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Sample records for behandling af den

  1. Neue Anforderungen an den Datenschutz

    NASA Astrophysics Data System (ADS)

    Dix, Alexander

    Eine von der Europäischen Kommission 2003 in Auftrag gegebene Studie hat die rasante technische Entwicklung hin zu "Ambient Intelligence Technologies“ als die größte Herausforderung für den Datenschutz bezeichnet, die sogar größer als die Herausforderung durch den internationalen Terrorismus nach dem 11. September sei.

  2. Two New Letters by Denning

    NASA Astrophysics Data System (ADS)

    Beech, Martin

    2010-06-01

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

  3. Characteristics of American marten den sites in Wyoming

    Treesearch

    Leonard F. Ruggiero; Dean E. Pearson; Stephen E. Henry

    1998-01-01

    We examined characteristics of den structures and den sites used by female American marten (Martes americana) for natal and maternal dens in the Sierra Madre Range, Wyoming. During 1988-95, we located 18 natal dens (parturition sites) and 97 maternal dens (sites where kits were present exclusive of parturition) used by 10 female marten. Important den structures...

  4. Hierarchical den selection of Canada lynx in western Montana

    Treesearch

    John R. Squires; Nicholas J. Decesare; Jay A. Kolbe; Leonard F. Ruggiero

    2008-01-01

    We studied den selection of Canada lynx (Lynx canadensis; hereafter lynx) at multiple ecological scales based on 57 dens from 19 females located in western Montana, USA, between 1999 and 2006. We considered 3 spatial scales in this analysis, including den site (11-m-radius circle surrounding dens), den area (100-m-radius circle), and den environ (1-...

  5. 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

  6. Health Information in Somali (Af-Soomaali )

    MedlinePlus

    ... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Lumbar Puncture - Af-Soomaali (Somali) Bilingual PDF Health Information Translations Neuromuscular Disorders EMG and Nerve Conduction Tests - Af-Soomaali (Somali) Bilingual PDF Health ...

  7. Contemporary treatment of class II dens invaginatus.

    PubMed

    Sathorn, C; Parashos, P

    2007-04-01

    To present the nonsurgical management of a tooth with class II dens invaginatus with an open apex utilizing contemporary techniques. Root canal treatment of teeth with complex root canal anatomy such as dens invaginatus can be problematic because infected pulpal tissues may remain in inaccessible areas of the canal system. The cleaning and debridement of such root canal systems are therefore challenging and may sometimes be considered impossible. An immature apical root-end development is another challenge in root canal treatment especially in controlling the apical extent of the filling material and achieving an apical seal. When difficulties in cleaning and filling combine, management options may include surgical intervention or extraction. This article reports the nonsurgical endodontic treatment of a case of an open apex and dens invaginatus utilizing the operating microscope, endodontic ultrasonic instruments and mineral trioxide aggregate. Teeth with class II dens evaginatus and an open apex may be managed successfully with contemporary nonsurgical materials and techniques.

  8. Rare associations of dens invaginatus and mesiodens.

    PubMed

    Sannomiya, Eduardo Kazuo; Asaumi, Jun-ichi; Kishi, Kanji; Dalben, Gisele da Silva

    2007-08-01

    Dens invaginatus is a developmental variation resulting from an alteration in the normal growth pattern of the dental papilla. Synonyms of this disturbance include dens in dente, invaginated odontome, tooth inclusion, and dentoid in dente. Radiographically, it is observed as infolding of a radiopaque ribbon-like structure, with equal density as enamel, extending from the cingulum into the root canal and sometimes reaching the root apex, assigning the appearance of a small tooth within the coronal pulp cavity. This article presents 2 case reports. The first describes an 8-year-old girl with dens invaginatus in a mesiodens; the second report describes a 16-year-old boy presenting with 2 mesiodens, both associated with dens invaginatus.

  9. 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

  10. Polar bear maternity denning in the Beaufort Sea

    USGS Publications Warehouse

    Amstrup, Steven C.; Gardner, Craig L.

    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.

  11. 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.

  12. A new AF gravitational instanton

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Teo, Edward

    2011-09-01

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

  13. 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…

  14. 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.

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

    DTIC Science & Technology

    1985-09-01

    1976. Murphy Dome AFS Industrial wastes from Murphy Dome shops are similar to other LRR istallations including primarily lubricating oils and some...mn ...am........................ .. . .. FIGURE 6.6 02 mu .. . (DoI0 * 4. .J~ . .... 00- oCL c0Z 6 o2 z xo% . COW 2 N w Z -wo O<W0 V AO~L Ul w L L

  16. 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

  17. Dysplastic dens of the axis: case report.

    PubMed

    Payer, M; Bijlenga, P; Delavelle, J

    2003-09-01

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

  18. Den use by arctic foxes in northern Alaska

    SciTech Connect

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

    1983-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2017-03-17

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

  1. 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.

  2. 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

  3. 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

  4. STBC AF relay for unmanned aircraft system

    NASA Astrophysics Data System (ADS)

    Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

    2015-01-01

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

  5. [Van den Spiegel and his line].

    PubMed

    van Gijn, Jan; Gijselhart, Joost P

    2012-01-01

    Adriaan van den Spiegel or Spigelius (1578-1625) was born in Flanders to protestant parents. His father was court surgeon to William, Prince of Orange. Adriaan studied medicine in Leiden and obtained a doctoral degree in Padua. In 1616, after a period as physician to the German-Dutch student community in Padua and as court physician in central Europe, he was appointed professor of anatomy and surgery, succeeding Fabritius (1533-1619) and Casserius (1552-1616). He planned to publish a modern atlas of anatomy with etchings from the legacy of Casserius, to replace Vesalius' De humani corporis fabrica libri septem of 1543. Unfortunately he was cut short by death, like his predecessor. Eventually his pupil Bucretius published the atlas in 1627, with 78 of Casserius' illustrations and 20 new ones. In the text Spigelius calls attention to the aponeurotic fascia of the transverse and oblique abdominal muscles, on either side of the rectus abdominis muscle. He proposes the name linea semilunaris, now the official term.

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

    DTIC Science & Technology

    1981-08-01

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

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

    PubMed

    Cho, S Y

    2006-03-01

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

  8. Mechanisms Underlying AF: Triggers, Rotors, Other?

    PubMed

    Krummen, David E; Hebsur, Shrinivas; Salcedo, Jon; Narayan, Sanjiv M; Lalani, Gautam G; Schricker, Amir A

    2015-04-01

    There is ongoing debate regarding the precise mechanisms underlying atrial fibrillation (AF). An improved understanding of these mechanisms is urgently needed to improve interventional strategies to suppress and eliminate AF, since the success of current strategies is suboptimal. At present, guidelines for AF ablation focus on pulmonary vein (PV) isolation for the prevention of arrhythmia. Additional targets are presently unclear, and include additional linear ablation and electrogram-guided substrate modification, without clear mechanistic relevance. PV and non-PV triggers are likely central in the first few seconds of AF initiation. Rapid activation from such triggers interacts with transitional mechanisms including conduction velocity slowing, action potential duration (APD) alternans, and steep APD restitution to cause conduction block and initiate functional reentry. However, complete suppression of potential triggers has proven elusive, and the intra-procedural mapping and targeting of transitional mechanisms has not been reported. A growing body of research implicates electrical rotors and focal sources as central mechanisms for the maintenance of AF. In several recent series, they were observed in nearly all patients with sustained arrhythmia. Ablation of rotor and focal source sites, prior to pulmonary vein isolation, substantially modulated atrial fibrillation in a high proportion of patients, and improved ablation outcomes versus pulmonary vein isolation alone. These results have subsequently been confirmed in multicenter series, and the improved outcomes have been found to persist to a mean follow-up of 3 years. Recently, rotors have been observed by multiple groups using diverse technologies. These findings represent a paradigm shift in AF, focusing on sustaining mechanisms, as is currently done with other arrhythmias such as atrioventricular node reentrant tachycardia. Studies are currently underway to assess the optimal strategy for the application

  9. 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.

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

    USGS Publications Warehouse

    Anthony, R. Michael

    1996-01-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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...

  16. Detecting denning polar bears with forward looking infra-red imagery (FLIR)

    USGS Publications Warehouse

    Amstrup, Steven C.; Weston-York, Geoff; McDonald, T.L.; Neilsen, R.; Simac, K.; Durner, G.M.

    2003-01-01

    Polar bears give birth in snow dens in mid winter, and remain in dens until early spring. Survival and development of neonates is dependent on the stable environment within the maternal den. Petroleum related activities currently span approximately 200 km of the Alaskan Beaufort Sea coastal area. New and proposed developments are expected to dramatically expand the area influenced by petroleum activities. These activities are a potential threat to polar bears, especially as they might disturb denning females.In order to help manage and mitigate potential disruptions of polar bear denning, we tested whether we could detect heat, rising through the roofs of maternal dens, with forward-looking infrared (FLIR) viewing devices. We tested detectability of dens by flying transects, over habitats known to hold dens, with FLIR equipped aircraft. We recorded flight and weather conditions at each observation and tallied whether or not the den was detected.

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

    USGS Publications Warehouse

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

    2001-01-01

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

  18. INTEGRAL entdeckt den Gamma-Himmel: Gamma-Astronomie

    NASA Astrophysics Data System (ADS)

    Schönfelder, Volker

    2004-11-01

    Das Gamma-Weltraumteleskop INTEGRAL der Europäischen Weltraumbehörde, ESA, hat in den ersten 15 Monaten seiner Mission eine Fülle interessanter, neuer Ergebnisse geliefert. Hauptinstrumente an Bord sind das hoch auflösende Spektrometer SPI und das Spektrometer IBIS. Hinzu kommt je ein Monitor für den Röntgen- und optischen Bereich. Die wichtigsten neuen Erkenntnisse stammen vor allem aus dem Bereich harter kompakter Röntgenquellen und aus dem Bereich der Gammalinien-Spektroskopie. Mit INTEGRAL wurde es erstmals möglich, den diffusen galaktischen Hintergrund zum Teil mit Einzelquellen identifizieren zu können. Ferner ließ sich in der Umgebung des galaktischen Zentrums die 511-keV-Linie von annihilierenden Positronen und Elektronen nachweisen. Schließlich trägt INTEGRAL auch entscheidend zum Studium der geheimnisvollen Gamma Ray Bursts bei.

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

    USGS Publications Warehouse

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

    2003-01-01

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

  20. 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

  1. 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.

  2. Management and Outcome of Dens Fracture Nonunions in Geriatric Patients.

    PubMed

    Joestl, Julian; Lang, Nikolaus W; Tiefenboeck, Thomas M; Hajdu, Stefan; Platzer, Patrick

    2016-02-03

    Dens fractures are known to have high rates of pseudarthrosis. The aim of this study was to define clinical and radiographic long-term outcomes, specifically in relation to osseous union, cervical spine movement, neurological sequelae, and quality of life, in a geriatric cohort (sixty-five years of age or older) treated operatively or nonoperatively for a dens fracture nonunion. Forty-four patients (twenty-eight women and sixteen men; average age, seventy-two years) met the inclusion criteria and were enrolled in this study. Sixteen patients (36%) underwent operative stabilization with posterior cervical arthrodesis, and twenty-eight (64%) were treated nonoperatively with a predefined protocol. All patients had a post-treatment follow-up period of at least five years. Radiographic evaluation showed osseous union at the site of the C1-C2 arthrodesis in all sixteen patients who had undergone surgical treatment. Clinical follow-up revealed that fourteen had satisfactory results following postoperative rehabilitation. In contrast, radiographic evaluation of the twenty-eight nonoperatively treated patients showed persistence of the pseudarthrosis of the dens in twenty-six and osseous union of the dens in two. All twenty-eight patients (100%) had a satisfactory clinical outcome. C1-C2 arthrodesis was a reliable treatment option for dens fracture nonunions that were unstable, those associated with neurological symptoms, and those causing persistent pain. Clinical and radiographic monitoring was an acceptable nonoperative treatment option but was associated with a very low rate of osseous union of the dens. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

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

    NASA Astrophysics Data System (ADS)

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

    2008-05-01

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

  4. 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

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

    PubMed Central

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

    2016-01-01

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

  6. Dens of northern flying squirrels in the Pacific Northwest.

    Treesearch

    A.B. Carey; T.M. Wilson; C.C. Maguire; B.L. Biswell

    1997-01-01

    Silvicultural prescriptions to enhance northern flying squirrel (Glaucoinys sabrinus) habitat have been suggested as an aid for recovery of the threatened northern spotted owl (Strix occidentalis caurina). Flying squirrels are hypothesized to be limited by den sites (cavities in trees) and by food (truffles). However, no...

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

    PubMed

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

    2016-01-01

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

  8. 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.

  9. 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.

  10. AF-GEOSPACE Version 2.1

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Tautz, M.; Roth, C.

    2004-05-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed and distributed by the Space Weather Center of Excellence at AFRL. A review of current (Version 2.0) and planned (Version 2.1) AF-GEOSpace capabilities will be given. A wide range of physical domains is represented enabling the software to address such things as solar disturbance propagation, radiation belt configuration, and ionospheric auroral particle precipitation and scintillation. The software is currently being used to aid with the design, operation, and simulation of a wide variety of communications, navigation, and surveillance systems. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; scientific model validation and comparison, physics research, and education. Version 2.0 provided a simplified graphical user interface, improved science and application modules, and significantly enhanced graphical performance. Common input data archive sets, application modules, and 1-D, 2-D, and 3-D visualization tools are provided to all models. Dynamic capabilities permit multiple environments to be generated at user-specified time intervals while animation tools enable displays such as satellite orbits and environment data together as a function of time. Building on the existing Version 2.0 software architecture, AF-GEOSpace Version 2.1 is currently under development and will include a host of new modules to provide, for example, geosynchronous charged particle fluxes, neutral atmosphere densities

  11. Vegetative characteristics of swift fox denning and foraging sites in southwestern South Dakota

    Treesearch

    Daniel W. Uresk; Kieth E. Severson; Jody Javersak

    2003-01-01

    Vegetative characteristics of swift fox (Vulpes velox) denning and foraging habitats were studied in southwestern South Dakota. We followed 14 radio-collared foxes over a two-year period and identified 17 den sites and 82 foraging sites. Height-density of vegetation (visual obstruction reading, VOR) was determined on each den and foraging site and on...

  12. Den use and selection by northern flying squirrels in fragmented landscapes

    Treesearch

    Sanjay Pyare; Winston P. Smith; Colin S. Shanley

    2010-01-01

    We studied den use and den-habitat selection by the Prince of Wales Island flying squirrel (Glaucomys sabrinus griseifrons) at multiple spatial scales in fragmented temperate rain-forest habitats because of the role dens play in the distribution, reproduction, and population density of this endemic subspecies. We observed differences in spatial...

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

    PubMed

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

    2010-08-03

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

  14. Surgical treatment of dens fractures in elderly patients.

    PubMed

    Platzer, Patrick; Thalhammer, Gerhild; Oberleitner, Gerhard; Schuster, Rupert; Vécsei, Vilmos; Gaebler, Christian

    2007-08-01

    A dens fracture is the most common cervical fracture in elderly patients. The purposes of this study were to analyze the functional and radiographic results after surgical treatment of dens fractures in patients over sixty-five years of age and to compare the two methods that were used for operative treatment. We reviewed the cases of fifty-six patients, with an average age of 71.4 years at the time of surgery, who had undergone surgical treatment of a dens fracture from 1988 to 2002. Thirty-seven fractures were stabilized with anterior screw fixation, and nineteen fractures had posterior cervical arthrodesis. Forty-five patients returned to their preinjury activity level and were satisfied with their treatment. Thirty-five patients had a full range of neck movement, and forty-seven patients were free of pain. Technical failures occurred in eight patients. The thirty-seven patients treated with anterior screw fixation had a good clinical outcome, with fracture-healing in thirty-three patients (89%) and technical failure in five patients (14%). All nineteen patients treated with posterior cervical arthrodesis had fracture union, with technical failure in three patients, but the functional results were worse than those after anterior screw fixation. With the inclusion of the six patients who had been excluded from the clinical and radiographic review, the overall morbidity rate was 16% (ten of sixty-two patients) and the overall mortality rate was 6% (four of sixty-two patients). A satisfactory outcome can be achieved with surgical treatment of a dens fracture in geriatric patients. It appears that anterior screw fixation may maintain better mobility of the cervical spine, but it appears to be associated with a higher rate of fracture nonunion and a greater potential for reoperation.

  15. 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. 

  16. 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.

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

    USGS Publications Warehouse

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

    2015-01-01

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

  18. 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.

  19. 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.

  20. AF-Shell 1.0 User Guide

    NASA Technical Reports Server (NTRS)

    McElroy, Mark W.

    2017-01-01

    This document serves as a user guide for the AF-Shell 1.0 software, an efficient tool for progressive damage simulation in composite laminates. This guide contains minimal technical material and is meant solely as a guide for a new user to apply AF-Shell 1.0 to laminate damage simulation problems.

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  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. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

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

    DTIC Science & Technology

    1982-09-01

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

  10. 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.

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

    DTIC Science & Technology

    1983-04-01

    TEMPERATURE DEPRESION F, ’O.AL 3 - 4 5- 6 8 9- 1 11 12 13 14 𔃿 t 11 1 9 :," 2. 4 :.! 2 2 5 . . I TAL .4’ 373 - .. .. 776 7 7 8 * ... .. H- j4 93 4 5 7...H ;AVETA: PSYCHROMETRIC SUMMARY; A:Z, %EAT ER SER VCLPI ’ 7 CARUP li i.L -AF -- AM---.- 7-. - _ PAGE 1 2 WET BLLB TEmPEPATURE DEPRESION F, " AL .’ 3

  12. Anatomy of the Alar Ligament: Part II: Variations of Its Attachment onto the Dens.

    PubMed

    Sardi, Juan P; Iwanaga, Joe; Schmidt, Cameron; Rustagi, Tarush; Chapman, Jens R; Oskouian, Rod J; Tubbs, R Shane

    2017-08-09

    Various authors have described the morphology of the alar ligaments; however, there are no reports of a cadaveric study focusing on their attachments onto the dens. The purpose of this study was to use fresh cadaveric specimens to describe in detail different attachment patterns of the alar ligaments onto the dens. This study used 22 sides from 11 fresh frozen cadaveric heads. Specimens were obtained from 8 men and 3 women who were 67-99 years old at death. Dissection of the exact attachment of the alar ligaments onto the dens was observed from posterior, superior, and anterior views under the surgical microscope. From a posterior view, 6 alar ligaments passed over the tip of the dens, and 16 alar ligaments attached onto the posterolateral part of the dens; the right and left ligaments had no continuity. From a superior view, the alar ligament was classified in 2 ways: depending on the covered area of the dens (entirely or posterior two thirds) and continuity of the alar ligament (transversely, separately, or combination). Fourteen alar ligaments covered the posterior two thirds of the dens. From an anterior view, in 1 specimen, the alar ligament extended to the anterior surface of the dens. Wide posterolateral anchoring to the dens coupled with the nearly horizontal trajectory explains the biomechanical advantage of the alar ligaments in undertaking a stabilizing function in limiting head rotation that would otherwise be ineffective in the case of weaker attachments or a more vertical orientation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Selection of wolf dens in relation to winter territories in northeastern Minnesota

    USGS Publications Warehouse

    Ciucci, P.; Mech, L.D.

    1992-01-01

    Locations of wolf (Canus lupus) dens in the Superior National Forest in northeastern Minnesota from 1969 through 1988 were analyzed in relation to winter territories. Dens situated within the central 60% of the territories were randomly located relative to territory centers. However, only 10.5% (2) of the dens were located within a 1-km-wide strip inside the territory boundaries, indicating possible avoidance of neighboring packs. A negative relationship (r2 = 0.27; P 1 year, and possibly the availability of a stable food source helped determine den location.

  14. Expression of a cloned denV gene of bacteriophage T4 in Escherichia coli

    SciTech Connect

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

    1985-07-01

    A 713-base-pair Hae III fragment from bacteriophage T4 encompassing the denV gene with its preceding promoter has been cloned in a pBR322-derived positive-selection vector and introduced into a variety of DNA repair-deficient uvr and rec and uvr,rec Escherichia coli strains. The denV gene was found to be expressed, probably from its own promoter, causing pyrimidine dimer incision-deficient uvrA, uvrB, uvrC strains to be rescued by the denV gene. A uvrD (DNA helicase II) strain was also complemented, but to a lesser extent. A wild-type strain did not seem to be affected at the UV doses tested. Surprisingly, all recA, recB, and recC strains tested also showed an increased UV resistance, perhaps by reinforcement of the intact uvr system in these strains. Complementation of denV- T4 strains and host-cell reactivation of lambda phage was also observed in denV+ E. coli strains. Equilibrium sedimentation showed that DNA repair synthesis occurred in a UV-irradiated uvrA E. coli strain carrying the cloned denV gene. Southern blotting confirmed earlier results that the denV gene is located at 64 kilobases on the T4 map. Phage T2 (denV-) did not hybridize to a denV-specific probe.

