WorldWideScience

Sample records for factor viia fragments

  1. Coagulation factor VIIa: prohemostatic drug and biomarker for thrombosis

    NARCIS (Netherlands)

    Schut, Anne Marieke

    2016-01-01

    Stollingsfactor VIIa: prohemostatisch medicijn en biomarker voor trombose Fysiologische activatie van de bloedstolling begint met de activatie van stollings factor VII tot factor VIIa. Een recombinante vorm van factor VIIa (rFVIIa) is ontwikkeld als medicijn om bloedstolling te stimuleren in patiënt

  2. Haemostatic effects of recombinant coagulation factor VIIa

    NARCIS (Netherlands)

    Lisman, Johannes Antonius

    2002-01-01

    Recombinant coagulation factor VIIa (rFVIIa) has recently become available for treatment of patients with inhibitor-complicated haemophilia. It has been postulated that rFVIIa could become a universal haemostatic agent. Case reports and small studies confirm efficacy and safety of rFVIIa in a

  3. Factor VIIa binding and internalization in hepatocytes

    DEFF Research Database (Denmark)

    Hjortoe, G; Sorensen, B B; Petersen, L C

    2005-01-01

    The liver is believed to be the primary clearance organ for coagulation proteases, including factor VIIa (FVIIa). However, at present, clearance mechanisms for FVIIa in liver are unknown. To obtain information on the FVIIa clearance mechanism, we investigated the binding and internalization...

  4. Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors.

    Science.gov (United States)

    Wurtz, Nicholas R; Parkhurst, Brandon L; Jiang, Wen; DeLucca, Indawati; Zhang, Xiaojun; Ladziata, Vladimir; Cheney, Daniel L; Bozarth, Jeffrey R; Rendina, Alan R; Wei, Anzhi; Luettgen, Joseph M; Wu, Yiming; Wong, Pancras C; Seiffert, Dietmar A; Wexler, Ruth R; Priestley, E Scott

    2016-12-08

    Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor. Optimization of this P1 binding group led to the first series of neutral, permeable FVIIa inhibitors with low nanomolar potency.

  5. Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Glunz, Peter W.; Zhang, Xiaojun; Zou, Yan; Delucca, Indawati; Nirschl, Alexandra H.; Cheng, Xuhong; Weigelt, Carolyn A.; Cheney, Daniel L.; Wei, Anzhi; Anumula, Rushith; Luettgen, Joseph M.; Rendina, Alan R.; Harpel, Mark; Luo, Gang; Knabb, Robert; Wong, Pancras C.; Wexler, Ruth R.; Priestley, E. Scott [BMS

    2017-03-16

    Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.

  6. Systemic Venous Thrombosis after Recombinant Factor VIIa in the Control of Bleeding after Cardiac Surgery

    OpenAIRE

    Mahmoud, Amr; Al-Ruzzeh, Sharif; McKeague, Helena; Cross, Mike

    2007-01-01

    Recombinant factor VIIa has been licensed in the United Kingdom since 1996 for the control of bleeding in hemophilic patients who are actively bleeding or are about to undergo surgery. Medical practitioners are also applying recombinant factor VIIa toward the control of bleeding in patients without hemophilia. Although the efficacy of recombinant factor VIIa has been shown in many patients, concerns have arisen about the risk of thrombotic adverse events.

  7. A loop of coagulation factor VIIa influencing macromolecular substrate specificity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Persson, Egon; Rasmussen, Hanne B;

    2006-01-01

    Coagulation factor VIIa (FVIIa) belongs to a family of proteases being part of the stepwise, self-amplifying blood coagulation cascade. To investigate the impact of the mutation Met(298{156})Lys in FVIIa, we replaced the Gly(283{140})-Met(298{156}) loop with the corresponding loop of factor Xa....../Met(298{156})Lys-FVIIa with almost the same activity and specificity profile. We conclude that a lysine residue in position 298{156} of FVIIa requires a hydrophilic environment to be fully accommodated. This position appears critical for substrate specificity among the proteases of the blood coagulation...

  8. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H;

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics...... tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results...... of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon...

  9. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders;

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic propert...

  10. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.

    2015-01-01

    Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective...

  11. Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors

    NARCIS (Netherlands)

    Mauser-Bunschoten, EP; Koopman, MMW; Goede-Bolder, ADE; Leebeek, FWG; Van der Meer, J; Kooij, GMV; Van der Linden, PWG

    2002-01-01

    We have prospectively monitored treatment of haemophilia patients with inhibitors by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain more insight in the underlying factors of the clinical efficacy of this administration method. At present, 43 treatment episodes of 14 d

  12. Use of Recombinant Factor VIIa in US Military Casualties for a Five-Year Period

    Science.gov (United States)

    2010-08-01

    Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled...particularly Factor VII level, in order that all of us could help learn the ideal plasma to red cell ratio by science rather than by some gestalt ? Dr. Slate

  13. Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa

    NARCIS (Netherlands)

    Hyseni, A.; Kemperman, H.; De Lange, D. W.; De Groot, P. G.; Linssen, M.; Kesecioglu, J.; Lisman, T.; Roest, M.

    2013-01-01

    BackgroundThe tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a c

  14. Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility

    DEFF Research Database (Denmark)

    Mosbæk, Charlotte Rode; Nolan, David; Persson, Egon

    2010-01-01

    Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa...

  15. Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Ladziata, Vladimir (Uladzimir); Glunz, Peter W.; Zou†, Yan; Zhang, Xiaojun; Jiang, Wen; Jacutin-Porte, Swanee; Cheney, Daniel L.; Wei, Anzhi; Luettgen, Joseph M.; Harper, Timothy M.; Wong, Pancras C.; Seiffert, Dietmar; Wexler, Ruth R.; Priestley, E. Scott (BMS)

    2016-10-01

    Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.

  16. Crystallization and preliminary crystallographic data for a ternary complex between tissue factor, factor VIIa and a BPTI-derived inhibitor

    Science.gov (United States)

    Stura, Enrico A.; Ruf, Wolfram; Wilson, Ian A.

    1996-10-01

    The binding of tissue factor (TF) with the serine protease coagulation factor VIIa (VIIa) is the initial trigger for activation of the coagulation protease cascades. In complex with TF, VIIa has profoundly enhanced function in the limited proteolytic activation of the natural substrate factors X and IX. Here we report the screening and identification of crystallization conditions to produce diffraction quality crystals of the complex between TF · VIIa and a potent inhibitor (5L 15) derived from mutagenesis of the bovine pancreatic trypsin inhibitor (BPTI) sequence. The complex crystals were obtained from the soluble extracellular domain of tissue factor, expressed in Escherichia coli as a fusion protein, VIIa expressed in mammalian cells and recombinant 5L15. Because only 1.5 mg of complex were available for this work, a reverse screening based strategy was used in the search and optimization of the crystallization conditions. Two different crystal forms were obtained from polyethylene glycol 4000 and monomethyl polyethylene glycol 2000 with cacodylate buffer at pH 6.5 in the presence of sodium and calcium ions. The addition of magnesium and zinc have profound effects on the crystallization. Both crystal forms are trigonal with cell parameters a = b = 129.3 Å, c = 110.8 Å and a = b = 67.2 Å, c = 314.8 Å diffracting to 7 and 3.2 Å resolution, respectively, each with one molecule in the asymmetric unit. Complete data sets have been collected from each of these forms to the resolution to which the crystals diffract. A structural understanding of the interaction of VIIa with its cofactor TF to form a binary enzyme, and its inhibition by 5L15 will provide a basis for the development of antithrombotic strategies.

  17. Influence of Cardiopulmonary Bypass on the Interaction of Recombinant Factor VIIa with Activated Platelets

    OpenAIRE

    Kjalke, Marianne; Runge, Marx; Rojkjaer, Rasmus; Steinbruchel, Daniel; Johansson, Pär I

    2009-01-01

    Recombinant factor VIIa (rFVIIa) interacts preferentially with coated platelets characterized by a high exposure of phosphatidyl serine (PS), FV, FVIII, FIX, and FX binding, and fibrinogen. Cardiopulmonary bypass (CPB) is known to impair platelet function. In this study, the influence of CPB on formation of coated platelets and the interaction of rFVIIa with the platelets were studied. Blood was either exposed to a closed CPB circuit or obtained from patients undergoing CPB-assisted cardiac s...

  18. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik;

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD...

  19. Protein anticoagulants targeting factor VIIa-tissue factor complex: a comprehensive review.

    Science.gov (United States)

    Shah, Karna; Bayoumi, Riad; Banerjee, Yajnavalka

    2013-01-01

    Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot. A comprehensive review delineating the structure-activity relationship of protein/peptide anticoagulants targeting FVIIa or TF-FVIIa complex is absent in the literature. In this article, we have addressed this deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF-FVIIa complex. Further, the current status of these anticoagulants, with regard to their performance in different clinical trials has also been presented. Lastly, the unexplored domains of these unique proteins have also been highlighted, which will facilitate further translational research in this paradigm, to improve strategies to counter and treat thromboembolic disorders.

  20. Off-label use of recombinant factor VIIa for treatment of haemorrhage: results from randomized clinical trials

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar

    2008-01-01

    Background Recombinant factor VIIa (rFVIIa) is used for haemophilic patients with inhibitors against coagulation factor VIII or IX, but there is also an off-label use of rFVIIa for patients with massive bleeding. The aim of the present study was to review the randomized clinical trials (RCT...

  1. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    , but no effects on clotting time indicating that haemodilution does not affect clot formation, but the clot formed at high haemodilution may not be so firm. In conclusion, the activity of recombinant activated factor VII was affected in vitro by pH, temperature, and haemodilution. Additional studies are necessary...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30...... activity in plasma. Significant effects of pH were observed for clotting time, clot formation time, maximum clot firmness, and factor VII coagulant activity in the direction of longer clot formation times and less firm clots with decreasing pH. Temperature had significant effects on clotting time, clot...

  2. Use of recombinant factor VIIa for emergency reversal of anticoagulation

    Directory of Open Access Journals (Sweden)

    Ingerslev J

    2007-01-01

    Full Text Available Context: There is limited data regarding the use of activated recombinant factor VII (rFVIIa in anticoagulated patients requiring reversal. Aims: To identify and describe characteristics of subjects who received rFVIIa as part of emergency treatment aimed at improving hemostasis. Settings and Design: Data was obtained from an international peer-reviewed registry haemostasis.com. This registry contains data reported by physicians, who had elected to use rFVIIa to control bleeding in an emergency clinical situation. The contributors′ approval for inclusion in the study was obtained and they were requested to validate and update information. Materials and Methods: Database review of cases receiving rFVIIa to manage bleeding coherent with the use of anticoagulant therapy. Statistical Analysis: The Wilcoxon signed rank test was used to compare requirements for blood products and crystalloids/colloids during the 24h preceding and following rFVIIa administration, as well as changes in the levels of clotting factors during that period. Results: Eighteen patients were treated with rFVIIa (median dose: 87.35 µg/kg; range: 20.0-106.0 µg/kg for bleeding. Anticoagulants requiring reversal included low-molecular-weight heparin (n = 6, unfractionated heparin (n =8, coumarin (n =3 and warfarin (n=1. All patients had failed to respond to traditional antidotes and blood products. Following administration, bleeding stopped in 10, markedly decreased in five and slowed in the remaining three. Amongst 12/16 patients, a response was observed within 2.0 h of first administration. The requirement for blood products and crystalloids/colloids decreased ( P < 0.05 after rFVIIa administration. rFVIIa was well tolerated. Conclusions: rFVIIa may play a role in control of untoward bleeding in subjects receiving anticoagulation therapy.

  3. Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation

    NARCIS (Netherlands)

    Lisman, T; Leebeek, FWG; Meijer, K; Van Der Meer, J; Nieuwenhuis, HK; De Groot, PG

    2002-01-01

    Cirrhosis is associated with a bleeding tendency, which is particularly pronounced during orthotopic liver transplantation (OLT). A novel approach to treating the bleeding diathesis of patients with cirrhosis is administration of recombinant factor VIIa (rFVIIa). This study examined whether the effi

  4. [Treatment of life-threatening bleeding in obstetrics and gynaecology --NovoSeven (recombinant factor VIIa)].

    Science.gov (United States)

    Nikolov, A; Dimitrov, A; Tanchev, S; Platikanov, V; Nacheva, A; Gateva, Zh; Gerganova, A

    2005-01-01

    The study offers the results from the application of recombinant factor VIIa (NovoSeven) in 19 patients with obstetric or gynaecological problems showing severe haemorrhage of non-surgical origin, which could not be controlled by standard therapy (surgery and resuscitation). Haematological and haemostaseological values as well as final outcome are being monitored. The role of the drug and its special indications in complex urgent treatment of life-threatening bleeding are being discussed. Conclusions. The use of NovoSeven (recombinant factor Vlla) on time and when indicated guarantees rapid and effective haemostasis. Thus laparotomy or relaparotomy can be avoided. If no effect is observed after the application of NovoSeven indicates bleeding from a major blood vessel, demanding laparotomy and surgery. The use of the drug leads to reducing the incidence of blood derivatives transfusions and (being a recombinant product)--no risk of transmissive infections.

  5. Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage.

    Science.gov (United States)

    Hsu, Chuan-Chih; Chen, Sheng-Hsien; Lin, Cheng-Hsien; Yung, Ming-Chi

    2014-10-01

    Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1β, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage

  6. Postpartum hemorrhage in a Jehovah's Witness patient controlled with Tisseel, tranexamic acid, and recombinant factor VIIa.

    Science.gov (United States)

    Arab, Tarek Samir; Al-Wazzan, Ahmad Bakr; Maslow, Ken

    2010-10-01

    The management of a patient refusing blood transfusion who subsequently experiences a severe postpartum hemorrhage is a particular clinical challenge. A 30-year-old nulliparous patient (who was a Jehovah's Witness) had labour induced for post-dates at 41+4 weeks' gestational age after an uncomplicated pregnancy. She delivered by Caesarean section for dystocia and suspected chorioamnionitis, and subsequently developed postpartum hemorrhage that required management with oxytocin, ergometrine, carboprost, uterine artery ligation, and Hayman compression sutures. The patient ultimately required two additional visits to the operating room, culminating in hysterectomy. Use of tranexamic acid, recombinant factor VIIa, and Tisseel was instrumental in halting the ongoing hemorrhage. Optimal management of a patient refusing administration of blood products requires a multidisciplinary approach as well as a combination of traditional and novel therapies.

  7. Effect of recombinant Factor VIIa on outcome of acute variceal bleeding

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; D'Amico, Gennaro; Rusch, Ea;

    2014-01-01

    BACKGROUND & AIMS: Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data...... vasoactive drug infusion and Child-Pugh score >8. RESULTS: 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal...... varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p=0.049). This difference was highly significant in patients with Child-Pugh score...

  8. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

    National Research Council Canada - National Science Library

    Jonge, de, E; Friederich, P.W; Vlasuk, G.P; Rote, W; Vroom, M.B; Levi, M.M; Poll, van der, T

    2003-01-01

    .... Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma...

  9. The Clinical and Laboratory Response to Recombinant Factor VIIa in Trauma and Surgical Patients with Acquired Coagulopathy

    Science.gov (United States)

    2006-08-01

    triad” of hypothermia, acidosis, and coagulopathy poses a significant problem in the care of critically ill surgical patients. The sequential and...coagulopathy. In 1990, recombinant factor VIIa (rFVIIa, Novoseven; Novo Nordisk, Bagsvaerd, Denmark) was introduced for the treatment of hemophilia ...No complications were attributable to the administration of rFVIIa. All but 1 patient in this series was determined to be free of continued

  10. Successful Treatment of Intractable Hemothorax with Recombinant Factor VIIa in a Nonhemophilic Patient

    Directory of Open Access Journals (Sweden)

    Yu-Feng Wei

    2006-01-01

    Full Text Available Recombinant factor VIIa (rFVIIa was developed for the treatment of bleeding in hemophilic patients with inhibitors. It has also been used to stop bleeding in nonhemophilic patients who fail to respond to conventional treatment. We report a case of catastrophic hemothorax in which bleeding was stopped by administration of rFVIIa. A 68-year-old woman with chronic hepatitis C-related liver cirrhosis was admitted due to pneumonia and parapneumonic effusion. The patient developed hemothorax and hypovolemic shock after thoracentesis. Conventional therapies including tube thoracostomy and transarterial embolization failed to stop the life-threatening bleeding. The bleeding stopped after administration of rFVIIa 100 μg/kg/BW at 2-hour intervals for a total of two doses on the 3rd day of hospitalization. Despite intensive care, however, the patient died due to nosocomial infection and multiple organ failure on the 12th day of hospitalization. Hemothorax in a nonhemophilic patient can be successfully treated with rFVIIa.

  11. Two coagulation factor X activators from Vipera a. ammodytes venom with potential to treat patients with dysfunctional factors IXa or VIIa.

    Science.gov (United States)

    Leonardi, Adrijana; Fox, Jay W; Trampus-Bakija, Alenka; Krizaj, Igor

    2008-10-01

    Two activators of coagulation factor X, 58kDa VAFXA-I and 70kDa VAFXA-II, were purified from the venom of long-nosed viper (Vipera ammodytes ammodytes) by chromatography on gel filtration, affinity, ion-exchange and hydroxyapatite media. Both enzymes are glycoproteins composed of a heavy chain and two C-type lectin-like light chains all joined by disulphide bonds. LC-MS and LC-MS/MS analysis of their tryptic fragments demonstrated that the heavy chain consists of three domains, metalloproteinase, disintegrin-like and cysteine-rich domains. The partial amino acid sequences of VAFXAs are very similar to those of the known factor X activators, RVV-X from Vipera russelli and VLFXA from Vipera lebetina venoms, as well as to other members of the reprolysin family of metalloproteinases. The VAFXAs activate factor X in a Ca(2+)-dependent manner with the same specificity as physiological activators. The activators weakly hydrolyzed insulin B-chain, fibrinogen and some components of the extracellular matrix in vitro, but did not activate prothrombin or plasminogen. VAFXAs inhibit collagen-induced platelet aggregation in vitro. They activate coagulation factor X to Xa without toxic effects. Their application in treating patients with dysfunctional factors IXa or VIIa to restore the normal blood coagulation process is thus promising.

  12. The M358R variant of α(1)-proteinase inhibitor inhibits coagulation factor VIIa.

    Science.gov (United States)

    Sheffield, William P; Bhakta, Varsha

    2016-02-12

    The naturally occurring M358R mutation of the plasma serpin α1-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg-Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg-Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10(2) M(-1)sec(-1). We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin.

  13. Effects of calcium signaling on coagulation factor VIIa-induced proliferation and migration of the SW620 colon cancer cell line.

    Science.gov (United States)

    Wu, Ying; Wang, Jing; Zhou, Hong; Yu, Xiaoyan; Hu, Lichao; Meng, Fanlu; Jiang, Shuanghong

    2014-12-01

    Tissue factor (TF)/VIIa/protease‑activated receptor 2 (PAR2) has been shown to trigger the ERK1/2 signaling pathway. This was shown to be closely associated with the proliferation and migration of SW620 colon cancer cells; however, the detailed mechanisms remain unclear. The aim of the present study was to elucidate the effects of calcium signaling on the proliferation and migration of SW620 cells induced by coagulation factor VIIa. The results demonstrated that VIIa and PAR2 agonist PAR2‑AP increased [Ca2+]i in SW620 cells. In addition, VIIa‑and PAR2‑AP‑induced ERK1/2 activation was inhibited by thapsigargin (TG)‑induced depletion of intracellular Ca2+ stores and EGTA‑mediated removal of extracellular Ca2+. It was also identified that VIIa and PAR2‑AP‑induced proliferation and migration of SW620 cells was modulated by EGTA and TG. Taken together, the present results indicate that VIIa triggers calcium signaling in SW620 cells, in a TF‑dependent manner, which is critical for VIIa‑induced ERK1/2 activation in SW620 cells. These results suggested that calcium signaling had a vital role in the proliferation and migration of SW620 cells.

