauderer, B. A.; Rest, A.; Chomiuk, L.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Huber, M. E.; Kirshner, R. P.; Lawrence, A.; Lunnan, R.; Marion, G. H.; Narayan, G.; Riess, A. G.; Roth, K. C.; Sanders, N. E.; Scolnic, D.; Smartt, S. J.; Smith, K.; Stubbs, C. W.; Tonry, J. L.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Magnier, E. A.; Martin, D. C.; Neill, J. D.; Price, P. A.; Wainscoat, R.

    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 ⊙, 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.

  18. Photometric properties for selected algol-type binaries. VIII. The triple systems DI Peg and AF Gem revisited

    SciTech Connect

    Yang, Yuan-Gui; Li, Shu-Zheng; Yang, Ying E-mail: yangyg@chnu.edu.cn

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are f{sub p} = 78.2(± 0.4)% for DI Peg, and f{sub p} = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O–C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P {sub 3} = 54.6(± 0.5) yr and P {sub 4} = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M {sub in} = 0.095 M {sub ☉} and M {sub out} = 0.170 M {sub ☉}, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  19. 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

    2015-04-01

    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.

  20. 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

  1. 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

    2015-04-01

    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. PMID:25855170

  2. Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

    PubMed

    Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

    2014-04-01

    Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

  3. 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

  4. 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

  5. [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. PMID:17465124

  6. [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.

  7. The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.

    PubMed

    Chen, Shoudeng; Yang, Ze; Wilkinson, Alex W; Deshpande, Aniruddha J; Sidoli, Simone; Krajewski, Krzysztof; Strahl, Brian D; Garcia, Benjamin A; Armstrong, Scott A; Patel, Dinshaw J; Gozani, Or

    2015-10-15

    AF10, a DOT1L cofactor, is required for H3K79 methylation and cooperates with DOT1L in leukemogenesis. However, the molecular mechanism by which AF10 regulates DOT1L-mediated H3K79 methylation is not clear. Here we report that AF10 contains a "reader" domain that couples unmodified H3K27 recognition to H3K79 methylation. An AF10 region consisting of a PHD finger-Zn knuckle-PHD finger (PZP) folds into a single module that recognizes amino acids 22-27 of H3, and this interaction is abrogated by H3K27 modification. Structural studies reveal that H3 binding triggers rearrangement of the PZP module to form an H3(22-27)-accommodating channel and that the unmodified H3K27 side chain is encased in a compact hydrogen-bond acceptor-lined cage. In cells, PZP recognition of H3 is required for H3K79 dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L-addicted leukemic cells. Together, our results uncover a pivotal role for H3K27-via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme DOT1L.

  8. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model.

    PubMed

    Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M; Claxton, David F; Wang, Hong-Gang

    2016-01-01

    Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9. PMID:27607576

  9. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model

    PubMed Central

    Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M; Claxton, David F; Wang, Hong-Gang

    2016-01-01

    Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9. PMID:27607576

  10. "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.

  11. Comparing the Disinfecting Efficacies of Micro 10, Deconex, Alprocid and Microzid AF on the Microorganisms on Radiographic Equipments

    PubMed Central

    Ezoddini Ardakani, Fatemeh; Zandi, Hengameh; Mohammadi, Zahed; Ayatollahi, Jamshid; Ayatollahi, Fatemeh; Behniafar, Behnaz

    2008-01-01

    Background and aims The exposure and processing of dental radiographs are not routinely associated with the spatter of blood or saliva; however, infection control is still an issue resulting from contaminated equipment, supplies, film packets or cassettes. This study aimed at comparing the efficacy of four commercially available disinfectants on microorganisms present on the equipment of radiology department. Materials and methods Samples from twelve sites of the radiology department were collected using a sterile swab smeared with normal saline, which was then dipped in a test tube. Experimental surfaces were then disinfected by the spray-wipe-spray method using one of Micro 10, Deconex, Alprocid or Microzid AF disinfectants, followed by resampling. The samples were subsequently cultured on blood agar and EMB plates and the colonies were counted. Isolates were identified by biochemical tests. For statistical analysis, Wilcoxon signed ranks test, Kruskal-Wallis, Chi-square and Fisher exact tests were used. Results Staphylococcus aureus and coagulase-negative staphylococci had the highest and Lactobacillus spp. had the lowest prevalence before disinfection. There were significant differences between the cfu/mL of bacteria before and after disinfection with any of the four disinfectant solutions. There was a significant difference between efficacy of Deconex and Alprocid (P = 0.014), Deconex and Microzid AF (P = 0.001), and Deconex and Micro 10 (P = 0.001). Conclusion According to the results, Deconex has the highest disinfectant efficacy compared to other solutions. PMID:23289058

  12. 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.

  13. 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.

  14. L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment

    PubMed Central

    Wang, Chih-Ching; Chen, Yi-Ru; Chang, Chi-Fon; Shiao, Ming-Shi; Chen, Yi-Cheng; Lin, Ta-Hsien

    2016-01-01

    β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer’s disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ. PMID:27104649

  15. 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.

  16. Security-reliability performance of cognitive AF relay-based wireless communication system with channel estimation error

    NASA Astrophysics Data System (ADS)

    Gu, Qi; Wang, Gongpu; Gao, Li; Peng, Mugen

    2014-12-01

    In this paper, both the security and the reliability performance of the cognitive amplify-and-forward (AF) relay system are analyzed in the presence of the channel estimation error. The security and the reliability performance are represented by the outage probability and the intercept probability, respectively. Instead of perfect channel state information (CSI) predominantly assumed in the literature, a certain channel estimation algorithm and the influence of the corresponding channel estimation error are considered in this study. Specifically, linear minimum mean square error estimation (LMMSE) is utilized by the destination node and the eavesdropper node to obtain the CSI, and the closed form for the outage probability and that for the intercept probability are derived with the channel estimation error. It is shown that the transmission security (reliability) can be improved by loosening the reliability (security) requirement. Moreover, we compare the security and reliability performance of this relay-based cognitive radio system with those of the direct communication system without relay. Interestingly, it is found that the AF relay-based system has less reliability performance than the direct cognitive radio system; however, it can lower the sum of the outage probability and the intercept probability than the direct communication system. It is also found that there exists an optimal training number to minimize the sum of the outage probability and the intercept probability.

  17. In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant phosphodiesterase (PDE) 2A inhibitor: potential relevance to cognitive deficits in schizophrenia.

    PubMed

    Redrobe, John P; Jørgensen, Morten; Christoffersen, Claus T; Montezinho, Liliana P; Bastlund, Jesper F; Carnerup, Martin; Bundgaard, Christoffer; Lerdrup, Linda; Plath, Niels

    2014-08-01

    Here, we present the pharmacological characterisation of Lu AF64280, a novel, selective, brain penetrant phosphodiesterase (PDE) 2A inhibitor, in in vitro/in vivo assays indicative of PDE2A inhibition, and in vivo models/assays relevant to cognitive processing or antipsychotic-like activity. The in vitro selectivity of Lu AF64280 was determined against a panel of PDE enzymes and 3',5'-cyclic guanosine monophosphate (cGMP) levels in the hippocampus were determined using in vivo microdialysis. Lu AF64280 potently inhibited hPDE2A (Ki = 20 nM), 50-fold above moderate inhibition of both hPDE9A (Ki = 1,000 nM) and hPDE10A (Ki = 1,800 nM), and displayed a >250-fold selectivity over all other full-length human recombinant PDE family members (Ki above 5,000 nM). Lu AF64280 (20 mg/kg) significantly increased cGMP levels in the hippocampus (p < 0.01 versus vehicle-treated mice), attenuated sub-chronic phencyclidine-induced deficits in novel object exploration in rats (10 mg/kg, p < 0.001 versus vehicle-treated), blocked early postnatal phencyclidine-induced deficits in the intradimensional/extradimensional shift task in rats (1 and 10 mg/kg, p < 0.001 versus vehicle-treated) and attenuated spontaneous P20-N40 auditory gating deficits in DBA/2 mice (20 mg/kg, p < 0.05 versus vehicle-treated). In contrast, Lu AF64280 failed to attenuate phencyclidine-induced hyperactivity in mice, and was devoid of antipsychotic-like activity in the conditioned avoidance response paradigm in rats, at any dose tested. Lu AF64280 represents a novel tool compound for selective PDE2A inhibition that substantiates a critical role of this enzyme in cognitive processes under normal and pathological conditions.

  18. Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of phosphodiesterase (PDE) 2A and PDE10A.

    PubMed

    Redrobe, John P; Rasmussen, Lars K; Christoffersen, Claus T; Bundgaard, Christoffer; Jørgensen, Morten

    2015-08-15

    Here, we present a preliminary pharmacological characterisation of Lu AF33241, a novel, brain penetrant phosphodiesterase inhibitor of (PDE) 2A and 10A tool compound, in in vitro/in vivo assays indicative of PDE2A and/or PDE10A inhibition, and in vivo models/assays relevant to cognitive processing and antipsychotic-like activity. An assay was also included to investigate potential effects on motor activity. The in vitro selectivity of Lu AF33241 was determined against a panel of PDE enzymes. Lu AF33241 potently inhibited both full-length recombinant hPDE2A (Ki=4.2nM) and hPDE10A (Ki=42nM). The compound moderately inhibited both hPDE1C (Ki=1200nM), hPDE7B (Ki=890nM), and hPDE11A (Ki=1800nM). Lu AF33241 displayed a Ki above 5000nM against all other tested members of the PDE family. Albeit within a narrow dose range, Lu AF33241 attenuated sub-chronic phencyclidine-induced deficits in novel object recognition (3 and 10mg/kg), displayed antipsychotic-like activity in the conditioned avoidance response paradigm (10mg/kg), and did not induce catalepsy within a dose-range of 2-6mg/kg. Further catalepsy studies are needed to investigate a predictive safety window. Lu AF33241 represents a novel PDE2A/PDE10A inhibitor tool compound that may serve to further the understanding of the roles played by these enzymes in various CNS disorders.

  19. 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.