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

    USGS Publications Warehouse

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

    2007-01-01

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

  16. 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.

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

    DTIC Science & Technology

    1983-04-01

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

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

    DTIC Science & Technology

    1983-06-01

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

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

    USGS Publications Warehouse

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

    2006-01-01

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

  20. Habitat characteristics at den sites of the Point Arena mountain beaver (Aplodontia rufa nigra)

    Treesearch

    William J. Zielinski; John E. Hunter; Robin Hamlin; Keith M. Slauson; M. J. Mazurek

    2010-01-01

    The Point Arena mountain beaver (Aplodontia rufa nigra) is a federally listed endangered species, but has been the subject of few studies. Mountain beavers use burrows that include a single subterranean den. Foremost among the information needs for this subspecies is a description of the above-ground habitat features associated with dens. Using...

  1. 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.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-09-22

    Animal social behaviour is not static with regard to environmental change. Flexibility in cooperative resource use may be an important response to resource decline, mediating the impacts of resource availability on fitness and demography. In forest ecosystems, hollow trees are key den resources for many species, but are declining worldwide owing to forestry. Altered patterns of den sharing may mediate the effects of the decline of this resource. We studied den-sharing interactions among hollow-dependent Australian mountain brushtail possums to investigate how spatial variation in hollow tree availability affects resource sharing and kin selection. Under reduced den availability, individuals used fewer dens and shared them less often. This suggests increased territoriality in the presence of resource competition. Further, there was a switch from kin avoidance to kin preference with decreasing hollow tree availability. This was driven primarily by a change in den sharing among siblings. The inclusive fitness benefits of den sharing with kin are likely to increase under resource-limiting conditions, but are potentially outweighed by the benefits of associating with non-relatives (avoidance of inbreeding or pathogen transmission) where dens are abundant. We discuss how predictions from social evolutionary theory can contribute to understanding animal responses to landscape change. This journal is © 2011 The Royal Society

  4. Crowned dens syndrome: a rare cause of acute neck pain.

    PubMed

    Uh, Mitchell; Dewar, Catharine; Spouge, David; Blocka, Kenneth

    2013-05-01

    Crowned dens syndrome (CDS) is a rare but underrecognized cause of severe neck pain in older adults. It is characterized by acute onset pain and stiffness of the cervical spine. Accompanying fever and elevated inflammatory markers often lead to misdiagnosis. It is frequently associated with calcium pyrophosphate deposition disease, hydroxyapatite crystals, and sometimes other inflammatory conditions. Periodontoid calcification is seen on cervical computed tomography (CT) scan but is not typically visible on plain radiographs, making CT scanning invaluable in diagnosis. We describe a case of CDS in a 59-year-old woman, who presented with severe neck pain, elevated inflammatory markers, and progressive evolution in the appearance of her CT scans. The pathophysiology, clinical and radiographic findings, and dramatic response to corticosteroid therapy are reviewed.

  5. Dens invaginatus in a geminated maxillary lateral incisor

    PubMed Central

    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. PMID:26002668

  6. Dens invaginatus in an impacted mesiodens: a morphological study.

    PubMed

    Cantín, M; Fonseca, G M

    2013-01-01

    Dens invaginatus (DI) is a dental anomaly originated from invagination of the enamel organ into the dental papilla, during odontogenesis. DI may be associated with other abnormalities such as dysmorphic mesiodens, and this unusual condition may be detected by chance on the conventional radiography. However, the three-dimensional nature and the exact morphological patterns of DI are impossible to appreciate from this method. We present a morphological study of impacted mesiodens in a 9-year-old girl, which the three coronal invaginations were detected only by Cone-Beam Computed Tomography (CBCT) in the pre-surgical examination. CBCT, radiographic and microscopic reproductions allow transfer of images to facilitate cooperation of working groups, examination as well as for teaching purposes.

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

    SciTech Connect

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

    1992-09-01

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

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

    SciTech Connect

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

    1992-09-01

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

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

    PubMed

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

    2017-01-17

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

  10. Atypical den use of Carolina Northern Flying Squirrels (Glaucomys sabrinus coloratus) in the southern Appalachian Mountains

    USGS Publications Warehouse

    Diggins, Corinne A.; Kelly, Christine A.; Ford, W. Mark

    2015-01-01

    Glaucomys sabrinus coloratus (Carolina Northern Flying Squirrel) is a federally endangered subspecies that occurs in high elevation forests of the southern Appalachian Mountains. Denning sites may be a limiting factor for this subspecies in areas where cavity trees are not abundant or where interspecific competition from other tree squirrels occurs. This shortage can result in use of unusual denning sites, such as subterranean dens. Herein, we report atypical denning habits of radio-collared Carolina Northern Flying Squirrels in southwestern Virginia and western North Carolina from 2008 to 2011 and 2014. Increased knowledge of denning habitats may be beneficial for conservation and habitat management of this subspecies, particularly in sub-optimal or degraded habitats.

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

    PubMed Central

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

    2017-01-01

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

  12. A retrospective study of the prevalence and characteristics of dens invaginatus in a sample of the Turkish population

    PubMed Central

    Çelenk, Peruze; Canger, Emin M.; Zengin, Zeynep; Sümer, Pınar

    2013-01-01

    Objective: The purpose of this study was to assess the prevalence of dens invaginatus and to classify the types of dens invaginatus in a sample of the Turkish population.. Study Design: A retrospective study was performed using periapical and panoramic radiographs of 5355 patients who presented to the Department of Oral Diagnosis and Radiology at the Ondokuz Mayıs University Dentistry Faculty between January 2009 and December 2010. Maxillary and mandibular anterior teeth were evaluated for the presence and characteristics of dens invaginatus. Statistical evaluation of the presence of dens invaginatus related to gender was performed by the Pearson chi-squared test. Results: Dens invaginatus was observed in 116 of 4556 subjects, with a frequency of 2.5%. There was only one periapical lesion in teeth with type I dens invaginatus, but 8.1% of patients with type II and 87.5% of patients with type III dens invaginatus had apical periodontitis at the time of referral. There were 116 (72%) females and 32 (27%) males with dens invaginatus. Conclusion: This data represents the only study carried out in a large population in Turkey, and no dens invaginatus was found in mandibular teeth. The most commonly observed type of dens invaginatus was type I (69.8%). Key words:Dens invaginatus, dens in dente, dental anomaly, Turkish. PMID:23229254

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

    USGS Publications Warehouse

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

    1988-01-01

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

  14. 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.

  15. Physical mapping and complete nucleotide sequence of the denV gene of bacteriophage T4.

    PubMed Central

    Radany, E H; Naumovski, L; Love, J D; Gutekunst, K A; Hall, D H; Friedberg, E C

    1984-01-01

    Phage T4 deletion mutants that are folate analog resistant (far) and contain deletions in the region of the T4 genome near denV have been isolated previously. We showed that one of these mutants (T4farP12) expressed normal denV gene activity, whereas another mutant (T4farP13) was defective in the denV gene. The rII-distal (right) physical endpoints of these deletions defined the limits of the interval in which the rII-proximal (left) endpoint of the denV gene should be located. The deletion endpoints were identified by restriction and Southern hybridization analyses of phage derivatives containing deoxycytidine instead of hydroxymethyldeoxycytidine in their DNAs. The results of these analyses localized the rII-proximal (left) end of the denV gene to a region between 62.4 and 64.3 kilobases on the T4 physical map. denV+ phage resulted from marker rescue with two of five denV- alleles tested, using plasmids containing a 1.8-kilobase fragment from this region or a 179-base-pair terminal fragment derived from it. Sequencing of the 179-base-pair fragment from wild-type DNA showed a 130-base-pair open reading frame with its termination codon at the rII-proximal end. Confirmation that this open reading frame is part of the denV coding sequence was obtained by identifying a TAG amber codon in the homologous DNA derived from a denV amber mutant strain. This mutant strain rescued the denV+ allele from plasmids containing the wild-type sequence. An adjacent overlapping restriction fragment was also cloned, permitting determination of the remaining denV gene sequence. Based on these results, the 3' end of the coding region of the denV locus was mapped to kilobase position 64.07 on the T4 physical map, and the 5' end was mapped to position 64.48. Images PMID:6092716

  16. 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

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

    PubMed

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

    2015-02-01

    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

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

    PubMed

    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).

  19. 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

  20. 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

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

    2016-10-18

    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.

  1. AF-GEOSpace Version 2.5: Space Environment Software

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  2. AF-GEOSpace Version 2.1 Release

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Perry, K. L.; Tautz, M.; Roth, C.

    2006-05-01

    AF-GEOSpace Version 2.1 is a graphics-intensive software program with space environment models and applications developed recently by the Space Weather Center of Excellence at AFRL. A review of new and planned AF-GEOSpace capabilities will be given. The software addresses a wide range of physical domains and addresses such topics as solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; determination of link outage regions for active ionospheric conditions; satellite magnetic conjugate studies, scientific model validation and comparison, physics research, and education. Previously, Version 2.0 provided a simplified graphical user interface, improved science and application modules, significantly enhanced graphical performance, common input data archive sets, and 1-D, 2-D, and 3- D visualization tools for all models. Dynamic capabilities permit multiple environments to be generated at user- specified time intervals while animation tools enable the display of satellite orbits and environment data together as a function of time. Building on the Version 2.0 software architecture, AF-GEOSpace Version 2.1 includes a host of new modules providing, for example, plasma sheet charged particle fluxes, neutral atmosphere densities, 3-D cosmic ray cutoff maps, low-altitude trapped proton belt flux specification, DMSP particle data displays, satellite magnetic field footprint mapping determination, and meteor sky maps and shower/storm fluxes with spacecraft impact probabilities. AF-GEOSpace Version 2.1 was

  3. van den Ende-Gupta syndrome of blepharophimosis, arachnodactyly, and congenital contractures.

    PubMed

    Guerra, Dania; Sanchez, Otto; Richieri-Costa, Antonio

    2005-08-01

    Here, we report on a Venezuelan child with manifestations of van den Ende-Gupta syndrome, including blepharophimosis, arachnodactyly, and congenital contractures. We also review cases from the literature. (c) 2005 Wiley-Liss, Inc.

  4. Rare association of dens invaginatus with impacted mesiodens - A case report.

    PubMed

    Patil, Prashant B; Chaudhari, Smitha G; Goel, Ankit; Agarwal, Pooja

    2012-01-01

    Mesiodens is a supernumerary tooth occupying the position in the maxillary anterior region. This additional tooth structure may cause disturbance in eruption or position of the adjacent teeth. About 8-25% of supernumerary teeth in the anterior region erupt spontaneously. Un-erupted supernumerary teeth are incidentally identified on a routine radiographic examination. Dens invaginatus is a rare tooth malformation showing an in-folding of enamel and dentine of affected tooth sometimes extending deep into the pulp cavity and the root portion. We report a case of un-erupted mesiodens causing midline diastema of permanent teeth subsequently corrected following extraction of mesiodens. Dens invaginatus was identified affecting the un-erupted mesiodens. It is rare to find dens invaginatus associated with a supernumerary tooth and only 10 such instances of dens invaginatus affecting supernumerary teeth have been reported in the English literature.

  5. Rare association of dens invaginatus with impacted mesiodens – A case report

    PubMed Central

    Patil, Prashant B.; Chaudhari, Smitha G.; Goel, Ankit; Agarwal, Pooja

    2012-01-01

    Mesiodens is a supernumerary tooth occupying the position in the maxillary anterior region. This additional tooth structure may cause disturbance in eruption or position of the adjacent teeth. About 8–25% of supernumerary teeth in the anterior region erupt spontaneously. Un-erupted supernumerary teeth are incidentally identified on a routine radiographic examination. Dens invaginatus is a rare tooth malformation showing an in-folding of enamel and dentine of affected tooth sometimes extending deep into the pulp cavity and the root portion. We report a case of un-erupted mesiodens causing midline diastema of permanent teeth subsequently corrected following extraction of mesiodens. Dens invaginatus was identified affecting the un-erupted mesiodens. It is rare to find dens invaginatus associated with a supernumerary tooth and only 10 such instances of dens invaginatus affecting supernumerary teeth have been reported in the English literature. PMID:25737852

  6. GPIM AF-M315E Propulsion System

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  7. AF Ari - Ein heller Bedeckungsveraenderlicher mit einem G-Riesen

    NASA Astrophysics Data System (ADS)

    Hauck, Norbert

    2011-03-01

    By combining existing and including new photometric data a first solution can now be presented: AF Ari is a well detached binary having an eccentric orbit and a period of 153 days. The secondary component is identified as an A-type dwarf. The mass of the G-type giant is estimated at 2.65 solar masses. Apparently, AF Ari is a new z (zeta) Aurigae type system and suited for double-lined spectroscopy. The english version of the article will be found behind the german version.

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

    PubMed Central

    Rani, Nidhi; Sroa, Renu B

    2015-01-01

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

  9. An AF9/ENL-targted peptide with therapeutic potential in mixed lineage leukemias.

    PubMed

    Barretto, Nisha N; Karahalios, Dean S; You, Dewen; Hemenway, Charles S

    2014-01-01

    Misregulation of transcription elongation is proposed to underlie the pathobiology of MLL leukemia. AF4, AF9, and ENL, common MLL fusion partners, are found in complex with positive transcription elongation factor b (P-TEFb). AF9 and its homolog ENL directly interact with AF4 within these complexes. Previously, we designed a peptide that mimics the AF9 binding domain of AF4 and reported that MLL leukemia cell lines are inhibited by it. Extending these studies, we have modified the peptide design in order to avoid recognition by proteases. The peptide is as effective as its predecessor in vitro and enhances survival in mice bearing MLL leukemia cell lines.

  10. 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.

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

    PubMed

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

    2016-04-05

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  13. 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

  14. 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…

  15. Action of AF64A on rat brain muscarinic receptors

    SciTech Connect

    Eva, C.; Costa, E.

    1986-03-01

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

  16. Optofluidic Waveguides in Teflon AF-Coated PDMS Microfluidic Channels

    PubMed Central

    Cho, Sung Hwan; Godin, Jessica; Lo, Yu-Hwa

    2010-01-01

    We report a new method for fabricating an optofluidic waveguide that is compatible with polydimethylsiloxane (PDMS). The light path follows the microfluidic channels, an architecture that can maximize detection efficiency and make the most economic use of chip area in many lab-on-chip applications. The PDMS-based microfluidic channels are coated with Teflon amorphous fluoropolymers (Teflon AF) which has a lower refractive index (n = 1.31) than water (n = 1.33) to form a water/Teflon AF optical waveguide. Driven by a vacuum pump, the Teflon AF solution was flowed through the channels, leaving a thin (5–15 µm) layer of coating on the channel wall as the cladding layer of optical waveguides. This coating process resolves the limitations of spin-coating processes by reducing the elasticity mismatch between the Teflon AF cladding layer and the PDMS device body. We demonstrate that the resulting optofluidic waveguide confines and guides the laser light through the liquid core channel. Furthermore, the light in such a waveguide can be split when the fluid flow is split. This new method enables highly integrated biosensors such as lab-on-chip flow cytometers and micro-fabricated fluorescence-activated cell sorter with on-chip excitation. PMID:20729984

  17. Optofluidic Waveguides in Teflon AF-Coated PDMS Microfluidic Channels.

    PubMed

    Cho, Sung Hwan; Godin, Jessica; Lo, Yu-Hwa

    2009-08-01

    We report a new method for fabricating an optofluidic waveguide that is compatible with polydimethylsiloxane (PDMS). The light path follows the microfluidic channels, an architecture that can maximize detection efficiency and make the most economic use of chip area in many lab-on-chip applications. The PDMS-based microfluidic channels are coated with Teflon amorphous fluoropolymers (Teflon AF) which has a lower refractive index (n = 1.31) than water (n = 1.33) to form a water/Teflon AF optical waveguide. Driven by a vacuum pump, the Teflon AF solution was flowed through the channels, leaving a thin (5-15 µm) layer of coating on the channel wall as the cladding layer of optical waveguides. This coating process resolves the limitations of spin-coating processes by reducing the elasticity mismatch between the Teflon AF cladding layer and the PDMS device body. We demonstrate that the resulting optofluidic waveguide confines and guides the laser light through the liquid core channel. Furthermore, the light in such a waveguide can be split when the fluid flow is split. This new method enables highly integrated biosensors such as lab-on-chip flow cytometers and micro-fabricated fluorescence-activated cell sorter with on-chip excitation.

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

    PubMed

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

    2012-01-01

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

  19. 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.

  20. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-09-14

    Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. 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.

  4. Extracting Uranium from Seawater: Promising AF Series Adsorbents

    SciTech Connect

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

    2016-04-20

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

  5. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGES

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

    2015-11-02

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

  6. 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.

  7. 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

  8. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  9. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  10. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  11. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  12. Termination of persistent atrial fibrillation during pulmonary vein isolation: insight from the MAGIC-AF trial.

    PubMed

    Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

    2016-10-04

    Controversy on the optimal ablation strategy for persistent atrial fibrillation (AF) exists with limited work evaluating a strategy of pulmonary vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF; ClinicalTrials.gov number: NCT01014741) study. The objective of the current study is to report the 1-year outcome after PVI alone in this unique patient group. The 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs was reported for the 35 patients in the MAGIC-AF study with persistent AF termination during or upon completion of PVI.Freedom from recurrent atrial arrhythmia was achieved in 60% of patients where AF terminated during PVI. Cavotricuspid isthmus flutter was common when AF terminated to a macro re-entrant flutter during PVI, and responsible for 92% of all flutter circuits with AF termination. Persistent AF termination during PVI may identify a subgroup of patients who experience a similar long-term clinical outcome with PVI ablation alone when compared with other more extensive persistent AF ablation strategies. Pulmonary vein isolation alone may be an appropriate tactic in this subgroup of persistent AF patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  13. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. 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

  15. Multiple dens invaginatus, mulberry molar and conical teeth. Case report and genetic considerations.

    PubMed

    Sedano, Heddie O; Ocampo-Acosta, Fabian; Naranjo-Corona, Rosa I; Torres-Arellano, Maria E

    2009-02-01

    Dens in dente, also known as dens invaginatus and dilated compound odontoma, is a malformation that can occur on primary, permanent, or supernumerary teeth that is characterized by a deep invagination of the surface of a crown or root covered with enamel. This abnormality in tooth morphology generally affect the maxillary lateral incisors but several cases of multiple dens invaginatus have been reported in the literature. A 15 year-old female patient is reported here presenting five dens invaginatus: four in the permanent mandibular incisors and one in the permanent, maxillary left central incisor, additionally the following dental findings were observed: a permanent mandibular left mulberry molar, molarization of some premolars, several microdontic conoid teeth, retention of five primary teeth, absence of several permanent teeth germs, a macrodontic molar with abnormal roots and several periapical radiolucencies associated to the dens invaginatus. There was no family history of similar dental findings to those observed in the patient. There are several genes that participate in the development of teeth, of those, the following five genes could be implicated as responsible or co-participators for some of the dental anomalies present in this patient: MSX1 (Muscle segment homeobox 1), DLX1 & DLX2 (Distal-less homeobox 1 & 2 genes), PAX9 (Paired box gene) and PITX2 (Pituitary homeobox transciption factor 2).

  16. Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene

    PubMed Central

    Catalina, Purificación; Rodríguez, René; Melen, Gustavo J.; Bueno, Clara; Arriero, Mar; García-Sánchez, Félix; Lassaletta, Alvaro; García-Sanz, Ramón

    2009-01-01

    MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4+ B-ALL. Unlike leukemic blasts, MLL-AF4+ BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4+ B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4+ BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors. PMID:19995953

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

    PubMed Central

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

    1998-01-01

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

  18. Characterization of physically vapor deposited AF2400 thin films

    SciTech Connect

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

    1993-11-01

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

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

    PubMed

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

    2002-06-01

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

  20. A mid-holocene fauna from Bear Den Cave, Sequoia National Park, California

    USGS Publications Warehouse

    Mead, Jim I.; McGinnis, Thomas W.; Keeley, Jon E.

    2006-01-01

    Test excavation of floor fill deposits in the first room in Bear Den Cave, Sequoia National Park, produced fossiliferous sediments down to at least 40 cm depth. Radiocarbon analysis of charcoal from this layer indicates an early-middle Holocene age of 7220 CAL BP. The fossil accumulation represents prey recovered from generations of ringtail (Bassariscus astutus) dung. Microvertebrate remains include salamanders, lizards, snakes, and mammals. The recovery of Aneides ferreus/vagransfrom early-middle Holocene deposits in Bear Den Cave is a first for this species group. Equally interesting is the recovery of Plethodon sp. Neither taxa live in the Sierra Nevada today. The fossil-rich deposits of Bear Den Cave indicate that future paleoecological studies will be productive in Sequoia National Park.