  14. Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Eckman Mark H

    2008-05-01

    Full Text Available Abstract Background Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER given the poor neurologic outcomes after ICH with conventional management. Methods We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE. We assumed no substantial cost differences in care between the two strategies except: 1 cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408; 2 cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death; and 3 differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home, and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE. Results In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER Conclusion Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.

  15. Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

    Directory of Open Access Journals (Sweden)

    H-Y Chou Sherry

    2012-12-01

    Full Text Available Abstract Background Recombinant factor VIIa (rFVIIa may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH, FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP and vitamin K alone. Methods We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%, deep venous thrombosis (DVT or pulmonary embolism (PE (22% vs 18%, coronary artery disease (CAD (38% vs 32%, and abnormal electrocardiogram (EKG (78% vs 85%. Troponin elevation following wICH was prevalent in both groups (47% vs 41%. Clinically significant myocardial infarction (MI, defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52. Past history of CAD (p=0.0061 and baseline abnormal EKG (p=0.02 were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18 and ischemic stroke (2% vs 0%; p=0.38 were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001 and 6 hours (p Conclusions Pre

  16. Recombinant Factor VIIa Reduces Bleeding after Blunt Liver Injury in a Pig Model of Dilutional Coagulopathy under Severe Hypothermia.

    Directory of Open Access Journals (Sweden)

    Henri M H Spronk

    Full Text Available Recombinant factor VIIa (rFVIIa is registered for use in haemophilia with inhibitors and other rare bleeding disorders, but has also been used in various other clinical conditions to terminate life-threatening bleeding. Underlying conditions (e.g. coagulopathy and dosing may affect treatment efficacy. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury.A grade III blunt liver injury was induced in 28 pigs after 70% haemodilution and cooling to 32.6-33.4°C. Ten minutes after trauma, animals randomly received placebo or 90, 180 or 360 μg/kg rFVIIa. Global coagulation parameters, thromboelastometry (TEM and plasma thrombin generation (TG were determined at different time points during the observation period of 120 minutes.Total blood loss was significantly lower following 90 μg/kg rFVIIa (1206 [1138-1470] mL relative to placebo (2677 [2337-3068] mL; p<0.05, with no increased effect with higher dose levels of rFVIIa. Following trauma and haemodilution, coagulation was impaired relative to baseline in both TEM and TG analysis. At 60 and 120 minutes after trauma, TEM variables improved in the rFVIIa-treated animals compared with the placebo group. Similarly, rFVIIa improved coagulation kinetics in TG. As was observed with blood loss, no significant effect between different rFVIIa dose levels was found in TEM or TG. Macro- and microscopic post-mortem examination did not reveal any signs of thromboembolic events.Early administration of 90 μg/kg rFVIIa reduced blood loss in pigs undergoing blunt liver injury even after severe haemodilution and hypothermia, with no further effect of higher dose levels. Coagulation assays showed impaired coagulation in coagulopathic animals, with a dose-independent improvement in animals treated with rFVIIa.

  17. Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate

    DEFF Research Database (Denmark)

    Sølbeck, Sacha; Nilsson, Caroline U; Engström, Martin

    2014-01-01

    different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC...

  18. Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease.

    Science.gov (United States)

    Razon, Yaron; Erez, Eldad; Vidne, Bernardo; Birk, Einat; Katz, Jacob; Tamari, Hanna; Dagan, Ovadia

    2005-03-01

    Postoperative bleeding and blood product requirements can be substantial in children undergoing open-heart surgery, and reexploration is required in 1% of cases. Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Denmark) is a hemostatic agent approved for the treatment of hemophilic patients with inhibitors to factor VIII or factor IX. It has also been used with success in other conditions. We present our experience with rFVIIa treatment for uncontrolled bleeding after open-heart surgery in five pediatric patients. The study group consisted of five patients after open-heart surgery with excessive blood loss. The patients were treated with rFVIIa after failure of conventional treatment to control the bleeding. Blood loss, blood product consumption, and coagulation test results were recorded before and after rFVIIa administration. In all cases, blood loss decreased considerably after rFVIIa administration (mean 7.8 ml x kg(-1) x h(-1)), almost eliminating the need for additional blood products, and the prolonged prothrombin time normalized. In two patients with thrombocytopathy, rFVIIa helped to discriminate surgical bleeding from bleeding caused by a defect in hemostasis. No side effects of rFVIIa treatment were noted. These cases support the impression that RFVIIa is efficient and safe in correcting hemostasis in children after cardiopulmonary bypass when other means fail. However, the data are still limited, and more extensive research is needed.

  19. A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice.

    Science.gov (United States)

    Shinagawa, Kazuhiko; Ploplis, Victoria A; Castellino, Francis J

    2009-05-01

    Eosinophil counts in the bronchoalveolar lavage fluid of wild-type (WT) mice increased after ovalbumin (OVA) challenge, a response that was diminished in comparably challenged low-expressing coagulation factor VII (FVII(tTA/tTA)) mice. Levels of T helper type 2 (Th2) cytokines, IL-4, IL-5, and IL-13, and eosinophil-attracting chemokines, eotaxin and RANTES, were also lower in the OVA-challenged FVII(tTA/tTA) mice. Eosinophils purified from low-FVII mice underwent apoptosis at a faster rate compared with WT eosinophils, and eosinophil migration in response to eotaxin was reduced in eosinophils obtained from FVII(tTA/tTA) mice. Airway hyperresponsiveness and mucous layer thickness were reduced in OVA-treated FVII(tTA/tTA) mice, and addition of exogenous coagulation factor X (FX) enhanced mucin production in human epithelial NCI-H292 cells. Correspondingly, incubation of FX with NCI-H292 cells resulted in activated (a) FX production, suggesting that the components required for FX activation were present on NCI-H292 cells. These results demonstrate that FVIIa functions in the asthmatic response to an allergen by stimulating lung eosinophilia, airway hyperresponsiveness, and mucin production, this latter effect through its ability to activate FX in conjunction with tissue factor.

  20. The length of the linker between the epidermal growth factor-like domains in factor VIIa is critical for a productive interaction with tissue factor

    Science.gov (United States)

    Persson, Egon; Madsen, Jesper J; Olsen, Ole H

    2014-01-01

    Formation of the factor VIIa (FVIIa)-tissue factor (TF) complex triggers the blood coagulation cascade. Using a structure-based rationale, we investigated how the length of the linker region between the two epidermal growth factor (EGF)-like domains in FVIIa influences TF binding and the allosteric activity enhancement, as well as the interplay between the γ-carboxyglutamic acid (Gla)-containing and protease domains. Removal of two residues from the native linker was compatible with normal cofactor binding and accompanying stimulation of the enzymatic activity, as was extension by two (Gly-Ser) residues. In sharp contrast, truncation by three or four residues abolished the TF-mediated stabilization of the active conformation of FVIIa and abrogated TF-induced activity enhancement. In addition, FVIIa variants with short linkers associated 80-fold slower with soluble TF (sTF) as compared with wild-type FVIIa, resulting in a corresponding increase in the equilibrium dissociation constant. Molecular modeling suggested that the shortest FVIIa variants would have to be forced into a tense and energetically unfavorable conformation in order to be able to interact productively with TF, explaining our experimental observations. We also found a correlation between linker length and the residual intrinsic enzymatic activity of Ca2+-free FVIIa; stepwise truncation resulting in gradually higher activity with des(83–86)-FVIIa reaching the level of Gla-domainless FVIIa. The linker appears to determine the average distance between the negatively charged Gla domain and a structural element in the protease domain, presumably of opposite charge, and proximity has a negative impact on apo-FVIIa activity. PMID:25234571

  1. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

    DEFF Research Database (Denmark)

    Bosch, Jaime; Thabut, Dominique; Albillos, Agustín;

    2008-01-01

    A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal...... events, were comparable between groups. CONCLUSION: Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do...

  2. Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa

    DEFF Research Database (Denmark)

    Larsen, Katrine S; Østergaard, Henrik; Bjelke, Jais R;

    2007-01-01

    of the selective active site in defining specificity. Being a trypsin-like serine protease, FVIIa had P1 specificity exclusively towards arginine and lysine residues. In the S2 pocket, threonine, leucine, phenylalanine and valine residues were the most preferred amino acids. Both S3 and S4 appeared to be rather...... promiscuous, however, with some preference for aromatic amino acids at both positions. Interestingly, a significant degree of interdependence between the S3 and S4 was observed and, as a consequence, the optimal substrate for FVIIa could not be derived directly from a subsite-directed specificity screen...... for FVIIa by marked changes in primary substrate specificity and decreased rates of antithrombin III inhibition. Interestingly, these changes do not necessarily coincide with an altered ability to activate Factor X, demonstrating that inhibitor and macromolecular substrate selectivity may be engineered...

  3. Recombinant factor VIIa in post-partum hemorrhage: A new weapon in obstetrician′s armamentarium

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2012-01-01

    Full Text Available Post-partum hemorrhage (PPH is a life-threatening obstetric complication and the leading cause of maternal death. The usual manner for its management includes, first, noninvasive and nonsurgical methods, and, then invasive and surgical methods. However, mortality and morbidity related to PPH still remains unacceptably high, contributing to hysterectomy in at least 50% of cases. Early, effective, and preferably noninvasive treatments that can reduce maternal mortality and morbidity due to this entity are therefore essential. One of the most spectacular advancements in the control of PPH has been the use of recombinant activated factor (rFVIIa, both as initial and a life- and uterus-saving therapy. rFVIIa also reduces costs of therapy and use of blood components in massive PPH. In cases of intractable bleeding with no other obvious indications for hysterectomy, administration of rFVIIa should be considered before surgery. A MEDLINE search was done to review relevant articles in English literature on use of rFVIIa in PPH. Data were constructed and issues were reviewed from there. Our experience in a series of three cases of PPH, two of atonic and one of traumatic, successfully managed using rFVIIa is also shared.

  4. A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

    Science.gov (United States)

    Mehta, Darshan A; Oladapo, Abiola O; Epstein, Joshua D; Novack, Aaron R; Neufeld, Ellis J; Hay, Joel W

    2016-02-01

    Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to

  5. A novel supplemental approach to capturing post-marketing safety information on recombinant factor VIIa in acquired hemophilia: the Acquired Hemophilia Surveillance project

    Directory of Open Access Journals (Sweden)

    Lentz SR

    2014-01-01

    Full Text Available Steven R Lentz,1 Anand Tandra,2 Robert Z Gut,3 David L Cooper31Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 2Hematology, Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA; 3Clinical, Medical, and Regulatory Affairs, Novo Nordisk, Inc, Princeton, NJ, USAAcquired hemophilia (AH is a rare (incidence is 1 per 1.5 million but often severe bleeding disorder characterized by autoantibodies to coagulation factor VIII (FVIII. It is associated with life-threatening bleeding and ∼20% mortality.1,2 Recombinant factor VIIa (rFVIIa; NovoSeven® RT, Novo Nordisk A/S, Bagsværd, Denmark received an indication from the US Food and Drug Administration (FDA in October 2006 for the treatment of bleeding episodes and the prevention of bleeding in surgical interventions or invasive procedures in patients with AH.3View original paper by Collins and colleagues.

  6. Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry.

    Science.gov (United States)

    Song, Hongjian; Olsen, Ole H; Persson, Egon; Rand, Kasper D

    2014-12-19

    Factor VIIa (FVIIa) is a trypsin-like protease that plays an important role in initiating blood coagulation. Very limited structural information is available for the free, inactive form of FVIIa that circulates in the blood prior to vascular injury and the molecular details of its activity enhancement remain elusive. Here we have applied hydrogen/deuterium exchange mass spectrometry coupled to electron transfer dissociation to pinpoint individual residues in the heavy chain of FVIIa whose conformation and/or local interaction pattern changes when the enzyme transitions to the active form, as induced either by its cofactor tissue factor or a covalent active site inhibitor. Identified regulatory residues are situated at key sites across one continuous surface of the protease domain spanning the TF-binding helix across the activation pocket to the calcium binding site and are embedded in elements of secondary structure and at the base of flexible loops. Thus these residues are optimally positioned to mediate crosstalk between functional sites in FVIIa, particularly the cofactor binding site and the active site. Our results unambiguously show that the conformational allosteric activation signal extends to the EGF1 domain in the light chain of FVIIa, underscoring a remarkable intra- and interdomain allosteric regulation of this trypsin-like protease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, T; Sørensen, B B; Hjortø, G M

    2007-01-01

    -regulated genes was also regulated by a PAR1 agonist peptide suggesting extensive redundancy between FVIIa/PAR2 signaling and thrombin/PAR1 signaling. The FVIIa regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent...... with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell signaling in MDA-MB-231 cells were regulated by thrombin and a PAR1 agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell...

  8. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, Tatjana; Sørensen, B B; Hjortø, G M

    2007-01-01

    -activated receptor 1 (PAR1) or PAR2 agonists using MDA-MB-231 breast carcinoma cells that constitutively express TF, PAR1 and PAR2. RESULTS AND CONCLUSIONS: Out of 8500 genes, FVIIa stimulation induced differential regulation of 39 genes most of which were not previously recognized as FVIIa regulated. All genes...... regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell...... signaling in MDA-MB-231 cells were regulated by thrombin and a PAR1 agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell line....

  9. Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

    Directory of Open Access Journals (Sweden)

    Sokol V Todi

    Full Text Available BACKGROUND: Myosin VIIA (MyoVIIA is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck, are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase. Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.

  10. Biochemical characterization of LR769, a new recombinant factor VIIa bypassing agent produced in the milk of transgenic rabbits.

    Science.gov (United States)

    Chevreux, G; Tilly, N; Leblanc, Y; Ramon, C; Faid, V; Martin, M; Dhainaut, F; Bihoreau, N

    2017-07-01

    The bypassing agent factor VII (FVIIa) is a first-line therapy for the treatment of acute bleeding episodes in patients with haemophilia and high-titre inhibitors. FVIIa is a highly post-translationally modified protein that requires eukaryotic expression systems to produce a fully active molecule. A recombinant FVIIa was produced in the milk of transgenic rabbits to increase expression and provide an efficient, safe and affordable product after purification to homogeneity (LR769). To present the biochemical and functional in vitro characteristics of LR769. Mass spectrometric analyses of the intact protein and of heavy and light chains revealed a fully activated, mature and properly post-translationally modified protein notably regarding N/O-glycosylations and γ-carboxylation. Primary structure analysis, performed by peptide mapping, confirmed 100% of the sequence and the low level or absence of product-derived impurities such as oxidized, deamidated and glycated forms. Low levels of aggregates and fragments were observed by different chromatographic methods. Higher order structure investigated by circular dichroism showed appropriate secondary/tertiary structures and conformational change in the presence of Ca(2+) ions. Finally, activated partial thromboplastin time and thrombin generation assays showed the ability of LR769 to decrease coagulation time and to generate thrombin in haemophiliac-A-plasmas, even in the presence of inhibitors. The innovative expression system used to produce LR769 yields a new safe and effective rhFVIIa for the treatment of haemophilia A or B patients with inhibitors. © 2017 LFB Biotechnologies. Haemophilia Published by John Wiley & Sons Ltd.

  11. RECOMBINANT FACTOR VIIa – NEW TREATMENT OPTION FOR CONTROL OF INTRACTABLE BLEEDING IN SURGICAL AND TRAUMA PATIENTS AND IN OTHER HAEMOSTASIS DISORDERS

    Directory of Open Access Journals (Sweden)

    Samo Zver

    2004-12-01

    Full Text Available Background. Recombinant factor VIIa (rFVIIa, which is currently registered only for the treatment of haemophilia A and B patients with inhibitors, is seen increasingly as a possible universal haemostatic agent in untractable bleedings. One possible mechanism for the efficacy rFVIIa may be a consequence of it’s from the tissue factor (TF and from the level of disfunction in haemostatic system independant activity, which generates »thrombin burst« formation. It seems that rFVIIa remains active only at the site of tissue injury/bleeding.Conclusions. There are two components of bleeding in surgery and trauma patients. One is bleeding from large calibre arteries and veins which requires surgical intervention. The other, which goes along with the first one, is coagulopathic bleeding. The latter is a consequence of consumptional and dilutional coagulopathy, hypothermia, multitransfusion syndrom and metabolic disbalances in patients. rFVIIa effects coagulopathic component of the bleeding. For effective treatment with rFVIIa in such patients, replacement therapy with erythrocytes, platelets and fresh frozen plasma is mandatory and requires a haematologist assistance in the treatment strategy.Most reported cases of effective rFVIIa usage are from the field of traumatology. Until now, there have been no universal recommendations when to start treatment with rFVIIa in a bleeding trauma patient. Most experience with rFVIIa are from Israel and their recommendations are perhaps the most valuable ones. rFVIIa was used several times during intra-operative and post-operative bleeding episodes. There are reports of clinical studies and usage in patients with/ after prostate surgery, cardiovascular operations and liver transplants.There are data about effective rFVIIa usage in neurology and neurosurgery patients (intracranial haemorrhages, obstetrics and gynecology field. Possible future indications are thrombocytopenias, thrombocytopathias (Glanzmann

  12. Recombinant Activated Factor VIIa (rFVIIa) Treatment in Very-Low-Birth-Weight (VLBW) Premature Infants with Acute Pulmonary Hemorrhage: A Single-Center, Retrospective Study.

    Science.gov (United States)

    Cosar, Hese; Isik, Halil; Cakır, Salih Cagrı; Yar, Nese; Goksen, Bulent; Tokbay, Hakan; Kertmen, Hasan; Erdoğan, Nihal; Durak, Ikbal

    2017-02-01

    We aimed to evaluate the efficacy of intravenous administration of recombinant activated factor VIIa (rFVIIa) for acute pulmonary hemorrhage treatment in very-low-birth-weight (VLBW) premature infants. This study was carried out retrospectively in premature infants with pulmonary hemorrhage that were ≤30 weeks gestational age or premature infants with pulmonary hemorrhage who were hospitalized in our neonatal intensive care unit between 01 January 2013 and 31 December 2015 were evaluated. Group 1 (n = 21) received rFVIIa support within the first 30 min of pulmonary hemorrhage plus conventional treatment, while Group 2 (n = 21) received conventional treatment only. The number of patients whose pulmonary hemorrhage was stopped within the first 2 h was significantly higher in Group 1 than Group 2 (n = 14 vs n = 4; p = 0.002). After pulmonary hemorrhage, hemoglobin values of Group 1 were higher than Group 2 (11.12 ± 1.06 vs 10.14 ± 1.59 g/dL; p = 0.024). Erythrocyte suspension (1.43 ± 4.51 vs 5.71 ± 7.46 mL/kg; p = 0.030) and fresh frozen plasma use (5.71 ± 8.10 vs 19.52 ± 12.44 mL/kg; p premature infants.

  13. Factors fragmenting the Russian Federation

    Energy Technology Data Exchange (ETDEWEB)

    Brown, E.