  20. DNA Methylation Is Linked to Deacetylation of Histone H3, but Not H4, on the Imprinted Genes Snrpn and U2af1-rs1

    PubMed Central

    Gregory, Richard I.; Randall, Tamzin E.; Johnson, Colin A.; Khosla, Sanjeev; Hatada, Izuho; O'Neill, Laura P.; Turner, Bryan M.; Feil, Robert

    2001-01-01

    The relationship between DNA methylation and histone acetylation at the imprinted mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation (ChIP) and resolution of parental alleles using single-strand conformational polymorphisms. The U2af1-rs1 gene lies within a differentially methylated region (DMR), while Snrpn has a 5′ DMR (DMR1) with sequences homologous to the imprinting control center of the Prader-Willi/Angelman region. For both DMR1 of Snrpn and the 5′ untranslated region (5′-UTR) and 3′-UTR of U2af1-rs1, the methylated and nonexpressed maternal allele was underacetylated, relative to the paternal allele, at all H3 lysines tested (K14, K9, and K18). For H4, underacetylation of the maternal allele was exclusively (U2af1-rs1) or predominantly (Snrpn) at lysine 5. Essentially the same patterns of differential acetylation were found in embryonic stem (ES) cells, embryo fibroblasts, and adult liver from F1 mice and in ES cells from mice that were dipaternal or dimaternal for U2af1-rs1. In contrast, in a region within Snrpn that has biallelic methylation in the cells and tissues analyzed, the paternal (expressed) allele showed relatively increased acetylation of H4 but not of H3. The methyl-CpG-binding-domain (MBD) protein MeCP2 was found, by ChIP, to be associated exclusively with the maternal U2af1-rs1 allele. To ask whether DNA methylation is associated with histone deacetylation, we produced mice with transgene-induced methylation at the paternal allele of U2af1-rs1. In these mice, H3 was underacetylated across both the parental U2af1-rs1 alleles whereas H4 acetylation was unaltered. Collectively, these data are consistent with the hypothesis that CpG methylation leads to deacetylation of histone H3, but not H4, through a process that involves selective binding of MBD proteins. PMID:11463825

  1. 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

  2. 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

  3. 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

  4. 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. PMID:27187611

  5. 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.

  6. Ceylonamides A-F, Nitrogenous Spongian Diterpenes That Inhibit RANKL-Induced Osteoclastogenesis, from the Marine Sponge Spongia ceylonensis.

    PubMed

    El-Desoky, Ahmed H; Kato, Hikaru; Angkouw, Esther D; Mangindaan, Remy E P; de Voogd, Nicole J; Tsukamoto, Sachiko

    2016-08-26

    Seven new spongian diterpenes, ceylonamides A-F (1-6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensis along with eight known spongian diterpenes, 8-15. Compounds 1-6 were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50 value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure-activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity. PMID:27526327

  7. Proteasome Inhibitors Evoke Latent Tumor Suppression Programs in Pro-B MLL Leukemias Through MLL-AF4

    PubMed Central

    Liu, Han; Westergard, Todd D.; Cashen, Amanda; Piwnica-Worms, David R.; Kunkle, Lori; Vij, Ravi; Pham, Can G.; DiPersio, John; Cheng, Emily H.; Hsieh, James J.

    2014-01-01

    SUMMARY Chromosomal translocations disrupting MLL generate MLL-fusion proteins that induce aggressive leukemias. Unexpectedly, MLL-fusion proteins are rarely observed at high levels, suggesting excessive MLL-fusions may be incompatible with a malignant phenotype. Here, we used clinical proteasome inhibitors, bortezomib and carfilzomib, to reduce the turnover of endogenous MLL-fusions and discovered that accumulated MLL-fusions induce latent, context-dependent tumor suppression programs. Specifically, in MLL pro-B lymphoid, but not myeloid, leukemias, proteasome inhibition triggers apoptosis and cell cycle arrest involving activation cleavage of BID by Caspase-8 and upregulation of p27, respectively. Furthermore, proteasome inhibition conferred preliminary benefit to MLL-AF4 leukemia patients. Hence, feasible strategies to treat cancer-type and oncogene specific cancers can be improvised through harnessing inherent tumor suppression properties of individual oncogenic fusions. PMID:24735925

  8. VizieR Online Data Catalog: Rotation in A-F stars (Ammler-von Eiff+, 2012)

    NASA Astrophysics Data System (ADS)

    Ammler-von Eiff, M.; Reiners, A.

    2012-04-01

    Measurements of projected rotational velocities and the rotational profile of stars with spectral types A-F are presented. This work completes previous measurements by line profile analysis. New spectra with high signal-to-noise ratio were taken with the high-resolution CES and FEROS spectrographs operated by ESO at La Silla, Chile. Stellar rotation is studied in inverse wavelength space analysing the first two zeros of the Fourier transform of the overall broadening profile. Rigid and differential rotation can be distinguished in the case of rapid rotation. New and previous measurements are compiled and made available. The data are supplemented by a homogeneous compilation of basic stellar data from photometry. Data are flagged when there are indications of multiplicity. (2 data files).

  9. 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.

  10. Plate description of active deformation in the Africa (AF)-Arabia (AR)-Eurasia (EU) zone of plate interaction

    NASA Astrophysics Data System (ADS)

    Vernant, P.; McClusky, S.; Reilinger, R.

    2006-12-01

    We present the results of 17 years of GPS monitoring in this zone of plate interaction and show that to the resolution of our observations (i.e., ~1-2 mm/yr; ~ ±10 % of relative plate motions), deformation is consistent with plate-block models with relative motion between adjacent plates/blocks accommodated by elastic strain accumulation. Relative plate motions are consistent with geologically recent (~ 3 Ma) plate motions where geologic estimates of relative plate motion have been determined (AR- Nubia: Red Sea; AR-Somalia: Gulf of Aden; AF-EU; AR-EU). Furthermore, fault slip rates derived from the GPS block motions are mostly equal to geologic slip rates determined for long enough time intervals to average out earthquake cycle effects. We conclude that a plate description (i.e., relative Euler vectors) is appropriate to describe the kinematics of continental deformation during the past few Myr in this zone of plate interaction.

  11. Relay-and-antenna selection and digital transceiver design for two-way AF-MIMO multiple-relay systems

    NASA Astrophysics Data System (ADS)

    Hu, Chia-Chang; Su, Hao-Hsian; Tang, Kang-Tsao

    2014-09-01

    This paper considers a two-way multiple-input multiple-output (MIMO) relaying system with multiple relays between two terminals nodes. The relay antenna selection scheme based on channel singular valued decomposition (SVD) is used to reduce energy consumption. To enhance the system performance, we apply a SVD-based algorithm with MSE criterion which calculates optimal linear transceivers precoding jointly at the source nodes and relay nodes for amplify-and-forward (AF) protocols. In computer simulations, we use an iteration method to compute the non-convex function of joint source and relays power allocation. The simulation results show the SVD-based precoding design with SVD-based relay and antenna selection scheme can achieve a superior system bit error rate (BER) performance and reduce the power consume of relay antennas.

  12. Versixanthones A-F, Cytotoxic Xanthone-Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009.

    PubMed

    Wu, Guangwei; Yu, Guihong; Kurtán, Tibor; Mándi, Attila; Peng, Jixing; Mo, Xiaomei; Liu, Ming; Li, Hui; Sun, Xinhua; Li, Jing; Zhu, Tianjiao; Gu, Qianqun; Li, Dehai

    2015-11-25

    Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I. PMID:26506221

  13. 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.

  14. Production of an extracellular alkaline metalloprotease from a newly isolated, moderately halophile, Salinivibrio sp. strain AF-2004.

    PubMed

    Ali Amoozegar, Mohammad; Zahra Fatemi, Azadeh; Reza Karbalaei-Heidari, Hamid; Reza Razavi, Mohamad

    2007-01-01

    An extracellular protease was produced under stress conditions of high temperature and high salinity by a newly isolated moderate halophile, Salinivibrio sp. strain AF-2004 in a basal medium containing peptone, beef extract, glucose and NaCl. A modification of Kunitz method was used for protease assay. The isolate was capable of producing protease in the presence of sodium chloride, sodium sulfate, sodium nitrate, sodium nitrite, potassium chloride, sodium acetate and sodium citrate. The maximum protease was secreted in the presence of 7.5 to 10% (w/v) sodium sulfate or 3% (w/v) sodium acetate (4.6 U ml(-1)). Various carbon sources including glucose, lactose, casein and peptone were capable of inducing enzyme production. The optimum pH, temperature and aeration for enzyme production were 9.0, 32 degrees C and 220 rpm, respectively. The enzyme production corresponded with growth and reached a maximum level during the mid-stationary phase. Maximum protease activity was exhibited in the medium containing 1% (w/v) NaCl at 60 degrees C, with 18% and 41% activity reductions at temperature 50 and 70 degrees C, respectively. The optimum pH for enzyme activity was 8.5, with 86% and 75% residual activities at pH 10 and 6, respectively. The activity of enzyme was inhibited by EDTA. These results suggest that the protease secreted by Salinivibrio sp. strain AF-2004 is industrially important from the perspectives of its activity at a broad pH ranges (5.0-10.0), its moderate thermoactivity in addition to its high tolerance to a wide range of salt concentration (0-10% NaCl).

  15. Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4)

    PubMed Central

    Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

    2015-01-01

    The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

  16. Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4).

    PubMed

    Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

    2015-01-01

    The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10 mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4 nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

  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. 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

    ... potential costs or burdens, explain how you arrived at your estimate in sufficient detail to allow for it to... enforcement of environmental laws, regulations, and policies. To help address potential environmental justice... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  19. Effect of long-term dietary arginyl-fructose (AF) on hyperglycemia and HbA1c in diabetic db/db mice.

    PubMed

    Lee, Kwang-Hyoung; Ha, Kyoung-Soo; Jo, Sung-Hoon; Lee, Chong M; Kim, Young-Cheul; Chung, Kwang-Hoe; Kwon, Young-In

    2014-05-12

    We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF) lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch) with and without AF (4% in the diet) for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001) and body weight (p < 0.001). The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001). Dietary treatment of acarbose® (0.04% in diet), a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level.

  20. 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.

  1. 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.

  2. Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

    PubMed Central

    Choi, Hyun-Woo; Kim, Hye-Ran; Baek, Hee-Jo; Kook, Hoon; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook

    2015-01-01

    Background Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. Methods Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. Results Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. Conclusions Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood. PMID:25553291

  3. Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia.

    PubMed

    Mizukawa, Benjamin; Wei, Junping; Shrestha, Mahesh; Wunderlich, Mark; Chou, Fu-Sheng; Griesinger, Andrea; Harris, Chad E; Kumar, Ashish R; Zheng, Yi; Williams, David A; Mulloy, James C

    2011-11-10

    The Rac family of small Rho GTPases coordinates diverse cellular functions in hematopoietic cells including adhesion, migration, cytoskeleton rearrangements, gene transcription, proliferation, and survival. The integrity of Rac signaling has also been found to critically regulate cellular functions in the initiation and maintenance of hematopoietic malignancies. Using an in vivo gene targeting approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively regulate expression of Bcl-2 family proteins toward a prosurvival balance. We demonstrate that disruption of downstream survival signaling through antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2 deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically.

  4. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

    PubMed Central

    Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

    2014-01-01

    Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

  5. 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.