  1. 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

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

    PubMed

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

    2013-07-26

    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.

  3. 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

  4. Adiabatic Compression Sensitivity of AF-M315E

    DTIC Science & Technology

    2015-07-01

    products of HAN (hydroxylammonium nitrate) based propellants such as AF-M315E are nitric acid and NOx gases. The presence of excess acids causes... Propellant Infusion Mission (GPIM) program. As the propulsion system developed by Aerojet- Rocketdyne for this propellant advances in maturity, studies...have been undertaken to address the knowledge gaps in the adiabatic compression sensitivity of the propellant as it relates to the system parameters for

  5. A Companion to the Eclipsing Variable AF Arietis

    NASA Astrophysics Data System (ADS)

    Ahad, Abdul

    2015-01-01

    In this paper the eclipsing variable star AF Arietis is shown to have a wide 12th magnitude companion, currently not included in the WDS catalog. The identified component appears to be following the same space motion as the 6th magnitude AB eclipsing pair and is situated at a broadly similar spectral distance from Earth, which suggest it might be a physical member of the system.

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

    DTIC Science & Technology

    2011-04-20

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

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

    DTIC Science & Technology

    1985-04-01

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

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

    PubMed

    Wu, Tongbin; Fu, Xiang-Dong

    2015-01-01

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

  9. 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.

  10. 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

  11. Association of Mesiodentes and Dens Invaginatus in a Child: A Rare Entity

    PubMed Central

    Sulabha, A. N.; Sameer, C.

    2012-01-01

    Supernumerary teeth are defined as any teeth in excess of normal number. Mesiodens is a supernumerary tooth, in the central region of premaxilla between two central incisors. Dens invaginatus is a developmental anomaly resulting from invagination in the surface of tooth crown before calcification has occurred. Radiographically, it is observed as infolding of a radioopaque ribbon like structure, with equal density as enamel, extending from cingulum into a root canal and sometimes reaching the root apex. This paper aims to present a rare association of dens invaginatus with two mesiodentes in a child causing the eruption disturbance and unaesthetic appearance in anterior maxilla. PMID:23198162

  12. Endodontic Treatment of Type II Dens Invaginatus in a Maxillary Lateral Incisor: A Case Report

    PubMed Central

    Helvacioglu-Yigit, Dilek; Aydemir, Seda

    2012-01-01

    Dens invaginatus is a developmental anomaly that results in an enamel-lined cavity intruding into the crown or root before the mineralization phase. It typically affects permanent maxillary lateral incisors, central incisors, and premolars. This paper describes the root canal treatment of Oehlers' type II dens invaginatus in maxillary left lateral incisors. A 16-year-old boy presented to the Faculty of Dentistry, University of Kocaeli, to receive his dental treatments. During the caries removal, the pulp was exposed then anendodontic treatment was initiated. Two canals, one of which represented the invagination, were instrumented, irrigated, and then obturated with a lateral condensation technique. PMID:23213576

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

    PubMed Central

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

    2011-01-01

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

  14. 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 S.; 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.

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

    PubMed Central

    Kralovicova, Jana; Vorechovsky, Igor

    2017-01-01

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

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

    PubMed

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

    2003-10-01

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

  17. Chinae, ROK AFS K-10, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1968-04-10

    34 . T2 A . : . . . . T .I’-.E (S ! . I . . A ._-" ., " ," . . . " ("L .- 2 i* * - * . ,. - . . S IF ......... MEA ..2 .’ TP ] ?RC C *C 2• . .. .:.. . , C...FVILLE. N. C. 2e,01 43?-78 Ch[NNhAE KCREA/ PCV AFS K-1 51-54956-61,64-C7 _ ’___ PERCENTAGE FREQUENCY OF OCCURRENCE L-- 7. (FROM HOURLY OBSERVATIONS

  18. 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.

  19. Raccoon Use of Den Trees and Plant Associations in Western Mesophytic Forests: Tree Attributes and Availability or Landscape Heterogeneity?

    Treesearch

    Winston P. Smith; Keith M. Endres

    2012-01-01

    We monitored 15 radio-collared raccoons (Procyon lotor) on Davies Island in March 1987 - May 1988 to determine the extent to which individual tree attributes or spatial configuration of plant associations (habitat types) across the land-scape influenced den use. Of 1091 verified den sites, 428 were in tree cavities. Raccoon occurrence among 4 cover...

  20. Growth characteristics of ChimeriVax-DEN2 vaccine virus in Aedes aegypti and Aedes albopictus mosquitoes.

    PubMed

    Johnson, Barbara W; Chambers, Trudy V; Crabtree, Mary B; Bhatt, Tejal R; Guirakhoo, Farshad; Monath, Thomas P; Miller, Barry R

    2002-09-01

    The chimeric yellow fever (YF) 17D-dengue type 2 (ChimeriVax-DEN2) vaccine virus developed by Acambis, Inc. (Cambridge, MA) contains the prM and E genes of wild-type (wt) dengue 2 (DEN-2) (strain PUO-218) virus in the YF vaccine virus (strain 17D) backbone. The potential of ChimeriVax-DEN2 virus to infect and be transmitted by Aedes aegypti, the principal DEN and YF virus mosquito vector, and Aedes albopictus, a species that occurs in areas of active transmission of YF and DEN viruses, was evaluated. Mosquitoes were intrathoracically (IT) inoculated with virus or were fed a virus-laden blood meal, and the replication kinetics of ChimeriVax-DEN2 were compared with the wt DEN-2 and YF 17D vaccine viruses. Replication of YF 17D virus is attenuated in cultured Ae. albopictus C6/36 mosquito cells and in Ae. aegypti and Ae. albopictus mosquitoes. Growth of ChimeriVax-DEN2 virus similarly was restricted in C6/36 cells and in mosquitoes. ChimeriVax-DEN2 replicated in 56% of IT inoculated Ae. aegypti, and virus disseminated to head tissue in 36%, with a mean viral titer of 1.8 log10 PFU/mosquito. Of mosquitoes, 16% of Ae. aegypti and 24% of Ae. albopictus were infected 14 days after a blood meal containing ChimeriVax-DEN2, but virus did not disseminate to head tissue. In contrast, DEN-2 replicated in all IT inoculated and orally infected Ae. aegypti (mean titer 5.5 log10 PFU/mosquito), and virus disseminated to head tissue in 95%. Of Ae. albopictus, 84% were infected after a blood meal containing DEN-2 virus; dissemination occurred in 36%. Replication of ChimeriVax-DEN2 virus in mosquitoes corresponded to that of YF 17D vaccine virus, which is restricted in its ability to infect and replicate in mosquitoes. Therefore, transmission of ChimeriVax-DEN2 virus by vector mosquitoes is unlikely.

  1. Relation of atrial fibrillation (AF) and change of lipoproteins: male patients with AF exhibited severe pro-inflammatory and pro-atherogenic properties in lipoproteins.

    PubMed

    Kim, Seong-Min; Kim, Jong-Min; Shin, Dong-Gu; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2014-07-01

    This study was designed to search putative biomarkers for detection of relatively young-onset atrial fibrillation (AF). We analyzed serum lipoproteins from male patients with paroxysmal AF (48±9years old, n=29) and controls with similar age (50±10years old, n=27), who visited our hospital for radiofrequency catheter ablation due to paroxysmal supraventricular tachycardia. Although the AF group showed normal serum cholesterol level, they exhibited 16% lower HDL-cholesterol and 13% higher serum cholesteryl ester transfer protein activity than those of the control group. The AF group showed elevated levels of serum triglyceride (TG) and C-reactive protein with hyperuricemia. However, there was no difference between serum levels of creatinine, troponin I, and serum amyloid A. All lipoproteins from the AF group contained higher level of TG, oxidized species, and advanced glycated end products. LDL from the AF group (AF-LDL) showed 2.7-fold more content of malondialdehyde than the control group (p<0.04) and exhibited higher sensitivity of oxidation. HDL-associated paraoxonase from the AF group showed impaired antioxidant ability and lowered expressional level of apoA-I (p<0.01) and paraoxonase (p<0.005) in HDL3. Lipoprotein properties were severely impaired in the AF group with increased extent of oxidation and inflammation. The modified lipoprotein properties with impaired antioxidant functions can be used as a putative biomarker for prognostic detection for the relatively young onset AF. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. Cloning and Characterization of Rainbow Trout Interleukin-17A/F2 (IL-17A/F2) and IL-17 Receptor A: Expression during Infection and Bioactivity of Recombinant IL-17A/F2

    PubMed Central

    Wang, Tiehui; Holland, Jason W.; Zou, Jun; Secombes, Christopher J.

    2013-01-01

    Lower vertebrates have been found to possess genes that have similar homology to both interleukin (IL)-17A and IL-17F, which have been termed IL-17A/F. In fish species, several of these genes can be present, but, to date, very little is known about their functional activity. This article describes the discovery and sequence analysis of a rainbow trout (Oncorhynchus mykiss) IL-17A/F2 molecule and an IL-17RA receptor. In addition, the bioactivity of the trout IL-17A/F2 is investigated for the first time in any species. The predicted IL-17A/F2 and IL-17RA proteins consist of 146 and 966 amino acids (aa), respectively, with both molecules containing conserved family motifs. Expression analysis revealed high constitutive expression of trout IL-17A/F2 in mucosal tissues from healthy fish, suggesting a potential role in mucosal immunity. When the modulation of IL-17A/F2 and IL-17RA in vitro was analyzed, it was observed that the two molecules were similarly affected. The expression of IL-17A/F2 was also induced in head kidney during bacterial, parasitic, and viral infections, revealing a possible function in defense against such pathogens. However, downregulation of IL-17RA was seen in some tissues and infections. The recombinant IL-17A/F2 protein was produced in Escherichia coli and was found to affect the expression of an antimicrobial peptide and the proinflammatory cytokines IL-6 and IL-8 in splenocytes. Consistent with mammalian IL-17 homologues, our expression and bioactivity results imply that trout IL-17A/F2 plays an important role in promoting inflammatory and host innate immune responses directed against different pathogen groups. PMID:23147036

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

    PubMed Central

    Canevello, Carola; Laffi, Nicola

    2014-01-01

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

  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. 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.

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

    ERIC Educational Resources Information Center

    Canning, Natalie

    2013-01-01

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

  7. [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.

  8. 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

  9. Den use and activity patterns in female Canada lynx (Lynx Canadensis) in the northern Rocky Mountains

    Treesearch

    Lucretia E. Olson; John R. Squires; Nicholas J. DeCesare; Jay A. Kolbe

    2011-01-01

    Knowledge of female behavior while rearing young can have important implications for species conservation. We located dens and analyzed activity (defined as movement between consecutive GPS locations) for nine female lynx with kittens in the northcentral Rocky Mountains in 2005 and 2007. We used GPS tracking collars to quantify the percentage of time a female spent...

  10. 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.

  11. 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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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

    ERIC Educational Resources Information Center

    Canning, Natalie

    2013-01-01

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

  13. 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/).

  14. Astronauts Lodewijk van den Berg observes growth of crystals in VCGS

    NASA Image and Video Library

    1985-04-30

    51B-06-010 (29 April-6 May 1985) --- Lodewijk van den Berg, 51-B payload specialist, observes the growth of mercuric iodide crystal in the vapor crystal growth system (VCGS) on the Spacelab 3 science module aboard the Space Shuttle Challenger.

  15. 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.

  16. Using Forward Looking Infrared (FLIR) imagery to detect polar bear maternal dens: Operations manual

    USGS Publications Warehouse

    York, Geoffrey S.; Amstrup, Steven C.; Simac, Kristin

    2004-01-01

    Recent research has shown that Forward Looking Infia-Red (FLIR) imagery can detect polar bear dens despite total snow cover over their deming habitat. FLIR imagers detect a AT or difference in temperature between objects in the imager's field of view. During the Arctic winter, the groundlsnow surface is typically cold, providing a dark background in the FLIR imager. Sources of heat appear as lighter or white areas. Dens, in particular, appear as small bright "hotspots", usually with kzy boundaries (Appendix 1). Most commonly, since bears chose deep snow drifts for deming, dens can be distinguished from the normally dark (cold) band of drifted snow surrounding them. This innovation has the potential to prevent human activities fiom disturbing deming polar bears by allowing managers to discover dens before potentially disruptive activities begin. This is important because expanding resource extraction in Alaska's Arctic regions may threaten the welfare of polar bears and their habitat. In recent years, exploration and development activities have expanded east and west of the original oil fields of Prudhoe Bay. Hydrocarbon extraction is now occurring or planned along much of the central Beaufort Sea coast. As development continues into the National Petroleum Reserve, the scope of expansion could include 213 of the northern coastal region of Alaska. Industrial activities are a potential threat to polar bears, especially as they might disturb bears in maternal dens (Lentfer and Hensel 1980, Stirling 1990, Stirling and Andriashek 1992, Amstrup 1993, Amstrup and Gardner 1994). As the number of humans and their activities have increased in recent years, there has been a concurrent increase in the number of female polar bears deming on land (Amstrup and Gardner 1994). Therefore, the probability of disrupting maternal deming can be expected to increase in the future. Using FLIR surveys to detect bears in dens could reduce or eliminate that probability. The purpose of this

  17. AFS dynamics in a short-lived active region

    NASA Astrophysics Data System (ADS)

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

    2005-11-01

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

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

    PubMed

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

    1997-03-01

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

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

    SciTech Connect

    Sharp, D.D.

    1980-11-01

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

  20. 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.

  1. Vulnus Cordis. Heart Suture. (Vulnus Cordis. Sutur af Hjertet),

    DTIC Science & Technology

    1977-10-12

    AD—A0’s6 830 ARMY MEDICAL INTELLIGENCE AND INFORMATION AGENCY WAS— ETC F/S 6/5 VULNUS CORalS. HEART SUTURE. (VULNUS CORDIS. SUTUR AF HJERTET),(U) OCT...Translated . ~~~~~~~ 285-288 ? ~ X J t~TU1~ Publisher: Date/Place Publication: 1896 Distribution Statement: S . 2~~1I9~ — I Vulnus cordis. Heart suture...Article by A. Cappelen, resident physician Norsk Meg, f. Laegevidensk. 11: 285—288, 1896. That ‘wounds of the heart should become th. object of surgical

  2. 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.

  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. 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.

  5. 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

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

    PubMed

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

    2013-01-01

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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. Rapid endodontic management of type II dens invaginatus using an MTA plug: a case report.

    PubMed

    Fayazi, Sara; Bayat-Movahed, Saeed; White, Shane N

    2013-01-01

    Dens invaginatus is an anomaly characterized by an infolding of enamel and dentin that can lead to caries and pulpal death while the tooth is still immature, and present difficulties with diagnosis and treatment. Generally such open apices are managed by long term apexifaction procedures. This article demonstrated rapid management of a maxillary lateral incisor having a type 2 dens invaginatus, necrotic pulp, open apex and very large periradicular lesion using calcium hydroxide for one week prior to placement of a mineral trioxide aggregate (MTA) plug. After setting of the MTA, the remaining canal space was obturated using a warm vertical gutta percha technique. At 6 months follow-up the patient was asymptomatic, the lesion had almost entirely resolved, and, the root was already completely surrounded by bone.

  12. 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.

  13. 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)

  14. 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.

  15. Dens evaginatus of anterior teeth (talon cusp): report of five cases.

    PubMed

    Segura-Egea, Juan J; Jiménez-Rubio, Alicia; Ríos-Santos, José V; Velasco-Ortega, Eugenio

    2003-04-01

    The talon cusp, or dens evaginatus of anterior teeth, is a relatively rare dental developmental anomaly characterized by the presence of an accessory cusplike structure projecting from the cingulum area or cementoenamel junction. This occurs in either maxillary or mandibular anterior teeth in both the primary and permanent dentition. This article reports five cases of talon cusp, two of them bilateral, affecting permanent maxillary central and lateral incisors and canines that caused clinical problems related to caries or occlusal interferences.

  16. Combined endodontic therapy and surgery in the treatment of dens invaginatus Type 3: case report.

    PubMed

    da Silva Neto, Ulisses Xavier; Hirai, Vinício Hidemitsu Goto; Papalexiou, Vula; Gonçalves, Silvana Beltrami; Westphalen, Vânia Portela Ditzel; Bramante, Clovis Monteiro; Martins, Wilson Denis

    2005-12-01

    An accurate understanding of the morphology of the root canal system is a prerequisite for successful root canal treatment. Invaginated teeth have a complex root canal configuration that cannot be instrumented effectively and should be treated by both endodontic therapy and surgery. A case of dens invaginatus Type 3 in a maxillary lateral incisor with a periapical lesion and its successful treatment by these combined methods is reported.

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

    PubMed

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

    2017-01-05

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

  18. 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.

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

    PubMed

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

    2017-01-01

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

  20. 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.

  1. 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.

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

    DTIC Science & Technology

    2015-10-01

    compared to U2AF1(WT) mice. U2AF1(S34F) stem cells are at a competitive disadvantage compared to control cells, suggesting that the increase in HSC cell...cell proliferation) in KLS cells compared to controls (pɘ.05, n=8-13). Competitive repopulation studies show a disadvantage for bone marrow cells

  3. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., refined oil; cotton, undelinted seed. (b) Aspergillus flavus AF36 is temporarily exempt from the... flavis AF 36 is temporarily exempt from the requirement of a tolerance on corn, field, forage; corn, field, grain; corn, field, stover; corn, pop, grain; corn, pop, stover; corn, sweet, forage; corn, sweet...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  5. 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 Impact...

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

    PubMed Central

    Sridharan, Vinod; Singh, Ravinder

    2007-01-01

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

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

    PubMed

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

    2008-05-01

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

  8. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial.

    PubMed

    Verma, Atul; Mantovan, Roberto; Macle, Laurent; De Martino, Guiseppe; Chen, Jian; Morillo, Carlos A; Novak, Paul; Calzolari, Vittorio; Guerra, Peter G; Nair, Girish; Torrecilla, Esteban G; Khaykin, Yaariv

    2010-06-01

    This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software. Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients (n = 100) were randomized to one of three arms. For CFE alone (n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites <120 ms were ablated until AF termination/non-inducibility. For PVI (n = 32), all four PV antra were isolated and confirmed using a circular catheter. For PVI + CFE (n = 34), all four PV antra were isolated, followed by AF induction and ablation of all CFE sites until AF termination/non-inducibility. Patients were followed at 3, 6, and 12 months with a visit, ECG, 48 h Holter. Atrial fibrillation symptoms were confirmed by loop recording. Repeat procedures were allowed within the first 6 months. The primary endpoint was freedom from AF >30 s at 1 year. Patients (age 57 +/- 10 years, LA size 42 +/- 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) (P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) (P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) (P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no mortality. In high

  9. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial†

    PubMed Central

    Verma, Atul; Mantovan, Roberto; Macle, Laurent; De Martino, Guiseppe; Chen, Jian; Morillo, Carlos A.; Novak, Paul; Calzolari, Vittorio; Guerra, Peter G.; Nair, Girish; Torrecilla, Esteban G.; Khaykin, Yaariv

    2010-01-01

    Aims This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software. Methods and results Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients (n = 100) were randomized to one of three arms. For CFE alone (n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites <120 ms were ablated until AF termination/non-inducibility. For PVI (n = 32), all four PV antra were isolated and confirmed using a circular catheter. For PVI + CFE (n = 34), all four PV antra were isolated, followed by AF induction and ablation of all CFE sites until AF termination/non-inducibility. Patients were followed at 3, 6, and 12 months with a visit, ECG, 48 h Holter. Atrial fibrillation symptoms were confirmed by loop recording. Repeat procedures were allowed within the first 6 months. The primary endpoint was freedom from AF >30 s at 1 year. Patients (age 57 ± 10 years, LA size 42 ± 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) (P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) (P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) (P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no

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

    PubMed

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

    2016-05-24

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

  11. 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

  12. Argyrophilic nucleolar organizer regions (AgNORs) in odontogenic myxoma (OM) and ameloblastic fibroma (AF).

    PubMed

    Martins, C; Carvalho, Y R; do Carmo, M A

    2001-09-01

    Ten cases of odontogenic myxoma (OM) and six cases of ameloblastic fibroma (AF) were subjected to comparative analysis by the AgNOR technique, in order to determine a possible difference in cell proliferation index between these lesions. The mean AgNOR number of the mesenchymal component of AF was compared with its epithelial component and the difference was not found to be statistically significant. The mean AgNOR index of the AF group was significantly higher than that of the OM group. Moreover, the mesenchymal component of AF demonstrated increased AgNOR numbers compared with that of OM (P<0.05). These results suggest that the epithelial and mesenchymal components of AF may have similar cell proliferative activity. However, the cell proliferative index of this lesion seems to be higher than that of OM.