    1993-10-06

    This paper examines the factors that threaten the future of the Russian Federation (RF). The observations are based on a study that focused on eight republics: Mordova, Udmurtia, Tatarstan, Mari El, Bashkortostan, Kabardino-Balkaria, Buryatia, and Altay Republic. These republics were selected for their geographic and economic significance to the RF. Tatarstan, Bashkortostan, Udmurtia, and Mari El are located on important supply routes, such as the Volga River and the trans-Siberian railroad. Some of these republics are relatively wealthy, with natural resources such as oil (e.g., Tatarstan and Bashkortostan), and all eight republics play significant roles in the military-industrial complex. The importance of these republics to the RF contrasts to the relative insignificance of the independence-minded Northern Caucasus area. The author chose not to examine the Northern Caucasus region (except Kabardino-Balkaria) because these republics may have only a minor impact on the rest of the RF if they secede. Their impact would be minimized because they lie on the frontiers of the RF. Many Russians believe that {open_quotes}it might be best to let such a troublesome area secede.{close_quotes}

  14. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  15. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

    NARCIS (Netherlands)

    Planinsic, RM; van der Meer, J; Testa, G; Grande, L; Candela, A; Porte, RJ; Ghobrial, RM; Isoniemi, H; Schelde, PB; Erhardtsen, E; Klintmalm, G; Emre, S

    Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however there has been a limited

  16. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

    NARCIS (Netherlands)

    Planinsic, RM; van der Meer, J; Testa, G; Grande, L; Candela, A; Porte, RJ; Ghobrial, RM; Isoniemi, H; Schelde, PB; Erhardtsen, E; Klintmalm, G; Emre, S

    2005-01-01

    Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however there has been a limited a

  17. Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: A randomized controlled trial

    NARCIS (Netherlands)

    Mennen, L.; Maat, M. de; Meijer, G.; Zock, P.; Grobbee, D.; Kok, F.; Kluft, C.; Schouten, E.

    1998-01-01

    A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and investi

  18. The incidence of thromboembolism formation following the use of recombinant factor VIIa in patients suffering from blunt force trauma compared with penetrating trauma: a systematic review.

    Science.gov (United States)

    Devlin, Raymond; Bonanno, Laura; Badeaux, Jennifer

    2016-03-01

    Rapid replacement of blood loss is critical in patients suffering from traumatic hemorrhage. When the availability of blood products is limited, certain interventions have shown promise in conserving blood supplies. Recombinant factor (rF) VIIa has been administered, as an off-label use, to assist in controlling hemorrhage in trauma patients. Although rFVIIa has a tendency to remain localized to areas of vascular insult, there may be an increase in thromboembolism formation when patients suffer multiple sites of injury as seen in blunt force trauma. This review aimed to synthesize the best available evidence regarding the incidence of thromboembolism formation after receiving rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of packed red blood cells [PRBCs], fresh frozen plasma [FFP], platelets and crystalloid solutions) in patients suffering from traumatic injuries (blunt force and penetrating trauma). Civilian and combat trauma patients who were 15 years and older suffering from blunt force and penetrating traumatic injuries. Use of rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of PRBCs, FFP, platelets and crystalloid solutions). This review considered both experimental and epidemiological study designs. Confirmed formation of thromboembolism (confirmation based on specific diagnostic tests such as ultrasound, ventilation-perfusion scan or angiography). The databases searched included CINAHL, Ovid MEDLINE, Web of Science, EMBASE and the Cochrane Control Register of Clinical Trials. Studies published after June 1986 were considered for inclusion in this review. Search for unpublished studies was performed. Studies selected for inclusion were critically appraised by two independent reviewers using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI). Data was extracted from articles using standardized

  19. Inactivation of factor VIIa by antithrombin in vitro, ex vivo and in vivo: role of tissue factor and endothelial cell protein C receptor.

    Directory of Open Access Journals (Sweden)

    Rit Vatsyayan

    Full Text Available Recent studies have suggested that antithrombin (AT could act as a significant physiologic regulator of FVIIa. However, in vitro studies showed that AT could inhibit FVIIa effectively only when it was bound to tissue factor (TF. Circulating blood is known to contain only traces of TF, at best. FVIIa also binds endothelial cell protein C receptor (EPCR, but the role of EPCR on FVIIa inactivation by AT is unknown. The present study was designed to investigate the role of TF and EPCR in inactivation of FVIIa by AT in vivo. Low human TF mice (low TF, ∼ 1% expression of the mouse TF level and high human TF mice (HTF, ∼ 100% of the mouse TF level were injected with human rFVIIa (120 µg kg(-1 body weight via the tail vein. At varying time intervals following rFVIIa administration, blood was collected to measure FVIIa-AT complex and rFVIIa antigen levels in the plasma. Despite the large difference in TF expression in the mice, HTF mice generated only 40-50% more of FVIIa-AT complex as compared to low TF mice. Increasing the concentration of TF in vivo in HTF mice by LPS injection increased the levels of FVIIa-AT complexes by about 25%. No significant differences were found in FVIIa-AT levels among wild-type, EPCR-deficient, and EPCR-overexpressing mice. The levels of FVIIa-AT complex formed in vitro and ex vivo were much lower than that was found in vivo. In summary, our results suggest that traces of TF that may be present in circulating blood or extravascular TF that is transiently exposed during normal vessel damage contributes to inactivation of FVIIa by AT in circulation. However, TF's role in AT inactivation of FVIIa appears to be minor and other factor(s present in plasma, on blood cells or vascular endothelium may play a predominant role in this process.

  20. Cargo binding activates myosin VIIA motor function in cells.

    Science.gov (United States)

    Sakai, Tsuyoshi; Umeki, Nobuhisa; Ikebe, Reiko; Ikebe, Mitsuo

    2011-04-26

    Myosin VIIA, thought to be involved in human auditory function, is a gene responsible for human Usher syndrome type 1B, which causes hearing and visual loss. Recent studies have suggested that it can move processively if it forms a dimer. Nevertheless, it exists as a monomer in vitro, unlike the well-known two-headed processive myosin Va. Here we studied the molecular mechanism, which is currently unknown, of activating myosin VIIA as a cargo-transporting motor. Human myosin VIIA was present throughout cytosol, but it moved to the tip of filopodia upon the formation of dimer induced by dimer-inducing reagent. The forced dimer of myosin VIIA translocated its cargo molecule, MyRip, to the tip of filopodia, whereas myosin VIIA without the forced dimer-forming module does not translocate to the filopodial tips. These results suggest that dimer formation of myosin VIIA is important for its cargo-transporting activity. On the other hand, myosin VIIA without the forced dimerization module became translocated to the filopodial tips in the presence of cargo complex, i.e., MyRip/Rab27a, and transported its cargo complex to the tip. Coexpression of MyRip promoted the association of myosin VIIA to vesicles and the dimer formation. These results suggest that association of myosin VIIA monomers with membrane via the MyRip/Rab27a complex facilitates the cargo-transporting activity of myosin VIIA, which is achieved by cluster formation on the membrane, where it possibly forms a dimer. Present findings support that MyRip, a cargo molecule, functions as an activator of myosin VIIA transporter function.

  1. Active ADP-ribosylation Factor-1 (ARF1) Is Required for Mitotic Golgi Fragmentation*S

    Science.gov (United States)

    Xiang, Yi; Seemann, Joachim; Bisel, Blaine; Punthambaker, Sukanya; Wang, Yanzhuang

    2012-01-01

    In mammalian cells the Golgi apparatus undergoes an extensive disassembly process at the onset of mitosis that is believed to facilitate equal partitioning of this organelle into the two daughter cells. However, the underlying mechanisms for this fragmentation process are so far unclear. Here we have investigated the role of the ADP-ribosylation factor-1 (ARF1) in this process to determine whether Golgi fragmentation in mitosis is mediated by vesicle budding. ARF1 is a small GTPase that is required for COPI vesicle formation from the Golgi membranes. Treatment of Golgi membranes with mitotic cytosol or with purified coatomer together with wild type ARF1 or its constitutive active form, but not the inactive mutant, converted the Golgi membranes into COPI vesicles. ARF1-depleted mitotic cytosol failed to fragment Golgi membranes. ARF1 is associated with Golgi vesicles generated in vitro and with vesicles in mitotic cells. In addition, microinjection of constitutive active ARF1 did not affect mitotic Golgi fragmentation or cell progression through mitosis. Our results show that ARF1 is active during mitosis and that this activity is required for mitotic Golgi fragmentation. PMID:17562717

  2. The various assays for measuring activity states of factor VIIa in plasma and therapeutic products: Diagnostic value and analytical usefulness in various pathophysiological states.

    Science.gov (United States)

    Amiral, Jean; Dunois, Claire; Amiral, Cédric; Seghatchian, Jerard

    2016-12-29

    The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms. The various methods available, and their characteristics are presented, with a special focus on two assays developed by our group for FVIIa (a clotting one and a chromogenic one). The FVIIa clotting assay shows evident superiority for measuring its activity in plasma, in pathophysiological conditions. The normal range is products, or for following recoveries in treated patients, including hemophiliacs with inhibitors, patients with severe bleeding risk (liver diseases, surgery, trauma, …), and lastly for measurement of its activity in therapeutic products.

  3. Local pulmonary administration of factor VIIa (rFVIIa in diffuse alveolar hemorrhage (DAH – a review of a new treatment paradigm

    Directory of Open Access Journals (Sweden)

    Nielsen JD

    2012-03-01

    without thromboembolic complication when FVIIa was administered locally via the air side, because the FVIIa does not penetrate the alveolo-capillary membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000–150,000, and 50,000 patients annually are at risk of developing DAH following hematopoietic stem cell transplant (HSCT and autoimmune diseases. Finally 50,000–100,000 patients may be falsely categorized as having acute respiratory distress syndrome/acute lung injury (ARDS/ALI because DAH and ARDS cannot be separated clinically. A new treatment paradigm of DAH is proposed as no other intervention has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is simple, a series of broncho-alveolar washes which become increasingly bloody. This test should be performed in all patients with pulmonary opacities in order to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is "drug of choice", because it stops bleeding in the life-threatening syndrome DAH. Hemostasis is obtained after only one to two small doses of FVIIa (50 µg/kg body weight per dose and after hemostasis the oxygen transport quickly improves.Conclusion: Intrapulmonary administration of rFVIIa is recommended as the treatment of choice for DAH and blast lung injury (BLI because the treatment has been shown to be successful and uncomplicated in spite of the fact that only a small series of DAH has been documented.Keywords: coagulation factor FVIIa, diffuse alveolar hemorrhage, hemosiderosis, blast lung injury, local pulmonary treatment, biologics, bronchoalveolar lavage, diagnosis, algorithm, new treatment recommendation

  4. Factors affecting calcium oxalate dihydrate fragmented calculi regrowth

    Directory of Open Access Journals (Sweden)

    Sanchis P

    2006-07-01

    the other three conditions. This observation suggests COD calculi residual fragments in the kidneys together with hypercalciuria and high urinary pH values may be a risk factor for stone growth. The study also showed the effectiveness of specific crystallization inhibitors in slowing calculi fragment growth.

  5. Stellarator Wendelstein VII-AS; Physics and engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sapper, J.; Renner, H. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-01-01

    The advanced stellarator Wendelstein VII-AS is a medium-sized experimental machine with the following properties and aims: a broadly optimized magnetic configuration with improved plasma equilibrium and smaller neoclassical transport losses compared to classical stellarators; operation with net-current-free plasma; field generation with a modular set of coils instead of the conventional helix/toroidal field coil; system; and good access for plasma heating methods, e.g., neutral beam injection, electron cyclotron heating, and ion cyclotron heating. The physics characteristics and the engineering design of the experiment as well as results from the initial operation period are reported.

  6. Recombinant coagulation factor VIIa labelled with the fac-99 mTc(CO)3-core: synthesis and in vitro evaluation of a putative new radiopharmaceutical for imaging in acute bleeding lesion

    DEFF Research Database (Denmark)

    Madsen, Jacob; Christensen, Jesper B.; Olsen, Ole H.

    2011-01-01

    Coagulation in blood is initiated when coagulation factor VII (FVII) binds to exposed TF and is activated to FVIIa, and the TF/ FVIIa complex may therefore provide a marker of vascular injury potentially applicable in diagnostic imaging of acute gastrointestinal (GI) bleeding. Methods: Recombinan...... for stabilizing the 99mTc(CO)3 1-ligand structure in FVIIa were identified. Conclusion: Radiolabelled rFVIIa derivatives may represent a novel tool for the diagnosis of acute gastrointestinal bleeding lesions....

  7. Design and engineering aspects of the main components for the Wendelstein VII-AS stellarator experiment

    Energy Technology Data Exchange (ETDEWEB)

    Mathis, R.; Sapper, J. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-02-01

    In this paper the design of the essential components of the newly constructed Wendelstein VII-AS stellarator experiment at Garching are described, and the first technical and experimental results are reported. (orig.).

  8. Hindi tagandamine võib viia võimukoalitsiooni lagunemiseni Kohtla-Järvel / Erik Gamzejev

    Index Scriptorium Estoniae

    Gamzejev, Erik, 1967-

    2003-01-01

    Ilmunud ka: Severnoje Poberezhje 26. sept. lk. 1. Keskerakonna soov saada endale Kohtla-Järve linnapea ametikoht võib viia Keskerakonna ja endiste Res Publica liikmete vahel sõlmitud koalitsiooni lagunemiseni

  9. Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression.

    Science.gov (United States)

    Roy, Abhishek; Ansari, Shabbir A; Das, Kaushik; Prasad, Ramesh; Bhattacharya, Anindita; Mallik, Suman; Mukherjee, Ashis; Sen, Prosenjit

    2017-08-18

    Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Creating novel activated factor XI inhibitors through fragment based lead generation and structure aided drug design.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Activated factor XI (FXIa inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1'-S2' FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1'-S2' binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1'-S2' binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.

  11. Spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentation in infertile men with metabolic syndrome and normal seminogram.

    Science.gov (United States)

    Elsamanoudy, Ayman Z; Abdalla, Hussein Abdelaziz; Hassanien, Mohammed; Gaballah, Mohammad A

    2016-01-01

    This is the first study to investigate spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentations in the spermatozoa of men diagnosed with metabolic syndrome (MS) who have normal seminograms with unexplained infertility, and to correlate these parameters with seminal glucose concentration. This study included 120 participants: 75 male subjects with MS (38 fertile and 37 infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen analysis, and biochemical measurement of seminal plasma insulin and glucose levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions were performed by the RT-PCR method. The percentage of spermatozoal DNA fragmentation was also estimated. The spermatozoal insulin and CIDEA gene expression, as well as the DNA fragmentation, were significantly higher in the infertile MS group than in the fertile MS group, and significantly higher in both the MS groups than in the control group. Seminal glucose concentration showed significant positive correlations with seminal insulin level, spermatozoa insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a positive correlation between spermatozoa CIDEA gene expression and DNA fragmentation. It can be concluded that MS may affect male fertility at the molecular level, through its possible inducing effect of spermatozoa CIDEA and insulin gene expression, DNA fragmentation, and increased seminal glucose.

  12. Active ADP-ribosylation factor-1 (ARF1) is required for mitotic Golgi fragmentation.

    Science.gov (United States)

    Xiang, Yi; Seemann, Joachim; Bisel, Blaine; Punthambaker, Sukanya; Wang, Yanzhuang

    2007-07-27

    In mammalian cells the Golgi apparatus undergoes an extensive disassembly process at the onset of mitosis that is believed to facilitate equal partitioning of this organelle into the two daughter cells. However, the underlying mechanisms for this fragmentation process are so far unclear. Here we have investigated the role of the ADP-ribosylation factor-1 (ARF1) in this process to determine whether Golgi fragmentation in mitosis is mediated by vesicle budding. ARF1 is a small GTPase that is required for COPI vesicle formation from the Golgi membranes. Treatment of Golgi membranes with mitotic cytosol or with purified coatomer together with wild type ARF1 or its constitutive active form, but not the inactive mutant, converted the Golgi membranes into COPI vesicles. ARF1-depleted mitotic cytosol failed to fragment Golgi membranes. ARF1 is associated with Golgi vesicles generated in vitro and with vesicles in mitotic cells. In addition, microinjection of constitutive active ARF1 did not affect mitotic Golgi fragmentation or cell progression through mitosis. Our results show that ARF1 is active during mitosis and that this activity is required for mitotic Golgi fragmentation.

  13. Molecular and structural advances in tissue factor-dependent coagulation.

    Science.gov (United States)

    Kirchhofer, D; Banner, D W

    1997-11-01

    The tissue factor:factor VIIa (TF-F.VIIa) complex is considered the physiological initiator of blood coagulation. Besides its role in normal hemostasis, this enzyme complex has been found to play an important role in various thrombotic disorders and thus has become an attractive target for the development of new anticoagulants. Recently, significant progress has been made in regard to structural and molecular aspects of TF-VIIa-initiated coagulation. A rather complete picture on how tissue factor binds to factor VIIa has emerged and is discussed in detail in this review. Also, the combined data of the TF-F.VIIa crystal structure, of naturally occurring F.VII variants, and of mutagenesis studies provide a framework to discuss molecular aspects of the tissue factor-mediated enhancement of F.VIIa catalytic efficiency and the recognition of macromolecular substrates. F.VIIa as a member of the serine protease family has an active site homologous to other coagulation factors. The release of the coordinates of the crystal structures of F.X and F.IX, together with the earlier determined thrombin structure, now allows a detailed comparison of these active centers with respect to the development of specific and potent active site inhibitors. This structural and molecular information about the TF-F.VIIa complex and other coagulation enzymes adds to our understanding of blood coagulation and should further the development of new classes of anticoagulants. (Trends Cardiovasc Med 1997;7:316-324). © 1997, Elsevier Science Inc.

  14. Structural features of Fab fragments of rheumatoid factor IgM-RF in solution

    Energy Technology Data Exchange (ETDEWEB)

    Volkov, V. V., E-mail: vvo@ns.crys.ras.ru [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation); Lapuk, V. A. [Russian Academy of Sciences, Zelinskii Institute of Organic Chemistry (Russian Federation); Shtykova, E. V.; Stepina, N. D.; Dembo, K. A.; Sokolova, A. V.; Amarantov, S. V. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation); Timofeev, V. P. [Russian Academy of Sciences, Engelhardt Institute of Molecular Biology (Russian Federation); Ziganshin, R. Kh. [Russian Academy of Sciences, Shemyakin Ovchinnikov Institute of Bioorganic Chemistry (Russian Federation); Varlamova, E. Yu. [Russian Academy of Medical Sciences, Hematology Research Center (Russian Federation)

    2008-05-15

    The structural features of the Fab fragments of monoclonal (Waldenstroem's disease) immunoglobulin M (IgM) and rheumatoid immunoglobulin M (IgM-RF) were studied by a complex of methods, including small-angle X-ray scattering (SAXS), electron spin resonance (ESR), and mass spectrometry (MS). The Fab-RF fragment was demonstrated to be much more flexible in the region of interdomain contacts, the molecular weights and the shapes of the Fab and Fab-RF macromolecules in solution being only slightly different. According to the ESR data, the rotational correlation time for a spin label introduced into the peptide sequence for Fab is twice as large as that for Fab-RF (21{+-}2 and 11{+-}1 ns, respectively), whereas the molecular weights of these fragments differ by only 0.5% (mass-spectrometric data), which correlates with the results of molecular-shape modeling by small-angle X-ray scattering. The conclusion about the higher flexibility of the Fab-RF fragment contributes to an understanding of the specificity of interactions between the rheumatoid factor and the antigens of the own organism.

  15. Oxidatively fragmented phosphatidylcholines activate human neutrophils through the receptor for platelet-activating factor.