  6. 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.

  7. 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. PMID:26063530

  8. 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.

  9. Endodontic Management of a Mandibular Incisor Exhibiting Concurrence of Fusion, Talon Cusp and Dens Invaginatus using CBCT as a Diagnostic Aid

    PubMed Central

    Kumar, Varun

    2016-01-01

    Teeth with aberrant anatomy present a challenge to the endodontist. Advanced tools like cone beam computed tomography aid in exploring the details of endodontic architecture in such cases. The aim of this case report is to highlight the advantage of CBCT in endodontic management of teeth with multiple dental anomalies. A mandibular lateral incisor associated with an extraoral sinus tract revealed unusual clinical anatomy. A provisional diagnosis of type III dens in dente was made based on radiographic findings. Considering the complex anatomy, CBCT was advised to get a confirmatory diagnosis. The anatomic details revealed by CBCT differed significantly from the provisional diagnosis. A final diagnosis of concurrence of fusion with a supernumerary tooth, talon cusp and type II dens invaginatus was established and endodontic treatment of the concerned tooth was carried out. Non-surgical endodontic treatment resulted in successful resolution of the sinus tract and healing of the periapical lesion. CBCT, thus proves to be an excellent diagnostic tool for management of teeth with unusual anatomy, paving way for a conservative treatment free of endodontic mishaps. PMID:27042591

  10. Endodontic Management of a Mandibular Incisor Exhibiting Concurrence of Fusion, Talon Cusp and Dens Invaginatus using CBCT as a Diagnostic Aid.

    PubMed

    Juneja, Ruchi; Kumar, Varun

    2016-02-01

    Teeth with aberrant anatomy present a challenge to the endodontist. Advanced tools like cone beam computed tomography aid in exploring the details of endodontic architecture in such cases. The aim of this case report is to highlight the advantage of CBCT in endodontic management of teeth with multiple dental anomalies. A mandibular lateral incisor associated with an extraoral sinus tract revealed unusual clinical anatomy. A provisional diagnosis of type III dens in dente was made based on radiographic findings. Considering the complex anatomy, CBCT was advised to get a confirmatory diagnosis. The anatomic details revealed by CBCT differed significantly from the provisional diagnosis. A final diagnosis of concurrence of fusion with a supernumerary tooth, talon cusp and type II dens invaginatus was established and endodontic treatment of the concerned tooth was carried out. Non-surgical endodontic treatment resulted in successful resolution of the sinus tract and healing of the periapical lesion. CBCT, thus proves to be an excellent diagnostic tool for management of teeth with unusual anatomy, paving way for a conservative treatment free of endodontic mishaps.

  11. Gestational and lactational exposure to bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring.

    PubMed

    Li, Jing; Sheng, Nan; Cui, Ruina; Feng, Yixing; Shao, Bing; Guo, Xuejiang; Zhang, Hongxia; Dai, Jiayin

    2016-11-01

    During prenatal and postnatal development, exposure to environmental chemicals with estrogenic activity, such as bisphenol AF (BPAF), may result in reproductive disorders. Currently, the mechanisms behind such disorders in male offspring induced by gestational and lactational exposure to BPAF remain poorly understood. Here, female rats from gestational day (GD) 3-19 were exposed to 100 mg BPAF/kg/day by oral gavage. On the day of birth (postnatal day (PD) 0), cross-fostering took place between treated and control litters, and cross-fostered mother rats were given BPAF 100 mg/kg/day during the postnatal period (PD 3 to PD 19). HPLC-MS/MS analysis showed that BPAF was transferred via cord blood and lactation, finally bio-accumulating in the offspring testes. Pups exposed to BPAF both prenatally and postnatally showed a significant increase in testis testosterone levels compared with that of the control, while all pups exposed to BPAF showed a significant decrease in testis inhibin B (INHB) levels. Compared with the control, RNA-seq revealed that 279 genes were significantly differentially expressed in the testes of pups exposed to BPAF both prenatally and postnatally, including genes involved in cell differentiation and meiosis. These results indicate that gestational and lactational exposure to BPAF in the mother can impair reproductive function in male offspring. PMID:27567155

  12. Rhizovarins A-F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189.

    PubMed

    Gao, Shu-Shan; Li, Xiao-Ming; Williams, Katherine; Proksch, Peter; Ji, Nai-Yun; Wang, Bin-Gui

    2016-08-26

    Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A-F (1-6). Among them, compounds 1-3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines. PMID:27462726

  13. 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.

  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. Uptake, depuration and bioconcentration of bisphenol AF (BPAF) in whole-body and tissues of zebrafish (Danio rerio).

    PubMed

    Shi, Jiachen; Yang, Yunjia; Zhang, Jing; Feng, Yixing; Shao, Bing

    2016-10-01

    Bisphenol AF (BPAF) is an analog of Bisphenol A (BPA) and is widely used as a raw material in the plastics industry. However, an understanding of the potential risks posed by BPAF in the aquatic environment is lacking. The bioconcentration factor (BCF) is a measure used to assess the secondary poisoning potential as well as risks to human health. In this work we measured the accumulation and elimination of BPAF in the whole-body and in liver, muscle and gonad tissues of zebrafish. BPAF uptake was relatively rapid with equilibrium concentrations reached after 24-72h of exposure. We observed gender differences both in whole-body and in tissue accumulation. Muscle was the primary BPAF storage tissue during the uptake phase in this study. In the elimination phase, BPAF concentrations declined rapidly during depuration, especially during the initial 2h, and the rate of elimination in males was faster than females from the whole-body and from tissues. The appearance of BPAF glucuronide (BPAF-G) at the start of the uptake phase indicated the rapid biotransformation of BPAF to BPAF-G in vivo. The high lipid content of female gonad could act to delay the diffusion of the xenobiotic within the body in a contaminated environment, but it also acts to delay xenobiotic elimination from the body. PMID:27362491

  16. Gestational and lactational exposure to bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring.

    PubMed

    Li, Jing; Sheng, Nan; Cui, Ruina; Feng, Yixing; Shao, Bing; Guo, Xuejiang; Zhang, Hongxia; Dai, Jiayin

    2016-11-01

    During prenatal and postnatal development, exposure to environmental chemicals with estrogenic activity, such as bisphenol AF (BPAF), may result in reproductive disorders. Currently, the mechanisms behind such disorders in male offspring induced by gestational and lactational exposure to BPAF remain poorly understood. Here, female rats from gestational day (GD) 3-19 were exposed to 100 mg BPAF/kg/day by oral gavage. On the day of birth (postnatal day (PD) 0), cross-fostering took place between treated and control litters, and cross-fostered mother rats were given BPAF 100 mg/kg/day during the postnatal period (PD 3 to PD 19). HPLC-MS/MS analysis showed that BPAF was transferred via cord blood and lactation, finally bio-accumulating in the offspring testes. Pups exposed to BPAF both prenatally and postnatally showed a significant increase in testis testosterone levels compared with that of the control, while all pups exposed to BPAF showed a significant decrease in testis inhibin B (INHB) levels. Compared with the control, RNA-seq revealed that 279 genes were significantly differentially expressed in the testes of pups exposed to BPAF both prenatally and postnatally, including genes involved in cell differentiation and meiosis. These results indicate that gestational and lactational exposure to BPAF in the mother can impair reproductive function in male offspring.

  17. 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.

  18. 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.

  19. Studies on electrochemical oxidation of estrogenic disrupting compound bisphenol AF and its interaction with human serum albumin.

    PubMed

    Wang, Xin; Yang, Jichun; Wang, Yuejiao; Li, Yanhui; Wang, Fang; Zhang, Lei

    2014-07-15

    Bisphenol AF (BPAF) is an environmental pollutant to disrupt endocrine system or cause cancer, thus the detection of trace BPAF is very important. In this study, a simple and highly sensitive electroanalytical method for the determination of BPAF was developed. In pH 6.0 phosphate buffer solutions, carboxyl functionalized multi-walled carbon nanotubes (MWCNT-COOH) modified glassy carbon electrode exhibits an enhanced effectiveness for the oxidation of BPAF. This electrode exhibited two linear relationships with BPAF concentration range of 0.02μmolL(-1) to 8.0μmolL(-1) and a detection limit of 0.0077μmolL(-1) (S/N=3). The proposed method was successfully applied to determine BPAF in real samples and the results were satisfactory. The MWCNT-COOH/GCE electrode showed good reproducibility, stability and anti-interference. The electrochemistry and spectroscopy methods are also described for the evaluation of BPAF-HSA interaction. In the presence of HSA, the peak currents of BPAF decreased linearly due to the formation of a super-molecular complex. The binding constant between BPAF and HSA, obtained by differential pulse voltammetry (DPV), was consistent with the fluorescence analysis. The molecular modeling studies were carried out to clearly describe the interaction between BPAF and HSA.

  20. Cloning, overexpression and biocatalytic exploration of a novel Baeyer-Villiger monooxygenase from Aspergillus fumigatus Af293

    PubMed Central

    2013-01-01

    The presence of several putative Baeyer-Villiger Monooxygenases (BVMOs) encoding genes in Aspergillus fumigatus Af293 was demonstrated for the first time. One of the identified BVMO-encoding genes was cloned and successfully overexpressed fused to the cofactor regenerating enzyme phosphite dehydrogenase (PTDH). The enzyme named BVMOAf1 was extensively characterized in terms of its substrate scope and essential kinetic features. It showed high chemo-, regio- and stereoselectivity not only in the oxidation of asymmetric sulfides, (S)-sulfoxides were obtained with 99% ee, but also in the kinetic resolution of bicyclo[3.2.0]hept-2-en-6-one. This kinetic resolution process led to the production of (1S,5R) normal lactone and (1R,5S) abnormal lactone with a regioisomeric ratio of 1:1 and 99% ee each. Besides, different reaction conditions, such as pH, temperature and the presence of organic solvents, have been tested, revealing that BVMOAf1 is a relatively robust biocatalyst. PMID:23767684

  1. 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. PMID:25059187

  2. 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

  3. MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.

    PubMed

    Stavropoulou, Vaia; Kaspar, Susanne; Brault, Laurent; Sanders, Mathijs A; Juge, Sabine; Morettini, Stefano; Tzankov, Alexandar; Iacovino, Michelina; Lau, I-Jun; Milne, Thomas A; Royo, Hélène; Kyba, Michael; Valk, Peter J M; Peters, Antoine H F M; Schwaller, Juerg

    2016-07-11

    To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients. PMID:27344946

  4. RUNX1 Is a Key Target in t(4;11) Leukemias that Contributes to Gene Activation through an AF4-MLL Complex Interaction

    PubMed Central

    Wilkinson, Adam C.; Ballabio, Erica; Geng, Huimin; North, Phillip; Tapia, Marta; Kerry, Jon; Biswas, Debabrata; Roeder, Robert G.; Allis, C. David; Melnick, Ari; de Bruijn, Marella F.T.R.; Milne, Thomas A.