  13. Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey

    PubMed Central

    Chiang, Chern-En; Naditch-Brûlé, Lisa; Brette, Sandrine; Silva-Cardoso, José; Gamra, Habib; Murin, Jan; Zharinov, Oleg J.; Steg, Philippe Gabriel

    2016-01-01

    Background Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients’ clinical characteristics, AF control, and symptom burden. Methods RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. Results Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF-related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. Conclusions In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID:26800084

  14. [Design of an atrial fibrillation and embolic risk registry in Mexico: CARMEN-AF].

    PubMed

    González-Hermosillo, Jesús A; Márquez, Manlio F; Ocampo-Peña, Salvador

    Atrial fibrillation (AF) is one of the most common arrhythmias, and its prevalence increase with age. It is associated with high risk of stroke. The prevention of such thromboembolism is done with oral anticoagulants, which in our country seem to be underused. CARMEN-AF registry aims primarily to determine the current status of thromboprophylaxis of non-valvular AF in Mexico. A secondary objective is to know the morbidity and mortality associated with non-valvular AF in at least one year of follow-up. CARMEN-AF registry is an observational, longitudinal, multicenter, and national survey about the use of oral anticoagulants in patients with non-valvular AF. Patients 18years old or older, diagnosed with AF during the last 6months, and with at least one risk factor of thromboembolism based in the CHA2DS2-Vasc score are being selected. Demographic and clinical data will be collected during the visits to their usual clinic with a follow-up of 2years. The recruitment began on September 19, 2014, and the inclusion of the last patient is expected on September 18, 2016. According to the reported incidence of AF globally and taking into account the total Mexican population, the inclusion of 1,200 patients is estimated. The Atrial Fibrillation and Embolic Risk Registry (CARMEN-AF) will reveal the current status of thromboprophylaxis in patients with non-valvular AF, and will allow to get an overview of the national and international clinical practice guidelines accomplishment in this area. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  15. 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.

  16. Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism.

    PubMed

    Afzal, Muhammad; Kazmi, Imran; Khan, Ruqaiyah; Rana, Poonam; Kumar, Vikas; Al-Abbasi, Fahad A; Zamzami, Mazin A; Anwar, Firoz

    2017-06-01

    Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2013-04-30

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

  18. 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.

  19. Cancer-Associated Mutations Mapped on High-Resolution Structures of the U2AF2 RNA Recognition Motifs.

    PubMed

    Glasser, Eliezra; Agrawal, Anant A; Jenkins, Jermaine L; Kielkopf, Clara L

    2017-09-12

    Acquired point mutations of pre-mRNA splicing factors recur among cancers, leukemias, and related neoplasms. Several studies have established that somatic mutations of a U2AF1 subunit, which normally recognizes 3' splice site junctions, recur among myelodysplastic syndromes. The U2AF2 splicing factor recognizes polypyrimidine signals that precede most 3' splice sites as a heterodimer with U2AF1. In contrast with those of the well-studied U2AF1 subunit, descriptions of cancer-relevant U2AF2 mutations and their structural relationships are lacking. Here, we survey databases of cancer-associated mutations and identify recurring missense mutations in the U2AF2 gene. We determine ultra-high-resolution structures of the U2AF2 RNA recognition motifs (RRM1 and RRM2) at 1.1 Å resolution and map the structural locations of the mutated U2AF2 residues. Comparison with prior, lower-resolution structures of the tandem U2AF2 RRMs in the RNA-bound and apo states reveals clusters of cancer-associated mutations at the U2AF2 RRM-RNA or apo-RRM1-RRM2 interfaces. Although the role of U2AF2 mutations in malignant transformation remains uncertain, our results show that cancer-associated mutations correlate with functionally important surfaces of the U2AF2 splicing factor.

  20. RNA Induces Conformational Changes in the SF1/U2AF65 Splicing Factor Complex

    PubMed Central

    Gupta, Ankit; Jenkins, Jermaine L.; Kielkopf, Clara L.

    2010-01-01

    Spliceosomes assemble on pre-mRNA splice sites through a series of dynamic ribonucleoprotein complexes, yet the nature of the conformational changes remains unclear. Splicing Factor 1 (SF1) and U2 Auxiliary Factor (U2AF65) cooperatively recognize the 3’ splice site during the initial stages of pre-mRNA splicing. Here, we used small-angle X-ray scattering to compare the molecular dimensions and ab initio shape restorations of SF1 and U2AF65 splicing factors, as well as the SF1/U2AF65 complex in the absence and presence of AdML splice site RNAs. The molecular dimensions of the SF1/U2AF65/RNA complex substantially contracted by 15 Å in the maximum dimension, relative to the SF1/U2AF65 complex in the absence of RNA ligand. In contrast, no detectable changes were observed for the isolated SF1 and U2AF65 splicing factors or their individual complexes with RNA, although slight differences in the shapes of their molecular envelopes were apparent. We propose that the conformational changes that are induced by assembly of the SF1/U2AF65/RNA complex serve to position the pre-mRNA splice site optimally for subsequent stages of splicing. PMID:21146534

  1. RNA induces conformational changes in the SF1/U2AF65 splicing factor complex.

    PubMed

    Gupta, Ankit; Jenkins, Jermaine L; Kielkopf, Clara L

    2011-02-04

    Spliceosomes assemble on pre-mRNA splice sites through a series of dynamic ribonucleoprotein complexes, yet the nature of the conformational changes remains unclear. Splicing factor 1 (SF1) and U2 auxiliary factor (U2AF(65)) cooperatively recognize the 3' splice site during the initial stages of pre-mRNA splicing. Here, we used small-angle X-ray scattering to compare the molecular dimensions and ab initio shape restorations of SF1 and U2AF(65) splicing factors, as well as the SF1/U2AF(65) complex in the absence and presence of AdML (adenovirus major late) splice site RNAs. The molecular dimensions of the SF1/U2AF(65)/RNA complex substantially contracted by 15 Å in the maximum dimension, relative to the SF1/U2AF(65) complex in the absence of RNA ligand. In contrast, no detectable changes were observed for the isolated SF1 and U2AF(65) splicing factors or their individual complexes with RNA, although slight differences in the shapes of their molecular envelopes were apparent. We propose that the conformational changes that are induced by assembly of the SF1/U2AF(65)/RNA complex serve to position the pre-mRNA splice site optimally for subsequent stages of splicing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. 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

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

    PubMed

    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

    2016-08-01

    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. 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. 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. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  4. 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

  5. Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

    PubMed

    Kim, M H; Lin, J; Hussein, M; Battleman, D

    2009-12-01

    Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on

  6. Mutations in the small subunit of the Drosophila U2AF splicing factor cause lethality and developmental defects.

    PubMed

    Rudner, D Z; Kanaar, R; Breger, K S; Rio, D C

    1996-09-17

    The essential eukaryotic pre-mRNA splicing factor U2AF (U2 small nuclear ribonucleoprotein auxiliary factor) is required to specify the 3' splice at an early step in spliceosome assembly. U2AF binds site-specifically to the intron polypyrimidine tract and recruits U2 small nuclear ribonucleoprotein to the branch site. Human U2AF (hU2AF) is a heterodimer composed of a large (hU2AF65) and small (hU2AF35) subunit. Although these proteins associate in a tight complex, the biochemical requirement for U2AF activity can be satisfied solely by the large subunit. The requirement for the small subunit in splicing has remained enigmatic. No biochemical activity has been found for hU2AF35 and it has been implicated in splicing only indirectly by its interaction with known splicing factors. In the absence of a biochemical assay, we have taken a genetic approach to investigate the function of the small subunit in the fruit fly Drosophila melanogaster. A cDNA clone encoding the small subunit of Drosophila U2AF (dU2AF38) has been isolated and sequenced. The dU2AF38 protein is highly homologous to hU2AF35 containing a conserved central arginine- and serine-rich (RS) domain. A recessive P-element insertion mutation affecting dU2AF38 causes a reduction in viability and fertility and morphological bristle defects. Consistent with a general role in splicing, a null allele of dU2AF38 is fully penetrant recessive lethal, like null alleles of the Drosophila U2AF large subunit.

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

    PubMed

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

    2008-08-25

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

  8. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2.

    PubMed

    Huisman, Menno V; Rothman, Kenneth J; Paquette, Miney; Teutsch, Christine; Diener, Hans-Christoph; Dubner, Sergio J; Halperin, Jonathan L; Ma, Chang Sheng; Zint, Kristina; Elsaesser, Amelie; Bartels, Dorothee B; Lip, Gregory Y H

    2017-02-21

    GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available. This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score ≥2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and

  9. 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).

  10. 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

  11. 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.

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

    SciTech Connect

    Sandage, A.; Tammann, G.A.

    1988-05-01

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

  13. Comparative Effects of R- and S-equol and Implication of Transactivation Functions (AF-1 and AF-2) in Estrogen Receptor-Induced Transcriptional Activity

    PubMed Central

    Shinkaruk, Svitlana; Carreau, Charlotte; Flouriot, Gilles; Bennetau-Pelissero, Catherine; Potier, Mylène

    2010-01-01

    Equol, one of the main metabolites of daidzein, is a chiral compound with pleiotropic effects on cellular signaling. This property may induce activation/inhibition of the estrogen receptors (ER) a or b, and therefore, explain the beneficial/deleterious effects of equol on estrogen-dependent diseases. With its asymmetric centre at position C-3, equol can exist in two enantiomeric forms (R- and S-equol). To elucidate the yet unclear mechanisms of ER activation/inhibition by equol, we performed a comprehensive analysis of ERa and ERb transactivation by racemic equol, as well as by enantiomerically pure forms. Racemic equol was prepared by catalytic hydrogenation from daidzein and separated into enantiomers by chiral HPLC. The configuration assignment was performed by optical rotatory power measurements. The ER-induced transactivation by R- and S-equol (0.1–10 µM) and 17b-estradiol (E2, 10 nM) was studied using transient transfections of ERα and ERβ in CHO, HepG2 and HeLa cell lines. R- and S-equol induce ER transactivation in an opposite fashion according to the cellular context. R-equol and S-equol are more potent in inducing ERα in an AF-2 and AF-1 permissive cell line, respectively. Involvement of ERα transactivation functions (AF-1 and AF-2) in these effects has been examined. Both AF-1 and AF-2 are involved in racemic equol, R-equol and S-equol induced ERα transcriptional activity. These results could be of interest to find a specific ligand modulating ER transactivation and could contribute to explaining the diversity of equol actions in vivo. PMID:22254026

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

    PubMed Central

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

    2016-01-01

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

  15. The Armed Forces Casualty Assistance Readiness Enhancement System (AF-CARES), Version 1.0

    DTIC Science & Technology

    2007-06-08

    15 Next of Kin ( NOK ) ................................................................................................... 15 Casualty...22 Recommendations for Future Work...1.0 Casualty Tab ........................................................................... 19 Figure 10: AF-CARES 1.0 NOK Data Tab

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

    DTIC Science & Technology

    2015-07-27

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

  17. Aerial view of Hanger AF at Cape Canaveral Air Force Station

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aerial view of Hanger AF at Cape Canaveral Air Force Station showing the solid rocket booster (SRB) disassembly facility, SRB casings from the Columbia's first launch and the retrieval vessels, UTC Freedom and Liberty.

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

    PubMed

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

    2012-02-14

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

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

    SciTech Connect

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

    1987-08-01

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

  20. 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.

  1. Management of atrial fibrillation in Greece: the MANAGE-AF study.

    PubMed

    Andrikopoulos, George; Pastromas, Sokratis; Mantas, Ioannis; Sakellariou, Dimitris; Kyrpizidis, Christos; Makridis, Pantelis; Goumas, Georgios; Stakos, Dimitris; Gotsis, Alexandros; Kartalis, Athanasios; Kazianis, Georgios; Babalis, Dimitrios; Toli, Konstantina; Tzeis, Stylianos; Papavasileiou, Maria; Kalogeropoulos, Petros; Vardas, Panos

    2014-01-01

    Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

  2. 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.

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

    PubMed

    Gound, Tom G; Maixner, David

    2004-06-01

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

  4. 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.

  5. Pheromonally mediated sexual isolation among denning populations of red-sided garter snakes, Thamnophis sirtalis parietalis.

    PubMed

    Lemaster, Michael P; Mason, Robert T

    2003-04-01

    Utilizing behavioral experiments and chemical analyses, we examined whether pheromonally mediated sexual isolation exists between denning populations of red-sided garter snakes (Thamtnophis sirtalis parietalis) in Manitoba, Canada. Simultaneous choice tests conducted during the breeding season revealed that adult males from a hibernaculum in central Manitoba displayed a strong courtship preference for females from their own population over females from a hibernaculum in western Manitoba, whereas males from the western Manitoba hibernaculum showed no such preference. In addition. trailing experiments testing the response of males from the two hibernacula to familiar and unfamiliar female trails showed similar results, demonstrating that the observed male preference is mediated through chemical cues. Subsequent chemical analysis of the female sexual attractiveness pheromone. a homologous series of long-chain saturated and (omega-9 cis-unsaturated methyl ketones responsible for eliciting male courtship behavior and trailing behavior in garter snakes, showed significant variation in the composition of the pheromone between the two populations. Specifically, the two populations varied in the relative concentrations of individual unsaturated methyl ketones expressed by females. These results suggest that sexual isolation exists to a degree among denning populations of red-sided garter snakes due to variation in the expression of the female sexual attractiveness pheromone.

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

    PubMed

    Guzik, Grzegorz

    2015-01-01

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

  7. 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

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

    DTIC Science & Technology

    2016-12-01

    Model , Hematopoiesis, RNA-seq, U2AF1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...Spliceosome Mouse model Hematopoiesis RNA-seq U2AF1 3. ACCOMPLISHMENTS: Task 1. Seek IACUC and DoD ACURO approval for the use of animals. Objectives...pre-clinical models using flow cytometry, progenitor assays, and bone marrow transplantation. In addition, trainees created plots, performed

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

    DTIC Science & Technology

    1986-06-01

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

  10. Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT).

    PubMed

    Guhl, Emily N; Schlusser, Courtney L; Henault, Lori E; Bickmore, Timothy W; Kimani, Everlyne; Paasche-Orlow, Michael K; Magnani, Jared W

    2017-09-18

    Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the Embodied Conversational Agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. Copyright © 2017. Published by Elsevier Inc.

  11. AF-M315E Propulsion System Advances and Improvements

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

  12. Tutorials in space physics using visualization with AF GEOSpace

    NASA Astrophysics Data System (ADS)

    Habash Krause, L.; Knipp, D.

    A set of tutorials has been developed to assist students of space physics with the visualization of three dimensional, time varying systems. AF GEOSpace is a suite of space environment specification models with a window driven interface that allows users to visualize data from well-established semi-empirical models in one, two, or three dimensions. An Open-GL windows environment provides for real-time navigation in a virtual environment representing near-Earth space, facilitating understanding of complex spatial structures of individual features and spatial relationships between constrained features. Modeled GEOSpace phenomena include realistic external magnetic fields (e.g., Hilmer-Voigt `95,) conductivity patterns in the auroral oval, VHF signal fading given a fixed ground station and a satellite altitude, and relativistic charged particle measurements made by a satellite given its orbital elements. The models included in GEOSpace are sensitive to solar and geomagnetic activity, so impacts unique to each of these types of activity are readily apparent to students using the tutorials. Thus, the students may actively discover, for example, that intensification of the pre-reversal enhancement in the equatorial post- sunset ionospheric vertical velocity is controlled primarily by solar and not geomagnetic activity, or that the compression of the magnetosphere may be so extreme during geomagnetic activity that satellites in geosynchronous orbit may experience direct exposure to the solar wind. Adding an element of student proactivity results in the students' accepting more responsibility for the learning process. This set of tutorials capitalizes on the students' positive response to learning through the discovery method, resulting in greater overall motivation to explore the near-Earth space environment.

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

    PubMed

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

    2016-07-01

    In order to investigate the oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39±0.27 and 0.99±0.38mg/L, respectively. pH was relatively stable around 7.11±0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85±7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity. Copyright © 2016. Published by Elsevier B.V.

  14. Rivaroxaban in patients with atrial fibrillation: from ROCKET AF to everyday practice.

    PubMed

    Barón-Esquivias, Gonzalo; Marín, Francisco; Sanmartín Fernandez, Marcelo

    2017-05-01

    Registries and non-interventional studies offer relevant and complementary information to clinical trials, since they have a high external validity. Areas covered: The information regarding the efficacy and safety of rivaroxaban compared with warfarin, or rivaroxaban alone in clinical practice was reviewed in this manuscript. For this purpose, a search on MEDLINE and EMBASE databases was performed. The MEDLINE and EMBASE search included both medical subject headings (MeSH) and keywords including: atrial fibrillation (AF) OR warfarin OR clinical practice OR ROCKET AF AND rivaroxaban. Case reports were not considered. Expert commentary: In ROCKET AF, rivaroxaban was at least as effective as warfarin for the prevention of stroke in patients with nonvalvular AF at high risk of stroke, but, importantly, with a lesser risk of intracranial, critical and fatal bleedings. A number of observational comparative and non-comparative studies, with more than 60,000 patients included treated with rivaroxaban, have analyzed the efficacy and safety of rivaroxaban in real-life patients with AF in different clinical settings. These studies have shown that in clinical practice, rates of stroke and major bleeding were consistently lower than those reported in ROCKET AF, likely due to the lower thromboembolic and bleeding risk observed in these patients.

  15. Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia.

    PubMed

    Okuda, Hiroshi; Stanojevic, Boban; Kanai, Akinori; Kawamura, Takeshi; Takahashi, Satoshi; Matsui, Hirotaka; Takaori-Kondo, Akifumi; Yokoyama, Akihiko

    2017-05-01

    The eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4-ENL-P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia.

  16. Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia

    PubMed Central

    Okuda, Hiroshi; Kanai, Akinori; Kawamura, Takeshi; Takahashi, Satoshi; Matsui, Hirotaka

    2017-01-01

    The eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4–ENL–P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion–AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia. PMID:28394257

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

    PubMed

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

    2010-01-18

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

  18. Influence of the facial pattern on ANB, AF-BF, and Wits appraisal.

    PubMed

    Tanaka, Jefferson Luis Oshiro; Ono, Evelise; Filho Medici, Edmundo; Cesar de Moraes, Luiz; Cezar de Melo Castilho, Julio; Leonelli de Moraes, Mari Eli

    2006-01-01

    To assess the correlation between Wits and AF-BF appraisals with the ANB angle, and verify the influence of the facial type on these appraisals. Lateral cephalometric radiographs from 118 untreated individuals were separated into 3 groups according to the facial pattern (brachyfacial, mesofacial, and dolichofacial). The radiographs were digitized and submitted to ANB angle and Wits and AF-BF appraisals on computer software. All radiographs were retraced for intraobserver and interobserver error tests. The Student's t test demonstrated no statistically significant differences on the intraobserver's test (P > .05). There were statistically significant differences in the readings of Wits values of the 3 groups and for AF-BF values in the brachyfacial and mesofacial groups (P <.05). The multiple linear regression tests demonstrated high correlation between ANB and AF-BF for the 3 groups (r2, 0.768). The same result was found for ANB and Wits (r2, 0.624). Facial pattern does not have an influence on the correlation between ANB and AF-BF nor between ANB and Wits, but it does influence the measurements of ANB, AF-BF, and Wits.

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

    PubMed Central

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

    2017-01-01

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

  20. 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

  1. 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.

  2. A Rare Bilateral Presentation of Multiple Dens Invaginatus, Shovel-Shaped Incisor and Talon Cusp With Mesiodens.

    PubMed

    Hegde, S; Jain, M; Shubha, A B

    2014-01-01

    The aim of this paper is to describe a unique and unusual case of concomitant appearance of morphological dental anomalies in the maxillary anterior region, along with its management in a patient with no systemic abnormality. This case report describes the clinical and radiographic features of talon cusp, dens invaginatus, shovel-shaped incisors and a supernumerary tooth occurring in a single patient, which is a rare presentation. All 4 permanent maxillary incisors had dens invaginatus, the permanent maxillary canines showed the presence of talon cusps, the permanent maxillary central incisors were shovel-shaped and an erupted mesiodens was also observed. Treatment included restorative, surgical and orthodontic approaches.

  3. Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways

    PubMed Central

    Chen, Li; Weinmeister, Robert; Kralovicova, Jana; Eperon, Lucy P.; Vorechovsky, Igor; Hudson, Andrew J.