    Science.gov (United States)

    Smiley, P L; Stremler, K E; Prescott, S M; Zimmerman, G A; McIntyre, T M

    1991-06-15

    Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) activates neutrophils (polymorphonuclear leukocytes, PMN) through a receptor that specifically recognizes short sn-2 residues. We oxidized synthetic [2-arachidonoyl]phosphatidylcholine to fragment and shorten the sn-2 residue, and then examined the phospholipid products for the ability to stimulate PMN. 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine was fragmented by ozonolysis to 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine. This phospholipid activated human neutrophils at submicromolar concentrations, and is effects were inhibited by specific PAF receptor antagonists WEB2086, L659,989, and CV3988. 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine next was fragmented by an uncontrolled free radical-catalyzed reaction: it was treated with soybean lipoxygenase to form its sn-2 15-hydroperoxy derivative (which did not activate neutrophils) and then allowed to oxidize under air. The secondary oxidation resulted in the formation of numerous fragmented phospholipids (Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11095-11103), some of which activated PMN. Hydrolysis of sn-2 residues with phospholipase A2 destroyed biologic activity, as did hydrolysis with PAF acetylhydrolase. PAF acetylhydrolase is specific for short or intermediate length sn-2 residues and does not hydrolyze the starting material (Stremler, K. E., Stafforini, D. M., Prescott, S. M., and McIntyre, T. M. (1991) J. Biol. Chem. 266, 11095-11103). Neutrophil activation was completely blocked by L659,989, a specific PAF receptor antagonist. We conclude that diacylphosphatidylcholines containing an sn-2 polyunsaturated fatty acyl residue can be oxidatively fragmented to species with sn-2 residues short enough to activate the PAF receptor of neutrophils. This suggests a new mechanism for the appearance of biologically active phospholipids, and shows

  16. CLONING AND SEQUENCING OF MATURED FRAGMENT OF HUMAN NEVER GROWTH FACTOR GENE

    Institute of Scientific and Technical Information of China (English)

    马巍; 吴玲; 王德利; 刘淼; 任惠民; 杨广笑; 王全颖

    2003-01-01

    Objective Molecular cloning and sequencing of the human matured fragment of human nerve growth factor(NGF) gene. Methods Extracting the human genomic DNA from the white blood cells as templates, the gene of NGF was cloned by using PCR and T-vector cloning method. Screening the positive clones and identified by the restriction enzymes, and then the cloned amplified fragment was sequenced and analyzed. Results DNA sequence comparison the cloned gene of NGF with the GenBank (V01511) sequence demonstrated that both of sequences were identical, 354bp length. Conclusion Cloning the NGF gene from the human genomic DNA has paved the way for further study on gene therapy of nerve system injury.

  17. Do fragmentation functions in factorization theorems correctly treat non-perturbative effects?

    CERN Document Server

    Collins, John

    2016-01-01

    Current all-orders proofs of factorization of hard processes are made by extracting the leading power behavior of Feynman graphs, i.e., by extracting asymptotics strictly order-by-order in perturbation theory. The resulting parton densities and fragmentation functions include non-perturbative effects. I show how there are missing elements in the proofs; these are related to and exemplified by string and cluster models of hadronization. The proofs rely on large rapidity differences between different parts of graphs for the process; but in reality large rapidity gaps are filled in

  18. DNA barcoding for identification of 'Candidatus Phytoplasmas' using a fragment of the elongation factor Tu gene.

    Directory of Open Access Journals (Sweden)

    Olga Makarova

    Full Text Available BACKGROUND: Phytoplasmas are bacterial phytopathogens responsible for significant losses in agricultural production worldwide. Several molecular markers are available for identification of groups or strains of phytoplasmas. However, they often cannot be used for identification of phytoplasmas from different groups simultaneously or are too long for routine diagnostics. DNA barcoding recently emerged as a convenient tool for species identification. Here, the development of a universal DNA barcode based on the elongation factor Tu (tuf gene for phytoplasma identification is reported. METHODOLOGY/PRINCIPAL FINDINGS: We designed a new set of primers and amplified a 420-444 bp fragment of tuf from all 91 phytoplasmas strains tested (16S rRNA groups -I through -VII, -IX through -XII, -XV, and -XX. Comparison of NJ trees constructed from the tuf barcode and a 1.2 kbp fragment of the 16S ribosomal gene revealed that the tuf tree is highly congruent with the 16S rRNA tree and had higher inter- and intra- group sequence divergence. Mean K2P inter-/intra- group divergences of the tuf barcode did not overlap and had approximately one order of magnitude difference for most groups, suggesting the presence of a DNA barcoding gap. The use of the tuf barcode allowed separation of main ribosomal groups and most of their subgroups. Phytoplasma tuf barcodes were deposited in the NCBI GenBank and Q-bank databases. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that DNA barcoding principles can be applied for identification of phytoplasmas. Our findings suggest that the tuf barcode performs as well or better than a 1.2 kbp fragment of the 16S rRNA gene and thus provides an easy procedure for phytoplasma identification. The obtained sequences were used to create a publicly available reference database that can be used by plant health services and researchers for online phytoplasma identification.

  19. Ekspertide ettepanek : 25% Eesti Energiast viia börsile / Vallo Toomet

    Index Scriptorium Estoniae

    Toomet, Vallo, 1960-

    2008-01-01

    Eesti Energia vajab lähema kümne aasta jooksul ligi 8 mld. krooni lisakapitali, majandus- ja kommunikatsiooniministeeriumis valminud analüüsi kohaselt oleks üks võimalusi lisakapitali kaasamiseks viia kuni 25% ettevõttest börsile. Minister Juhan Partsi, ministeeriumi asekantsleri Einari Kiseli seisukohtadest. Lisa: Euroopa nõudmise leevenevad

  20. Fragmentation and Hadronization

    OpenAIRE

    Webber, B. R.

    1999-01-01

    Experimental data, theoretical ideas and models concerning jet fragmentation and the hadronization process are reviewed, concentrating on the following topics: factorization and small-x resummation of fragmentation functions, hadronization models, single-particle yields and spectra in Z decay, comparisons between quark and gluon jets, current and target fragmentation in deep inelastic scattering, heavy quark fragmentation, Bose-Einstein correlations and WW fragmentation.

  1. Crystal Structure of the Fab Fragment of an Anti-factor IX Antibody 10C12

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-Li; ZENG Tu; HUANG Ming-Dong

    2008-01-01

    10C12 is an anticoagulant antibody identified from a phage display single-chain Fv human antibody library. It can be directed at the calcium-stabilized Gla domain of Factor-IX, an important coagulation factor in intrinsic pathway of blood coagulation cascade, and interfere with membrane anchoring of Factor IX, thus inhibiting blood coagulation function. 10C12 has been demonstrated as an effective anti-coagulant in attenuating thrombosis in several different animal models. Here, we report the crystal structure of the Fab fragment of 10C12. The crystal contains two Fab molecules in the asymmetric unit with identical conformation, forming a lattice with large cavities. In addition, comparison of this free Fab with the antigen-bound structure of 10C12 shows no change in CDR conformations and the relative disposition of the variable subunits of H and L chains, suggesting the rigid conformation of this 10C12 Fab and a lock-and-key mechanism of antibody-antigen recognition for 10C 12.

  2. Human antibody fragments specific for the epidermal growth factor receptor selected from large non-immunised phage display libraries.

    Science.gov (United States)

    Souriau, Christelle; Rothacker, Julie; Hoogenboom, Hennie R; Nice, Edouard

    2004-09-01

    Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (ka and kd). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.

  3. Human plasma platelet-activating factor acetylhydrolase. Oxidatively fragmented phospholipids as substrates.

    Science.gov (United States)

    Stremler, K E; Stafforini, D M; Prescott, S M; McIntyre, T M

    1991-06-15

    Human plasma platelet-activating factor (PAF) acetylhydrolase hydrolyzes the sn-2 acetyl residue of PAF, but not phospholipids with long chain sn-2 residues. It is associated with low density lipoprotein (LDL) particles, and is the LDL-associated phospholipase A2 activity that specifically degrades oxidatively damaged phospholipids (Stremler, K. E., Stafforini, D. M., Prescott, S. M., Zimmerman, G. A., and McIntyre, T. M. (1989) J. Biol. Chem. 264, 5331-5334). To identify potential substrates, we synthesized phosphatidylcholines with sn-2 residues from two to nine carbon atoms long, and found the V/k ratio decreased as the sn-2 residue was lengthened: the C5 homolog was 50%, the C6 20%, while the C9 homolog was only 2% as efficient as PAF. However, the presence of an omega-oxo function radically affected hydrolysis: the half-life of the sn-2 9-aldehydic homolog was identical to that of PAF. We oxidized [2-arachidonoyl]phosphatidylcholine and isolated a number of more polar phosphatidylcholines. We treated these with phospholipase C, derivatized the resulting diglycerides for gas chromatographic/mass spectroscopic analysis, and found a number of diglycerides where the m/z ratio was consistent with a series of short to medium length sn-2 residues. We treated the polar phosphatidylcholines with acetylhydrolase and derivatized the products for analysis by gas chromatography/mass spectroscopy. The liberated residues were more polar than straight chain standards and had m/z ratios from 129 to 296, consistent with short to medium chain residues. Therefore, oxidation fragments the sn-2 residue of phospholipids, and the acetylhydrolase specifically degrades such oxidatively fragmented phospholipids.

  4. Clinical Factors Associated with Sperm DNA Fragmentation in Male Patients with Infertility

    Science.gov (United States)

    Komiya, Akira; Kato, Tomonori; Kawauchi, Yoko; Watanabe, Akihiko; Fuse, Hideki

    2014-01-01

    Objective. The clinical factors associated with sperm DNA fragmentation (SDF) were investigated in male patients with infertility. Materials and Methods. Fifty-four ejaculates from infertile Japanese males were used. Thirty-three and twenty-one were from the patients with varicoceles and idiopathic causes of infertility, respectively. We performed blood tests, including the serum sex hormone levels, and conventional and computer-assisted semen analyses. The sperm nuclear vacuolization (SNV) was evaluated using a high-magnification microscope. The SDF was evaluated using the sperm chromatin dispersion test (SCDt) to determine the SDF index (SDFI). The SDFI was compared with semen parameters and other clinical variables, including lifestyle factors. Results. The SDFI was 41.3 ± 22.2% (mean ± standard deviation) and did not depend on the cause of infertility. Chronic alcohol use increased the SDFI to 49.6 ± 23.3% compared with 33.9 ± 18.0% in nondrinkers. The SDFI was related to adverse conventional semen parameters and sperm motion characteristics and correlated with the serum FSH level. The SNV showed a tendency to increase with the SDFI. The multivariate analysis revealed that the sperm progressive motility and chronic alcohol use were significant predictors of the SDF. Conclusion. The SCDt should be offered to chronic alcohol users and those with decreased sperm progressive motility. PMID:25165747

  5. The effect of habitat fragmentation and abiotic factors on fen plant occurrence

    NARCIS (Netherlands)

    Soomers, H.; Karssenberg, D.J.; Verhoeven, J.T.A.; Verweij, P.A.; Wassen, M.J.

    2013-01-01

    Human landscape modification has led to habitat fragmentation for many species. Habitat fragmentation, leading to isolation, decrease in patch size and increased edge effect, is observed in fen ecosystems that comprise many endangered plant species. However, until now it has remained unclear whether

  6. The effect of habitat fragmentation and abiotic factors on fen plant occurrence

    NARCIS (Netherlands)

    Soomers, H.; Karssenberg, D.J.; Verhoeven, J.T.A.; Verweij, P.A.; Wassen, M.J.

    2013-01-01

    Human landscape modification has led to habitat fragmentation for many species. Habitat fragmentation, leading to isolation, decrease in patch size and increased edge effect, is observed in fen ecosystems that comprise many endangered plant species. However, until now it has remained unclear

  7. Structural study of human growth hormone-releasing factor fragment (1?29) by vibrational spectroscopy

    Science.gov (United States)

    Carmona, P.; Molina, M.; Lasagabaster, A.

    1995-05-01

    The conformational structure of fragment 1-29 of human growth hormone releasing factor, hGHRF (1-29), in aqueous solution and in the solid state is investigated by infrared and Raman spectroscopy. The polypeptide backbone is found to be unordered in the solid state. However, the spectra of the peptide prepared as 5% (w/w) aqueous solutions show that approximately 28% of the peptide is involved in intermolecular β-sheet aggregation. The remainder of the peptide exists largely as disordered and β-sheet conformations with a small portion of α-helices. Tyrosine residues are found to be exposed to the solvent. The secondary structures are quantitatively examined through infrared spectroscopy, the conformational percentages being near those obtained by HONDAet al. [ Biopolymers31, 869 (1991)] using circular dichroism. The fast hydrogen/deuterium exchange in peptide groups and the absence of any NMR sign indicative of ordered structure [ G. M. CLOREet al., J. Molec. Biol.191, 553 (1986)] support that the solution conformations of the non-aggregated peptide interconvert in dynamic equilibrium. Some physiological advantages that may derive from this conformational flexibility are also discussed

  8. Unsustainable charcoal production as a contributing factor to woodland fragmentation in southeast Kenya

    Directory of Open Access Journals (Sweden)

    Ruuska, Eeva

    2013-06-01

    Full Text Available Drawing from a holistic research approach, this paper contributes to the studies of land cover change and sustainable development in Kenya, and to the planning of sustainable future in Dakatcha Woodland, SE Kenya. As an un-protected global hotspot for biodiversity, Dakatcha Woodland has suffered from unsustainable forest resource use. The relation of charcoal production to land cover change and its socio-economic impact are studied in detail. A supervised land cover classification formed using four SPOT satellite images from 2005/06 and 2011 revealed that the woodland is fragmenting and the Important Bird Area (IBA demarcation should be reconsidered. Through in-situ observation, household questionnaires and semi-structured expert interviews it was found that more than half of the 90 households assessed are involved in charcoal production which is higher figure than peer studies have suggested, and that the charcoal network offers income to many, but bears an negative impact on the environment. It was discovered that, like in Kenya, in Dakatcha Woodland, too, the demand for woodfuels (charcoal and fuelwood is one of the key drivers of deforestation and land degradation. As such, woodfuel energy is a cross cutting issue, tying together forest resources, livelihoods and sustainable development, and thus demands further research. Forest management of Dakatcha Woodland must be planned in accordance with all stakeholders in a sustainable manner, drawing from agroforestry and participatory forest management systems, and keeping environmental factors in mind for the maintenance of ecosystem services.

  9. Analüütikud soovitavad Eesti Energia börsile viia / Piret Reiljan

    Index Scriptorium Estoniae

    Reiljan, Piret, 1983-

    2008-01-01

    Kohalikud analüütikud soovitavad viia Eesti Energia börsile, kuna see elavdaks aktsiaturgu ja tõmbaks ligi välisinvestoreid. Vt. samas: Raivo Vare: raske aeg töötab Eesti Energia börsiletoomise kasuks; Analüüs ootab pääsu valitsuskabinetti; Juhid ei püsi enam Eesti Energias. Diagrammid: Majandusnäitajad; Varade maht

  10. Analüütikud soovitavad Eesti Energia börsile viia / Piret Reiljan

    Index Scriptorium Estoniae

    Reiljan, Piret, 1983-

    2008-01-01

    Kohalikud analüütikud soovitavad viia Eesti Energia börsile, kuna see elavdaks aktsiaturgu ja tõmbaks ligi välisinvestoreid. Vt. samas: Raivo Vare: raske aeg töötab Eesti Energia börsiletoomise kasuks; Analüüs ootab pääsu valitsuskabinetti; Juhid ei püsi enam Eesti Energias. Diagrammid: Majandusnäitajad; Varade maht

  11. DNA Barcoding for Identification of "Candidatus Phytoplasmas" Using a Fragment of the Elongation Factor Tu Gene

    DEFF Research Database (Denmark)

    Makarova, Olga; Contaldo, Nicoletta; Paltrinieri, Samanta

    2012-01-01

    /Principal Findings We designed a new set of primers and amplified a 420–444 bp fragment of tuf from all 91 phytoplasmas strains tested (16S rRNA groups -I through -VII, -IX through -XII, -XV, and -XX). Comparison of NJ trees constructed from the tuf barcode and a 1.2 kbp fragment of the 16S ribosomal gene revealed...... by plant health services and researchers for online phytoplasma identification....

  12. Asexual reproduction in a zoanthid by fragmentation: The role of exogenous factors

    OpenAIRE

    A. Acosta; Sammarco, PW; Duarte, LF

    2001-01-01

    Fragmentation is an important characteristic of the life history, population dynamics, and genetic structure of at least five metazoan phyla. This study represents a first report of modes of fragmentation and their relative importance to population growth in Palythoa caribaeorum (Cnidaria, Zoanthidea). Several populations at two coastal sites in Brazil (Praia Portinho, on Sao Sebastiao island, and Ponta Recife, on the Sao Paulo coast) were followed for 1 yr. Two depths in the sub-tidal were e...

  13. Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.

    Science.gov (United States)

    Boëda, Batiste; El-Amraoui, Aziz; Bahloul, Amel; Goodyear, Richard; Daviet, Laurent; Blanchard, Stéphane; Perfettini, Isabelle; Fath, Karl R; Shorte, Spencer; Reiners, Jan; Houdusse, Anne; Legrain, Pierre; Wolfrum, Uwe; Richardson, Guy; Petit, Christine

    2002-12-16

    Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia.

  14. Life, limb or off-label recombinant VIIa use in the setting of limited blood assets: a case study.

    Science.gov (United States)

    Carr, Marcus E; Vickaryous, Brian

    2013-06-01

    Due to the lack of adequate controlled trials, the off-label use of recombinant factor VIIa (rFVIIa) to control hemorrhage in trauma patients remains controversial. The decision regarding when to initiate rFVIIa therapy is particularly problematic. Whereas most reports and trials have delayed use until significant bleeding has occurred, there is some evidence that coagulopathy develops early in some trauma patients, raising the possibility that early rFVIIa use may be more clinically efficacious. Herein, we report the case of a hemodynamically unstable patient with massive blood loss from multiple gunshot wounds and who had a potentially salvageable upper extremity. Rapid hemorrhage despite efforts to surgically control the bleeding resulted in virtual exhaustion of the facilities' limited blood component supply. Hemorrhage was controlled when rFVIIa was added to hypotensive resuscitation allowing salvage of the arm and significant conservation of blood products. This case raises the question as to whether earlier off-label use of this agent should be considered when amputation for hemorrhage control is being considered and/or conservation of limited blood assets is needed.

  15. NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P;

    1989-01-01

    The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5...

  16. Factors Related to Spatial Patterns of Rural Land Fragmentation in Texas

    Science.gov (United States)

    Kjelland, Michael E.; Kreuter, Urs P.; Clendenin, George A.; Wilkins, R. Neal; Wu, X. Ben; Afanador, Edith Gonzalez; Grant, William E.

    2007-08-01

    Fragmentation of family-owned farms and ranches has been identified as the greatest single threat to wildlife habitat, water supply, and the long-term viability of agriculture in Texas. However, an integrative framework for insights into the pathways of land use change has been lacking. The specific objectives of the study are to test the hypotheses that the nonagricultural value (NAV) of rural land is a reliable indicator of trends in land fragmentation and that NAV in Texas is spatially correlated with population density, and to explore the idea that recent changes in property size patterns are better represented by a categorical model than by one that reflects incremental changes. We propose that the State-and-Transition model, developed to describe the dynamics of semi-arid ecosystems, provides an appropriate conceptual framework for characterizing categorical shifts in rural property patterns. Results suggest that changes in population density are spatially correlated with NAV and farm size, and that rural property size is spatially correlated with changes in NAV. With increasing NAV, the proportion of large properties tends to decrease while the area represented by small properties tends to increase. Although a correlation exists between NAV and population density, it is the trend in NAV that appears to be a stronger predictor of land fragmentation. The empirical relationships established herein, viewed within the conceptual framework of the State-and-Transition model, can provide a useful tool for evaluating land use policies for maintaining critical ecosystem services delivered from privately owned land in private land states, such as Texas.