    2013-01-01

    Summary The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product. PMID:23352661

  5. Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11)(q21;q23)/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Marchesi, F.; Girardi, K.; Avvisati, G.

    2011-01-01

    Translocation t(4;11)(q21;q23) leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11)(q21;q23)/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide. PMID:22190943

  6. 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

  7. Anti-leukemic activity of Newcastle disease virus strains AF2240 and V4-UPM in murine myelomonocytic leukemia in vivo.

    PubMed

    Alabsi, Aied M; Ali, Rola; Ideris, Aini; Omar, Abdul Rahman; Bejo, Mohd Hair; Yusoff, Khatijah; Ali, Abdul Manaf

    2012-05-01

    Newcastle disease virus (NDV) is a member of the Paramyxoviridae that has caused severe economic losses in poultry industry worldwide. Several strains of NDV were reported to induce cytolysis to cancerous cell lines. It has prompted much interest as anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. In this study, two NDV strains, viserotropic-velogenic strain AF2240 and lentogenic strain V4-UPM, showed cytolytic activity and apoptosis induction against Mouse myelomoncytic leukemia (WEHI 3B). The cytolytic effects of NDV strains were determined using microtetrazolium (MTT) assay. The cytolytic dose - fifty percent (CD(50)) were 2 and 8HAU for AF2240 and V4-UPM strains, respectively. Cells treated with NDV strains showed apoptotic features compared to the untreated cells under fluorescence microscope. NDV induced activation of caspase-3 and DNA laddering in agarose gel electrophoresis which confirmed the apoptosis. The anti-leukemic activity of both strains was evaluated on myelomoncytic leukemia BALB/c mice. The results indicated that both NDV strains significantly decreased liver and spleen weights. It also decreased blasts cell percentage in blood, bone marrow and spleen smears of treated mice (p<0.05). Histopathological studies for spleen and liver confirmed the hematological results of blood and bone marrow. From the results obtained, the exposure to both NDV stains AF2240 and V4-UPM showed similar results for Ara-c. In conclusion NDV strains AF2240 and V4-UPM can affect WEHI 3B leukemia cells in vitro and in vivo.

  8. Ligand- and coactivator-mediated transactivation function (AF2) of the androgen receptor ligand-binding domain is inhibited by the cognate hinge region.

    PubMed

    Wang, Q; Lu, J; Yong, E L

    2001-03-01

    Transactivation functions (AF2) in the ligand-binding domains (LBD) of many steroid receptors are well characterized, but there is little evidence to support such a function for the LBD of the androgen receptor (AR). We report a mutant AR, with residues 628-646 in the hinge region deleted, which exhibited transactivation activity that was more than double that of the wild type (WT) AR. Although no androgen-dependent AF2 activity could be observed for the WT ARLBD fused to a heterologous DNA-binding domain, the mutant ARLBD(Delta628-646) was 30-40 times more active than the WT ARLBD. In the presence of the p160 coactivator TIF2, AR(Delta628-646) was significantly more active than similarly treated WT AR. Deletion of residues 628-646 also enhanced TIF2-ARLBD activity 8-fold, an effect not present when the LBD-interacting LXXLL motifs of TIF2 were mutated, suggesting that the negative modulatory activity of residues 628-646 were exerted via coactivator pathways. Although the AP-1 (c-Jun/c-Fos) system and NcoR have been reported to interact with and repress the activity of some steroid receptors, c-Jun, c-Fos, c-Jun/c-Fos, nor NcoR function was consistently affected by the absence or presence of residues 628-646, implying that the AR hinge region exerts its silencing effects in a manner independent of these corepressors. Our data provide evidence for the novel finding that strong androgen-dependent AF2 exists in the ARLBD and is the first report of a negative regulatory domain in the AR. Because mutations in this region are commonly associated with prostate cancer, it is important to characterize the mechanisms by which the hinge region exerts its repressor effect on ligand-activated and coactivator-mediated AF2 activity of the ARLBD.

  9. AF-DX 116, a presynaptic muscarinic receptor antagonist, potentiates the effects of glucose and reverses the effects of insulin on memory.

    PubMed

    Kopf, S R; Boccia, M M; Baratti, C M

    1998-11-01

    Male Swiss mice were tested 24 h after training in a one-trial step-through inhibitory avoidance task. Low subeffective doses of d-(+)-glucose (10 mg/kg, ip), but not its stereoisomer l-(-)-glucose (30 mg/kg,ip), administered immediately after training, and AF-DX 116 (0.3 mg/kg,ip), a presynaptic muscarinic receptor antagonist, given 10 min after training, interact to improve retention. Insulin (8 IU/kg, ip) impaired retention when injected immediately after training, and the effects were reversed, in a dose-related manner, by AF-DX 116 (0.3, 1.0, or 3.0 mg/kg, ip) administered 10 min following insulin. Since AF-DX 116 possibly blocks autoreceptors mediating the inhibition of acetylcholine release from cholinergic nerve terminals, the present data support the view that changes in the central nervous system glucose availability, subsequent to modification of circulating glucose levels, influence the activity of central cholinergic mechanisms involved in memory storage of an inhibitory avoidance response in mice. PMID:9774523

  10. MLL-AF9– and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C

    PubMed Central

    Zhu, Nan; Chen, Mo; Eng, Rowena; DeJong, Joshua; Sinha, Amit U.; Rahnamay, Noushin F.; Koche, Richard; Al-Shahrour, Fatima; Minehart, Janna C.; Chen, Chun-Wei; Deshpande, Aniruddha J.; Xu, Haiming; Chu, S. Haihua; Ebert, Benjamin L.; Roeder, Robert G.; Armstrong, Scott A.

    2016-01-01

    Self-renewal is a hallmark of both hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs); therefore, the identification of mechanisms that are required for LSC, but not HSC, function could provide therapeutic opportunities that are more effective and less toxic than current treatments. Here, we employed an in vivo shRNA screen and identified jumonji domain–containing protein JMJD1C as an important driver of MLL-AF9 leukemia. Using a conditional mouse model, we showed that loss of JMJD1C substantially decreased LSC frequency and caused differentiation of MLL-AF9– and homeobox A9–driven (HOXA9-driven) leukemias. We determined that JMJD1C directly interacts with HOXA9 and modulates a HOXA9-controlled gene-expression program. In contrast, loss of JMJD1C led to only minor defects in blood homeostasis and modest effects on HSC self-renewal. Together, these data establish JMJD1C as an important mediator of MLL-AF9– and HOXA9-driven LSC function that is largely dispensable for HSC function. PMID:26878175

  11. Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.

    PubMed Central

    Domer, P H; Fakharzadeh, S S; Chen, C S; Jockel, J; Johansen, L; Silverman, G A; Kersey, J H; Korsmeyer, S J

    1993-01-01

    A chromosomal translocation, t(4;11)-(q21;q23), is associated with an aggressive mixed-lineage leukemia. A yeast artificial chromosome was used to clone the chromosomal breakpoint of this translocation in the RS4;11 cell line. The breakpoint sequences revealed an inverted repeat bordered by a consensus site for topoisomerase II binding and cleavage as well as chi-like elements. The der(11) chromosome encodes a fusion RNA and predicted chimeric protein between the 11q23 gene MLL and a 4q21 gene designated AF4. The sequence of the complete open reading frame for this fusion transcript reveals the MLL protein to have homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis. Images Fig. 3 PMID:7689231

  12. AF-DX 116, a presynaptic muscarinic receptor antagonist, potentiates the effects of glucose and reverses the effects of insulin on memory.

    PubMed

    Kopf, S R; Boccia, M M; Baratti, C M

    1998-11-01

    Male Swiss mice were tested 24 h after training in a one-trial step-through inhibitory avoidance task. Low subeffective doses of d-(+)-glucose (10 mg/kg, ip), but not its stereoisomer l-(-)-glucose (30 mg/kg,ip), administered immediately after training, and AF-DX 116 (0.3 mg/kg,ip), a presynaptic muscarinic receptor antagonist, given 10 min after training, interact to improve retention. Insulin (8 IU/kg, ip) impaired retention when injected immediately after training, and the effects were reversed, in a dose-related manner, by AF-DX 116 (0.3, 1.0, or 3.0 mg/kg, ip) administered 10 min following insulin. Since AF-DX 116 possibly blocks autoreceptors mediating the inhibition of acetylcholine release from cholinergic nerve terminals, the present data support the view that changes in the central nervous system glucose availability, subsequent to modification of circulating glucose levels, influence the activity of central cholinergic mechanisms involved in memory storage of an inhibitory avoidance response in mice.

  13. The application of ICP-SMS, GF-AAS and HG-AFS to the analysis of water and sediment samples from a temperate stratified estuary.

    PubMed

    Townsend, A T; O'Sullivan, J; Featherstone, A M; Butler, E C; Mackey, D J

    2001-02-01

    Three atomic spectrometry techniques, namely sector field inductively coupled plasma mass spectroscopy, graphite furnace atomic absorption spectrometry and hydride generation atomic fluorescence spectroscopy (ICP-SMS, GF-AAS and HG-AFS, respectively), housed at separate independent laboratories, were used to analyse water and sediment samples collected from the Huon River Estuary, SE Tasmania (Australia) in the Austral spring 1998. A dithiocarbamate-chelation/back-extraction technique was used to separate and preconcentrate Co, Ni, Cu, Zn, Cd and Pb from eight collected water samples prior to analysis by ICP-SMS and GF-AAS. A number of other elements in the waters were analysed directly (Mn, Fe and Zn by GF-AAS; As by HG-AFS), or following sample dilution (1 + 19: V, Mn, Fe, As, Mo, Ba and U by ICP-SMS). Where possible, previously corroborated GF-AAS and HG-AFS techniques were used to verify obtained ICP-SMS results. From the analysis of four reference waters (SLEW-1 and -2, SLRS-3 and NASS-5), good agreement, to within +/- 10-20%, was typically found between certified (or information only values) and measured results (irrespective of analytical technique). Exceptions included Zn (and sometimes Fe) that could not be quantified by ICP-SMS due to elevated blank signals, and As which was found to lie below ICP-SMS detection limits. For Huon Estuary water samples, inter-method agreement was within +/- 10-20% (for those elements amenable to analysis by more than one technique). Nitric acid extracts of two certified reference materials (Buffalo River Sediment and BCSS-1) and six Huon Estuary sediments were analysed by ICP-SMS (for Al, Sc, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd and Pb) and HG-AFS (for As). Results from the certified reference materials indicated extraction efficiencies of 60 70% (for most elements). A close correlation between ICP-SMS and HG-AFS was obtained for leachable As in the sediments. In terms of potential inorganic contaminants, the Huon Estuary

  14. [Determination of Total Selenium and Arsenic in Coal by Wet Digestion Hydride Generation Atomic Fluorescence Spectrometry (HG-AFS)].