    2017-01-01

    Abstract The selection of 3΄ splice sites (3΄ss) is an essential early step in mammalian RNA splicing reactions, but the processes involved are unknown. We have used single molecule methods to test whether the major components implicated in selection, the proteins U2AF35 and U2AF65 and the U2 snRNP, are able to recognize alternative candidate sites or are restricted to one pre-specified site. In the presence of adenosine triphosphate (ATP), all three components bind in a 1:1 stoichiometry with a 3΄ss. Pre-mRNA molecules with two alternative 3΄ss can be bound concurrently by two molecules of U2AF or two U2 snRNPs, so none of the components are restricted. However, concurrent occupancy inhibits splicing. Stoichiometric binding requires conditions consistent with coalescence of the 5΄ and 3΄ sites in a complex (I, initial), but if this cannot form the components show unrestricted and stochastic association. In the absence of ATP, when complex E forms, U2 snRNP association is unrestricted. However, if protein dephosphorylation is prevented, an I-like complex forms with stoichiometric association of U2 snRNPs and the U2 snRNA is base-paired to the pre-mRNA. Complex I differs from complex A in that the formation of complex A is associated with the loss of U2AF65 and 35. PMID:27683217

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

    PubMed

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

    2016-11-15

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

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

    PubMed Central

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

    2016-01-01

    An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3′ splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3′ splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein–RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3′ splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants. PMID:27799531

  6. Headache in a patient with crowned dens: report of a new case.

    PubMed

    Viana, Michele; Sainaghi, Pier P; Stecco, Alessandro; Mortara, Franco; Sprenger, Till; Goadsby, Peter J

    2014-01-01

    Crowned dens syndrome (CDS) is a clinical-radiological entity characterized by acute attacks of neck pain with fever, rigidity, general signs of inflammation, and calcification of the periodontoid articular structures. Case report with 42 months follow-up. An 81-year-old man, who had never suffered from headache before July 2010, developed strictly left-sided headaches. The pain was restricted to the left side of the scalp and felt more intense in the frontal area. The intensity was moderate to high with a throbbing quality. The pain had an orthostatic component and was worsened by neck hyperextension and Valsalva maneuvers. Neurological and general examinations were normal, except for a reduced range of motion of the neck. He was prescribed indomethacin orally 25 mg t.i.d. and had a partial response. After a week, he was given a dosage of 50 mg t.i.d. with complete remission of the pain. Brain magnetic resonance imaging was normal, while an magnetic resonance imaging of the cervical spine showed a non-homogeneous mass behind the odontoid process of C2, narrowing the subarachnoid space in C1, stretching the posterior longitudinal ligament, and touching the left vertebral artery. A computed tomography scan showed calcification of the soft tissue around the odontoid process and a thickening of the left C2 root. After 4 months, the indomethacin dosage was reduced step-by-step. Indomethacin was discontinued in March 2012. Since then, the headache has not recurred. We here present the case of a patient with headache and radiological findings of crowned dens. However, the clinical presentation differed from previous CDS cases in the literature in that the pain was unilateral with frontal localization and throbbing quality, as well as an orthostatic component and lack of either fever or inflammatory signs. The differential diagnosis also includes a remitting form of hemicrania continua, presenting with an atypical presentation, with neuroimaging incidental finding of

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  8. 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

  9. Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus.

    PubMed

    Park, Yong-Sung; Kim, Tae-Hyoung; Yun, Cheol-Won

    2017-07-03

    Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 ( Aspergillus fumigatusMac1 homolog) and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA-binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae, and AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1 resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1 failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of A. fumigatus failed to grow in copper-limited media, and its growth was restored by introducing ctrC We found that AfMac1 specifically bound to the promoter region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was identified from the promoter region of ctrC, and the addition of mutant ctrC lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus Furthermore, deletion of Afmac1 significantly reduced strain virulence and activated conidial killing activity by neutrophils and macrophages. Taken together, these results suggest that AfMac1 is a copper transcription factor that regulates cellular copper homeostasis in A. fumigatus. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

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

    PubMed Central

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

    2017-01-01

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

  11. Pre-clinical laboratory evaluation of the new 'AF' arterial line filter range.

    PubMed

    Yarham, Gemma; Mulholland, John

    2010-07-01

    The presence of emboli was recognised relatively early in the history of open heart surgery. The emboli produced during cardiopulmonary bypass have the predisposition to distribute into, and ultimately obstruct, microvessels of all tissues. The Sorin Group has recently developed a new range of arterial line filters. Before the Sorin AF range of filters was released for pre-launch clinical trials, our group performed in vitro laboratory testing of the AF range against a selection of commercially available filters on the global market. The Sorin AF620 and AF640 demonstrate both the smallest prime volume and smallest surface contact area (92ml and 290 cm(2), respectively).The results of the GME Handling Efficiency experiments ranged by 39.6%, from 95.9% to 56.3%. In terms of an air bolus handling, the results of the Limit Bolus experiment ranged by 97 ml, from 147.5 ml down to 50 ml. The pressure drop across all the filters was measured under steady state experimental conditions. All of the above investigations were considered against surface area and prime volume. It is clear from the results that some commercially available arterial line filters perform better than others, not only in overall performance, but also with regard to individual characteristics. Evaluating arterial line filters for hospital-specific use has to balance pressure drop, surface area, micro air handling, prime volume and gross air handling; all points need to be considered. In the AF620 and AF640, Sorin boast that they are the two smallest prime and smallest surface area filters commercially available on the global market. The Sorin AF filter range performs well in all of the areas we investigated and will be a competitive option for centres, irrespective of which characteristics they use to evaluate and select their arterial line filter.

  12. Self-detection of atrial fibrillation in an aged population: the LietoAF Study.

    PubMed

    Virtanen, Raine; Kryssi, Verneri; Vasankari, Tuija; Salminen, Marika; Kivelä, Sirkka-Liisa; Airaksinen, K E Juhani

    2014-11-01

    Early detection of atrial fibrillation (AF) in older people is important because AF is often asymptomatic and its first manifestation may be a disabling stroke. The objective of the LietoAF Study is to assess the motivation and capability of older people to learn pulse palpation and continue regular pulse measurements, and whether this self-assessment is helpful in the detection of new AF. The LietoAF Study is an intervention study. A total of 205 people aged ≥75 years were randomly selected to participate in the programme where a trained nurse gave individual education on pulse palpation. At 1 month, the eligible participants came to the first follow-up visit to assess the success of pulse self-monitoring. A total of 139 participants (68%) learned pulse palpation and performed regular measurements during the early follow-up period. The significant independent predictors for learning and motivation were high Mini-Mental State Examination score (>24) (OR 7.5, 95% CI 1.5-37.3, p = 0.014), computer use at home (OR 4.7, 95% CI 1.9-11.5, p = 0.001), independence at daily activities (OR 4.2, 95% CI 1.4-13.6, p = 0.013) and low heart rate (OR 1.04, 95% CI 1.0-1.08, p = 0.037). Education did not cause extra visits to local healthcare centres and did not affect quality of life. Four participants observed a new asymptomatic AF during the 1-month follow-up. Active older people are motivated and seem to learn pulse palpation. Our early experience suggests that simple nurse-based education is effective and useful in the early detection of asymptomatic AF. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

    PubMed

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

    2017-02-01

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

  14. 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

  15. VizieR Online Data Catalog: Southern Stars embedded in nebulosity (van den Bergh+, 1975)

    NASA Astrophysics Data System (ADS)

    van den Bergh, S.; Herbst, W.

    2000-05-01

    A survey of the Milky Way southward of the Palomar Sky Survey for the identification of reflection nebulae was carried out at the Cerro Tololo Inter-American Observatory in Chile. Plates in blue light were obtained at the Curtis Schmidt telescope covering a strip of plus or minus six degrees of the galactic equator. Red sensitive plates for comparison were also obtained with the same telescope covering the same area near the galactic plane. Observatory staff members and some students of the University of Toronto, Canada assisted in identifying stars embedded in nebulosity as shown by the plates. Although this catalogue roughly complements the Catalogue of Reflection Nebulae of van den Berg (1966AJ.....71..990V, Cat. ), the region here surveyed is more narrowly confined to the galactic equator. (2 data files).

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

    PubMed

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

    1998-01-01

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

  17. 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

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

    PubMed

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

    1997-09-01

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

  19. MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.

    PubMed

    Prange, K H M; Mandoli, A; Kuznetsova, T; Wang, S-Y; Sotoca, A M; Marneth, A E; van der Reijden, B A; Stunnenberg, H G; Martens, J H A

    2017-06-08

    In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11. We uncovered both common as well as specific MLL-AF9 and MLL-AF4 target genes, which were all marked by H3K79me2, H3K27ac and H3K4me3. Apart from promoter binding, we also identified MLL-AF9 and MLL-AF4 binding at specific subsets of non-overlapping active distal regulatory elements. Despite this differential enhancer binding, MLL-AF9 and MLL-AF4 still direct a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34(+) and monocyte-specific genes. Comparing these data sets identified several zinc finger transcription factors (TFs) as potential MLL-AF9 co-regulators. Together, these results suggest that MLL fusions collaborate with specific subsets of TFs to deregulate the RUNX1 gene program in 11q23 AMLs.

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

    SciTech Connect

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

    1987-09-01

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

  1. 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

  2. Absence of the dens in a 9.5-year-old rottweiler with non-progressive clinical signs

    PubMed Central

    Patton, Kristin M.; Almes, Kelli M.; de Lahunta, Alexander

    2010-01-01

    Absence of the dens is rarely described in large breed dogs. In this rottweiler, mild neurological deficits seen at 6 mo of age did not progress for the 9.5 y of the dog’s life despite lack of surgical intervention. This finding underscores the marked differences between small and large breeds. PMID:21119869

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

    PubMed

    Mondoni, A; Rossi, G; Probert, R

    2012-05-01

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

  4. 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

  5. Rater Biases in Genetically Informative Research Designs: Comment on Bartels, Boomsma, Hudziak, van Beijsterveldt, and van den Oord (2007)

    ERIC Educational Resources Information Center

    Hoyt, William T.

    2007-01-01

    Rater biases are of interest to behavior genetic researchers, who often use ratings data as a basis for studying heritability. Inclusion of multiple raters for each sibling pair (M. Bartels, D. I. Boomsma, J. J. Hudziak, T. C. E. M. van Beijsterveldt, & E. J. C. G. van den Oord, 2007) is a promising strategy for controlling bias variance and may…

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

    PubMed

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

    2007-01-01

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

  7. Dens invagination and root dilaceration in double multilobed mesiodentes in 14-year-old patient with anorexia nervosa.

    PubMed

    Bagińska, J; Rodakowska, E; Piszczatowski, Sz; Kierklo, A; Duraj, E; Konstantynowicz, J

    2017-01-01

    This paper describes a rare case of erupted double supernumerary teeth with unusual morphology in a 14-year-old patient with an eating disorder. The coexistence of dental morphological anomalies: multilobed mesiodens, multiple dens in dente of different types and root dilaceration have not been previously reported. The paper highlights anatomical and radiological aspects of dental abnormalities and clinical implications of delayed treatment.

  8. Acceleration of Regeneration of Large Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2016-09-01

    plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Zhongyu Li, MD, PhD RECIPIENT: Wake Forest University Health Sciences...Gap Peripheral Nerve Injuries Using 5a. CONTRACT NUMBER Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5b. GRANT...include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up to 72 hours after seeding. The

  9. AF Ablation Guided by Spatiotemporal Electrogram Dispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach.

    PubMed

    Seitz, Julien; Bars, Clément; Théodore, Guillaume; Beurtheret, Sylvain; Lellouche, Nicolas; Bremondy, Michel; Ferracci, Ange; Faure, Jacques; Penaranda, Guillaume; Yamazaki, Masatoshi; Avula, Uma Mahesh R; Curel, Laurence; Siame, Sabrina; Berenfeld, Omer; Pisapia, André; Kalifa, Jérôme

    2017-01-24

    The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949). Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

  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. Downregulated protein expression of transcriptional activator ELK-1 in atrial myocardium of chronic AF patients.

    PubMed

    Zeng, Xiangjun; Xiao, Xuejun; Wu, Yueheng; Huang, Huanlei

    2015-01-01

    The structural alterations in atrial myocytes appear to be an adaptive response of dedifferentiation during chronic atrial fibrillation (AF). Transcriptional activator ELK-1, one of the members of ETS family, has been shown to play an important role in regulating cell differentiation, It is reasonable to presume that ELK-1 participate in the molecular and structural remodeling by which AF is sustained. To prove this hypothesis, the expression of ELK-1 protein in chronically fibrillating atria compared to that in normal rhythmic atria was detected. Right atrial myocardium were obtained from twenty-four patients undergoing valve replacement surgery, twelve patients were in chronic AF (>6 months), whereas the others were in sinus rhythm (SR). The protein expression level of ELK-1 was quantified by Western blot analysis, and the cellular localization and expression pattern of ELK-1 was examined by immunohistochemical staining and indirect immunofluorescence. Western blot analysis showed that the protein expression of ELK-1 was significantly reduced in the atrial tissue of chronic AF patients compared to that in the controls. Immunohistochemistry showed that ELK-1 immunostaining occurred in both cytosolic and nuclear compartments of atrial myocardium. Indirect immunofluorescence showed that the nuclei of normal rhythmic atrial cells were densely labeled, whereas the nuclei in chronically fibrillating atrial cells were very faintly labeled. Our results suggest that the downregulated expression of transcriptional activator ELK-1 may play an important role in the pathogenesis of AF.

  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. 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.

  14. First CCD Photometry of the Interacting Binary AF Geminorum: Evidence for a Gravitationally Bound Third Object?

    NASA Astrophysics Data System (ADS)

    Yuhas, Bernard J.; Reed, Phillip A.; Chambliss, Carlson R.

    2013-07-01

    AF Geminorum (AF Gem) is an unusual Algol-type eclipsing binary star system in that the primary eclipse is a transit of the cooler, more evolved secondary star in front of the main sequence primary star. Our observations of AF Gem were made using the 0.61-meter Ritchey-Chrétien telescope at the Kutztown University Observatory (Kutztown, Pennsylvania) over 9 nights from 28 Nov 2012 to 6 Feb 2013. A total of 5350 data images were obtained of AF Gem during this time, and the results of our photometry suggest evidence for a third light source which may be gravitationally bound to the system. We present the first CCD photometric study in BVRI for this system, resolve the third light source from our photometry, provide a consistent orbital solution using the Wilson-Devinney code, and present a detailed ephemeris analysis. With an orbital period of 1.24 days, an overall decreasing ephemeris, and a possible third body in the system, AF Gem certainly warrants future photometric and spectroscopic observations.

  15. 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.

  16. [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.

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

    PubMed Central

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

    2005-01-01

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

  18. Risk of atrial fibrillation after atrial flutter ablation: impact of AF history, gender, and antiarrhythmic drug medication.

    PubMed

    Brembilla-Perrot, Béatrice; Girerd, Nicolas; Sellal, Jean Marc; Olivier, Arnaud; Manenti, Vladimir; Villemin, Thibaut; Beurrier, Daniel; de Chillou, Christian; Louis, Pierre; Selton, Olivier; de la Chaise, Arnaud Terrier

    2014-08-01

    Atrial fibrillation (AF) and flutter (AFL) are frequently associated. We assessed the frequency and identified the predictors of AF occurrence after AFL ablation. A total of 1,121 patients referred for AFL ablation were followed for a mean duration of 2.1 ± 2.7 years. Antiarrhythmic drugs were stopped after ablation in patients with no AF prior to ablation, or continued otherwise. A total of 356 patients (31.7%) had a history of AF prior to AFL ablation. Patients with AF prior to ablation were more likely to be females (OR = 1.35, CI = 1.00-1.83, P = 0.05). After ablation, 260 (23.2%) patients experienced AF. In the multivariable model, AF prior to ablation (OR = 1.90, CI = 1.42-2.54, P < 0.001) and female gender (OR = 1.77, CI = 1.29-2.42, P < 0.001) were associated with a higher risk of AF after ablation. In patients without prior AF, class I antiarrhythmics and amiodarone prior to AFL ablation were independently associated with higher risk of AF after ablation (OR = 2.11, CI = 1.15-3.88, P = 0.02 and OR = 1.60, CI = 1.08-2.36, P = 0.02, respectively). In patients who experienced AF after ablation, 201/260 (77.3%) had a CHA2DS2-VASc ≥1. Two patients with AF prior to ablation had a stroke during the follow-up whereas none of the patients without AF prior to ablation had a stroke. AF occurrence after AFL ablation is frequent (>20%), especially in patients with a history of AF, in female patients, and in patients treated with class I antiarrythmics/amiodarone prior to AFL. Since most patients who experience AF after AFL ablation have a CHA2DS2-VASc ≥1, the decision to stop anticoagulants after ablation should be considered on an individual basis. © 2014 Wiley Periodicals, Inc.

  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. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II (STAR AF II): design and rationale.

    PubMed

    Verma, Atul; Sanders, Prashanthan; Macle, Laurent; Deisenhofer, Isabel; Morillo, Carlos A; Chen, Jian; Jiang, Chen-yang; Ernst, Sabine; Mantovan, Roberto

    2012-07-01

    The optimal ablation approach for patients with persistent atrial fibrillation (AF) remains unknown. In particular, it is unclear if pulmonary vein (PV) antral isolation (PVI) is sufficient as a lone strategy for persistent AF. Furthermore, if additional substrate ablation is to be added, the ideal approach to substrate ablation is yet to be determined. The aim of this study is to determine the optimal strategy of catheter ablation of persistent AF by comparing the efficacy of 3 strategies: PVI vs PVI plus complex fractionated electrogram (CFE) ablation (PVI + CFE) vs PVI plus linear ablation (PVI + Lines). The STAR AF II study (ClinicalTrials.gov NCT01203748) is a prospective, multicenter, randomized trial with a blinded assessment of outcomes. A total of 549 patients will be randomized in a 1:4:4 fashion to one of the investigation arms: PVI, PVI + CFE, and PVI + Lines, respectively. Patients undergoing a first-time ablation procedure for symptomatic, persistent AF that is refractory to at least 1 antiarrhythmic medication will be included. Persistent AF will be defined as a sustained episode lasting >7 days and <3 years. Patients with a left atrial parasternal size ≥60 mm will be excluded. The primary end point is freedom from documented AF >30 seconds at 18 months after 1 or 2 ablation procedures with or without antiarrhythmic medications. The STAR AF II study is a randomized trial designed to evaluate the optimal approach for catheter ablation of persistent AF. Copyright © 2012 Mosby, Inc. All rights reserved.

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

    PubMed

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

    2015-08-21

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

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

    PubMed Central

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

    2014-01-01

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

  3. 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

  4. Small-molecule inhibitors of AF6 PDZ-mediated protein-protein interactions.

    PubMed

    Vargas, Carolyn; Radziwill, Gerald; Krause, Gerd; Diehl, Anne; Keller, Sandro; Kamdem, Nestor; Czekelius, Constantin; Kreuchwig, Annika; Schmieder, Peter; Doyle, Declan; Moelling, Karin; Hagen, Volker; Schade, Markus; Oschkinat, Hartmut

    2014-07-01

    PDZ (PSD-95, Dlg, ZO-1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ-mediated protein-protein interactions has important implications in disease-related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1-fused gene from chromosome 6), which is an essential component of cell-cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile-Gln-Ser-Val-Glu-Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6-Bcr interaction and interfere with epidermal growth factor (EGF)-dependent signaling. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. [Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

    PubMed

    Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

    2013-10-01

    This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

  6. Midterm observations and recommendations from the evaluation of the AF4Q initiative.

    PubMed

    Alexander, Jeffrey A; Scanlon, Dennis P; McHugh, Megan C; Christianson, Jon B; Mittler, Jessica N; Hasnain-Wynia, Romana; Beich, Jeff

    2012-09-01

    To offer midterm observations and recommendations based on how Aligning Forces for Quality (AF4Q) alliances are faring in their journey toward improving healthcare quality at the community level. This study used a mixed method design. Longitudinal evaluation data to date were analyzed, including results from multiple surveys, qualitative analysis of key informant interviews, review of secondary documents and analysis of secondary data, and ongoing tracking of the activities of the 16 participating alliances. The observations and recommendations are based on consensus achieved by the AF4Q evaluation team investigators after in-depth iterative discussions. Six formative observations are identified and discussed: (1) stakeholder support and participation has been maintained despite changes in economic and political environments; (2) progress on program goals has been slow; (3) the "alignment" in the AF4Q initiative has been slow to materialize; (4) the AF4Q initiative has established a productive network of peer communities; (5) the impact of the AF4Q initiative, and the time to observe impact, vary by community, based on history and context; and (6) sustainability is the major future challenge for the AF4Q initiative. Multi-stakeholder alliances' efforts to improve quality should be viewed as "pieces of the health reform puzzle" rather than stand-alone solutions. As healthcare reform is challenged politically, alliances can practice the bipartisanship that focuses conversation on what is good for the community and how best to achieve community goals amid a potential sea of change in both federal and state policy and funding.

  7. Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways.