  17. Factors affecting soil fauna feeding activity in a fragmented lowland temperate deciduous woodland.

    Directory of Open Access Journals (Sweden)

    Jake E Simpson

    Full Text Available British temperate broadleaf woodlands have been widely fragmented since the advent of modern agriculture and development. As a result, a higher proportion of woodland area is now subject to edge effects which can alter the efficiency of ecosystem functions. These areas are particularly sensitive to drought. Decomposition of detritus and nutrient cycling are driven by soil microbe and fauna coactivity. The bait lamina assay was used to assess soil fauna trophic activity in the upper soil horizons at five sites in Wytham Woods, Oxfordshire: two edge, two intermediate and one core site. Faunal trophic activity was highest in the core of the woodland, and lowest at the edge, which was correlated with a decreasing soil moisture gradient. The efficiency of the assay was tested using four different bait flavours: standardised, ash (Fraxinus excelsior L., oak (Quercus robur L., and sycamore (Acer pseudoplatanus L.. The standardised bait proved the most efficient flavour in terms of feeding activity. This study suggests that decomposition and nutrient cycling may be compromised in many of the UK's small, fragmented woodlands in the event of drought or climate change.

  18. Factors affecting bird richness in a fragmented cork oak forest in Morocco

    Science.gov (United States)

    Cherkaoui, Imad; Selmi, Slaheddine; Boukhriss, Jihen; Hamid, Rguibi-Idrissi; Mohammed, Dakki

    2009-03-01

    The cork oak forest of Ma'amora in north-western Morocco was the largest cork oak forest in the world until the beginning of the 20th century. Due to growing land use for agriculture and urbanization, however, this forest has become fragmented into relatively small and isolated patches. The effects of this fragmentation on the diversity of wild animal communities have never been investigated despite the importance of such investigations in elaborating long-term conservation plans of the biodiversity of this forest system. In this study of a sample of 44 forest patches we assessed the relationships between species numbers of wintering, breeding and spring migrant birds and patch size, shape, isolation and vegetation structure. We found that species richnesses of the three studied bird assemblages were strongly related to local vegetation structure, namely to the diversity and abundance of trees and bushes. Patches with higher diversity and cover of trees and bushes support higher numbers of bird species. However, patch size, shape and isolation were not significant predictors of bird richness. These results suggest that bird communities in the studied forest patches were more likely shaped by local habitat suitability rather than the amount of habitat or patch isolation. The results also demonstrate negative effects of current human pressures, namely logging, grazing and disturbance, on the diversity of bird communities in this forest system. This emphasizes the need for urgent management efforts aiming at reducing the negative impacts of forest use by humans on bird diversity in this forest system.

  19. Electrochemical detection of vascular endothelial growth factors (VEGFs) using VEGF antibody fragments modified Au NPs/ITO electrode.

    Science.gov (United States)

    Kim, Gang-Il; Kim, Kyung-Woo; Oh, Min-Kyu; Sung, Yun-Mo

    2010-03-15

    A new electrochemical technique for the detection of vascular endothelial growth factors (VEGFs) as a cancer-related biomarker is presented in this paper. Gold nanoparticles (Au NPs) were self-assembled onto an indium tin oxide (ITO) electrode to prepare a modified sandwich type electrochemical immunoassay platform. VEGF antibodies were cleaved into two half-fragments by 2-mercaptoethylamine-HCl (2-MEA) and the fragments were immobilized onto the Au NP substrates by their thiol groups. Through this strategy, randomly oriented attachment of antibodies was prevented which frequently occurs in a general use of whole antibody and reduces the number of available sites for the attachment of target molecules. VEGF target molecules were applied to the immunoelectrodes and they combined with the antibody fragments covering the Au NP electrode, forming antigen-antibody complexes. Then, ferrocene-tagged antibodies, which release electrons under a proper applied potential, were added to the system and they combined with the VEGF molecules pre-attached to the antibody fragments. The redox current of ferrocene measured by the differential pulse voltammetry (DPV) increased almost linearly from 1.27 x 10(-4) to 4.17 x 10(-4)A according to the increase in the concentration of the VEGF target molecules from 100 to 600 pg/ml. The measured current values represent the concentration of the VEGF since they are proportional to the number of ferrocene molecules which is in turn proportional to the concentration of VEGF target molecules. Using this modified sandwich immunoassay with the Au NP/ITO electrode, VEGFs as low as 100 pg/ml were detected with high specificity.

  20. Mechanisms Driving Galling Success in a Fragmented Landscape: Synergy of Habitat and Top-Down Factors along Temperate Forest Edges.

    Science.gov (United States)

    Kelch, Nina-S; Neves, Frederico S; Fernandes, G Wilson; Wirth, Rainer

    2016-01-01

    Edge effects play key roles in the anthropogenic transformation of forested ecosystems and their biota, and are therefore a prime field of contemporary fragmentation research. We present the first empirical study to address edge effects on the population level of a widespread galling herbivore in a temperate deciduous forest. By analyzing edge effects on abundance and trophic interactions of beech gall midge (Mikiola fagi Htg.), we found 30% higher gall abundance in the edge habitat as well as lower mortality rates due to decreased top-down control, especially by parasitoids. Two GLM models with similar explanatory power (58%) identified habitat specific traits (such as canopy closure and altitude) and parasitism as the best predictors of gall abundance. Further analyses revealed a crucial influence of light exposure (46%) on top-down control by the parasitoid complex. Guided by a conceptual framework synthesizing the key factors driving gall density, we conclude that forest edge proliferation of M. fagi is due to a complex interplay of abiotic changes and trophic control mechanisms. Most prominently, it is caused by the microclimatic regime in forest edges, acting alone or in synergistic concert with top-down pressure by parasitoids. Contrary to the prevailing notion that specialists are edge-sensitive, this turns M. fagi into a winner species in fragmented temperate beech forests. In view of the increasing proportion of edge habitats and the documented benefits from edge microclimate, we call for investigations exploring the pest status of this galling insect and the modulators of its biological control.

  1. FACTOR-XII FRAGMENT AND KALLIKREIN GENERATION IN PLASMA DURING INCUBATION WITH BIOMATERIALS

    NARCIS (Netherlands)

    VANDERKAMP, KWHJ; VANOEVEREN, W

    Blood biocompatibility of medical devices is in many ways dependent on surface characteristics and biochemical blood material interactions. In this study, the contact system, in which the activation of factor XII and plasma kallikrein is included, is highlighted. This article describes a simple

  2. A Supramolecular Host-Guest Carrier System for Growth Factors Employing VHH Fragments

    NARCIS (Netherlands)

    Cabanas-Danés, J.; Rodrigues, E.D.; Landman, Ellie B.M.; Weerd, van J.; Blitterswijk, van C.A.; Verrips, T.; Huskens, J.; Karperien, H.B.J.; Jonkheijm, Pascal

    2014-01-01

    A supramolecular strategy is presented for the assembly of growth factors employing His6-tagged single-domain antibodies (VHH). A combination of orthogonal supramolecular interactions of β-cyclodextrin (βCD)-adamantyl (Ad) host-guest and N-nitrilotriacetic acid (NTA)-histidine (His) interactions was

  3. Factorization of the fragmentation cross sections in relativistic pA and. cap alpha. A interactions

    Energy Technology Data Exchange (ETDEWEB)

    Abashidze, L.I.; Avdeichikov, V.V.; Beznogikh, G.G.; Bogatin, V.I.; Budilov, V.A.; Gorshkov, N.L.; Zlomanchuk, Y.; Zhidkov, N.K.; Lozhkin, O.V.; Mruvchinski, S.

    1985-08-01

    We have experimentally demonstrated the factorization of the cross sections for production of the isotopes /sup 3//sup ,//sup 4/He with kinetic energy T> or approx. =100 MeV emitted at an angle 90/sup 0/ in the lab from the nuclei C, Cu, and Au in bombardment by ..cap alpha.. particles with energy 3.33 GeV/nucleon and by protons with energy 6.6 GeV.

  4. LDFF, the large molecular weight DNA fragmentation factor, is responsible for the large molecular weight DNA degradation during apoptosis in Xenopus egg extracts

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang LU; Chuan Mao ZHANG; Zhong He ZHAI

    2004-01-01

    DNA degradation is a biochemical hallmark in apoptosis. It has been demonstrated in many cell types that there are two stages of DNA fragmentation during the apoptotic execution. In the early stage, chromatin DNA is cut into large molecular weight DNA fragments, although the responsible nuclease(s) has not been recognized. In the late stage, the chromatin DNA is cleaved further into short oligonucleosomal fragments by a well-characterized nuclease in apoptosis,the caspase-activated DNase (CAD/DFF40). In this study, we demonstrate that large molecular weight DNA fragmentation also occurs in Xenopus egg extracts in apoptosis. We show that the large molecular weight DNA fragmentation factor (LDFF) is not the Xenopus CAD homolog XCAD. LDFF is activated by caspase-3. The large molecular weight DNA fragmentation activity of LDFF is Mg2+-dependent and Ca2+-independent, can occur in both acidic and neutral pH conditions and can tolerate 45℃ treatment. These results indicate that LDFF in Xenopus egg extracts might be a new DNase (or DNases) responsible for the large DNA fragmentation.

  5. Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes

    Energy Technology Data Exchange (ETDEWEB)

    Samanta, Uttamkumar; Kirby, Stephen D.; Srinivasan, Prabhavathi; Cerasoli, Douglas M.; Bahnson, Brian J.; (Delaware); (USAMRIID)

    2009-09-02

    The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P{sub R} and P{sub S} stereoisomers at the P-chiral center. The tabun complex displayed only the P{sub R} stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.

  6. Mechanisms Driving Galling Success in a Fragmented Landscape: Synergy of Habitat and Top-Down Factors along Temperate Forest Edges.

    Directory of Open Access Journals (Sweden)

    Nina-S Kelch

    Full Text Available Edge effects play key roles in the anthropogenic transformation of forested ecosystems and their biota, and are therefore a prime field of contemporary fragmentation research. We present the first empirical study to address edge effects on the population level of a widespread galling herbivore in a temperate deciduous forest. By analyzing edge effects on abundance and trophic interactions of beech gall midge (Mikiola fagi Htg., we found 30% higher gall abundance in the edge habitat as well as lower mortality rates due to decreased top-down control, especially by parasitoids. Two GLM models with similar explanatory power (58% identified habitat specific traits (such as canopy closure and altitude and parasitism as the best predictors of gall abundance. Further analyses revealed a crucial influence of light exposure (46% on top-down control by the parasitoid complex. Guided by a conceptual framework synthesizing the key factors driving gall density, we conclude that forest edge proliferation of M. fagi is due to a complex interplay of abiotic changes and trophic control mechanisms. Most prominently, it is caused by the microclimatic regime in forest edges, acting alone or in synergistic concert with top-down pressure by parasitoids. Contrary to the prevailing notion that specialists are edge-sensitive, this turns M. fagi into a winner species in fragmented temperate beech forests. In view of the increasing proportion of edge habitats and the documented benefits from edge microclimate, we call for investigations exploring the pest status of this galling insect and the modulators of its biological control.

  7. Mechanisms Driving Galling Success in a Fragmented Landscape: Synergy of Habitat and Top-Down Factors along Temperate Forest Edges

    Science.gov (United States)

    Kelch, Nina-S.; Neves, Frederico S.; Fernandes, G. Wilson

    2016-01-01

    Edge effects play key roles in the anthropogenic transformation of forested ecosystems and their biota, and are therefore a prime field of contemporary fragmentation research. We present the first empirical study to address edge effects on the population level of a widespread galling herbivore in a temperate deciduous forest. By analyzing edge effects on abundance and trophic interactions of beech gall midge (Mikiola fagi Htg.), we found 30% higher gall abundance in the edge habitat as well as lower mortality rates due to decreased top-down control, especially by parasitoids. Two GLM models with similar explanatory power (58%) identified habitat specific traits (such as canopy closure and altitude) and parasitism as the best predictors of gall abundance. Further analyses revealed a crucial influence of light exposure (46%) on top-down control by the parasitoid complex. Guided by a conceptual framework synthesizing the key factors driving gall density, we conclude that forest edge proliferation of M. fagi is due to a complex interplay of abiotic changes and trophic control mechanisms. Most prominently, it is caused by the microclimatic regime in forest edges, acting alone or in synergistic concert with top-down pressure by parasitoids. Contrary to the prevailing notion that specialists are edge-sensitive, this turns M. fagi into a winner species in fragmented temperate beech forests. In view of the increasing proportion of edge habitats and the documented benefits from edge microclimate, we call for investigations exploring the pest status of this galling insect and the modulators of its biological control. PMID:27310599

  8. DNA fragmentation in apoptosis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Cleavage of chromosomal DNA into oligonucleosomal size fragments is an integral part of apoptosis. Elegant biochemical work identified the DNA fragmentation factor (DFF) as a major apoptotic endonuclease for DNA fragmentation in vitro. Genetic studies in mice support the importance of DFF in DNA fragmentation and possibly in apoptosis in vivo. Recent work also suggests the existence of additional endonucleases for DNA degradation. Understanding the roles of individual endonucleases in apoptosis, and how they might coordinate to degrade DNA in different tissues during normal development and homeostasis, as well as in various diseased states, will be a major research focus in the near future.

  9. ImmunoPET of tissue factor expression in triple-negative breast cancer with a radiolabeled antibody Fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Sixiang [University of Wisconsin, Materials Science Program, Madison, WI (United States); Hong, Hao; Orbay, Hakan; Yang, Yunan; Ohman, Jakob D. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Graves, Stephen A.; Nickles, Robert J. [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Liu, Bai; Wong, Hing C. [Altor BioScience, Miramar, FL (United States); Cai, Weibo [University of Wisconsin, Materials Science Program, Madison, WI (United States); University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States); University of Wisconsin, Departments of Radiology and Medical Physics, Madison, WI (United States)

    2015-07-15

    To date, there is no effective therapy for triple-negative breast cancer (TNBC), which has a dismal clinical outcome. Upregulation of tissue factor (TF) expression leads to increased patient morbidity and mortality in many solid tumor types, including TNBC. Our goal was to employ the Fab fragment of ALT-836, a chimeric anti-human TF mAb, for PET imaging of TNBC, which can be used to guide future TNBC therapy. ALT-836-Fab was generated by enzymatic papain digestion. SDS-PAGE and FACS studies were performed to evaluate the integrity and TF binding affinity of ALT-836-Fab before NOTA conjugation and {sup 64}Cu-labeling. Serial PET imaging and biodistribution studies were carried out to evaluate the tumor targeting efficacy and pharmacokinetics in the MDA-MB-231 TNBC model, which expresses high levels of TF on the tumor cells. Blocking studies, histological assessment, as well as RT-PCR were performed to confirm TF specificity of {sup 64}Cu-NOTA-ALT-836-Fab. ALT-836-Fab was produced with high purity, which exhibited superb TF binding affinity and specificity. Serial PET imaging revealed rapid and persistent tumor uptake of {sup 64}Cu-NOTA-ALT-836-Fab (5.1 ± 0.5 %ID/g at 24 h post-injection; n = 4) and high tumor/muscle ratio (7.0 ± 1.2 at 24 h post-injection; n = 4), several-fold higher than that of the blocking group and tumor models that do not express significant level of TF, which was confirmed by biodistribution studies. TF specificity of the tracer was also validated by histology and RT-PCR. {sup 64}Cu-NOTA-ALT-836-Fab exhibited prominent tissue factor targeting efficiency in MDA-MB-231 TNBC model. The use of a Fab fragment led to fast tumor uptake and good tissue/muscle ratio, which may be translated into same-day immunoPET imaging in the clinical setting to improve TNBC patient management. (orig.)

  10. Antiepidermal growth factor variant III scFv fragment: effect of radioiodination method on tumor targeting and normal tissue clearance

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, Sriram [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Vaidyanathan, Ganesan [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Kuan, C.-T. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States) and Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States) and Department of Biomedical Engineering, Duke University, Durham, NC 27708 (United States)]. E-mail: zalut001@duke.edu

    2006-01-15

    Introduction: MR1-1 is a single-chain Fv (scFv) fragment that binds with high affinity to epidermal growth factor receptor variant III, which is overexpressed on gliomas and other tumors but is not present on normal tissues. The objective of this study was to evaluate four different methods for labeling MR1-1 scFv that had been previously investigated for the radioiodinating of an intact anti-epidermal growth factor receptor variant III (anti-EGFRvIII) monoclonal antibody (mAb) L8A4. Methods: The MR1-1 scFv was labeled with {sup 125}I/{sup 131}I using the Iodogen method, and was also radiohalogenated with acylation agents bearing substituents that were positively charged-N-succinimidyl-3-[*I]iodo-5-pyridine carboxylate and N-succinimidyl-4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB)-and negatively charged-N-succinimidyl-3-[*I]iodo-4-phosphonomethylbenzoate ([*I]SIPMB). In vitro internalization assays were performed with the U87MG{delta}EGFR cell line, and the tissue distribution of the radioiodinated scFv fragments was evaluated in athymic mice bearing subcutaneous U87MG{delta}EGFR xenografts. Results and Conclusion: As seen previously with the anti-EGFRvIII IgG mAb, retention of radioiodine activity in U87MG{delta}EGFR cells in the internalization assay was labeling method dependent, with SGMIB and SIPMB yielding the most prolonged retention. However, unlike the case with the intact mAb, the results of the internalization assays were not predictive of in vivo tumor localization capacity of the labeled scFv. Renal activity was dependent on the nature of the labeling method. With MR1-1 labeled using SIPMB, kidney uptake was highest and most prolonged; catabolism studies indicated that this uptake primarily was in the form of {epsilon}-N-3-[*I]iodo-4-phosphonomethylbenzoyl lysine.

  11. Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool.

    Science.gov (United States)

    Tsumura, Ryo; Sato, Ryuta; Furuya, Fumiaki; Koga, Yoshikatsu; Yamamoto, Yoshiyuki; Fujiwara, Yuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2015-12-01

    Tissue factor (TF) is expressed strongly in various types of cancer, especially cancers that are often refractory to treatment, such as pancreatic cancer. In this study, we compared the differences in the biophysical and pharmacological properties of whole IgG and the Fab fragment of anti-human TF monoclonal antibody (1849 antibodies), in order to determine their suitability for application in the diagnosis and treatment of cancers. In the biophysical examination, we investigated the characteristics of 1849-whole IgG and 1849-Fab by SPR sensing and confocal fluorescence microscopy analysis using recombinant human TF antigen and TF-overexpressing human pancreatic cancer cell line, BxPC3, respectively. After conjugation with Alexa-Flour-647, in vivo imaging was conducted in mice bearing BxPC3 xenograft tumors. Furthermore, the distribution of the conjugates in tumors and major organs was evaluated by ex vivo study. The in vitro experiments showed that 1849 antibodies had high affinity against TF antigen. In addition, 1849-Fab showed a faster dissociation rate from the antigen than 1849-whole IgG. In mice, 1849-Fab-Alexa-Flour-647 showed rapid renal clearance and faster tumor accumulation, achieving a high contrast signal over nearby normal tissues in the early phase and enhanced tumor penetration after administration. On the other hand, 1849-whole IgG-Alexa-Flour-647 showed slow clearance from the blood and sustained high tumor accumulation. These results suggest that 1849-Fab may be a useful tool for pancreatic cancer diagnosis.