    PubMed

    Ni, Run-xiang; Luo, Kun-li

    2015-05-01

    In the present work we presented a new method for determination of total Se and As in coal by electric hot plate-mixed acids-hydride generation atomic fluorescence spectrometry (HG-AFS), the wet digestion method. The detailed operation procedures of the new method are as follows: About 0. 05~0. 10 g of powdered (200 mesh) coal sample was placed in a glass beaker, 10 mL of nitric acid (HNO3) and 2 mL of perchloric acid (HClO4) were added to the beaker in sequence, then the beaker was covered with a watching glass and placed in a fume cupboard standing overnight. The beaker was placed on an electric hot plate (180 °C) for sample decomposition the next day. The beaker was moved away from the electric hot plate when white smoke arose in the beaker, the sample color turned white or grey and the solution turned clear. Three milliliter of hydrochloric acid (HCl) solution (6 mol . L-1) was added to the beaker after the temperature of the beaker returned to room temperature. The beaker was heated on the electric hot plate again, and then moved away when white smoke started arising again. One milliliter of HCI was added in the beaker after the temperature of the beaker returned to room temperature. After that, the digested sample was transferred to a 25 mL test tube which was filled with ultrapure water to the tube's full volume. This solution was used for Se determination directly. Three milliliter of the Se test solution prepared above was transferred to a 15 mL glass test tube, 1 mL of thiourea/ascorbic acid solution (2. 5 g . mL-1) and 1 mL of the concentrated HCl was added to the 15 mL test tube. The test tube was then filled with ultrapure water to its full volume. The solution was used for As determination after shaking well and 40 min standing. Finally, Se and As concentrations in these prepared solutions were measured by using the AFS-9780 instrument (Beijing Haiguang Instrument Co. , LTD, Beijing, China). Two Chinese Coal Certified Reference Materials (GBW11115

  15. [Comparison of soil heavy metals determined by AAS/AFS and portable X-ray fluorescence analysis].

    PubMed

    Ran, Jing; Wang, De-Jian; Wang, Can; Bo, Lu-Ji; Zheng, Ji-Cheng; Yao, Li-Peng

    2014-11-01

    Total concentrations of Cu, Pb, As, Cr, Ni and Zn were determined for 53 soil samples using portable X-ray fluorescence (PXRF) system in in-situ and ex-situ (Lab.) conditions. PXRF metal concentrations were statistically compared with analytical results from traditional AAS/AFS analysis. The ability of PXRF instrument to produce comparable analytical results to the reference method was assessed by linear regression. To investgate the effects of soil moisture on PXRF, the in-situ moisture content of all soil samples was quantified and the metal concentrations of selected samples with known moisture contents were measured too. The results showed that the detection limits of PXRF for Cu, Pb, As, Cr, Ni and Zn were 10.6, 8.1, 5.7, 22.5, 21.6 and 10.4 mg kg(-1) respectively. A good degree of linearity was found for Pb, Cr, Ni and Zn in in-situ condition. While in ex-situ condition, quantitative level data were achieved across the entire range of samples tested for Cu, Pb, Cr, Ni and Zn. X-ray fluorescence spectrometry was shown to be an effective tool for quantification and rapid assessment of heavy metals in soils. Soil moisture content did affected the performance of PXRF, the mean percent difference for soil samples in-situ with moisture content less than 15% and higher than 25% was -17% and -31% respectively. In ex-situ condition, as the soil moisture content increased from air dried level to 30%, the mean percent difference decreased from 10% to -24%. The dilution effect of moisture in soils may cause discrepancies with conventional analytical results and induce worse data quality, and it should be controlled within 0-25% in in-situ condition.

  16. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    PubMed

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  17. Type I Interferon signaling constrains IL-17A/F secretion by γδ T cells during bacterial infections

    PubMed Central

    Henry, Thomas; Kirimanjeswara, Girish S.; Ruby, Thomas; Jones, Jonathan W.; Peng, Kaitian; Perret, Magali; Ho, Lena; Sauer, John-Demian; Iwakura, Yoichiro; Metzger, Dennis W.; Monack, Denise M.

    2010-01-01

    Recognition of intracellular bacteria by macrophages leads to secretion of type I Interferons. However, the role of type I IFN during bacterial infection is still poorly understood. Francisella tularensis, the causative agent of tularemia, is a pathogenic bacterium that replicates in the cytosol of macrophages leading to secretion of type I IFN. Here, we investigated the role of type I IFN in a mouse model of tularemia. Mice deficient for type I IFN receptor (IFNAR1−/−) are more resistant to intradermal infection with F. tularensis subspecies novicida (F. novicida). Increased resistance to infection was associated with a specific increase in IL-17A/F and a corresponding expansion of an IL-17A+ γδ T cell population, indicating that type I IFN negatively regulate the number of IL-17A+ γδ T cells during infection. Furthermore, IL-17A-deficient mice contained fewer neutrophils compared to WT mice upon infection, indicating that IL-17A contributes to neutrophil expansion during F. novicida infection. Accordingly, an increase in IL-17A in IFNAR1−/− mice correlated with an increase in splenic neutrophil numbers. Similar results were obtained in a mouse model of pneumonic tularemia using the highly virulent Francisella tularensis subspecies tularensis SchuS4 strain and in a mouse model of systemic Listeria monocytogenes infection. Our results indicate that the type I IFN-mediated negative regulation of IL-17A+ γδ T cell expansion is conserved during bacterial infections. We propose that this newly described activity of type I IFN signaling might participate in the resistance of the IFNAR1−/− mice to infection with F. novicida and other intracellular bacteria. PMID:20176744

  18. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    PubMed

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models.

  19. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    PubMed Central

    Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

    2015-01-01

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  20. Cone-Beam Computed Tomography-Guided Management of C-Shaped Type III Dens Invaginatus With Peri-invagination Periodontitis in a Maxillary Canine: A Case Report.

    PubMed

    Mittal, Priya; Jadhav, Ganesh R; Syed, Shibli; Bhujbal, Nikita D

    2016-06-01

    Dens invaginatus (DI) is a developmental anomaly seen infrequently in maxillary canines. This article describes cone-beam computed tomography-guided nonsurgical management of type III (subtype B) DI in a permanent maxillary canine associated with a sinus tract and peri-invagination periodontitis in a 17-year-old female. After gaining access to the root canal, thorough chemo-mechanical preparation was performed and usage of intracanal medicament of calcium hydroxide was prescribed for 3 weeks, during which the sinus tract healed completely. Obturation was completed by a technique of down-packing master-cone gutta-percha, followed by backfilling with thermoplasticized gutta-percha. At 12-months follow-up, the patient was asymptomatic with complete resolution of the sinus tract and radiographic evidence of healing of periapical pathology. PMID:27525733

  1. 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

  2. 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.

  3. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial

    PubMed Central

    Mahaffey, Kenneth W.; Stevens, Susanna R.; White, Harvey D.; Nessel, Christopher C.; Goodman, Shaun G.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Califf, Robert M.; Fox, Keith A.A.; Breithardt, Günter

    2014-01-01

    Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73–1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59–3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. PMID:24132190

  4. Pseudoxylallemycins A-F, Cyclic Tetrapeptides with Rare Allenyl Modifications Isolated from Pseudoxylaria sp. X802: A Competitor of Fungus-Growing Termite Cultivars.

    PubMed

    Guo, Huijuan; Kreuzenbeck, Nina B; Otani, Saria; Garcia-Altares, Maria; Dahse, Hans-Martin; Weigel, Christiane; Aanen, Duur K; Hertweck, Christian; Poulsen, Michael; Beemelmanns, Christine

    2016-07-15

    Based on fungus-fungus pairing assays and HRMS-based dereplication strategy, six new cyclic tetrapeptides, pseudoxylallemycins A-F (1-6), were isolated from the termite-associated fungus Pseudoxylaria sp. X802. Structures were characterized using NMR spectroscopy, HRMS, and Marfey's reaction. Pseudoxylallemycins B-D (2-4) possess a rare and chemically accessible allene moiety amenable for synthetic modifications, and derivatives A-D showed antimicrobial activity against Gram-negative human-pathogenic Pseudomonas aeruginosa and antiproliferative activity against human umbilical vein endothelial cells and K-562 cell lines. PMID:27341414

  5. 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

  6. Localization of tritiated 1-(2, 4-dichlorobenzyl)-/sup 1/H-indazole-3-carboxylic acid ((/sup 3/H) AF 1890) in rat testis using freeze-drying autoradiography

    SciTech Connect

    Hilderbrandt-Stark, H.E.; Mills, J.W.; Fawcett, D.W.

    1982-09-01

    Tritiated 1-(2, 4-dichlorobenzyl)-/sup 1/H-indazole-3-carboxylic acid ((/sup 3/H)AF 1890) was localized within rat testis using freeze-drying autoradiographic techniques. Ligated seminiferous tubule preparations were exposed in vitro to 80 microCi of (/sup 3/H)AF 1890 in the absence or presence of excess unlabeled AF 1890 for 30 min at 31 degrees C. Autoradiographs showed a generalized distribution of silver grains over the seminiferous epithelium, in the tubular lumen, and in the interstitial spaces. In addition, clusters of grains were concentrated over the seminiferous epithelium in regions of spermatid heads and tails and in the basal portion of the Sertoli cell cytoplasm, and over Leydig cells in the interstitial space. The generalized distribution was reduced and the grain clusters eliminated by incubation in an excess of unlabeled AF 1890. (/sup 3/H)inulin was used to assess the effectiveness of the tubular ligation because inulin does not normally penetrate the blood-testis barrier. This extracellular marker was not localized in the tubular lumen or in the seminiferous epithelium. Therefore, the labeling observed with (/sup 3/H)AF 1890 indicates that this compound crosses the blood-testis barrier.

  7. 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.