    PubMed

    Chen, Li; Weinmeister, Robert; Kralovicova, Jana; Eperon, Lucy P; Vorechovsky, Igor; Hudson, Andrew J; Eperon, Ian C

    2017-02-28

    The selection of 3΄ splice sites (3΄ss) is an essential early step in mammalian RNA splicing reactions, but the processes involved are unknown. We have used single molecule methods to test whether the major components implicated in selection, the proteins U2AF35 and U2AF65 and the U2 snRNP, are able to recognize alternative candidate sites or are restricted to one pre-specified site. In the presence of adenosine triphosphate (ATP), all three components bind in a 1:1 stoichiometry with a 3΄ss. Pre-mRNA molecules with two alternative 3΄ss can be bound concurrently by two molecules of U2AF or two U2 snRNPs, so none of the components are restricted. However, concurrent occupancy inhibits splicing. Stoichiometric binding requires conditions consistent with coalescence of the 5΄ and 3΄ sites in a complex (I, initial), but if this cannot form the components show unrestricted and stochastic association. In the absence of ATP, when complex E forms, U2 snRNP association is unrestricted. However, if protein dephosphorylation is prevented, an I-like complex forms with stoichiometric association of U2 snRNPs and the U2 snRNA is base-paired to the pre-mRNA. Complex I differs from complex A in that the formation of complex A is associated with the loss of U2AF65 and 35. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

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

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

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

    SciTech Connect

    Kim, Jeonghee; Chung, In Kwon

    2014-01-17

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

  10. 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.

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

    PubMed Central

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

    2012-01-01

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

  12. 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.

  13. 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

  14. 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.

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

    PubMed

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

    2012-06-01

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

  16. Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT).

    PubMed

    Steuter, J A; Villanueva, M L H; Loberiza, F R; Armitage, J O; Bociek, R G; Ganti, A K; Tarantolo, S R; Vose, J M; Easley, A; Bierman, P J

    2013-07-01

    The use of autologous hematopoietic SCT (auto-HSCT) has expanded to include older patients. Increasing age is a well-appreciated risk factor for the development of atrial fibrillation and/or atrial flutter (AF/AFL) in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF/AFL post transplant may also increase. However, few data evaluating other risk factors for the development of AF/AFL following auto-HSCT exist. Therefore, we performed a retrospective study to determine the incidence of AF/AFL following auto-HSCT and to determine the risk factors associated with the development of AF/AFL. Patients who developed AF/AFL were compared with a group of patients who received auto-HSCT within the same time period (April 1999 to May 2005) and were within 5 years of age. Of the 516 patients who underwent auto-HSCT at the University of Nebraska Medical Center 44 (8.5%) developed AF/AFL at a median time of 4 days (range, days 1-9) following auto-HSCT. In multivariate analysis, risk factors for developing AF/AFL were older age, odds ratio and 95% CI of 1.14 (1.07-1.21), elevated serum creatinine level, 2.69 (1.00-7.22), history of previous arrhythmia, 9.33 (3.01-28.99), and history of previous mediastinal irradiation, 11.12 (1.33-92.96).

  17. (/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.

  18. Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing

    PubMed Central

    Billon-Galés, Audrey; Krust, Andrée; Fontaine, Coralie; Abot, Anne; Flouriot, Gilles; Toutain, Céline; Berges, Hortense; Gadeau, Alain-Pierre; Lenfant, Françoise; Gourdy, Pierre; Chambon, Pierre; Arnal, Jean-François

    2011-01-01

    17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF20). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF20 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF20 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF20 in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF20 LDL-r−/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect. PMID:21788522

  19. 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. Copyright © 2013 Wiley Periodicals, Inc.

  20. 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. © 2015 Wiley Periodicals, Inc.

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

    NASA Astrophysics Data System (ADS)

    Piatti, Andrés E.

    2016-12-01

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

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

    PubMed

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

    1998-02-01

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

  3. An unusual morphological anomaly in an incisor crown. Anterior dens evaginatus.

    PubMed

    Llena-Puy, Mari Carmen; Forner-Navarro, Leopoldo

    2005-01-01

    Exophytic growth of a portion of the tissue structure is one of the various clinical manifestations of the morphological anomalies that can affect the crown of the anterior teeth. The crown form disorder presented in this paper consists of an asymptomatic bulge on part of the vestibular surface of the tooth, due to enamel and dentine growth, with no radiological evidence of the pulp having extended into the protrusion of mineralised tissues. In this case, it only affects one tooth and is not associated with any other dental morphology or structure disorder, or with any of the syndromes that have been described in association with this anomaly. The term to describe this situation in the anterior teeth is not clearly defined in the relevant literature, which employs various names such as talon cusp, accentuated cingulum (when it affects the lingual or palatal surface) or dens evaginatus (evaginated tooth, evaginated odontome), the term that is always used when it is present in the posterior teeth.

  4. 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. © 2014 Wiley Periodicals, Inc.

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

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

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

  6. 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

  7. Purification of a new antifungal compound produced by Lactobacillus plantarum AF1 isolated from kimchi.

    PubMed

    Yang, E J; Chang, H C

    2010-04-30

    The aim of this study was to purify and to identify an antifungal compound of Lactobacillus plantarum AF1, which was isolated from kimchi, and to determine if Lb. plantarum AF1 can prevent fungal growth in a particular food model system. The antifungal compound was purified using SPE and recycling prep-HPLC and its structure was elucidated using NMR and ESI-MS. The active compound from Lb. plantarum AF1 is C(12)H(22)N(2)O(2), 3,6-bis(2-methylpropyl)-2,5-piperazinedion has a molecular mass of 226. This is a new antifungal compound produced by lactic acid bacteria (LAB). To investigate the potential application of the antifungal compound to eliminate fungal spoilage in food and feed, soybean was used as a model. White mycelia and dark green spores of Aspergillus flavus ATCC 22546 were observed in the control soybeans after 1 to 2days incubation. However, fungal growth was not observed in the soybeans treated with a 4-fold concentrated supernatant of Lb. plantarum AF1 culture, even after 2days. The end products produced from kimchi LAB, like 3,6-bis(2-methylpropyl)-2,5-piperazinedion identified in this study, may be a promising alternative to chemical preservatives as a potential biopreservative which prevent fungal spoilage and mycotoxin formation in food and feed. Copyright 2010 Elsevier B.V. All rights reserved.

  8. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., refined oil; cotton, undelinted seed. (b) An exemption from the requirement of a tolerance is established... 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...

  9. First Report of an Infant Botulism Case Due to Clostridium botulinum Type Af

    PubMed Central

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

    2014-01-01

    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. PMID:25502535

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

    PubMed Central

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

    2014-01-01

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

  11. 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.

  12. 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.

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

    PubMed

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

    2010-04-02

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

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

    PubMed

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

    2014-05-29

    The use of novel yeast strains for winemaking improves quality and provides variety including subtle characteristic differences in fine wines. Here we report the first genome of a yeast strain native to Uruguay, Hanseniaspora vineae T02/19AF, which has been shown to positively contribute to aroma and wine quality. Copyright © 2014 Giorello et al.

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

    ERIC Educational Resources Information Center

    Dixon, Helen; Hawe, Eleanor

    2016-01-01

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

  16. 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, when...

  17. 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, when...

  18. 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.

  19. 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

  20. 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.

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

    PubMed

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

    2005-12-01

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

  2. Talon cusps occurring concurrently with dens invaginatus on a permanent maxillary lateral incisor: a case report and literature review.

    PubMed

    Colak, Hakan; Yilmaz, Cicek; Keklik, Hakan; Colak, Tugba

    2014-01-01

    A talon cusp is a prominent accessory horn-like structure that projects from the cingulum or cementoenamel junction of the maxillary or mandibular teeth. It can occur in primary and permanent dentition and can lead to occlusal interference, irritation of the tongue, pulpal necrosis, caries, and periodontal problems. Talon cusp has been reported to affect both sexes, and may be unilateral or bilateral. Talon cusps occur most often on the palatal surface of permanent maxillary incisors. A comprehensive literature review revealed only 6 reported cases of facial talon cusps. A talon cusp occurring simultaneously with dens invaginatus in a tooth is extremely rare; to date, only 9 case reports have been published. This article presents a unique case of concurrent dens invaginatus and palatal and facial talon cusps in the right maxillary central incisor of a 12-year-old girl.

  3. Open apex type III dens invaginatus: a rare case report of an endodontic retreatment with an anatomical redesign.

    PubMed

    Silva, Emmanuel Joao Nogueira Leal Da; Zaia, Alexandre Augusto

    2012-01-01

    Dens invaginatus is a critical condition for endodontic treatment. It frequently presents a complex internal anatomy and might be associated with incomplete root and apical development. This article presents one of the few reported cases of endodontic retreatment of Type III dens invaginatus. First, the internal anatomy was modified using burs under an operating microscope. Next, conventional chemical and mechanical preparation with hand files and 2.5% sodium hypochlorite was performed. Finally, an intracanal dressing with calcium hydroxide was used for nine months, at which point the anatomical features in the root canal system could be accessed. Adequate periradicular healing was observed and regression of the lesion was noted at the two-year follow-up. This case reinforces the idea that knowledge about the biologic aspects of endodontics, combined with adherence to technical standards, is helpful in resolving complex cases.

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2017-01-01

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

  6. Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

    PubMed

    Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

    Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

  7. 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

  8. 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.

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

    SciTech Connect

    Opperman, E; Kenneth Yates, K

    2007-10-19

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

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

    PubMed

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

    2010-12-22

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

  11. Diethylnitrosamine (DEN) induces irreversible hepatocellular carcinogenesis through overexpression of G1/S-phase regulatory proteins in rat.

    PubMed

    Park, Dae-Hun; Shin, Jae Wook; Park, Seung-Kee; Seo, Jae-Nam; Li, Lan; Jang, Ja-June; Lee, Min-Jae

    2009-12-15

    Hepatocellular carcinoma (HCC) is the fifth most frequent cause of cancer deaths in males and was the third most frequent cause of cancer deaths in 2007 throughout the world. The incidence rate is 2-3 times higher in developing countries than in developed countries. Animal models have enabled study of the mechanism of HCC and the development of possible strategies for treatment. Diethylnitrosamine (DEN) is a representative chemical carcinogen with the potential to cause tumors in various organs, including the liver, skin, gastrointestinal tract, and respiratory system. Specifically in HCC, DEN is a complete carcinogen. Many lines of evidence have demonstrated a relationship between carcinogenesis and cell cycle regulation. In this study we found that cell cycle regulatory proteins were critically involved in cancer initiation and promotion by DEN. Cyclin D1, cyclin E, cdk4, and p21(CIP1/WAF1) are factors whose expression levels may be useful as criteria for the classification of hepatic disease. In particular, cdk4 had a pivotal role in the transition to the neoplastic stage. In conclusion, we suggest that changes in the level of cdk4 may be useful as a biomarker for detection of HCC.

  12. 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

  13. 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.

  14. 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)

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  18. 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

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

    PubMed

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

    2010-10-08

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

  20. 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.

  1. A prospective, multicenter evaluation of ablating complex fractionated electrograms (CFEs) during atrial fibrillation (AF) identified by an automated mapping algorithm: acute effects on AF and efficacy as an adjuvant strategy.

    PubMed

    Verma, Atul; Novak, Paul; Macle, Laurent; Whaley, Bonnie; Beardsall, Marianne; Wulffhart, Zaev; Khaykin, Yaariv

    2008-02-01

    Complex fractionated electrograms (CFEs) are continuous electrograms (EGMs) of very short cycle length (CL) representing substrate for atrial fibrillation (AF) perpetuation. Ablation of CFEs may result in AF slowing, termination, and prevention, but identifying them can be subjective. The purpose of this study was to prospectively assess (1) whether an automated algorithm can identify CFE regions, (2) the acute effects of ablating these regions on AF, and (3) the long-term efficacy as an adjuvant strategy to pulmonary vein antrum isolation (PVAI). Thirty-five patients (three centers, 61 +/- 9 years, left atrium [LA] 43 +/- 9 mm, ejection fraction 53% +/- 7%) with symptomatic paroxysmal (n = 21) or persistent (n = 14) AF were studied. A decapolar lasso (2-mm spacing) was used for mapping. A three-dimensional shell of the LA and pulmonary veins (PVs) was created. If not already in AF, AF was induced by burst pacing (with or without isoproterenol). Atrial EGMs during AF were mapped/analyzed using an automated CFE algorithm. The algorithm measures the time between discrete deflections in a local EGM over 5 seconds (based on selectable width and peak-to-peak [>0.03 mV] criteria). The mean CL of the local EGM is projected onto the LA shell as a color-coded display. Regions of CL <120 ms (published criteria) were targeted for ablation/elimination. Atrial fibrillation cycle length (AFCL) and regularity were measured from the CS. After CFE ablation, further ablation was done to achieve complete PVAI. AF was spontaneous (n = 20) or induced (n = 15) in all patients. CFEs were most commonly found along the septum (97%), anterior LA (97%), PV antra (83%), base of appendage (83%), and annulus (71%). CFE ablation alone prolonged the AFCL (171 +/- 27 vs. 304 +/- 41 ms; P = .03) and regularized AF to left/right flutter (AFL) in 74% of patients. CFE ablation terminated AF/AFL in 19 patients (54%)-the other 16 were cardioverted-and AF became noninducible in 77%. CFE ablation alone

  2. ‘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

  3. The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.

    PubMed

    Dutta, S; Krause, A; Vosberg, S; Herold, T; Ksienzyk, B; Quintanilla-Martinez, L; Tizazu, B; Chopra, M; Graf, A; Krebs, S; Blum, H; Greif, P A; Vetter, A; Metzeler, K; Rothenberg-Thurley, M; Schneider, M R; Dahlhoff, M; Spiekermann, K; Zimber-Strobl, U; Wolf, E; Bohlander, S K

    2016-05-01

    The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B-cell marker B220, and had clonal B-cell receptor rearrangements. Using whole-exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia.

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

    PubMed

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

    2009-02-01

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

  5. Identification and characterization of a laminin-binding protein of Aspergillus fumigatus: extracellular thaumatin domain protein (AfCalAp).

    PubMed

    Upadhyay, Santosh Kumar; Mahajan, Lakshna; Ramjee, Sandhya; Singh, Yogendra; Basir, Seemi Farhat; Madan, Taruna

    2009-06-01

    Aspergillus fumigatus, an opportunistic fungal pathogen, infects the human host via inhalation of airborne conidia. Adhesion of fungal conidia, to host cells and extracellular matrix (ECM) components associated with host tissue surfaces, is thought to be the primary step in the pathogenesis and dissemination of infection. To identify novel adhesion proteins (adhesins) of A. fumigatus, we screened its proteome in silico using SPAAN (software program for prediction of adhesins and adhesin-like proteins using neural networks). One of the predicted adhesin-encoding genes with a P(ad) (probability of being adhesin) value >0.9, the gene encoding extracellular thaumatin domain protein (AfCalA), was cloned and expressed in Escherichia coli. Recombinant AfCalAp showed significant binding with laminin and murine lung cells. Anti-AfCalAp antibodies inhibited the binding of AfCalAp to laminin in a dose-dependent manner. Significant binding of anti-AfCalAp antibodies to 2 h swollen conidia suggests the presence of AfCalAp on the conidial surface. AfCalA transcript was not detectable in resting conidia but was detected in conidia incubated with RPMI 1640 medium in the presence and absence of lung epithelial cell line (A539)-derived ECM. Elevated levels of IgE antibodies specific to AfCalAp were observed in the sera of two out of seven patients with allergic bronchopulmonary aspergillosis. The study confirms the relevance of the bioinformatic approach for predicting fungal adhesins and establishes AfCalAp as a novel laminin-binding protein of A. fumigatus.

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

    DTIC Science & Technology

    1980-06-01

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

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

    DTIC Science & Technology

    1983-08-10

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

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

    PubMed

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

    2015-02-24

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

  9. Use of concomitant aspirin in patients with atrial fibrillation: Findings from the ROCKET AF trial.

    PubMed

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

    2016-09-01

    We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in 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), in particular, those with known coronary artery disease (CAD). Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009). Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice.

    PubMed

    Shah, Rohan; Patel, Manesh R

    2017-03-01

    The safety and efficacy of the oral anticoagulant rivaroxaban were studied 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). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical

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

    PubMed

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

    2017-04-01

    Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9-driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. Cancer Res; 77(7); 1753-62. ©2017 AACR. ©2017 American Association for Cancer Research.

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

    PubMed

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

    2010-06-01

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

  13. Ficusnotins A-F: Rare diarylbutanoids from the leaves of Ficus nota.

    PubMed

    Latayada, Felmer S; Uy, Mylene M; Akihara, Yui; Ohta, Emi; Nehira, Tatsuo; Ômura, Hisashi; Ohta, Shinji

    2017-09-01

    Six diarylbutanoids, designated as ficusnotins A-F, with a rare carbon skeleton consisting of two aromatic rings separated by an unbranched C4-chain have been isolated from the leaves of Ficus nota (Blanco) Merr. (Moraceae). The structures were determined on the basis of spectroscopic data, as well as X-ray crystallographic analysis. The isolated compounds were evaluated for their antibacterial activity against Bacillus subtilis. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    SciTech Connect

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

    2006-07-01

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

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

    PubMed

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

    2014-12-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    DTIC Science & Technology

    2010-07-26

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

  18. A comparison of ANB, WITS, AF-BF, and APDI measurements.

    PubMed

    Oktay, H

    1991-02-01

    In the present study, the relationships among ANB, Wits, AF-BF, and APDI measurements used in the assessment of the anteroposterior jaw disorders were examined on the cephalometric radiographs of 63 male and 82 female subjects, and high correlations were found among them. Furthermore, relationships were explored between these parameters and some measurements that were thought to have influenced them. The results of the geometric studies could not be proved on the basis of statistical evaluation.

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

    DTIC Science & Technology

    1981-05-01

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

  20. Blytheville AFB, Arkansas, Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1987-10-01

    AMOUNTS IN INCfOES .t I I I I I I 9 7 I 13 I 2S I 37 I 19 I 61 I OVER I I DARSI TOTALI IONIHLY...ION 46141 . ItYTIIIVILLC AF P AR FP310 jr EEcopo: 77-Ab MOlNTH: SEF HOuD56Llj: 0600-06(10...VARIA 1I L TO 16 LS I , 35., jr .6 1 .3 .1 .1 Ion., 6.89

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

    PubMed Central

    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. PMID:26779514

  2. Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells

    PubMed Central

    Liu, Y; Cheng, H; Gao, S; Lu, X; He, F; Hu, L; Hou, D; Zou, Z; Li, Y; Zhang, H; Xu, J; Kang, L; Wang, Q; Yuan, W; Gao, S; Cheng, T

    2014-01-01

    The ‘Yamanaka factors' (Oct4, Sox2, Klf4 and c-Myc) are able to generate induced pluripotent stem (iPS) cells from different cell types. However, to what degree primary malignant cells can be reprogrammed into a pluripotent state has not been vigorously assessed. We established an acute myeloid leukemia (AML) model by overexpressing the human mixed-lineage leukemia-AF9 (MLL-AF9) fusion gene in mouse hematopoietic cells that carry Yamanaka factors under the control of doxycycline (Dox). On addition of Dox to the culture, the transplantable leukemia cells were efficiently converted into iPS cells that could form teratomas and produce chimeras. Interestingly, most chimeric mice spontaneously developed the same type of AML. Moreover, both iPS reprogramming and leukemia reinitiation paths could descend from the same leukemia-initiating cell. RNA-seq analysis showed reversible global gene expression patterns between these interchangeable leukemia and iPS cells on activation or reactivation of MLL-AF9, suggesting a sufficient epigenetic force in driving the leukemogenic process. This study represents an important step for further defining the potential interplay between oncogenic molecules and reprogramming factors during MLL leukemogenesis. More importantly, our reprogramming approach may be expanded to characterize a range of hematopoietic malignancies in order to develop new strategies for clinical diagnosis and treatment. PMID:24150221

  3. Influence of Environmental Factors on the Production of Penitrems A-F by Penicillium crustosum.

    PubMed

    Kalinina, Svetlana A; Jagels, Annika; Cramer, Benedikt; Geisen, Rolf; Humpf, Hans-Ulrich

    2017-07-01

    Filamentous fungi produce a multitude of secondary metabolites, some of them known as mycotoxins, which are toxic to vertebrates and other animal groups in low concentrations. Among them, penitrems, which belong to the group of indole-diterpene mycotoxins, are synthesized by Penicillium and Aspergillus genera and exhibit potent tremorgenic effects. This is the first complex study of the penitrems A-F production under the influence of different abiotic factors, e.g., media, incubation time, temperature, pH, light, water activity, and carbon and nitrogen source as well as oxidative and salt stress. For this purpose, penitrems A-F were isolated from Penicillium crustosum cultures and used as analytical standards. Among the carbon sources, glucose supplemented to the media at the concentration of 50 g/L, showed the strongest inducing effect on the biosynthesis of penitrems. Among nitrogen sources, glutamate was found to be the most favorable supplement, significantly increasing production of these secondary metabolites. CuSO4-promoted oxidative stress was also shown to remarkably stimulate biosynthesis of all penitrems. In contrast, the salt stress, caused by the elevated concentrations of NaCl, showed an inhibitory effect on the penitrem biosynthesis. Finally, cheese model medium elicited exceptionally high production of all members of the penitrems family. Obtained results give insides into the biosynthesis of toxicologically relevant penitrems A-F under different environmental factors and can be utilized to prevent food contamination.