  12. Relationship between Potential Sperm Factors Involved in Oocyte Activation and Sperm DNA Fragmentation with Intra-Cytoplasmic Sperm Injection Clinical Outcomes

    Directory of Open Access Journals (Sweden)

    Marziyeh Tavalaee

    2016-10-01

    Full Text Available Objective: The present study aimed to simultaneously evaluate the association between expression of three potential factors [post-acrosomal sheath WW domain-binding protein (PAWP, phospholipase Cζ (PLCζ, and truncated form of the kit receptor (TR-KIT] as candidates of oocyte activation with fertilization rate and early embryonic development. Materials and Methods: In this experimental study, semen samples were collected from 35 intra-cytoplasmic sperm injection (ICSI candidates and analyzed according to World Health Organization criteria (2010. Each sample was divided into two parts. The first part was processed for insemination by density-gradient centrifugation (DGC and the second part was prepared for assessment of sperm morphology (Papanicolaou staining, DNA fragmentation [transferase dUTP nick end labeling (TUNEL], and three Sperm-borne oocyte-activating factor (s (SOAFs-PLCζ, PAWP, and TR-KIT. Results: Significant positive correlations existed between the percentages of PLCζ, PAWP, and TR-KIT with fertilization rate. In addition, significant negative correlations existed between the percentage of DNA fragmentation with the percentages of PLCζ and PAWP. We did not find a relationship between percentages of PLCζ, PAWP, and TR-KIT with embryo quality and pregnancy rate (P>0.05. There was a significant negative correlation between percentage of DNA fragmentation with fertilization and embryo quality. Conclusion: Oocyte activation was associated with the studied sperm factors (PAWP, PLCζ, and TR-KIT. These factors might hold the potential to be considered as diagnostic factors in the assessment of semen samples to evaluate their potential to induce oocyte activation. In addition, we observed a significant association between DNA fragmentation with fertilization, as well as embryo quality and expression of PAWP and PLCζ, which indicated that men with high degrees of DNA fragmentation might require artificial oocyte activation. Whether

  13. Relationship between Potential Sperm Factors Involved in Oocyte Activation and Sperm DNA Fragmentation with Intra-Cytoplasmic Sperm Injection Clinical Outcomes

    Science.gov (United States)

    Tavalaee, Marziyeh; Kiani-Esfahani, Abbas; Nasr-Esfahani, Mohammad Hossein

    2017-01-01

    Objective The present study aimed to simultaneously evaluate the association between expression of three potential factors [post-acrosomal sheath WW domain-binding protein (PAWP), phospholipase Cζ (PLCζ), and truncated form of the kit receptor (TR-KIT)] as candidates of oocyte activation with fertilization rate and early embryonic development. Materials and Methods In this experimental study, semen samples were collected from 35 intra-cytoplasmic sperm injection (ICSI) candidates and analyzed according to World Health Organization criteria (2010). Each sample was divided into two parts. The first part was processed for insemination by density-gradient centrifugation (DGC) and the second part was prepared for assessment of sperm morphology (Papanicolaou staining), DNA fragmentation [transferase dUTP nick end labeling (TUNEL)], and three Sperm-borne oocyte-activating factor (s) (SOAFs)-PLCζ, PAWP, and TR-KIT. Results Significant positive correlations existed between the percentages of PLCζ, PAWP, and TR-KIT with fertilization rate. In addition, significant negative correlations existed between the percentage of DNA fragmentation with the percentages of PLCζ and PAWP. We did not find a relationship between percentages of PLCζ, PAWP, and TR-KIT with embryo quality and pregnancy rate (P>0.05). There was a significant negative correlation between percentage of DNA fragmentation with fertilization and embryo quality. Conclusion Oocyte activation was associated with the studied sperm factors (PAWP, PLCζ, and TR-KIT). These factors might hold the potential to be considered as diagnostic factors in the assessment of semen samples to evaluate their potential to induce oocyte activation. In addition, we observed a significant association between DNA fragmentation with fertilization, as well as embryo quality and expression of PAWP and PLCζ, which indicated that men with high degrees of DNA fragmentation might require artificial oocyte activation. Whether such action

  14. Relationship between Potential Sperm Factors Involved in Oocyte Activation and Sperm DNA Fragmentation with Intra-Cytoplasmic Sperm Injection Clinical Outcomes.

    Science.gov (United States)

    Tavalaee, Marziyeh; Kiani-Esfahani, Abbas; Nasr-Esfahani, Mohammad Hossein

    2017-01-01

    The present study aimed to simultaneously evaluate the association between expression of three potential factors [post-acrosomal sheath WW domain-binding protein (PAWP), phospholipase Cζ (PLCζ), and truncated form of the kit receptor (TR-KIT)] as candidates of oocyte activation with fertilization rate and early embryonic development. In this experimental study, semen samples were collected from 35 intra-cytoplasmic sperm injection (ICSI) candidates and analyzed according to World Health Organization criteria (2010). Each sample was divided into two parts. The first part was processed for insemination by density-gradient centrifugation (DGC) and the second part was prepared for assessment of sperm morphology (Papanicolaou staining), DNA fragmentation [transferase dUTP nick end labeling (TUNEL)], and three Sperm-borne oocyte-activating factor (s) (SOAFs)-PLCζ, PAWP, and TR-KIT. Significant positive correlations existed between the percentages of PLCζ, PAWP, and TR-KIT with fertilization rate. In addition, significant negative correlations existed between the percentage of DNA fragmentation with the percentages of PLCζ and PAWP. We did not find a relationship between percentages of PLCζ, PAWP, and TR-KIT with embryo quality and pregnancy rate (P>0.05). There was a significant negative correlation between percentage of DNA fragmentation with fertilization and embryo quality. Oocyte activation was associated with the studied sperm factors (PAWP, PLCζ, and TR-KIT). These factors might hold the potential to be considered as diagnostic factors in the assessment of semen samples to evaluate their potential to induce oocyte activation. In addition, we observed a significant association between DNA fragmentation with fertilization, as well as embryo quality and expression of PAWP and PLCζ, which indicated that men with high degrees of DNA fragmentation might require artificial oocyte activation. Whether such action should take place, and its cost and benefits should

  15. Quantum fragmentation

    CERN Document Server

    Peschanski, R

    1993-01-01

    Phenomenological and theoretical aspects of fragmentation for elementary particles (resp. nuclei) are discussed. It is shown that some concepts of classical fragmentation remain relevant in a microscopic framework, exhibiting non-trivial properties of quantum relativistic field theory (resp. lattice percolation). Email contact: pesch@amoco.saclay.cea.fr

  16. ASSESSMENT OF T-2 TOXIN EFFECT AND ITS COMBINATION WITH GROWTH FACTOR AND METABOLIC HORMONES ON 17β-ESTRADIOL SECRETION BY RABBIT OVARIAN FRAGMENTS IN VITRO

    Directory of Open Access Journals (Sweden)

    Adriana Kolesárová

    2015-02-01

    Full Text Available Assessment of T-2 effect and its combination with growth factor IGF-I, metabolic hormones leptin and ghrelin on 17β-estradiol secretion by rabbit ovarian fragments was studied. Rabbit ovarian fragments were incubated without (control group or with alone T-2 toxin (0.01; 0.1; 1; 10; and 100 ng.mL-1, or its combination with insulin-like growth factor I - IGF-I (100 ng.mL-1, leptin (1000 ng.mL-1 or ghrelin (500 ng.mL-1 for 24 hours. Secretion of 17β-estradiol was determined by ELISA. T-2 toxin was not shown to be potential regulator of 17β-estradiol secretion in rabbit ovarian fragments. On the other hand T-2 toxin at all used doses combined with IGF-I significantly (P<0.05 inhibited 17β-estradiol secretion by the fragments. Similarly, 17β-estradiol secretion was significantly (P<0.05 inhibited by T-2 toxin at the highest used doses (10 and 100 ng.mL-1 combined with leptin (1000 ng.mL-1. On the other hand T-2 toxin combined with ghrelin was not shown to be potential regulator of 17β-estradiol secretion in rabbit ovarian fragments. Results in this study showed that trichothecene as T-2 toxin combined with IGF-I or leptin was able to modulate 17β-estradiol secretion in rabbit ovarian fragments in vitro. We suggest their possible involvement to the process of steroidogenesis.

  17. Tissue factor residues that putatively interact with membrane phospholipids.

    Directory of Open Access Journals (Sweden)

    Ke Ke

    Full Text Available Blood clotting is initiated by the two-subunit enzyme consisting of the plasma protease, factor VIIa (the catalytic subunit, bound to the integral membrane protein, tissue factor (the regulatory subunit. Molecular dynamics simulations have predicted that certain residues in the tissue factor ectodomain interact with phosphatidylserine headgroups to ensure optimal positioning of the tissue factor/factor VIIa complex relative to its membrane-bound protein substrates, factors IX and X. In this study, we individually mutated to alanine all the putative phosphatidylserine-interactive residues in the tissue factor ectodomain and measured their effects on tissue factor cofactor function (activation of factors IX and X by tissue factor/factor VIIa, and clotting of plasma. Some tissue factor mutants exhibited decreased activity in all three assays, with the most profound defects observed from mutations in or near the flexible loop from Lys159 to Gly164. The decreased activity of all of these tissue factor mutants could be partially or completely overcome by increasing the phosphatidylserine content of tissue factor-liposomes. Additionally, yeast surface display was used to screen a random library of tissue factor mutants for enhanced factor VIIa binding. Surprisingly, mutations at a single amino acid (Lys165 predominated, with the Lys165→Glu mutant exhibiting a 3-fold enhancement in factor VIIa binding affinity. Our studies reveal the functional contributions of residues in the C-terminal half of the tissue factor ectodomain that are implicated in interacting with phosphatidylserine headgroups to enhance tissue factor cofactor activity, possibly by allosterically modulating the conformation of the adjacent substrate-binding exosite region of tissue factor.

  18. Zinc(II) interactions with brain-derived neurotrophic factor N-terminal peptide fragments: inorganic features and biological perspectives.

    Science.gov (United States)

    Travaglia, Alessio; La Mendola, Diego; Magrì, Antonio; Pietropaolo, Adriana; Nicoletti, Vincenzo G; Grasso, Giuseppe; Malgieri, Gaetano; Fattorusso, Roberto; Isernia, Carla; Rizzarelli, Enrico

    2013-10-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal differentiation, growth, and survival; it is involved in memory formation and higher cognitive functions. The N-terminal domain of BDNF is crucial for the binding selectivity and activation of its specific TrkB receptor. Zn(2+) ion binding may influence BDNF activity. Zn(2+) complexes with the peptide fragment BDNF(1-12) encompassing the sequence 1-12 of the N-terminal domain of BDNF were studied by means of potentiometry, electrospray mass spectrometry, NMR, and density functional theory (DFT) approaches. The predominant Zn(2+) complex species, at physiological pH, is [ZnL] in which the metal ion is bound to an amino, an imidazole, and two water molecules (NH2, N(Im), and 2O(water)) in a tetrahedral environment. DFT-based geometry optimization of the zinc coordination environment showed a hydrogen bond between the carboxylate and a water molecule bound to zinc in [ZnL]. The coordination features of the acetylated form [AcBDNF(1-12)] and of a single mutated peptide [BDNF(1-12)D3N] were also characterized, highlighting the role of the imidazole side chain as the first anchoring site and ruling out the direct involvement of the aspartate residue in the metal binding. Zn(2+) addition to the cell culture medium induces an increase in the proliferative activity of the BDNF(1-12) peptide and of the whole protein on the SHSY5Y neuroblastoma cell line. The effect of Zn(2+) is opposite to that previously observed for Cu(2+) addition, which determines a decrease in the proliferative activity for both peptide and protein, suggesting that these metals might discriminate and modulate differently the activity of BDNF.

  19. Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro

    Science.gov (United States)

    2011-11-01

    Support. St. Louis, MO: Mosby JEMS/Elsevier; 2007. 11. Gutierrez G, Reines HD, Wulf- Gutierrez ME. Clinical review: hemor- rhagic shock. Crit Care. 2004;8...Clin North Am. 2007;87:55–72, vi. 18. Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring

  20. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven)

    DEFF Research Database (Denmark)

    Viuff, D.; Lauritzen, B.; Pusateri, A.E.

    2008-01-01

    are poorly understood. METHODS: Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5...... bleeding time (BT) in rabbits. RESULTS: Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P... the BT (Pacidosis or hypothermia Udgivelsesdato: 2008/9...

  1. Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients.

    Science.gov (United States)

    Molino, Daniela; De Santo, Natale G; Marotta, Rosa; Anastasio, Pietro; Mosavat, Mahrokh; De Lucia, Domenico

    2004-09-01

    Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition

  2. Fragmented Authoritarianism or Integrated Fragmentation

    DEFF Research Database (Denmark)

    Brødsgaard, Kjeld Erik

    of these business leaders prompts the question of whether we are seeing the development of distinct interest groups that could challenge Party and state authority and create a fragmented polity. However, through the nomenklatura system the Party has an important instrument of control to wield over business groups...... and the Party-state, I suggest the notion of integrated fragmentation....

  3. Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa.

    Science.gov (United States)

    Schweitzer, Barbara A; Neumann, William L; Rahman, Hayat K; Kusturin, Carrie L; Sample, Kirby R; Poda, Gennadiy I; Kurumbail, Ravi G; Stevens, Anna M; Stegeman, Roderick A; Stallings, William C; South, Michael S

    2005-06-15

    We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.

  4. Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-α in aging.

    Science.gov (United States)

    Opp, Mark R; George, Amrita; Ringgold, Kristyn M; Hansen, Kim M; Bullock, Kristin M; Banks, William A

    2015-11-01

    The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis factor-α (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood-brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism's responses to those insults occurs with aging.

  5. Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

    Directory of Open Access Journals (Sweden)

    Philippe Thullier

    Full Text Available The lethal toxin (LT of Bacillus anthracis, composed of the protective antigen (PA and the lethal factor (LF, plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF to form the edema toxin (ET, which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236, of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260 was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

  6. Magma Fragmentation

    Science.gov (United States)

    Gonnermann, Helge M.

    2015-05-01

    Magma fragmentation is the breakup of a continuous volume of molten rock into discrete pieces, called pyroclasts. Because magma contains bubbles of compressible magmatic volatiles, decompression of low-viscosity magma leads to rapid expansion. The magma is torn into fragments, as it is stretched into hydrodynamically unstable sheets and filaments. If the magma is highly viscous, resistance to bubble growth will instead lead to excess gas pressure and the magma will deform viscoelastically by fracturing like a glassy solid, resulting in the formation of a violently expanding gas-pyroclast mixture. In either case, fragmentation represents the conversion of potential energy into the surface energy of the newly created fragments and the kinetic energy of the expanding gas-pyroclast mixture. If magma comes into contact with external water, the conversion of thermal energy will vaporize water and quench magma at the melt-water interface, thus creating dynamic stresses that cause fragmentation and the release of kinetic energy. Lastly, shear deformation of highly viscous magma may cause brittle fractures and release seismic energy.

  7. Framing Fragmentation

    DEFF Research Database (Denmark)

    Bundgaard, Charlotte

    2009-01-01

    , contain distinctive architectural traits, not only based on rational repetition, but also supporting composition and montage as dynamic concepts. Prefab architecture is an architecture of fragmentation, individualization and changeability, and this sets up new challenges for the architect. This paper...... into separate parts or systems: skeleton, skin, services, internal cladding, etc. Each building part/system is being conceived, produced, delivered and maintained by different construction companies. Basically the building is being fragmented into separate parts living their separate lives. The architect has...... to create architectural meaning and give character to an architecture of fragmentation. Layers are both seen as conceptual as well as material frames which define certain strong properties or meanings in the architectural work. Defining layers is a way of separating and organizing; it both defines...

  8. Loomemajandus - Eesti loojad on valmis, Eesti tööstus veel mitte / Erik Terk, Külliki Tafel-Viia, Silja Lassur ; intervjueerinud Mikk Salu

    Index Scriptorium Estoniae

    Terk, Erik, 1952-

    2009-01-01

    Eestis korraldatud uuringu "Eesti loomemajanduse potentsiaal ja arenguks vajalikud riikud toetusmeetmed" tulemustest lähtudes püütakse leida optimaalseid suhteid loovinimeste toetusmeetmete ja iseorganiseerumise vahel. Vestlusringis Eesti Tuleviku-uuringute Instituudi direktor Erik Terk ja teadurid Silja Lassur ja Külliki Tafel-Viia

  9. Fragmentation of monoclonal antibodies

    Science.gov (United States)

    Vlasak, Josef

    2011-01-01

    Fragmentation is a degradation pathway ubiquitously observed in proteins despite the remarkable stability of peptide bond; proteins differ only by how much and where cleavage occurs. The goal of this review is to summarize reports regarding the non-enzymatic fragmentation of the peptide backbone of monoclonal antibodies (mAbs). The sites in the polypeptide chain susceptible to fragmentation are determined by a multitude of factors. Insights are provided on the intimate chemical mechanisms that can make some bonds prone to cleavage due to the presence of specific side-chains. In addition to primary structure, the secondary, tertiary and quaternary structures have a significant impact in modulating the distribution of cleavage sites by altering local flexibility, accessibility to solvent or bringing in close proximity side chains that are remote in sequence. This review focuses on cleavage sites observed in the constant regions of mAbs, with special emphasis on hinge fragmentation. The mechanisms responsible for backbone cleavage are strongly dependent on pH and can be catalyzed by metals or radicals. The distribution of cleavage sites are different under acidic compared to basic conditions, with fragmentation rates exhibiting a minimum in the pH range 5–6; therefore, the overall fragmentation pattern observed for a mAb is a complex result of structural and solvent conditions. A critical review of the techniques used to monitor fragmentation is also presented; usually a compromise has to be made between a highly sensitive method with good fragment separation and the capability to identify the cleavage site. The effect of fragmentation on the function of a mAb must be evaluated on a case-by-case basis depending on whether cleavage sites are observed in the variable or constant regions, and on the mechanism of action of the molecule. PMID:21487244

  10. Development of a polymerase chain reaction-restriction fragment length polymorphism method for identification of the Fusarium genus using the transcription elongation factor-1α gene.

    Science.gov (United States)

    Zarrin, Majid; Ganj, Farzaneh; Faramarzi, Sama

    2016-12-01

    Fusarium species are well-known plant pathogens and food contaminants that have also appeared as one of the most important groups of medically significant fungi. The sequences of the translation elongation factor (TEF)-1α gene have been broadly employed for species detection. A total of 50 strains of Fusarium spp., including environmental, clinical and reference isolates were used for the current study. The primer sets, Fu3f and Fu3r, were used to amplify an ~420-bp DNA fragment of the TEF-1α gene. Double digestion with two restriction enzymes, XhoI and SduI was used for discrimination of the Fusarium species in the TEF-1α gene fragment. Double digestion of the TEF-1α gene fragment from five clinically important Fusarium species were clearly differentiated from each other: The F. solani species complex, F. oxysporum species complex, F. verticillioides, F. proliferatum and F. fujikuroi. This method facilitates detection and enables verification of the Fusarium genus; therefore, it may be applied for disease control.

  11. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor.

    Science.gov (United States)

    Inohara, N; Koseki, T; Chen, S; Wu, X; Núñez, G

    1998-05-01

    DFF45 is a subunit of the DNA fragmentation factor (DFF) that is cleaved by caspase-3 during apoptosis. However, the mechanism by which DFF45 regulates apoptotic cell death remains poorly understood. Here we report the identification and characterization of two mammalian genes, CIDE-A and CIDE-B, encoding highly related proteins with homology to the N-terminal region of DFF45. CIDE-A and CIDE-B were found to activate apoptosis in mammalian cells, which was inhibited by DFF45 but not by caspase inhibitors. Expression of CIDE-A induced DNA fragmentation in 293T cells, which was inhibited by DFF45, further suggesting that DFF45 inhibits the apoptotic activities of CIDEs. In addition to mammalian CIDE-A and CIDE-B, we identified DREP-1, a Drosophila melanogaster homolog of DFF45 that could inhibit CIDE-A-mediated apoptosis. Mutant analysis revealed that the C-terminal region of CIDE-A was necessary and sufficient for killing whereas the region with homology to DFF45 located in the N-terminus was required for DFF45 to inhibit CIDE-A-induced apoptosis. CD95/Fas-mediated apoptosis was enhanced by CIDEs but inhibited by DFF45. These studies suggest that DFF45 is evolutionarily conserved and implicate CIDEs as DFF45-inhibitable effectors that promote cell death and DNA fragmentation.