  8. 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 Central

    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. PMID:24699529

  9. Supporting Treatment decision making to Optimise the Prevention of STROKE in Atrial Fibrillation: The STOP STROKE in AF study. Protocol for a cluster randomised controlled trial

    PubMed Central

    2012-01-01

    Background Suboptimal uptake of anticoagulation for stroke prevention in atrial fibrillation has persisted for over 20 years, despite high-level evidence demonstrating its effectiveness in reducing the risk of fatal and disabling stroke. Methods The STOP STROKE in AF study is a national, cluster randomised controlled trial designed to improve the uptake of anticoagulation in primary care. General practitioners from around Australia enrolling in this ‘distance education’ program are mailed written educational materials, followed by an academic detailing session delivered via telephone by a medical peer, during which participants discuss patient de-identified cases. General practitioners are then randomised to receive written specialist feedback about the patient de-identified cases either before or after completing a three-month posttest audit. Specialist feedback is designed to provide participants with support and confidence to prescribe anticoagulation. The primary outcome is the proportion of patients with atrial fibrillation receiving oral anticoagulation at the time of the posttest audit. Discussion The STOP STROKE in AF study aims to evaluate a feasible intervention via distance education to prevent avoidable stroke due to atrial fibrillation. It provides a systematic test of augmenting academic detailing with expert feedback about patient management. Trial registration Australian Clinical Trials Registry Registration Number: ACTRN12611000076976. PMID:22770423

  10. 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.

  11. 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.

  12. 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.

  13. Plastic flow and failure in HY100, HY130 and AF1410 alloy steels under high strain rate and impact loading conditions

    NASA Astrophysics Data System (ADS)

    Rajendran, A. M.; Last, H. R.; Garrett, R. K., Jr.

    1995-03-01

    This report presents the results from impact experiments, constitutive/failure modeling, and metallurgical failure analyses for three steels: HY100, HY130, and AF1410. The main objectives of this effort are: (1) to obtain fundamental engineering data in terms of stress-strain curves up to failure at different temperatures and strain rates, (2) to evaluate the observed differences in the macroscopic behaviors through microscopic metallurgical studies, and (3) to describe the flow and failure behaviors using already available material strength and spall models. The high strain rate and impact experiments considered are the split Hopkinson bar (SHB) and the planar plate impact tests, respectively. In addition, the baseline data include quasi-static (QS) tests at low strain rates. The QS and SHB data provide stress-strain curves at different strain rates and temperatures. The experimental data illustrate the effects of two important loading parameters (strain rate and temperature) on the flow and failure behaviors of HY100, HY130, and AF1410 steels.

  14. 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.

  15. 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

  16. 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. PMID:26017363

  17. 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

  18. 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.

  19. 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

  20. Early detection of colon cancer by increased serum level of Krebs von den Lungen-6 in a patient with dermatomyositis-associated interstitial pneumonia.

    PubMed

    Fukuhara, Naoko; Tanino, Yoshinori; Sato, Suguru; Fukuhara, Atsuro; Uematsu, Manabu; Nikaido, Takefumi; Misa, Kenichi; Sato, Yasuko; Saito, Junpei; Wang, Xintao; Munakata, Mitsuru

    2015-09-14

    Krebs von den Lungen-6 (KL-6) is a high-molecular-weight glycoprotein which is elevated in serum of patients with interstitial pneumonia (IP). Serum KL-6 level is clinically used for the diagnosis of IP as well as the evaluation of its disease activity. KL-6 is originally identified when exploring novel soluble antigens in patients with lung cancer, and is known to be elevated in patients with several malignant tumors. The risk of malignant tumors is high in IP patients with polymyositis and dermatomyositis (PM/DM), and follow-up of KL-6 levels may allow earlier detection of such tumors. However, to date, there are only a few reports showing the usefulness of following-up serum KL-6 levels for finding malignant tumors in IP patients with PM/DM. Here, we described the first patient in whom increased serum KL-6 led to the diagnosis of colon cancer during follow-up of DM-associated IP.

  1. [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.

  2. 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

  3. Solution conformation of [AF]dG opposite a -1 deletion site in a DNA duplex: intercalation of the covalently attached aminofluorene ring into the helix with base displacement of the C8-modified Syn guanine into the major groove.

    PubMed

    Mao, B; Cosman, M; Hingerty, B E; Broyde, S; Patel, D J

    1995-05-01

    This paper reports on the solution structure of the [AF]dG adduct positioned opposite a deletion site in a DNA oligomer duplex that defines the alignment of the covalent aminofluorene--C8-guanine adduct relative to the deletion site. The combined NMR molecular mechanics computational studies were undertaken on the [AF]dG adduct embedded in the d(C5-[AF]G6-C7).d(G16-G17) sequence context in a duplex containing 11 residues on the modified strand and 10 on the partner, with no base opposite the modification. The exchangeable and nonexchangeable protons of the aminofluorene moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. The solution conformation of the [AF]G.del 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. The aminofluorene ring of [AF]dG6 is intercalated between intact Watson-Crick dC5.dG17 and dC7.dG16 base pairs with the guanine base of [AF]dG6 in a syn alignment displaced into the major groove. The syn glycosidic torsion angle at [AF]dG6 is supported by both carbon and proton chemical shift data for the sugar resonances of the modified guanine residue. The long axis of the aminofluorene ring is parallel to the long axis of the flanking dG.dC base pairs with the AF ring undergoing rapid 180 degrees flips on the NMR time scale. The intercalation site is wedge shaped with a pronounced propeller-twisting and buckling of the dC5.dG17 base pair. The guanine base of [AF]dG6, which is positioned in the major groove, is inclined relative to the helix axis and stacks over the 5'-flanking dC5 residue in the solution structure. The intercalative-base displacement structure of the [AF]dG.del 11-mer duplex exhibits several unusually shifted proton resonances that can be readily accounted for by the ring current

  4. Lack of Concordance between Empirical Scores and Physician Assessments of Stroke and Bleeding Risk in Atrial Fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry

    PubMed Central

    Steinberg, Benjamin A.; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C.; Hylek, Elaine; Ansell, Jack; Go, Alan S.; Chang, Paul; Kowey, Peter; Gersh, Bernard J.; Mahaffey, Kenneth W.; Singer, Daniel E; Piccini, Jonathan P.; Peterson, Eric D.

    2014-01-01

    Background Physicians treating patients with atrial fibrillation (AF) must weigh the benefits of anticoagulation in preventing stroke versus the risk of bleeding. While empirical models have been developed to predict such risks, the degree to which these coincide with clinicians’ estimates is unclear. Methods and Results We examined 10,094 AF patients enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) registry between June, 2010 and August, 2011. Empirical stroke and bleeding risks were assessed using the CHADS2 and ATRIA scores, respectively. Separately, physicians were asked to categorize their patients’ stroke and bleeding risks: low- (<3%); intermediate- (3-6%); and high-risk (>6%). Overall, 72% (n=7251) in ORBIT-AF had high-risk CHADS2 scores (≥2). However, only 16% were assessed as high stroke risk by physicians. While 17% (n=1749) had high ATRIA bleeding risk (score ≥5), only 7% (n=719) were considered so by physicians. The associations between empirical and physician-estimated stroke and bleeding risks were low (weighted Kappa 0.1 and 0.11, respectively). Physicians weighed hypertension, heart failure, and diabetes less significantly than empirical models in estimating stroke risk; physicians weighted anemia and dialysis less significantly than empirical models when estimating bleeding risks. Anticoagulation use was highest among patients with high stroke risk, assessed by either empirical model or physician estimates. In contrast, physician and empirical estimates of bleeding had limited impact on treatment choice. Conclusions There is little agreement between provider-assessed risk and empirical scores in AF. These differences may explain, in part, current divergence of anticoagulation treatment decisions from guideline recommendations. PMID:24682387

  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. PMID:27561277

  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. Direct online HPLC-CV-AFS method for traces of methylmercury without derivatisation: a matrix-independent method for urine, sediment and biological tissue samples.

    PubMed

    Brombach, Christoph-Cornelius; Gajdosechova, Zuzana; Chen, Bin; Brownlow, Andrew; Corns, Warren T; Feldmann, Jörg; Krupp, Eva M

    2015-01-01

    Mercury (Hg) is a global pollutant which occurs in different species, with methylmercury (MeHg) being the critical compound due to its neurotoxicity and bioaccumulation through the food chain. Methods for trace speciation of MeHg are therefore needed for a vast range of sample matrices, such as biological tissues, fluids, soils or sediments. We have previously developed an ultra-trace speciation method for methylmercury in water, based on a preconcentration HPLC cold vapour atomic fluorescence spectrometry (HPLC-CV-AFS) method. The focus of this work is mercury speciation in a variety of sample matrices to assess the versatility of the method. Certified reference materials were used where possible, and samples were spiked where reference materials were not available, e.g. human urine. Solid samples were submitted for commonly used digestion or extraction processes to obtain a liquid sample for injection into the analytical system. For MeHg in sediment samples, an extraction procedure was adapted to accommodate MeHg separation from high amounts of Hg(2+) to avoid an overload of the column. The recovery for MeHg determination was found to be in the range of 88-104% in fish reference materials (DOLT-2, DOLT-4, DORM-3), lobster (TORT-2), seaweed (IAEA-140/TM), sediments (ERM(®)-CC580) and spiked urine and has been proven to be robust, reliable, virtually matrix-independent and relatively cost-effective. Applications in the ultra-trace concentration range are possible using the preconcentration up to 200 mL, while for higher MeHg-containing samples, lower volumes can be applied. A comparison was carried out between species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICP-MS) as the gold standard and HPLC-CV-AFS for biological tissues (liver, kidney and muscle of pilot whales), showing a slope of 1.008 and R (2) = 0.97, which indicates that the HPLC-CV-AFS method achieves well-correlated results for MeHg in

  10. Direct online HPLC-CV-AFS method for traces of methylmercury without derivatisation: a matrix-independent method for urine, sediment and biological tissue samples.

    PubMed

    Brombach, Christoph-Cornelius; Gajdosechova, Zuzana; Chen, Bin; Brownlow, Andrew; Corns, Warren T; Feldmann, Jörg; Krupp, Eva M

    2015-01-01

    Mercury (Hg) is a global pollutant which occurs in different species, with methylmercury (MeHg) being the critical compound due to its neurotoxicity and bioaccumulation through the food chain. Methods for trace speciation of MeHg are therefore needed for a vast range of sample matrices, such as biological tissues, fluids, soils or sediments. We have previously developed an ultra-trace speciation method for methylmercury in water, based on a preconcentration HPLC cold vapour atomic fluorescence spectrometry (HPLC-CV-AFS) method. The focus of this work is mercury speciation in a variety of sample matrices to assess the versatility of the method. Certified reference materials were used where possible, and samples were spiked where reference materials were not available, e.g. human urine. Solid samples were submitted for commonly used digestion or extraction processes to obtain a liquid sample for injection into the analytical system. For MeHg in sediment samples, an extraction procedure was adapted to accommodate MeHg separation from high amounts of Hg(2+) to avoid an overload of the column. The recovery for MeHg determination was found to be in the range of 88-104% in fish reference materials (DOLT-2, DOLT-4, DORM-3), lobster (TORT-2), seaweed (IAEA-140/TM), sediments (ERM(®)-CC580) and spiked urine and has been proven to be robust, reliable, virtually matrix-independent and relatively cost-effective. Applications in the ultra-trace concentration range are possible using the preconcentration up to 200 mL, while for higher MeHg-containing samples, lower volumes can be applied. A comparison was carried out between species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICP-MS) as the gold standard and HPLC-CV-AFS for biological tissues (liver, kidney and muscle of pilot whales), showing a slope of 1.008 and R (2) = 0.97, which indicates that the HPLC-CV-AFS method achieves well-correlated results for MeHg in

  11. 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.