  4. 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.

  5. 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.

  6. 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...

  7. 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...

  8. Draft Genome Sequence of Komagataeibacter rhaeticus Strain AF1, a High Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

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

    2014-07-24

    Here, we present the draft genome sequence of Komagatabaeicter rhaeticus strain AF1, which was isolated from Kombucha tea and is capable of producing high levels of cellulose. Copyright © 2014 dos Santos et al.

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed

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

    1993-12-01

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

  12. Comparison of radiofrequency catheter ablation of drivers and circumferential pulmonary vein isolation in atrial fibrillation: a noninferiority randomized multicenter RADAR-AF trial.

    PubMed

    Atienza, Felipe; Almendral, Jesús; Ormaetxe, José Miguel; Moya, Angel; Martínez-Alday, Jesús Daniel; Hernández-Madrid, Antonio; Castellanos, Eduardo; Arribas, Fernando; Arias, Miguel Ángel; Tercedor, Luis; Peinado, Rafael; Arcocha, Maria Fe; Ortiz, Mercedes; Martínez-Alzamora, Nieves; Arenal, Angel; Fernández-Avilés, Francisco; Jalife, José

    2014-12-16

    Empiric circumferential pulmonary vein isolation (CPVI) has become the therapy of choice for drug-refractory atrial fibrillation (AF). Although results are suboptimal, it is unknown whether mechanistically-based strategies targeting AF drivers are superior. This study sought to determine the efficacy and safety of localized high-frequency source ablation (HFSA) compared with CPVI in patients with drug-refractory AF. This prospective, multicenter, single-blinded study of 232 patients (age 53 ± 10 years, 186 males) randomized those with paroxysmal AF (n = 115) to CPVI or HFSA-only (noninferiority design) and those with persistent AF (n = 117) to CPVI or a combined ablation approach (CPVI + HFSA, superiority design). The primary endpoint was freedom from AF at 6 months post-first ablation procedure. Secondary endpoints included freedom from atrial tachyarrhythmias (AT) at 6 and 12 months, periprocedural complications, overall adverse events, and quality of life. In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months after a single procedure but, after redo procedures, was noninferior to CPVI at 12 months for freedom from AF and AF/AT. Serious adverse events were significantly reduced in the HFSA group versus CPVI patients (p = 0.02). In persistent AF, there were no significant differences between treatment groups for primary and secondary endpoints, but CPVI + HFSA trended toward more serious adverse events. In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months but was noninferior to CPVI at 1 year in achieving freedom of AF/AT and a lower incidence of severe adverse events. In persistent AF, CPVI + HFSA offered no incremental value. (Radiofrequency Ablation of Drivers of Atrial Fibrillation [RADAR-AF]; NCT00674401). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-02-12

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

  14. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

    PubMed

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

    2012-01-01

    The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

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

    SciTech Connect

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

    2016-03-24

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

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

    SciTech Connect

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

    2006-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Ayer, Raghavan; Machmeier, P. M.

    1996-09-01

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

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

    PubMed

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

    2016-02-27

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

  19. 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

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

    PubMed

    Zou, D; Hai, Y; Ma, H

    1995-04-01

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

  1. Joint DEnKF-albedo assimilation scheme that considers the common land model subgrid heterogeneity and a snow density-based observation operator for improving snow depth simulations

    NASA Astrophysics Data System (ADS)

    Xu, Jianhui; Zhang, Feifei; Zhao, Yi; Shu, Hong; Zhong, Kaiwen

    2016-07-01

    For the large-area snow depth (SD) data sets with high spatial resolution in the Altay region of Northern Xinjiang, China, we present a deterministic ensemble Kalman filter (DEnKF)-albedo assimilation scheme that considers the common land model (CoLM) subgrid heterogeneity. In the albedo assimilation of DEnKF-albedo, the assimilated albedos over each subgrid tile are estimated with the MCD43C1 bidirectional reflectance distribution function (BRDF) parameters product and CoLM calculated solar zenith angle. The BRDF parameters are hypothesized to be consistent over all subgrid tiles within a specified grid. In the SCF assimilation of DEnKF-albedo, a DEnKF combining a snow density-based observation operator considers the effects of the CoLM subgrid heterogeneity and is employed to assimilate MODIS SCF to update SD states over all subgrid tiles. The MODIS SCF over a grid is compared with the area-weighted sum of model predicted SCF over all the subgrid tiles within the grid. The results are validated with in situ SD measurements and AMSR-E product. Compared with the simulations, the DEnKF-albedo scheme can reduce errors of SD simulations and accurately simulate the seasonal variability of SD. Furthermore, it can improve simulations of SD spatiotemporal distribution in the Altay region, which is more accurate and shows more detail than the AMSR-E product.

  2. Endodontic retreatment of dens invaginatus presenting with gutta-percha overfilling at the attached gingiva and chronic apical periodontitis: unusual clinical report.

    PubMed

    Robazza, Carlos Roberto Colombo; Alves e Motta, Julio Cesar; de Carli, Marina Lara; de Oliveira Pedreira, Fernanda Rafaelly; Hanemann, Joao Adolfo Costa

    2013-05-01

    This work describes the retreatment of an unusual case of dens invaginatus with gutta-percha overfilling at the gingival mucosa and chronic apical periodontitis in a 34-year-old woman. Initial periapical radiograph showed the presence of type II dens invaginatus with poor quality obturation, root perforation and chronic apical periodontitis of tooth 22. Dens invaginatus is a tooth malformation caused by infolding of the dental papilla during tooth development. This anomaly has been associated with increased prevalence of pulpal and periapical diseases. Conventional endodontic retreatment was performed using rotary files and calcium hydroxide paste as intracanal dressing. After 7 days, root canal was filled with guttapercha points and Sealapex® sealer. Obturation was radiographically followed and, after 3 years, absence of fistula and periapical radiolucency was observed, thus conventional endodontic therapy proved to be successful. Conventional endodontic retreatment of type II dens invaginatus has been successful for a 3-year period, showing a better treatment alternative. Conservative endodontic retreatment of dens invaginatus should be considered to promote periapical healing with complete reconstitution of bone and periodontal ligament regeneration without signs of recurrence over a period of 3 years. Moreover, it preserves the entire tooth.

  3. Loss of AF-6/afadin induces cell invasion, suppresses the formation of glandular structures and might be a predictive marker of resistance to chemotherapy in endometrial cancer.

    PubMed

    Yamamoto, Takuro; Mori, Taisuke; Sawada, Morio; Matsushima, Hiroshi; Ito, Fumitake; Akiyama, Makoto; Kitawaki, Jo

    2015-04-12

    AF-6/afadin plays an important role in the formation of adherence junctions. In breast and colon cancer, loss of AF-6/afadin induces cell migration and cell invasion. We aimed to elucidate the role of AF-6/afadin in human endometrial cancer. Morphology and AF-6/afadin expression in endometrial cancer cell lines was investigated by 3-dimensional culture. We used Matrigel invasion assay to demonstrate AF-6/afadin knockdown induced invasive capability. Cell proliferation assay was performed to estimate chemoresistance to doxorubicin, paclitaxel and cisplatin induced by AF-6/afadin knockdown. The associations between AF-6/afadin expression and clinicopathological status were determined by immunohistochemical analysis in endometrial cancer tissues. Informed consent was obtained from all patients before the study. The majority of cell clumps in 3-dimensional cultures of Ishikawa cells that strongly expressed AF-6/afadin showed round gland-like structures. In contrast, the cell clumps in 3-dimensional cultures of HEC1A and AN3CA cells-both weakly expressing AF-6/afadin-showed irregular gland-like structures and disorganized colonies with no gland-like structures, respectively. AF-6/afadin knockdown resulted in reduced number of gland-like structures in 3-dimensional cultures and enhancement of cell invasion and phosphorylation of ERK1/2 and Src in the highly AF-6/afadin-expressing endometrial cancer cell line. Inhibitors of MAPK/ERK kinase (MEK) (U0126) and Src (SU6656) suppressed the AF-6/afadin knockdown-induced invasive capability. AF-6/afadin knockdown induced chemoresistance to doxorubicin, paclitaxel and cisplatin in Ishikawa cells, not in HEC1A. Immunohistochemical analysis showed that AF-6/afadin expression was significantly associated with myometrial invasion and high histological grade. AF-6/afadin regulates cell morphology and invasiveness. Invasive capability is partly regulated through the ERK and Src pathway. The inhibitors to these pathways might be

  4. 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

  5. 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

  6. Bumpus in the snake den: effects of sex, size, and body condition on mortality of red-sided garter snakes.

    PubMed

    Shine, R; LeMaster, M P; Moore, I T; Olsson, M M; Mason, R T

    2001-03-01

    Huge breeding aggregations of red-sided garter snakes (Thamnophis sirtalis parietalis) at overwintering dens in Manitoba provide a unique opportunity to identify sources of mortality and to clarify factors that influence a snake's vulnerability to these factors. Comparisons of sexes, body sizes, and body condition of more than 1000 dead snakes versus live animals sampled at the same time reveal significant biases. Three primary sources of mortality were identified. Predation by crows, Corvus brachyrhynchos (590 snakes killed), was focussed mostly on small snakes of both sexes. Crows generally removed the snake's liver and left the carcass, but very small snakes were sometimes brought back to the nest. Suffocation beneath massive piles of other snakes within the den (301 dead animals) involved mostly small males and (to a lesser extent) large females; snakes in poor body condition were particularly vulnerable. Many emaciated snakes (n = 142, mostly females) also died without overt injuries, probably due to depleted energy reserves. These biases in vulnerability are readily interpretable from information on behavioral ecology of the snakes. For example, sex biases in mortality reflect differences in postemergence behavior and locomotor capacity, the greater attractiveness of larger females to males, and the high energy costs of reproduction for females.

  7. Growth characteristics of ChimeriVax-Den vaccine viruses in Aedes aegypti and Aedes albopictus from Thailand.

    PubMed

    Higgs, Stephen; Vanlandingham, Dana L; Klingler, Kimberly A; McElroy, Kate L; McGee, Charles E; Harrington, Laura; Lang, Jean; Monath, Thomas P; Guirakhoo, Farshad

    2006-11-01

    Four chimeric yellow fever (YF) 17D-dengue (DEN) candidate vaccine viruses (ChimeriVax-DEN; Acambis, Cambridge, MA) were characterized in Aedes aegypti and Ae. albopictus mosquitoes collected from Thailand. The four vaccine viruses contained the relevant prM and E genes of wild-type dengue viruses (DENV; serotypes 1-4) substituted for the equivalent genes in the YF vaccine virus (17D) backbone. Each chimera conferred protection against the homologous DENV serotype; a tetravalent mix of all four chimeras stimulates an immune response against all serotypes. Field-collected mosquitoes from Thailand were fed on blood containing each of the viruses under study and held 21 days after infection. Infection and dissemination rates were based on antigen detection in the body or head tissues, respectively. All four wild-type DENV serotypes infected and disseminated, but the candidate vaccine viruses were highly attenuated in mosquitoes with respect to infection and especially with respect to dissemination. Considering the low level viremias anticipated in humans vaccinated with these viruses, it is predicted that the risks of infection and transmission by mosquitoes in nature is minimal.

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

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

  9. 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

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

    PubMed

    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

    2015-02-01

    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. 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). 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. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study.

    PubMed

    Turakhia, Mintu P; Santangeli, Pasquale; Winkelmayer, Wolfgang C; Xu, Xiangyan; Ullal, Aditya J; Than, Claire T; Schmitt, Susan; Holmes, Tyson H; Frayne, Susan M; Phibbs, Ciaran S; Yang, Felix; Hoang, Donald D; Ho, P Michael; Heidenreich, Paul A

    2014-08-19

    Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). The goal of this study was to evaluate the association of digoxin with mortality in AF. Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis. Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin. Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.

    PubMed

    Wong, Ka Sing Lawrence; Hu, Dai Yi; Oomman, Abraham; Tan, Ru-San; Patel, Manesh R; Singer, Daniel E; Breithardt, Günter; Mahaffey, Kenneth W; Becker, Richard C; Califf, Robert; Fox, Keith A A; Berkowitz, Scott D; Hacke, Werner; Hankey, Graeme J

    2014-06-01

    In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. http://www.clinicaltrials.gov. Unique identifier: NCT00123456. © 2014 American Heart Association, Inc.

  15. 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.

  16. Decision making for oral anticoagulants in atrial fibrillation: the ATA-AF study.

    PubMed

    Gussoni, Gualberto; Di Pasquale, Giuseppe; Vescovo, Giorgio; Gulizia, Michele; Mathieu, Giovanni; Scherillo, Marino; Panuccio, Domenico; Lucci, Donata; Nozzoli, Carlo; Fabbri, Gianna; Colombo, Fabrizio; Riva, Letizia; Baldo, Concetta I; Maggioni, Aldo P; Mazzone, Antonino

    2013-06-01

    Oral anticoagulants offer the best long-term protection against ischemic stroke in patients with atrial fibrillation (AF). However, vitamin K antagonists (VKA) are cumbersome to use and their prescription is far from guidelines recommendations. We report the results of a large survey on the attitudes of prescription of VKA in patients with AF. 7148 patients were enrolled by 196 Internal Medicine (MED) and 164 Cardiology (CARD) centers, and VKA specifically analyzed. Thrombotic and hemorrhagic risks were evaluated by means of CHADS2 and CHA2DS2VASc scores, and a study-specific bleeding score (modified HAS-BLED). 63.9% of non-valvular patients had a CHADS2 score≥2 (MED: 75.3%-CARD: 53.1%), and 28.4% a bleeding score≥3 (41.9% MED-15.8% CARD). VKA were prescribed in 55.5% of non-valvular patients (46.3% MED and 64.2% CARD), in 81% of high-risk valvular patients and in 58.8% of the overall study population. Among patients at high risk of bleeding (score≥3), VKA were prescribed in 26.9% of subjects, while, in the subgroup at high risk of thrombosis (CHADS2 Score<2), these were prescribed in 54.4%. Age≥75, paroxysmal AF, cognitive impairment, need for assistance, CHADS2<2 and bleeding score≥3 were independent predictors of non-use of VKA. Oral anticoagulants are more frequently used in CARD than in MED, plausibly due to greater complexity of MED patients. Stratification of thrombotic and hemorrhagic risk significantly drives the choice for VKA. However the fraction of patients in whom prescription or non-prescription is based on other individual characteristics is not negligible. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

    Zhong, Shuping

    2013-01-01

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

  18. Radialgeschwindigkeiten und eine verbesserte Loesung für Doppelsternsystem AF Ari

    NASA Astrophysics Data System (ADS)

    Hauck, Norbert

    2013-03-01

    An improved solution for eclipsing binary AF Ari has been found by simultaneous fitting new radial-velocity data of the primary giant component and old photometry data to computed curves. The orbital period of 153 days and eccentricity of 0.36 has been confirmed. The new calibration has resulted in somewhat increased radii and masses of the components: 11.7 Rsun and 2.9 Msun for the G-type giant as well as 2.3 Rsun and 2.0 Msun for the A star. The english version of the paper will be found after the german article. Norbert Hauck is member of the BAV.

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

    PubMed

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

    2015-09-01

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

  20. Spectral analysis of LBV stars in M31: AF And and Var 15

    NASA Astrophysics Data System (ADS)

    Valeev, A. F.; Sholukhova, O.; Fabrika, S.

    2015-01-01

    We study spectra of two bona fide LBV stars in M31: AF And and Var 15. The spectra were obtained with the 6-m telescope (Russia) from 2005 to 2012. The model spectra were calculated with the CMFGEN code. We have not found strong changes in the spectra of the LBV stars in that time interval, however a certain variability has been detected. We estimate the star and wind parameters, such as luminosity, temperature, raduis, mass loss rate, escape velocity, hydrogen content, and reddening. We study the stars on the Hertzsprung-Russell diagram and find their initial masses using evolutionary tracks by Meynet et al. (1994).

  1. Different image integration modalities to guide AF ablation: impact on procedural and fluoroscopy times.

    PubMed

    Pratola, Claudio; Baldo, Elisa; Artale, Paolo; Marcantoni, Lina; Toselli, Tiziano; Percoco, Gianfranco; Sassone, Biagio; Ferrari, Roberto

    2011-04-01

    Different image integration modalities are available for atrial fibrillation (AF) ablation, but their impact on procedural and fluoroscopy times has not been evaluated yet. Sixty patients (mean age 52.2 ± 12.0 years, 48.3% men, 75% paroxysmal AF) undergoing pulmonary vein (PV) encircling with PV disconnection for symptomatic drug-refractory AF were randomized to ablation with CARTO electroanatomical mapping (Biosense Webster, Diamond Bar, CA, USA) integrated with: (1) preprocedural magnetic resonance imaging (MRI; Group 1); (2) intracardiac echocardiography (ICE; Group 2); (3) preprocedural MRI and ICE (Group 3). PV disconnection was achieved in all patients. Total procedural time (Group 1: 124.7 ± 47.0; Group 2: 112.5 ± 30.4; Group 3: 108.6 ± 34.7 minutes) and total ablation time were similar between groups (P = ns). MRI integration alone required a higher fluoroscopy time (23.8 ± 6.9 in Group 1 vs 11.0 ± 2.3 and 13.9 ± 4.2 minutes in Groups 2 and 3, respectively; P < 0.005) and a longer time spent in the left atrium (109.0 ± 43.5 in Group 1 vs 78.2 ± 29.7 and 74.8 ± 34.3 minutes in Groups 2 and 3, respectively; P = 0.03) in comparison to ICE integration. Addition of MRI to ICE integration showed a tendency for a higher fluoroscopy time in comparison to ICE integration alone (P = 0.06). At a mean follow-up of 9.1 ± 2.2 months, there were no significant differences in AF recurrences among the groups (P = ns). ICE image integration significantly reduces the fluoroscopy time and the time spent in the left atrium in comparison to MRI integration alone. Addition of MRI to ICE integration does not reduce total procedural time and seems to lead to higher fluoroscopy time in comparison to ICE integration alone. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

  2. Alconbury RAF United Kingdom Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1984-04-01

    AD A746 q13 ALCONBURY RAF UNITED KINGDOM REVISFD UNIFORM SUMMARY OF 1/5SURFACE WEAIER 0..(t0) AIR FORCE ENVIRONMENTAL I CNICAI APPI CATI(NS CENTER...PROCESSING DIVISION USAFETAC Air Weather Service ( MAC) 0SURFACL V, LI’. ILI, I.LRVATIONS F4 ALCOjIwURY RAF UK HSIA #0362 N 52 22 W 000 13 EIEV 16OFIT EGWZ...A RAIWOKUTNMBS Air Force Environmental Technical Appi. Center Scott AFS, IL 62225 1 1 CONTROLLING OFFICE NAME AND ADDRESS OZ. REPORT DATS USAFETAC

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

    PubMed

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

    2009-08-01

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

  4. 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.

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

    DTIC Science & Technology

    1974-08-07

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

  6. 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.

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

    PubMed

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

    2009-11-05

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

  8. A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

    PubMed Central

    Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

    2017-01-01

    Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination

  9. Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.

    PubMed

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

    2013-05-14

    This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin

  10. Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

    PubMed

    Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

    2017-08-26

    Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT2R2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support,education, and patient

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

    PubMed

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

    2009-12-01

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

  12. 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.

  13. The vegetative compatibility group to which the US biocontrol agent Aspergillus flavus AF36 belongs is also endemic to Mexico.

    PubMed

    Ortega-Beltran, A; Grubisha, L C; Callicott, K A; Cotty, P J

    2016-04-01

    To assess frequencies of the Aspergillus flavus atoxigenic vegetative compatibility group (VCG) YV36, to which the biocontrol agent AF36 belongs, in maize-growing regions of Mexico. Over 3500 A. flavus isolates recovered from maize agroecosystems in four states of Mexico during 2005 through 2008 were subjected to vegetative compatibility analyses based on nitrate nonutilizing mutants. Results revealed that 59 (1·6%) isolates belong to VCG YV36. All 59 isolates had the MAT1-2 idiomorph at the mating-type locus and the single nucleotide polymorphism in the polyketide synthase gene that confers atoxigenicity. Additional degradation of the aflatoxin gene cluster was detected in three isolates. Microsatellite loci analyses revealed low levels of genetic diversity and no linkage disequilibrium within VCG YV36. The VCG to which the biocontrol agent AF36 belongs, YV36, is also native to Mexico. The North American Free Trade Agreement should facilitate adoption of AF36 for use by Mexico in aflatoxin prevention programs. An USEPA registered biocontrol agent effective at preventing aflatoxin contamination of crops in the US, is also native to Mexico. This should facilitate the path to registration of AF36 as the first biopesticide for aflatoxin mitigation of maize in Mexico. Economic and health benefits to the population of Mexico should result once aflatoxin mitigation programs based on AF36 applications are implemented. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  14. 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

  15. 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

  16. 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.