  12. The effects of insulin-like growth factorI (IGF I) complex from seminal plasma on capacitation, membrane integrity andDNA fragmentation in goat spermatozoa

    Institute of Scientific and Technical Information of China (English)

    Suherni Susilowati; Indah Norma Triana; Abdul Malik

    2015-01-01

    Objective:To evaluate the effects of the insulin-like growth factor I (IGF I) complex from seminal plasma on capacitation, membrane integrity and DNA fragmentation.Methods:A total of 0.5 mL of fresh semen was added to 1 mL of Bracket-Oliphant (BO) medium, and the sample was then centrifuged at a speed of 1 800 rpm for 10 minutes. The samples were analyzed before and after centrifugation for sperm viability, motility, membrane integrity and capacitation. The centrifuged samples were divided into three groups, each consisting of 3í 106spermatozoa. BO medium was added to group 1, BO ¬+ 12 ng IGF I complex medium was added to group 2, and 12 ng IGF I complex was added to group 3. Then, the samples were incubated for 15 minutes. Results:The result showed that sperm motility, viability and membrane integrity were significantly lower (P<0.05) after centrifugation. Furthermore, the sperm capacitation was significantly increased (P<0.05) after centrifugation. The percentages of sperm capacitation, membrane integrity and DNA fragmentation were significantly different (P< 0.05) in all media, including BO, BO + IGF-I complex and the IGF-I complex alone. Conclusions:Sperm quality include motility, viability and membrane integrity were lower after centrifugation. whereas DNA fragmentation after incubation in the IGF-I complex medium also was lower compared to that of specimens in the BO and BO + IGF-I complex media.

  13. Factors affecting the production of a single-chain antibody fragment by Aspergillus awamori in a stirred tank reactor.

    Science.gov (United States)

    Sotiriadis, A; Keshavarz, T; Keshavarz-Moore, E

    2001-01-01

    A recombinant strain of Aspergillus awamori expressing anti-lysozyme single chain antibody fragments (scFv), under the control of a xylanase promoter, was studied in order to investigate the impact of medium, induction regime and protease production on the expression of the product. Experiments with the time of induction showed that the optimum results are achieved when induction is started in the late exponential phase (21 h after inoculation) improving the titer of the product from 14.5 mg L(-1), obtained in the early exponential phase (7 h after inoculation), to 16.2 mg L(-1). A 100% increase of the carbon (fructose) and nitrogen (ammonium sulfate) sources in the growth medium resulted in an increase in product concentration from 16.2 to 108.9 mg L(-1) and an increase in maximum dry cell weight from 7.5 to 11.5 g L(-1). A 50% reduction in the concentration of the inducer resulted in an increase in the product yield from 10 mg g(-1) dry cell weight to 12 mg g(-1). Proteolytic enzymes were produced during the fermentation up to concentrations equivalent to 1.4 g L(-1) trypsin, but they had no detrimental effect on the concentration of the antibody fragment.

  14. FRAGMENTATION AND CONFLICT AMONG ISLAMIC POLITICAL PARTIES IN INDONESIA DURING REFORMASI ERA (1998-2009: Anatomy, Factors and Implications

    Directory of Open Access Journals (Sweden)

    Sri Yunanto

    2013-12-01

    Full Text Available Since independence of the Republic of Indonesia, Muslims, as the majority population, have established diverse Islamic political parties. The nature of such parties has changed from the days of the Old Order to the New Order and Reformasi eras. Despite similar anatomies between Islamic parties of the Old Order and those of Reformasi, Islamic political parties profess different ideological missions. While the beginning of Old Order saw the confederation of Islamic political parties, Masyumi, seeking to promote the establishment of an Islamic State, none of the Islamic political parties which mushroomed during Reformasi era expressly struggled for the establishment of an Islamic state. However, the Islamic political parties had to weather similar problems of internal conflict and fragmentation. Different ideological strands, policy stances and leadership styles are believed to be amongst the pivotal root causes of their domestic troubles. With their popular votes and parliamentary seats significantly reduced, they prove to be no competition to the nationalist political parties.

  15. Epidermal growth factor (EGF) fragment-guided anticancer theranostic particles for pH-responsive release of doxorubicin.

    Science.gov (United States)

    Kang, Myun Koo; Mao, Wei; Lee, Jun Bae; Yoo, Hyuk Sang

    2017-03-15

    EGF fragment (EGFfr) and doxorubicin were chemically co-decorated on single magnetic nanoparticles (MNPs) for concomitant cancer targeting and treatment. Magnetic nanoparticles were prepared by the precipitation of ferric chloride hydrates in an ammonia solution and subsequent surface-functionalization with amines. The terminal thiol group of the EGF fragment was first conjugated to surface amines of the MNPs using a heterofunctional crosslinker, and doxorubicin was sequentially conjugated to the MNPs via a hydrazone linker, where the degree of subsitution of the surface amines to EGFfr was varied from 1% to 40%. The decorated doxorubicin showed clear pH-dependency in the release profile, and doxorubicin showed fast release at pH 5.0 in comparison to pH 7.4. The EGF-decorated MNPs were tested for differential cellular uptakes against EGF overexpressing cells (A549), and the uptake levels gradually increased to 10% and saturated, which was quantified by ICP-OES. Internalized doxorubicin was also visualized by confocal microscopy, and A549 cells with EGF-decorated MNPs with EGF decoration showed higher fluorescence intensity of doxorubicin than those with non-decorated MNPs. Anti-cancer activity of the MNPs was compared at various concentrations of doxorubicin and EGFfr. Decoration of EGFfr significantly increased the anti-cancer activity of doxorubicin-incorporated MNPs in A549 cells; however, EGFfr alone did not affect the viability of the cells. Thus, we concluded that MNPs with optimized EGFfr and doxorubicin ratios showed higher targeting and drug payload against EGF receptor overexpressing cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Bespoke Fragments

    DEFF Research Database (Denmark)

    Kruse Aagaard, Anders

    2016-01-01

    The Ph.D. -project Bespoke Fragments seeks to explore and utilise the space emerging between the potentials of digital drawing and fabrication and the field of materials and their properties and capacities. Within this span, the project is situated in a shuttling between the virtual and the actual......, the emergence of virtual space is no longer limited to the computer's digital world, but extends into the materials' world. Creation and uncertainty are allowed as virtual parameters in both the digital and reality. Based on this notion the project suggests utilising that exact potential to develop...

  17. CONTROL OF FRAGMENTATION BY BLASTING

    Directory of Open Access Journals (Sweden)

    Branko Božić

    1998-12-01

    Full Text Available The degree of fragmentation influences the economy of the excavation operations. Characteristics of blasted rock such as fragment size, volume and mass are fundamental variables effecting the economics of a mining operation and are in effect the basis for evaluating the quality of a blast. The properties of fragmentation, such as size and shape, are very important information for the optimization of production. Three factors control the fragment size distribution: the rock structure, the quantity of explosive and its distribution within the rock mass. Over the last decade there have been considerable advances in our ability to measure and analyze blasting performance. These can now be combined with the continuing growth in computing power to develop a more effective description of rock fragmentation for use by future blasting practitioners. The paper describes a view of the fragmentation problem by blasting and the need for a new generation of engineering tools to guide the design and implementation of blasting operations.

  18. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding.

    Science.gov (United States)

    Smith, M P; Ludlam, C A; Collins, P W; Hay, C R; Wilde, J T; Grigeri, A; Melsen, T; Savidge, G F

    2001-10-01

    We examined recombinant activated factor VII (rVIIa) administered by continuous infusion to eight patients with inhibitors to factor VIII, undergoing elective surgery. rVIIa was infused at a fixed rate of 16.5 microg/kg/h for a median of 13.5 days (range 1-26). There was effective haemostasis at this infusion rate in only one of two minor procedures and two of six major operations. Three patients experienced excessive bleeding despite plasma factor VII activity around 10 IU/ml. Serious bleeding occurred in two other patients caused by procedural errors unrelated to rVIIa and required re-operation. The median rVIIa clearance on day 1 was 57 ml/h/kg (range 18-100) and on day 3 was 100 ml/h/kg (range 61-200). Clearance on the final infusion day was not significantly different from day 3. The infusion did not induce pathological activation of the coagulation mechanism. The only thrombotic adverse events were two episodes of superficial thrombophlebitis of the infused vein in one subject. In conclusion, the 16.5 microg/kg/h infusion rate reliably achieves plasma factor VII activity levels of 10 IU/ml, but this level does not provide reliable haemostasis.

  19. Purification of FLAG-tagged eukaryotic initiation factor 2B complexes, subcomplexes, and fragments from Saccharomyces cerevisiae.

    Science.gov (United States)

    Mohammad-Qureshi, Sarah S; Haddad, Raphaël; Palmer, Karren S; Richardson, Jonathan P; Gomez, Edith; Pavitt, Graham D

    2007-01-01

    The eukaryotic initiation factor 2B (eIF2B) is a five-subunit guanine nucleotide exchange factor, that functions during translation initiation to catalyze the otherwise slow exchange of GDP for GTP on its substrate eIF2. Assays to measure substrate interaction and guanine nucleotide release ability of eIF2B require the complex to be purified free of interacting proteins. We have also found that a subcomplex of two subunits, gamma and epsilon or the largest one, epsilon alone, promotes this activity. Within eIF2Bepsilon, the catalytic center requires the C-terminal 200 residues only. Here, we describe our protocols for purifying the Saccharomyces cerevisiae eIF2B complexes and the catalytic subunit using FLAG-tagged proteins overexpressed in yeast cells. Using commercially available FLAG-affinity resin and high salt buffer, we are able to purify active eIF2B virtually free of contaminants.

  20. Next-Generation Sequencing of Genomic DNA Fragments Bound to a Transcription Factor in Vitro Reveals Its Regulatory Potential

    Directory of Open Access Journals (Sweden)

    Yukio Kurihara

    2014-12-01

    Full Text Available Several transcription factors (TFs coordinate to regulate expression of specific genes at the transcriptional level. In Arabidopsis thaliana it is estimated that approximately 10% of all genes encode TFs or TF-like proteins. It is important to identify target genes that are directly regulated by TFs in order to understand the complete picture of a plant’s transcriptome profile. Here, we investigate the role of the LONG HYPOCOTYL5 (HY5 transcription factor that acts as a regulator of photomorphogenesis. We used an in vitro genomic DNA binding assay coupled with immunoprecipitation and next-generation sequencing (gDB-seq instead of the in vivo chromatin immunoprecipitation (ChIP-based methods. The results demonstrate that the HY5-binding motif predicted here was similar to the motif reported previously and that in vitro HY5-binding loci largely overlapped with the HY5-targeted candidate genes identified in previous ChIP-chip analysis. By combining these results with microarray analysis, we identified hundreds of HY5-binding genes that were differentially expressed in hy5. We also observed delayed induction of some transcripts of HY5-binding genes in hy5 mutants in response to blue-light exposure after dark treatment. Thus, an in vitro gDNA-binding assay coupled with sequencing is a convenient and powerful method to bridge the gap between identifying TF binding potential and establishing function.

  1. Triggered fragmentation in gravitationally unstable discs: forming fragments at small radii

    Directory of Open Access Journals (Sweden)

    Meru Farzana

    2013-04-01

    Full Text Available We carry out three dimensional radiation hydrodynamical simulations of gravitationally unstable discs using to explore the movement of mass in a disc following its fragmentation. Compared to a more quiescent state before it fragments, the radial velocity of the gas increases by up to a factor of ≈ 2 – 3 after fragmentation. While the mass movement occurs both inwards and outwards, the inwards motion can cause the inner spirals to be suciently dense that they may become unstable and potentially fragment. Consequently, the dynamical behaviour of fragmented discs may cause subsequent fragmentation at smaller radii after an initial fragment has formed in the outer disc.

  2. Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family.

    Science.gov (United States)

    Liang, Liang; Zhao, Mujun; Xu, Zhenhua; Yokoyama, Kazunari K; Li, Tsaiping

    2003-02-15

    DNA fragmentation is one of the critical steps in apoptosis, which is induced by DNA fragmentation factor (DFF). DFF is composed of two subunits, a 40 kDa caspase-activated nuclease (DFF40) and a 45 kDa inhibitor (DFF45). Recently a novel family of cell-death-inducing DFF45-like effectors (CIDEs) has been identified. Among CIDEs, two from human (CIDE-A and CIDE-B) and three from mouse (CIDE-A, CIDE-B and FSP27) have been reported. In this study human CIDE-3, a novel member of CIDEs, was identified upon sequence analysis of a previously unidentified cDNA that encoded a protein of 238 amino acids. It was shown to be a human homologue of mouse FSP27, and shared homology with the CIDE-N and CIDE-C domains of CIDEs. Apoptosis-inducing activity was clearly shown by DNA-fragmentation assay of the nuclear DNA of CIDE-3 transfected 293T cells. The expression pattern of CIDE-3 was different from that of CIDE-B. As shown by Northern-blot analysis, CIDE-3 was expressed mainly in human small intestine, heart, colon and stomach, while CIDE-B showed strong expression in liver and small intestine and at a lower level in colon, kidney and spleen. Green-fluorescent-protein-tagged CIDE-3 was revealed in some cytosolic corpuscles. Alternative splicing of the CIDE-3 gene was also identified by reverse transcription PCR, revealing that two transcripts, CIDE-3 and CIDE-3alpha, were present in HepG2 and A375 cells. CIDE-3 comprised a full-length open reading frame with 238 amino acids; in CIDE-3alpha exon 3 was deleted and it encoded a protein of 164 amino acids. Interestingly the CIDE-3alpha isoform still kept the apoptosis-inducing activity and showed the same pattern of subcellular localization as CIDE-3. Consistent with its chromosome localization at 3p25, a region associated with high frequency loss of heterozygosity in many tumours, CIDE-3 may play an important role in prevention of tumorigenesis.

  3. Preparation and characterization of anti-tissue factor single-chain variable fragment antibody for cancer diagnosis.

    Science.gov (United States)

    Sato, Ryuta; Obonai, Toshifumi; Tsumura, Ryo; Tsumoto, Kouhei; Koga, Yoshikatsu; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2014-12-01

    Tissue factor (TF), which serves as the initiator of the extrinsic blood coagulation cascade, has been found to be overexpressed in various solid tumors, especially brain tumors, pancreatic cancer, and gastric cancer. Overexpression of TF is considered to contribute to the high incidence of thrombotic complications and poor prognosis in patients with such cancers. Therefore, detection or targeting of TF may be a promising approach for the diagnosis and treatment of solid tumors that are known to overexpress the protein. Here, we used the recombinant DNA technology to develop an anti-TF single-chain Fv (scFv) of small size and high affinity for its target. The biochemical characteristics of the anti-TF scFv were evaluated using surface plasmon resonance (SPR) sensing and flow cytometry. The data obtained showed that the affinity of the anti-TF scFv was 2.04 × 10(-8) (KD), and that the protein showed significant binding to the cancer cells. Then, Alexa 647-labeled anti-TF scFv and anti-TF IgG were administered to mice bearing chemically induced spontaneous tumors. The maximum tumor to background ratios of anti-TF scFv and anti-TF IgG were obtained 3 and 24 h after the injections, respectively. This study indicates anti-TF scFv may be suitable as an imaging probe for the diagnosis of solid tumors.

  4. Tissue factor pathway inhibitor endocytosis.

    Science.gov (United States)

    Schwartz, A L; Broze, G J

    1997-10-01

    Tissue factor pathway inhibitor (TFPI), a 42 kD protein, provides the physiological inhibition of tissue factor initiated coagulation by inhibition of both factor Xa and factor VIIa/tissue factor. In plasma, most TFPI is lipoprotein bound with an additional "releasable" pool bound to the endothelial cell surface. TFPI clearance is via receptor mediated endocytosis into liver. Heparin sulfate proteoglycans and LRP (low density lipoprotein receptor-related protein), an extremely large (∼600 kD) cell surface protein, primarily mediate this clearance, although additional TFPI binding sites and endocytosis pathways exist. (Trends Cardiovasc Med 1997; 7:234-239). © 1997, Elsevier Science Inc.

  5. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Bhavya S Doshi

    Full Text Available Development of inhibitory antibodies to coagulation factor VIII (fVIII is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVIII antibodies are treated with bypassing agents including recombinant factor VIIa (rfVIIa. However, some patients display poor hemostatic response to bypass therapy and improved treatment options are needed. Recently, we demonstrated that fVIII inhibitors display widely variable kinetics of inhibition that correlate with their respective target epitopes. Thus, it was hypothesized that for antibodies that display slow rates of inhibition, supplementation of rfVIIa with fVIII would result in improved thrombin generation and be predictive of clinical responses to this novel treatment regimen. In order to test this hypothesis, 10 murine monoclonal antibodies (MAbs with non-overlapping epitopes spanning fVIII, differential inhibition titers, and inhibition kinetics were studied using a thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the one with fast and complete (classically defined as "type I" kinetics displayed significant inhibition of thrombin generation with no improvement upon supplementation of rfVIIa with fVIII. The other two MAbs that displayed incomplete (classically defined as "type II" inhibition did not suppress the potentiation of thrombin generation by fVIII. All antibodies that did not completely inhibit fVIII activity demonstrated potentiation of thrombin generation by the addition of fVIII as compared to rfVIIa alone. In conclusion, fVIII alone or in combination with rfVIIa corrects the thrombin generation defect produced by the majority of anti-fVIII MAbs better than single agent rfVIIa. Therefore, combined fVIII/rfVIIa

  6. Distribution of genes encoding putative virulence factors and fragment length polymorphisms in the vrrA gene among Brazilian isolates of Bacillus cereus and Bacillus thuringiensis.

    Science.gov (United States)

    Zahner, Viviane; Cabral, Diana Aparecida; Régua-Mangia, Adriana Hamond; Rabinovitch, Leon; Moreau, Gaétan; McIntosh, Douglas

    2005-12-01

    One hundred twenty-one strains of the Bacillus cereus complex, of which 80 were isolated from a variety of sources in Brazil, were screened by PCR for the presence of sequences (bceT, hblA, nheBC, plc, sph, and vip3A) encoding putative virulence factors and for polymorphisms in variable-number tandem repeats (VNTR), using a variable region of the vrrA open reading frame as the target. Amplicons were generated from isolates of B. cereus and Bacillus thuringiensis for each of the sequences encoding factors suggested to play a role in infections of mammals. Intriguingly, the majority of these sequences were detected more frequently in Bacillus thuringiensis than in B. cereus. The vip3A sequence, which encodes an insecticidal toxin, was detected exclusively in B. thuringiensis. VNTR analysis demonstrated the presence of five different fragment length categories in both species, with two of these being widely distributed throughout both taxa. In common with data generated from previous studies examining European, Asian, or North American populations, our investigation of Brazilian isolates supports the notion that B. cereus and B. thuringiensis should be considered to represent a single species.