  12. Functional dissection of an enhancer-like element located within the second intron of the human U2AF1L4 gene.

    PubMed

    Didych, D A; Smirnov, N A; Kotova, E S; Akopov, S B; Nikolaev, L G; Sverdlov, E D

    2011-08-01

    A detailed functional and evolutionary analysis of an enhancer element of the human genome (enhancer 12) located in the second intron of the U2AF1L4 gene, which we identified earlier, is presented. Overlapping fragments of the studied genome region were analyzed for enhancer activity, and the site responsible for the activity of this element was identified using transient transfections of HeLa cells. Comparison of the enhancer 12 sequence with orthologous sequences from seven primate species revealed the existence of evolutionarily conserved sequences within this element. One of the identified conservative regions is likely responsible for the enhancer activity and is able to specifically interact in vitro with proteins of HeLa cell nuclear extract. The ability of orthologous primate sequences to compete with enhancer 12 for binding with HeLa cell nuclear extract proteins and to enhance the activity of the reporter gene in transient transfection of HeLa cells is demonstrated. PMID:22022969

  13. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

    PubMed Central

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-01-01

    Abstract Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs. Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs. Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels. Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID:27368027

  14. LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization.

    PubMed

    Iyer, Anita K; Zhang, Yao-Hua; McCabe, Edward R B

    2007-01-01

    Small heterodimer partner (SHP; NR0B2) is an unusual orphan member of the nuclear receptor superfamily that functions as a corepressor of other nuclear receptors through heterodimeric interactions. Mutations in SHP are associated with mild obesity and insulin resistance. The protein domain structure of SHP is similar to Dosage-sensitive sex reversal adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1 (DAX1; NR0B1). Mutations in DAX1 cause AHC with associated hypogonadotropic hypogonadism. DAX1A is an alternatively spliced isoform of DAX1 that lacks the last 80 amino acids of the DAX1 C-terminal repressor domain and is replaced by a novel 10-amino acid motif. We have previously shown homodimerization of SHP and DAX1 individually, heterodimerization of DAX1 with SHP, and heterodimerization of DAX1 with DAX1A. In these studies, we investigated the domains and residues of SHP involved in SHP homodimerization and DAX1-SHP heterodimerization and also further characterized DAX1-DAX1 homodimerization and DAX1-DAX1A heterodimerization. We showed involvement of the SHP LXXLL motifs and AF-2 domain in SHP homodimerization and DAX1-SHP heterodimerization. We demonstrated redundancy of the LXXLL motifs in DAX1 homodimerization. While DAX1A subcellular localization is mostly cytoplasmic, DAX1-DAX1A heterodimers existed in the nucleus, suggesting differential functions for DAX1A in each compartment. We showed that the AF-2 domain of DAX1 is involved in DAX1-DAX1A heterodimerization. These results indicate that NR0B family members use similar mechanisms for homodimerization as well as heterodimerization. These resemble coactivator-receptor interactions that may have potential functional consequences for molecular mechanisms of the NR0B family. PMID:17686645

  15. 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

  16. 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.

  17. An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells

    PubMed Central

    Hasegawa, Kana; Tanaka, Satomi; Fujiki, Fumihiro; Morimoto, Soyoko; Nakajima, Hiroko; Tatsumi, Naoya; Nakata, Jun; Takashima, Satoshi; Nishida, Sumiyuki; Tsuboi, Akihiro; Oka, Yoshihiro; Oji, Yusuke; Kumanogoh, Atsushi; Sugiyama, Haruo; Hosen, Naoki

    2015-01-01

    Leukemia differs substantially with respect to stromal milieu from tumors that progress locally as solid masses, and the physiological importance of immunosurveillance in leukemia remains unclear. However, currently available mouse leukemia models have critical limitations in the context of analyzing immunological regulation of leukemia development. In this study, we transferred mouse MLL/AF9 leukemia-initiating cells into immunocompetent recipient mice without any pre-conditioning such as irradiation, and then analyzed the spontaneous T cell response to an immunogenic antigen expressed in leukemia cells. When the minimum numbers of leukemia-initiating cells for engraftment were transferred, leukemia cells were eradicated by the adaptive immune response in most, if not all, wild-type mice, but not in Rag2-/- recipient mice, which lack adaptive immunity. By contrast, mice transplanted with larger numbers of leukemia cells always developed leukemia. In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3. These results provide the first clear demonstration that the spontaneous CTL response to a tumor-cell antigen has the potential to eradicate leukemia, whereas antigen-specific CTLs are exhausted in animals with advanced leukemia. This immunocompetent mouse leukemia model provides a useful platform for developing effective immunotherapies against leukemia. PMID:26658107

  18. The high affinity ligand binding conformation of the nuclear 1,25-dihydroxyvitamin D3 receptor is functionally linked to the transactivation domain 2 (AF-2).

    PubMed Central

    Nayeri, S; Kahlen, J P; Carlberg, C

    1996-01-01

    The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, is a transcription factor that mediates all genomic actions of the hormone. The activation of VDR by ligand induces a conformational change within its ligand binding domain (LBD). Due to the lack of a crystal structure analysis, biochemical methods have to be applied in order to investigate the details of this receptor-ligand interaction. The limited protease digestion assay can be used as a tool for the determination of a functional dissociation constant (K(df)) of VDR with any potential ligand. This method provided with the natural hormone VD two protease-resistant fragments of the VDR LBD and with the 20-epi conformation of VD, known as MC1288, even an additional fragment of intermediate size. These fragments were interpreted as different receptor conformations and their decreasing size was found to be associated with decreasing ligand binding affinity. A critical amino acid for VDR's high ligand binding conformation has been identified by C-terminal receptor truncations and point mutations as phenylalanine 422. This amino acid appears to directly contact the ligand and belongs to the ligand-inducible activation function-2 (AF-2) domain. Moreover, functional assays supported the observation that high affinity ligand binding is directly linked to transactivation function. PMID:8948643

  19. Talaromycolides A-C, Novel Phenyl-Substituted Phthalides Isolated from the Green Chinese Onion-Derived Fungus Talaromyces pinophilus AF-02.

    PubMed

    Zhai, Ming-Ming; Niu, Hai-Tao; Li, Jie; Xiao, Hui; Shi, Yan-Ping; Di, Duo-Long; Crews, Phillip; Wu, Quan-Xiang

    2015-11-01

    The green Chinese onion (Allium fistulosum L.), which is widely cultivated and has been naturalized in many places, is an important spice and vegetable in East and Southeast Asia. It is used to treat the common cold in China. In the ongoing search for antibacterial activity in fungi derived from natural, pungently scented vegetables, the secondary metabolites of Talaromyces pinophilus AF-02, which was isolated from the stem of the green Chinese onion, were investigated. The genus Talaromyces (Trichocomaceae) is an important fungal genus because of its ubiquity and the role of many of its species in food and agriculture production. Three new phthalide derivatives, talaromycolides A-C, 1-3; a new long-chain dicarboxylic acid, 11; and 12 known compounds were isolated from methanolic extracts of this fungus. Their structures were determined via extensive NMR, HR-ESI-MS, and CD spectroscopic analyses. Compounds 1-3 are rare phthalide derivatives with a novel linkage position between the phenyl and phthalide moieties. The biological properties of 1-16 were evaluated using six different bacteria, and 1-3, 5, and 11 exhibited significant antibacterial activity in response to some of the tested strains. PMID:26466717

  20. 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. PMID:16930681

  1. 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.

  2. 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.

  3. 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.

  4. Estimates of Z' couplings within data on the AF B for Drell-Yan process at the LHC at √{s }=7 and 8 TeV

    NASA Astrophysics Data System (ADS)

    Pevzner, A.; Skalozub, V.

    2016-07-01

    A model-independent search for the Abelian Z' gauge boson in the Drell-Yan process at the LHC at √{s }=7 and 8 TeV is fulfilled. Estimations of the Z' axial-vector coupling af2 to the standard model fermions, the couplings of the axial vector to lepton vector currents afvl, and the couplings of the axial vector to quark vector currents afvq are derived within data on the forward-backward asymmetry presented by the CMS Collaboration. The analysis takes into consideration the behavior of the differential cross section, which exhibits itself if the derived already special relations between the couplings proper to the renormalizable theories are accounted for. In particular, they hold in all the models of Abelian Z' usually considered in the model-dependent analysis of the LHC data. The coupling values are estimated at ˜92 % confidence level by means of the maximum likelihood function. They weakly depend on the Z' mass in the investigated interval 1.2 TeV

  5. Simultaneous Determination of Se and Te in Ores by HG-AFS After Online Preconcentration with Nano-TiO2 Immobilized on Silica Gel.

    PubMed

    Zhou, Jing-rong; Deng, Dong-yan; Huang, Ke; Tian, Yun-fei; Hou, Xian-deng

    2015-09-01

    A simple, sensitive and interference-free method was established for simultaneous determination of trace selenium and tellurium in ore samples by HG-AFS, by using nano-TiO2 immobilized on a silica gel packed microcolumn for online preconcentration. Selenium and tellurium were selectively adsorbed to the microcolumn in acidic condition and then completely eluted with 2% (m/v) NaOH solution. The experimental conditions for hydride generation, adsorption, elution and potential interference were investigated in detail. Under the optimum conditions, the detection limits of selenium and tellurium by the proposed method with 180 s sampling time were 4.0 and 3.6 ng · L(-1), with sensitivity enhancement of 20- and 13-fold compared to conventional hydride generation method, respectively. The relative standard deviation (RSD, n=5) of this method for 1 μg · L(-1) Se(IV) and Te(IV) were 0.7% and 2.3%, respectively. This method was applied to determination of selenium and tellurium in several ore samples. PMID:26669138

  6. Simultaneous determination of endocrine disrupting compounds bisphenol F and bisphenol AF using carboxyl functionalized multi-walled carbon nanotubes modified electrode.