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed

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

    2013-02-01

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

  19. 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.

  20. 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.

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

    PubMed

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

    2016-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-07-17

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  5. EPA Region 2 AIRS FACILITY SUBSYSTEM (AIRS-AFS) GIS Layer

    EPA Pesticide Factsheets

    This ArcGIS 10.2 point feature class contains identification, location and status information for EPA Region 2 facilities (NYS, NJ, Puerto Rico and the US Virgin Islands) registered in the Aerometric Information Retrieval System - Air Facility Subsystem. (AIRS/AFS). The AFS subsystem contains emissions, compliance, and permit data for stationary sources regulated by the U.S. EPA and state and local air pollution agencies. This information is used by states in preparation of State Implementation Plans (SIPs), to track the compliance status of point sources with various regulatory programs, and report emissions estimates for pollutants regulated under the Clean Air Act.All data for EPA Region 2 Regulated Facility GIS layers are extracted from the Facility Registry System (FRS) of Envirofacts on a monthly basis using R2GIS SQL procedures and Linked Server definitions. The attributes for each media specific R2GIS Regulated Facility layer provides the ID, name, address and environmental interest (permit designation or regulated activity) from the parent media program system and the best available coordinates from the FRS Geospatial Tables except for the Region 2 CERLIS layers were all locational data is from the CERCLIS database only. There are a small percentage of EPA Regulated Facilities for which no coordinate information has been registered in any of the related EPA or State Program System Databases. These facilities will have attribute table records in the Fa

  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. 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).

  8. A Numerical Analysis of Selected Elastic-Plastic Fracture Parameters for DEN(T) Plates under Plane Strain Conditions

    NASA Astrophysics Data System (ADS)

    Graba, M.

    2017-02-01

    This paper provides a numerical analysis of selected parameters of fracture mechanics for double-edge notched specimens in tension, DEN(T), under plane strain conditions. The analysis was performed using the elastic-plastic material model. The study involved determining the stress distribution near the crack tip for both small and large deformations. The limit load solution was verified. The J-integral, the crack tip opening displacement, and the load line displacement were determined using the numerical method to propose the new hybrid solutions for calculating these parameters. The investigations also aimed to identify the influence of the plate geometry and the material characteristics on the parameters under consideration. This paper is a continuation of the author's previous studies and simulations in the field of elastic-plastic fracture mechanics.

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

    PubMed

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

    2017-02-01

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

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

    PubMed

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

    2008-12-01

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

  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. MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia.

    PubMed

    Monroe, Sara C; Jo, Stephanie Y; Sanders, Daniel S; Basrur, Venkatesha; Elenitoba-Johnson, Kojo S; Slany, Robert K; Hess, Jay L

    2011-01-01

    The aim of this study was to better understand how mixed lineage leukemia (MLL) fusion proteins deregulate the expression of genes critical for leukemia. The transforming domain of one of the most common MLL fusion partners, AF9, was immunopurified after expression in myeloblastic M1 cells, and associating proteins were identified by mass spectrometric analysis. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction was used to determine how binding of associating proteins compare across Hoxa9 and Meis1 in cell lines with and without MLL fusion proteins and how binding is altered during gene down-regulation and differentiation. Consistent with earlier purifications of ENL and AF4 from 293 cells, the 90 amino acid C-terminal domain of AF9 associates with many other MLL translocation partners including Enl, Af4, Laf4, Af5q31, Ell, and Af10. This complex, termed elongation assisting proteins (EAPs), also contains the RNA polymerase II C-terminal domain kinase Cdk9/Cyclin T1/T2 (pTEFb) and the histone H3 lysine 79 methyltransferase Dot1L. Myeloid cells transformed by MLL fusions show higher levels and a broader distribution of EAP components at genes critical for leukemia. Inhibition of EAP components pTEFb and Dot1l show that both contribute significantly to activation of Hoxa9 and Meis1 expression. EAP is dynamically associated with the Hoxa9 and Meis1 loci in hematopoietic cells and rapidly dissociates during induction of differentiation. In the presence of MLL fusion proteins, its dissociation is prevented. The findings suggest that MLL fusion proteins deregulate genes critical for leukemia by excessive recruitment and impaired dissociation of EAP from target loci. Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  13. MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia

    PubMed Central

    Monroe, Sara C.; Jo, Stephanie Y.; Sanders, Daniel S.; Basrur, Venkatesha; Elenitoba-Johnson, Kojo S.; Slany, Robert K.; Hess, Jay L.

    2011-01-01

    Objective The aim of this study was to better understand how MLL fusion proteins deregulate the expression of genes critical for leukemia. Materials and Methods The transforming domain of one of the most common MLL fusion partners, AF9, was immuno-purified after expression in myeloblastic M1 cells and associating proteins were identified by mass spectrometric analysis. Chromatin immunoprecipitation followed by quantitative PCR was used to determine how binding of associating proteins compare across Hoxa9 and Meis1 in cell lines with and without MLL fusion proteins and how binding is altered during gene down-regulation and differentiation. Results Consistent with earlier purifications of ENL and AF4 from 293 cells, the 90 amino acid C- terminal domain of AF9 associates with many other MLL translocation partners including Enl, Af4, Laf4, Af5q31, Ell, and Af10. This complex termed EAP for Elongation Assisting Proteins, also contains the RNA polymerase II C terminal domain kinase Cdk9/Cyclin T1/T2 (pTEFb) and the histone H3 lysine 79 methyltransferase Dot1L. Myeloid cells transformed by MLL fusions show higher levels and a broader distribution of EAP components at genes critical for leukemia. Inhibition of EAP components pTEFb and Dot1l show that both contribute significantly to activation of Hoxa9 and Meis1 expression. EAP is dynamically associated with the Hoxa9 and Meis1 loci in hematopoietic cells and rapidly dissociates during induction of differentiation. In the presence of MLL fusion proteins, its dissociation is prevented. Conclusion The findings suggest that MLL fusion proteins deregulate genes critical for leukemia by excessive recruitment and impaired dissociation of EAP from target loci. PMID:20854876

  14. 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.

  15. 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

  16. Non-surgical endodontic treatment for dens invaginatus type III using cone beam computed tomography and dental operating microscope: a case report.

    PubMed

    Kato, Hiroshi

    2013-01-01

    Dens invaginatus is a morphological abnormality of the tooth in which the coronal tooth enamel and dentin fold inwards towards the pulp cavity. Dens invaginatus type III (Oehlers: 1957) is characterized by infolding of the enamel and dentin as far as the root apex. This report describes a case of surgical and non-surgical endodontic therapy for a maxillary lateral incisor with type III dens invaginatus, necrotic pulp, and an associated large periradicular lesion. The patient was a 16-year-old man. Periapical radiographs suggested the presence of an untreated area of invagination. Cone beam computed tomography (CBCT) was then used for three-dimensional observation of the morphological details of this area. The CBCT scans revealed invagination and its relationship with the pulp chamber. A dental operating microscope was used to access two primary root canals and the area of invagination. The root canals were then localized, negotiated, enlarged, and filled with calcium hydroxide. Two months later, the canal and invagination were obturated with core-based gutta-percha (FlexPoint Neo: FP core-carrier technique) and restored. Cone beam computed tomography and microscopic techniques allow even complicated cases of dens invaginatus to be diagnosed and treated using non-surgical root canal management.

  17. 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

  18. Upper Pleistocene Gulo gulo (Linne, 1758) remains from the Srbsko Chlum-Komin Hyena den cave in the Bohemian Karst, Czech Republic, with comparisons to contemporary wolverines

    Treesearch

    Cajus G. Diedrich; Jeffrey P. Copeland

    2010-01-01

    Wolverine bone material is described from the famous Upper Pleistocene cave Srbsko Chlum-Komin in the Bohemian Karst, Czech Republic, along with an overview of recently known Czech sites. The Gulo gulo Linne material was found in one of the largest Ice Age spotted-hyena dens in Europe. As a result of non-systematic excavations, the taphonomy is partly unclear. Lower-...

  19. 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…

  20. AF03, an alternative squalene emulsion-based vaccine adjuvant prepared by a phase inversion temperature method.

    PubMed

    Klucker, Marie-Françoise; Dalençon, François; Probeck, Patricia; Haensler, Jean

    2012-12-01

    AF03 is a squalene-based emulsion adjuvant that is present in the adjuvanted pandemic influenza vaccine, Humenza™. In this report, we describe the design and development of this novel adjuvant formulation from the selection of the oil and surfactant system used in the adjuvant composition to the phase inversion temperature emulsification process that afforded AF03 as a long-term stable and well calibrated oil-in-water emulsion. The emulsion was characterized by its particle sizes, surface and interfacial tensions, viscosity, and long-term stability. Copyright © 2012 Wiley Periodicals, Inc.

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

    DTIC Science & Technology

    1982-07-01

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

  2. VizieR Online Data Catalog: Algol-type binaries. VIII. DI Peg & AF Gem (Yang+, 2014)

    NASA Astrophysics Data System (ADS)

    Yang, Y.-G.; Yang, Y.; Li, S.-Z.

    2014-10-01

    In the 2012-2013 observing season, DI Peg and AF Gem were observed using the 60cm telescope and the 85cm telescope at Xinglong station (XLs) of National Astronomical Observatories of Chinese (NAOC). The standard Johnson-Cousins UBVRcIc photometric systems were mounted upon two small telescopes. On five consecutive nights from 2012 October 9 to 13, the multi-color photometry of DI Peg was made with the 60cm telescope. The other variable star, AF Gem, was observed using the 85cm telescope on 7 nights from 2013 January 1 to 7. (5 data files).

  3. The Atrial Fibrillation Therapies after ER visit: Outpatient Care for Patients with Acute AF - The AFTER3 Study.

    PubMed

    Angaran, Paul; Mariano, Zara; Dragan, Vlad; Zou, Lily; Atzema, Clare L; Mangat, Iqwal; Dorian, Paul

    2015-01-01

    Visits to the emergency room (ER) for atrial fibrillation/flutter (AF) are common, but follow-up care is rarely systematically organized and is often delayed. We conducted a pilot program to develop a systematic, protocol-based system of care for patients presenting to the ER with a primary diagnosis of AF. Consecutive patients presenting to the ER with ECG-documented AF at an urban teaching hospital were treated according to a guideline-based care protocol, including a patient toolkit at ER discharge, and systematic referral to a rapid access AF clinic. Consenting patients received questionnaires on AF knowledge, patient satisfaction, and the AFEQT questionnaire at first visit and three-month follow-up. Of the 321 patients with AF, 244 (76%) were discharged from the ER and 166 (68%) were referred to the AF clinic for urgent follow-up. Among 166 referred, 144 (87%) were seen, within a median 10.5 days (IQR 6-16.5 days); 128 (89%) patients agreed to participate in the study and 81% received a toolkit in the ER. The mean age of patients seen in AF clinic was 63.6±13.2 years and 59% were male. Eighty-seven percent were aware of their diagnosis, stroke risk (82%), possible complications (90%), treatment options (86%) and benefits of adherence (86%). Severity of Atrial Fibrillation class was > 2 in 51% at baseline; AFEQT scores increased from baseline (56.4±25.5) to three months post-ER visit (76.4±20.0), a moderately large improvement in QOL (p<0.0001). Seventy eight percent of patients with CHA2DS2-VASc score > 1 were treated with an oral anticoagulant. A systematic program to improve patient transition of care from the ER to community clinic was associated with prompt, guideline-based care, and high levels of patient disease awareness. Quality of life scores improved substantially between the index ER visit and 3 months post-visit.

  4. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Ligand-independent FLT3 activation does not cooperate with MLL-AF4 to immortalize/transform cord blood CD34+ cells.

    PubMed

    Montes, R; Ayllón, V; Prieto, C; Bursen, A; Prelle, C; Romero-Moya, D; Real, P J; Navarro-Montero, O; Chillón, C; Marschalek, R; Bueno, C; Menendez, P

    2014-03-01

    MLL-AF4 fusion is hallmark in high-risk infant pro-B-acute lymphoblastic leukemia (pro-B-ALL). Our limited understanding of MLL-AF4-mediated transformation reflects the absence of human models reproducing this leukemia. Hematopoietic stem/progenitor cells (HSPCs) constitute likely targets for transformation. We previously reported that MLL-AF4 enhanced hematopoietic engraftment and clonogenic potential in cord blood (CB)-derived CD34+ HSPCs but was not sufficient for leukemogenesis, suggesting that additional oncogenic lesions are required for MLL-AF4-mediated transformation. MLL-AF4+ pro-B-ALL display enormous levels of FLT3, and occasionally FLT3-activating mutations, thus representing a candidate cooperating event in MLL-AF4+ pro-B-ALL. We have explored whether FLT3.TKD (tyrosine kinase domain) mutation or increased expression of FLT3.WT (wild type) cooperates with MLL-AF4 to immortalize/transform CB-CD34+ HSPCs. In vivo, FLT3.TKD/FLT3.WT alone, or in combination with MLL-AF4, enhances hematopoietic repopulating function of CB-CD34+ HSPCs without impairing migration or hematopoietic differentiation. None of the animals transplanted with MLL-AF4+FLT3.TKD/WT-CD34+ HSPCs showed any sign of disease after 16 weeks. In vitro, enforced expression of FLT3.TKD/FLT3.WT conveys a transient overexpansion of MLL-AF4-expressing CD34+ HSPCs associated to higher proportion of cycling cells coupled to lower apoptotic levels, but does not augment clonogenic potential nor confer stable replating. Together, FLT3 activation does not suffice to immortalize/transform MLL-AF4-expressing CB-CD34+ HSPCs, suggesting the need of alternative (epi)-genetic cooperating oncogenic lesions.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2017-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

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

    PubMed

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

    2016-11-01

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

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

    DTIC Science & Technology

    1983-08-24

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

  12. 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

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

    DTIC Science & Technology

    1985-03-01

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

  14. 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

  15. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    DTIC Science & Technology

    1988-02-01

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

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

    DTIC Science & Technology

    1984-09-01

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

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

    PubMed

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

    2009-01-30

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

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

    PubMed

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

    2016-01-01

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

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

    DTIC Science & Technology

    1988-01-18

    Clyde Consultants 701 Sesame Street Anchorage, AK 99503 71/46/2 71/21/1 RECORD OF DECISION Installation: The Cape Newenham AFS, is located in the...Q S-0 .- ( L to ea a -- 0 a) eoS -r-cc M A -( /5 W 4-) M 0 W) (0 4-.0 ’a - )4- -- -- 0 .0 CU E )) 0 > D. > 0 L W( ’ t’aS u to o4- E ’A W) (a( (a-a0 410...0- L4- 4-) U) to ~ Cl L EO LO. 41~ 0x - 4) 0 ) 0 0) 4-) LA- 4) 04-) a:) L/ Lu a) C Lu 0 L. +.) ~z .4-’ 41.0 0 L&i -LIi LIi JL ) Lf) 2E Li- V) L t J

  1. 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.

  2. 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…

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

    PubMed

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

    2017-03-18

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

  4. Model-based estimation of the attributable fraction for cross-sectional, case-control and cohort studies using the R package AF.

    PubMed

    Dahlqwist, Elisabeth; Zetterqvist, Johan; Pawitan, Yudi; Sjölander, Arvid

    2016-06-01

    The attributable fraction (or attributable risk) is a widely used measure that quantifies the public health impact of an exposure on an outcome. Even though the theory for AF estimation is well developed, there has been a lack of up-to-date software implementations. The aim of this article is to present a new R package for AF estimation with binary exposures. The package AF allows for confounder-adjusted estimation of the AF for the three major study designs: cross-sectional, (possibly matched) case-control and cohort. The article is divided into theoretical sections and applied sections. In the theoretical sections we describe how the confounder-adjusted AF is estimated for each specific study design. These sections serve as a brief but self-consistent tutorial in AF estimation. In the applied sections we use real data examples to illustrate how the AF package is used. All datasets in these examples are publicly available and included in the AF package, so readers can easily replicate all analyses.

  5. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

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

  6. 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…

  7. Detection of atrial fibrillation by permanent pacemakers: observations from the STOP AF trial.

    PubMed

    Plummer, C J; McComb, J M

    2003-12-01

    Pacemaker telemetry is increasingly being used to infer the presence or absence of arrhythmias in clinical practice. To evaluate the reliability of these data in patients with sick-sinus syndrome, a sub-study of eighteen consecutive patients in the Systematic Trial of Pacing to prevent Atrial Fibrillation (STOP AF) implanted with dual-chamber pacemakers had simultaneous 24-hour Holter recordings and pacemaker telemetry down-loaded. Whilst heart rate data were very similar, telemetry data achieved only 57% sensitivity with 64% specificity for the presence of atrial fibrillation on Holter recording over 24 hours. False-positive results were due to far-field sensing while false-negatives were seen with very short episodes of atrial fibrillation. The pacemaker's anti-tachycardia responses were not specific for the detection of atrial fibrillation. There are very few published reports correlating pacemaker diagnostic data and stored electrograms with external Holter monitoring. We believe that more validation studies of are needed before pacemaker diagnostic data can be used with confidence in clinical practice. It is unlikely that current devices with sophisticated detection algorithms will fail to detect prolonged episodes of arrhythmia and their capacity to confirm events with stored electrograms, intervals and markers reduces the possibility of false-positives, but care must be taken in the interpretation of stored data from devices without these capabilities. Equally, it cannot be assumed that if intracardiac electrograms from one episode confirm the presence of an arrhythmia, that all recorded events have been similarly correctly interpreted. We have shown in a sub-study of STOP-AF that simple mathematical models using heart rate bin analysis are not reliable for detection of arrhythmias with short durations. Despite these limitations, the potential of implanted pacemakers to record cardiac rhythm and trends, such as heart-rate variability, over time remains an

  8. Plateau waveform shape allows a much higher patient shock energy tolerance in AF patients.

    PubMed

    Boriani, Giuseppe; Edvardsson, Nils; Biffi, Mauro; Silvestri, Paolo; Martignani, Cristian; Valzania, Cinzia; Diemberger, Igor; Moulder, J Christopher; Mouchawar, Gabriel; Poci, Dritan; Branzi, Angelo; Kroll, Mark W

    2007-07-01

    To evaluate the possible pain reduction of the plateau waveform in atrial fibrillation (AF) patients. Previous studies have indicated that reduced amplitude waveforms would be less painful than a conventional (65/65% tilt) biphasic waveform. Computer modeling suggested that a moderately long (10-12 msec) plateau (flat topped) shock waveform would deliver equivalent effectiveness with the lowest possible peak amplitude. We enrolled 27 patients at two sites with persistent AF with a total of 220 shocks delivered during internal atrial cardioversion using an interleaved crossover design. Patient response was scored in three ways: (1) a verbally reported discomfort score, (2) visual analog scale (VAS), and (3) a blinded observer reporting a contraction score. All scores were significantly reduced (P < 0.0001) by the plateau waveform with impressive statistics: Verbal discomfort (3.51 +/- 0.13 to 2.89 +/- 0.12), VAS (7.00 +/- 0.56 to 5.91 +/- 0.36), and contraction scores (1.94 +/- 0.12 to 1.62 +/- 0.12). The average pain threshold shift (TS) for the Verbal score was 2.34, while that for the VAS score was 2.30. (This means that the patient typically could tolerate 2.34 times as much energy with the plateau waveform for the same level of verbally reported discomfort.) The contraction TS was less at 1.57. Response scores were also corrected for the shock sequence number to control for the sensitization effect from multiple shocks. This increased the TS for the Verbal score to 3.58, but the shock number was not significant for the VAS. A pulmonary artery electrode return was associated with lower pain compared with a coronary sinus position. A plateau shaped biphasic waveform resulted in significantly increased shock energy pain tolerances. Controlling for session sensitization, patients tolerated over three times as much energy for the same verbally reported discomfort score.

  9. 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

  10. 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.

  11. 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. © 2014, The American College of Clinical Pharmacology.

  12. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    USDA-ARS?s Scientific Manuscript database

    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...

  13. Modulation of the metabolic response to an endotoxin challenge in Brahman heifers through OmniGen-AF supplementation

    USDA-ARS?s Scientific Manuscript database

    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...

  14. 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

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

    PubMed

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

    2016-10-04

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

  16. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 419A(f)(6) is based on the totality of the arrangement and all related facts and circumstances, including any related insurance contracts. Accordingly, all agreements and understandings (including... the participating employers, and those differences are not merely reflective of differences in current...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 419A(f)(6) is based on the totality of the arrangement and all related facts and circumstances, including any related insurance contracts. Accordingly, all agreements and understandings (including... the participating employers, and those differences are not merely reflective of differences in current...

  18. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 419A(f)(6) is based on the totality of the arrangement and all related facts and circumstances, including any related insurance contracts. Accordingly, all agreements and understandings (including... the participating employers, and those differences are not merely reflective of differences in current...

  19. 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...

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

    SciTech Connect

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

    1987-03-02

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