    PubMed

    Yang, Jichun; Wang, Xin; Zhang, Danfeng; Wang, Lingling; Li, Qi; Zhang, Lei

    2014-12-01

    A novel, simple and selective electrochemical method was developed for simultaneous determination of bisphenol F (BPF) and bisphenol AF (BPAF) in aqueous media (phosphate buffer solution, pH 6.0) on carboxyl functionalized multi-walled carbon nanotubes modified glassy carbon electrode (MWCNT-COOH/GCE) using differential pulse voltammetry (DPV). In DPV, MWCNT-COOH/GCE could separate the oxidation peak potentials of BPF and BPAF present in the same solution though, at the bare GCE, the peak potentials were indistinguishable. The results showed that the electrochemical sensor exhibited excellent electrocatalytic activity towards the oxidation of the two analytes. The peak current in DPV of BPF and BPAF increased linearly with their concentration in the ranges of 0.6-1.6 mmol/L BPF and 0.6-1.6 mmol/L BPAF. The detection limits were 0.1243 mmol/L and 0.1742 mmol/L (S/N=3) correspondingly. The modified electrode was successfully used to simultaneously determine BPF and BPAF in real samples.

  7. 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.

  8. The plant pathogen Streptomyces scabies 87-22 has a functional pyochelin biosynthetic pathway that is regulated by TetR- and AfsR-family proteins.

    PubMed

    Seipke, Ryan F; Song, Lijiang; Bicz, Joanna; Laskaris, Paris; Yaxley, Alice M; Challis, Gregory L; Loria, Rosemary

    2011-09-01

    Siderophores are high-affinity iron-chelating compounds produced by bacteria for iron uptake that can act as important virulence determinants for both plant and animal pathogens. Genome sequencing of the plant pathogen Streptomyces scabies 87-22 revealed the presence of a putative pyochelin biosynthetic gene cluster (PBGC). Liquid chromatography (LC)-MS analyses of culture supernatants of S. scabies mutants, in which expression of the cluster is upregulated and which lack a key biosynthetic gene from the cluster, indicated that pyochelin is a product of the PBGC. LC-MS comparisons with authentic standards on a homochiral stationary phase confirmed that pyochelin and not enantio-pyochelin (ent-pyochelin) is produced by S. scabies. Transcription of the S. scabies PBGC occurs via ~19 kb and ~3 kb operons and transcription of the ~19 kb operon is regulated by TetR- and AfsR-family proteins encoded by the cluster. This is the first report, to our knowledge, of pyochelin production by a Gram-positive bacterium; interestingly regulation of pyochelin production is distinct from characterized PBGCs in Gram-negative bacteria. Though pyochelin-mediated iron acquisition by Pseudomonas aeruginosa is important for virulence, in planta bioassays failed to demonstrate that pyochelin production by S. scabies is required for development of disease symptoms on excised potato tuber tissue or radish seedlings. PMID:21757492

  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 Central

    Brunger, Axel T.; Das, Debanu; Deacon, Ashley M.; Grant, Joanna; Terwilliger, Thomas C.; Read, Randy J.; Adams, Paul D.; Levitt, Michael; Schröder, Gunnar F.

    2012-01-01

    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. PMID:22505259

  10. 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

  11. 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.

  12. 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.

  13. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  14. Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

    PubMed Central

    Nakamura, Minoru; Nishida, Nao; Kawashima, Minae; Aiba, Yoshihiro; Tanaka, Atsushi; Yasunami, Michio; Nakamura, Hitomi; Komori, Atsumasai; Nakamuta, Makoto; Zeniya, Mikio; Hashimoto, Etsuko; Ohira, Hiromasa; Yamamoto, Kazuhide; Onji, Morikazu; Kaneko, Shuichi; Honda, Masao; Yamagiwa, Satoshi; Nakao, Kazuhiko; Ichida, Takafumi; Takikawa, Hajime; Seike, Masataka; Umemura, Takeji; Ueno, Yoshiyuki; Sakisaka, Shotaro; Kikuchi, Kentaro; Ebinuma, Hirotoshi; Yamashiki, Noriyo; Tamura, Sumito; Sugawara, Yasuhiko; Mori, Akira; Yagi, Shintaro; Shirabe, Ken; Taketomi, Akinobu; Arai, Kuniaki; Monoe, Kyoko; Ichikawa, Tatsuki; Taniai, Makiko; Miyake, Yasuhiro; Kumagi, Teru; Abe, Masanori; Yoshizawa, Kaname; Joshita, Satoru; Shimoda, Shinji; Honda, Koichi; Takahashi, Hiroki; Hirano, Katsuji; Takeyama, Yasuaki; Harada, Kenichi; Migita, Kiyoshi; Ito, Masahiro; Yatsuhashi, Hiroshi; Fukushima, Nobuyoshi; Ota, Hajime; Komatsu, Tatsuji; Saoshiro, Takeo; Ishida, Jinya; Kouno, Hirotsugu; Kouno, Hirotaka; Yagura, Michiyasu; Kobayashi, Masakazu; Muro, Toyokichi; Masaki, Naohiko; Hirata, Keiichi; Watanabe, Yukio; Nakamura, Yoko; Shimada, Masaaki; Hirashima, Noboru; Komeda, Toshiki; Sugi, Kazuhiro; Koga, Michiaki; Ario, Keisuke; Takesaki, Eiichi; Maehara, Yoshihiko; Uemoto, Shinji; Kokudo, Norihiro; Tsubouchi, Hirohito; Mizokami, Masashi; Nakanuma, Yasuni; Tokunaga, Katsushi; Ishibashi, Hiromi

    2012-01-01

    For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10−14 for rs4979462, and combined OR = 1.39, p = 2.38 × 10−8 for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10−8, 3.66 × 10−9, and 3.04 × 10−9, respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10−6 and 1.42 × 10−7, respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals. PMID:23000144

  15. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628

    PubMed Central

    Finnema, Sjoerd J.; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A.; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-01-01

    Background: Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. Methods: A novel neurokinin 3 receptor radioligand, [18F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[18F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. Results: The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Conclusion: Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. PMID:26993630

  16. Über den Einfluß von Wirbelströmen auf die Frequenzabhängigkeit der komplexen Permeabilität hochpermeabler Mangan-Zink-Ferrite

    NASA Astrophysics Data System (ADS)

    Dietzmann, G.; Schaefer, M.

    Nach der Einleitung, in der die Bedeutung der Wirbelströme für den Anstieg der Verluste mit der Frequenz in hochpermeablen Mn-Zn-Ferriten dargelegt wird, werden in Abschn. 2 gemessene Ortskurven der komplexen Permeabilität von Mn-Zn-Ferriten mit Werten der Anfangspermeabilität von 4000 bis 8000 und des spezifischen Widerstandes von 7 bis 138 cm (bei R. T.) vorgestellt. In Abschn. 3 wird der Versuch erläutert, einen gewissen Anfangsteil dieser Ortskurve durch theoretische Wirbelstromortskurven der komplexen Permeabilität, bei denen die Relaxation der komplexen Leitfähigkeit in Form eines von GRANT angegebenen Ausdruckes berücksichtigt ist, wiederzugeben. Die Ergebnisse, die in Abschn. 4 diskutiert werden, erlauben den Schluß, daß die mit der Relaxation der Leitfähigkeit verknüpften kapazitiven Wirbelströme für den Charakter des Anfangsverlaufes der an Ringkernen gemessenen Ortskurven der komplexen Permeabilität von hochpermeablen Mn-Zn-Ferriten bestimmend sein können.Translated AbstractOn the Effect of Eddy Currents on the Magnetic Spectra of High-permeability Manganese-zinc FerritesAfter stressing the importance of eddy currents on the increase of magnetic losses with frequency on high-permeability Mn-Zn-ferrites (in the introduction), experimental curves in the complex plane of the variation of the complex permeability with frequency of Mn-Zn-Ferrites with an initial permeability of 4000 up to 8000 and resistivity of 7 up to 130 ohm . cm are presented in section 2. In section 3 the attempt is stated of reproducing a certain initial part of the curve of complex permeability by theoretical eddy current curves, taking into account the relaxation of complex conductivity in form of an expression given by GRANT. The results discussed in section 4 permit the conclusion, that the capacitive eddy currents due to the relaxation of conductivity may be the essential factor determining the character of the initial turn of the complex magnetic dispersion curve

  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. 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…

  19. AFS Orientation Handbook. Third Edition.

    ERIC Educational Resources Information Center

    AFS International/Intercultural Programs, Inc., New York, NY.

    Designed for persons involved in cross-cultural training sessions for international high school student exchange programs, this handbook features orientation resources developed in North and South America, Europe, and Asia. Following a brief introduction, Section 2 describes volunteer training seminars in Argentina which covered publicity, local…

  20. Localized corrosion susceptibility of Al-Li-Cu-Mg-Zn alloy AF/C458 due to interrupted quenching from solutionizing temperature

    NASA Astrophysics Data System (ADS)

    Kertz, J. E.; Gouma, P. I.; Buchheit, R. G.

    2001-10-01

    Isothermal time-temperature-localized corrosion-behavior curves were determined for the Al-1.8Li-2.70Cu-0.6Mg-0.3Zn alloy AF/C458, to understand the effect of slow or delayed quenching on localized corrosion susceptibility. Alloy samples were subject to a series of systematic interrupted quenching experiments conducted at temperatures ranging from 480 °C to 230 °C for times ranging from 5 to 1000 seconds. Individual samples were then exposed to an oxidizing aqueous chloride solution consisting of 57 g/L NaCl plus 10 mL/L H2O2 to induce localized attack. The localized corrosion mode was characterized by optical microscopy. Additionally, the microstructure of selected samples was characterized by transmission electron microscopy (TEM) to relate the corrosion mode and morphology to microstructural features. Results showed that only pitting attack was exhibited by samples subjected to isothermal treatment at temperatures greater than 430 °C. At temperatures ranging from 280 °C to 430 °C, isothermal treatment tended to induce susceptibility to intergranular attack (IGA) and intersubgranular attack (ISGA) for all treatment times investigated. For isothermal treatments at temperatures lower than 280 °C, only pitting was observed for treatment times less than about 30 seconds, while IGA and ISGA were observed for longer treatment times. Comparisons showed that the time-temperature domains for IGA and ISGA were virtually coincident. Based on this finding and the results from TEM characterization, IGA and ISGA appear to be related to the precipitation of a Zn-modified T 1 (Al2(Cu,Zn)Li) precipitate, which can occur both on low-angle and high-angle grain boundaries in this alloy. When the alloy is resistant to IGA and ISGA, the grain boundaries are decorated by θ' (Al2Cu), and T B (Al7Cu4Li) phase particles, or subgrain boundaries are populated by a comparatively low density of T 1 precipitates. It is, therefore, speculated that θ' and T B are more corrosion