  7. Spin-alignment and g-factor measurement of the I{sup {pi}}=12{sup +} isomer in {sup 192}Pb produced in the relativistic-energy fragmentation of a {sup 238}U beam

    Energy Technology Data Exchange (ETDEWEB)

    Kmiecik, M.; Maj, A.; Ciemala, M.; Grebosz, J.; Lach, M.; Maier, K.H.; Mazurek, K.; Meczynski, W.; Myalski, S.; Styczen, J.; Zieblinski, M. [H. Niewodniczanski Inst. of Nuclear Physics PAN, Krakow (Poland); Gerl, J.; Becker, F.; Caceres, L.; Doornenbal, P.; Gorska, M.; Grawe, H.; Kojuharov, I.; Prokopowicz, W.; Saito, N.; Saito, T.R.; Wollersheim, H.J. [GSI, Darmstadt (Germany); Neyens, G.; Mallion, S.; Vermeulen, N. [Inst. voor Kern- en Stralingsfysica, K.U. Leuven (Belgium); Atanasova, L.; Detistov, P. [Univ. of Sofia ' St. Kl. Ohridski' (Bulgaria). Faculty of Physics; Balabanski, D.L. [Univ. degli Studi di Camerino (Italy); INFN sez. Perugia, Dipt. di Fisica, Camerino (Italy); Bulgarian Academy of Sciences, Inst. for Nuclear Research and Nuclear Energy, Sofia (Bulgaria); Bednarczyk, P. [H. Niewodniczanski Inst. of Nuclear Physics PAN, Krakow (Poland); GSI, Darmstadt (Germany); Benzoni, G.; Blasi, N.; Brambilla, S.; Million, B.; Wieland, O. [INFN Sez. di Milano (Italy); Bracco, A.; Camera, F.; Crespi, F.C.L.; Leoni, S.; Montanari, D. [INFN Sez. di Milano (Italy); Univ. degli Studi di Milano (Italy); Chamoli, S.K.; Hass, M.; Lakshmi, S. [Weizman Inst. of Science, Rehovot (Israel); Chmel, S. [Fraunhofer INT, Euskirchen (Germany); Daugas, J.M. [CEA, DAM, DIF, Arpajon Cedex (France); Georgiev, G. [Univ. Paris-Sud 11, CNRS/IN2P3, CSNSM, Orsay-Campus (France); Gladnishki, K. [Univ. of Sofia ' St. Kl. Ohridski' (Bulgaria). Faculty of Physics; Univ. degli Studi di Camerino (Italy); INFN sez. Perugia, Dipt. di Fisica, Camerino (Italy); Hoischen, R.; Rudolph, D. [Lund Univ., Dept. of Physics, Lund (Sweden); Ilie, G. [Univ. zu Koeln, Inst. fuer Kernphysik, Koeln (Germany); National Inst. for Physics and Nuclear Engineering, Bucharest (Romania); Ionescu-Bujor, M. [National Inst. for Physics and Nuclear Engineering, Bucharest (Romania); Jolie, J. [Univ. zu Koeln, Institut fuer Kernphysik, Koeln (Germany)] [and others

    2010-08-15

    The feasibility of measuring g -factors using the TDPAD method applied to high-energy, heavy fragmentation products is explored. The 2623keV I{sup {pi}}=12{sup +} isomer in {sup 192}Pb with {tau}=1.57{mu}s has been produced using the fragmentation of a 1A GeV {sup 238}U beam. The results presented demonstrate for the first time that such heavy nuclei produced in a fragmentation reaction with a relativistic beam are sufficiently well spin-aligned. Moreover, the rather large value of the alignment, 28(10)% of the maximum possible, is preserved during the separation process allowing the determination of magnetic moments. The measured values of the lifetime, {tau}=1.54(9) {mu}s, and the g-factor, g=-0.175(20), agree with the results of previous investigations using fusion-evaporation reactions. (orig.)

  8. Endothelial-derived tissue factor pathway inhibitor regulates arterial thrombosis but is not required for development or hemostasis.

    NARCIS (Netherlands)

    White, T.A.; Johnson, T.; Zarzhevsky, N.; Tom, C.; Delacroix, S.; Holroyd, E.W.; Maroney, S.A.; Singh, R.; Pan, S.; Fay, W.P.; Deursen, J.M.A. van; Mast, A.E.; Sandhu, G.S.; Simari, R.D.

    2010-01-01

    The antithrombotic surface of endothelium is regulated in a coordinated manner. Tissue factor pathway inhibitor (TFPI) localized at the endothelial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex. Systemic homozygotic deletion of the first Kunitz (K1) domain of TFPI

  9. Differential Roles of Cell Death-inducing DNA Fragmentation Factor-α-like Effector (CIDE) Proteins in Promoting Lipid Droplet Fusion and Growth in Subpopulations of Hepatocytes.

    Science.gov (United States)

    Xu, Wenyi; Wu, Lizhen; Yu, Miao; Chen, Feng-Jung; Arshad, Muhammad; Xia, Xiayu; Ren, Hao; Yu, Jinhai; Xu, Li; Xu, Dijin; Li, John Zhong; Li, Peng; Zhou, Linkang

    2016-02-26

    Lipid droplets (LDs) are dynamic subcellular organelles whose growth is closely linked to obesity and hepatic steatosis. Cell death-inducing DNA fragmentation factor-α-like effector (CIDE) proteins, including Cidea, Cideb, and Cidec (also called Fsp27), play important roles in lipid metabolism. Cidea and Cidec are LD-associated proteins that promote atypical LD fusion in adipocytes. Here, we find that CIDE proteins are all localized to LD-LD contact sites (LDCSs) and promote lipid transfer, LD fusion, and growth in hepatocytes. We have identified two types of hepatocytes, one with small LDs (small LD-containing hepatocytes, SLHs) and one with large LDs (large LD-containing hepatocytes, LLHs) in the liver. Cideb is localized to LDCSs and promotes lipid exchange and LD fusion in both SLHs and LLHs, whereas Cidea and Cidec are specifically localized to the LDCSs and promote lipid exchange and LD fusion in LLHs. Cideb-deficient SLHs have reduced LD sizes and lower lipid exchange activities. Fasting dramatically induces the expression of Cidea/Cidec and increases the percentage of LLHs in the liver. The majority of the hepatocytes from the liver of obese mice are Cidea/Cidec-positive LLHs. Knocking down Cidea or Cidec significantly reduced lipid storage in the livers of obese animals. Our data reveal that CIDE proteins play differential roles in promoting LD fusion and lipid storage; Cideb promotes lipid storage under normal diet conditions, whereas Cidea and Cidec are responsible for liver steatosis under fasting and obese conditions.

  10. g-factors of isomers around N approx 40, Z approx 28 from time-dependent Larmor precession on spin-aligned projectile-like fragments

    CERN Document Server

    Neyens, G; Grzywacz, R; Hass, M; De Oliveira-Santos, F; Lewitowicz, M; Balabanski, D L; Bingham, C; Borcea, C; Coulier, N; Coussement, R; Daugas, J M; De France, G; Goldring, G; aGórska, M; Grawe, H; Oleari, C; Macovei, I; Mach, H; Page, R; Pfützner, M; Penionzhkevich, Yu E; Podolyák, Z; Regan, P H; Rykaczewski, K; Sawicka, M; Smirnova, N A; Sobolev, Y; Teughels, S; Vyvey, K

    2002-01-01

    First and preliminary results of an experiment aimed at measuring g-factors of isomeric states in neutron-rich nuclei in the vicinity of sup 6 sup 8 Ni are reported. Isomers near the predicted N=40 sub-shell closure in sup 6 sup 9 Cu, sup 6 sup 7 Ni and sup 6 sup 6 Co have been populated in the fragmentation of a sup 7 sup 6 Ge, 61.4 MeV/u beam onto a 145 mg/cm sup 2 sup 9 Be target at GANIL. Here we report the results for the 357(2) ns, I suppi=13/2 sup + isomer in sup 6 sup 9 Cu for which a preliminary gyromagnetic ratio of |g|=0.195(9) was derived. The Larmor precession of the spin-oriented isomeric ensemble was measured by recording gamma-ion correlations in a 20 mu s time window. This pioneering experiment has indicated interesting nuclear structure information and shows promising possibilities for future studies of this kind.

  11. Expression of anti-tumor necrosis factor alpha (TNFα) single-chain variable fragment (scFv) in Spirodela punctata plants transformed with Agrobacterium tumefaciens.

    Science.gov (United States)

    Balaji, Parthasarathy; Satheeshkumar, P K; Venkataraman, Krishnan; Vijayalakshmi, M A

    2016-05-01

    Therapeutic antibodies against tumor necrosis factor alpha (TNFα) have been considered effective for some of the autoimmune diseases such as rheumatoid arthritis, Crohn's diseases, and so on. But associated limitations of the current therapeutics in terms of cost, availability, and immunogenicity have necessitated the need for alternative candidates. Single-chain variable fragment (scFv) can negate the limitations tagged with the anti-TNFα therapeutics to a greater extent. In the present study, Spirodela punctata plants were transformed with anti-TNFα through in planta transformation using Agrobacterium tumefaciens strain, EHA105. Instead of cefotaxime, garlic extract (1 mg/mL) was used to remove the agrobacterial cells after cocultivation. To the best of our knowledge, this report shows for the first time the application of plant extracts in transgenic plant development. 95% of the plants survived screening under hygromycin. ScFv cDNA integration in the plant genomic DNA was confirmed at the molecular level by PCR. The transgenic protein expression was followed up to 10 months. Expression of scFv was confirmed by immunodot blot. Protein expression levels of up to 6.3% of total soluble protein were observed. β-Glucuronidase and green fluorescent protein expressions were also detected in the antibiotic resistant plants. The paper shows the generation of transgenic Spirodela punctuata plants through in planta transformation.

  12. Social capital, narratives of fragmentation, and schizophrenia: an ethnographic exploration of factors shaping African-Caribbeans' social capital and mental health in a North London community.

    Science.gov (United States)

    Eliacin, Johanne

    2013-09-01

    Recent research studies have proposed the concept of social capital-broadly defined as social networks, community cohesion, and participation-as a social risk factor for health disparities and the high rates of schizophrenia among individuals of Caribbean heritage in England. However, many of the existing studies lack sociohistorical contexts and do not capture the experiential dimensions of individuals' social capital. This paper adds to the debate by examining the mechanisms and sociocultural processes that shape the understandings and experiences of social capital in a sample of British African-Caribbeans. Drawing on ethnographic and survey data collected over 2 years in a North London community, the paper focuses on participants' every day experiences and the stories they tell about their community and social fragmentation. These stories suggest that social changes and historical forces interact to affect the social capital and emotional well-being of local African-Caribbean residents. I argue that my participants' collective narratives about their social environment contribute to the emotional tone of the community, and create added stressors that may impact their mental health.

  13. Klassiõpetaja peab särama / Ly Melesk, Kairis Kontus, Leida Talts, Viia Hang...[jt.] ; küsitles Anu Mõttus

    Index Scriptorium Estoniae

    2007-01-01

    Vestlusringis on Tallinna Kuristiku Gümnaasiumi klassiõpetajad Viia Hang ja Ly Melesk, Tallinna Ülikooli 5. kursuse üliõpilane ja Tallinna Lepistiku Lasteaed-Algkooli õpetaja Kairis Kontus, Tallinna Ülikooli algõpetuse õppetooli juhataja Leida Talts ning algõpetuse õppetooli pedagoogika ja algõpetuse metoodika õppejõud Mare Müürsepp. Kui hästi on Tallinna Ülikool ja tema eelkäijad suutnud algklassiõpetajaid ette valmistada ja mis neil igapäevatöös toime tulla aitab

  14. Truncated N-terminal huntingtin fragment with expanded-polyglutamine (htt552-100Q)suppresses brain-derived neurotrophic factor transcription in astrocytes

    Institute of Scientific and Technical Information of China (English)

    Linhui Wang; Fang Lin; Jin Wang; Junchao Wu; Rong Han; Lujia Zhu; Guoxing Zhang; Marian DiFiglia; Zhenghong Qin

    2012-01-01

    Although huntingtin (htt) can be cleaved at many sites by caspases,calpains,and aspartyl proteases,amino acid (aa) 552 was defined as a preferred site for cleavage in human Huntington disease (HD) brains in vivo.To date,the normal function of wild-type N-terminal htt fragment 1-552 aa (htt552) and its pathological roles of mutant htt552 are still unknown.Although mutant htt (mhtt) is also expressed in astrocytes,whether and how mhtt contributes to the neurodegeneration through astrocytes in HD remains largely unknown.In this study,a glia HD model,using an adenoviral vector to express wild-type htt552 (htt552-18Q) and its mutation (htt552-100Q) in rat primary cortical astrocytes,was generated to investigate the influence of htt552 on the transcription of brainderived neurotrophic factor (BDNF). Results from enzyme linked immunosorbent assay showed that the level of BDNF in astrocyte-conditioned medium was decreased in the astrocytes expressing htt552-100Q.Quantitative real-time polymerase chain reaction demonstrated that htt552-100Q reduced the transcripts of the BDNF Ⅲ and Ⅳ, hence, repressed the transcription of BDNF.Furthermore,immunofluorescence showed that aggregates formed by htt552-100Q entrapped transcription factors cAMP-response element-binding protein and stimulatory protein 1,which might account for the reduction of BDNF transcription.These findings suggest that mhtt552 reduces BDNF transcription in astrocytes,which might contribute to the neuronal dysfunction in HD.

  15. TBM滚刀破岩过程影响因素数值模拟研究%Numerical simulaiton of influence factors for rock fragmentation by TBM cutters

    Institute of Scientific and Technical Information of China (English)

    孙金山; 陈明; 陈保国; 卢文波; 周传波

    2011-01-01

    全断面岩石掘进机(TBM)的破岩效率主要受刀盘设计和岩体特征的影响.采用颗粒流方法建立了岩石试件与滚刀的数值模型,对TBM滚刀破岩过程的影响因素进行了分析.研究表明,单刃滚刀交替作用下强度较低的岩石中易形成规则的张拉裂纹而生成较大岩碴;强度较高的岩石中滚刀的侧向挤压促使形成块度较小的片状岩碴;双刃滚刀作用下岩石表面受到强烈挤压后出现较大的拉应力,使岩石更易破碎,且仅在强度较高的岩石中才易形成透镜状岩碴.滚刀破岩过程中存在能耗最小的最佳间距,该最佳间距随着岩石强度的增大而减小.滚刀破岩过程中,结构面对裂纹扩展具有显著的控制性作用,并阻隔损伤向结构面下的岩石中渗透;随着结构面与滚刀侵入方向夹角的减小,结构面将引导裂纹向岩石深部扩展,而当夹角较大时,结构面则会引导裂纹横向扩展,易导致大块岩碴的形成.%The cutterhead and rock mass characteristics affect the excavation efficiency of full face rock tunnel boring machine (TBM) strongly.The numerical models are made by the particle flow code method (PFC2D) to simulate the rock fragmentation under TBM disc cutters.Numerical simulation tests show that some factors influence the rock fragmentation process strongly.In the relative weak rocks, the regular tension cracks and the big mucks form more easily, when the disc cutters penetrate rocks altemately; in hard rocks,the formation of small disc shape mucks depends on the lateral extrusion of cutter rings.Under the double disc cutters, the rocks crush more easily because of the tension stress which comes form strong compression of cuaers, and the disc shape mucks only form in very hard rocks.There is optimal cutter spacing for different strength rocks, which increase with rock strength decreases.In the process of rock fragmentation, discontinuities control the propagation process of cracks

  16. Assessment of T-2 toxin effect and its metabolite HT-2 toxin combined with insulin-like growth factor I, leptin and ghrelin on progesterone secretion by rabbit ovarian fragments.

    Science.gov (United States)

    Maruniakova, Nora; Kadasi, Attila; Sirotkin, Alexander V; Leśniak, Agnieszka; Ferreira, Ana M M; Bulla, Jozef; Kolesarova, Adriana

    2015-01-01

    Assessment of A-trichothecene mycotoxins (T-2 and HT-2 toxins) effect combined with growth factor IGF-I, and the metabolic hormones leptin and ghrelin on progesterone secretion by rabbit ovarian fragments was studied. Rabbit ovarian fragments were incubated without (control group) or with T-2/HT-2 toxin, or their combinations with insulin-like growth factor I (IGF-I), leptin or ghrelin at various concentrations for 24 h. Secretion of progesterone was determined by ELISA. First, T-2 toxin and HT-2 toxins at all doses used (0.01, 0.1, 1, 10, and 100 ng mL(-1)) were not shown to be potential regulators of progesterone secretion in rabbit ovarian fragments. Second, T-2 toxin but not HT-2 toxin combined with IGF-I was shown to be potential regulator of progesterone secretion in rabbit ovarian fragments. T-2 toxin at all doses used (0.01; 0.1; 1; 10; and 100 ng mL(-1)) combined with IGF-I (at dose 100 ng mL(-1)) significantly (P < 0.05) decreased progesterone secretion by rabbit ovarian fragments. Third, T-2 toxin and HT-2 toxin at all doses used in the study (0.01, 0.1, 1, 10, and 100 ng mL(-1)) combined with leptin (at dose 1000 ng mL(-1)) were not shown to be potential regulators of progesterone secretion in rabbit ovarian fragments. Furthermore, T-2 toxin and HT-2 toxin at all doses used in the study (0.01, 0.1, 1, 10, and 100 ng mL(-1)) combined with ghrelin (500 ng mL(-1)) were not shown to be potential regulators of progesterone secretion in rabbit ovarian fragments. Results in this study showed that trichothecene as T-2 toxin combined with IGF-I but not HT-2 toxin was able to decrease progesterone secretion in rabbit ovarian fragments in vitro. Experimental results of T-2 and HT-2 toxins combined with leptin and ghrelin did not confirm ability to modulate progesterone secretion by ovarian fragments in rabbits.

  17. DNA Fragmentation Factor 45 (DFF45 Gene at 1p36.2 Is Homozygously Deleted and Encodes Variant Transcripts in Neuroblastoma Cell Line

    Directory of Open Access Journals (Sweden)

    Hong Wei Yang

    2001-01-01

    Full Text Available Recently, loss of heterozygosity (LOH studies suggest that more than two tumor suppressor genes lie on the short arm of chromosome 1 (1p in neuroblastoma (NB. To identify candidate tumor suppressor genes in NB, we searched for homozygous deletions in 20 NB cell lines using a high-density STS map spanning chromosome 1 p36, a common LOH region in NB. We found that the 45-kDa subunit of the DNA fragmentation factor (DFF45 gene was homozygously deleted in an NB cell line, NB-1. DFF45 is the chaperon of DFF40, and both molecules are necessary for caspase 3 to induce apoptosis. DFF35, a splicing variant of DFF45, is an inhibitor of DFF40. We examined 20 NB cell lines for expression and mutation of DFF45 gene by reverse transcription (RT-polymerase chain reaction (PCR and RT-PCR-single-strand conformation polymorphism. Some novel variant transcripts of the DFF45 gene were found in NB cell lines, but not in normal adrenal gland and peripheral blood. These variants may not serve as chaperons of DFF40, but as inhibitors like DFF35, thus disrupting the balance between DFF45 and DFF40. No mutations of the DFF45 gene were found in any NB cell line, suggesting that the DFF45 is not a tumor suppressor gene for NB. However, homozygous deletion of the DFF45 gene in the NB-1 cell line may imply the presence of unknown tumor suppressor genes in this region.

  18. The effects of insulin-like growth factor I (IGF-I complex from seminal plasma on capacitation, membrane integrity and DNA fragmentation in goat spermatozoa

    Directory of Open Access Journals (Sweden)

    Suherni Susilowati

    2015-09-01

    Conclusions: Sperm quality include motility, viability and membrane integrity were lower after centrifugation. Whereas DNA fragmentation after incubation in the IGF-I complex medium also was lower compared to that of specimens in the BO and BO + IGF-I complex media.

  19. Coal char fragmentation during pulverized coal combustion

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, L.L.

    1995-07-01

    A series of investigations of coal and char fragmentation during pulverized coal combustion is reported for a suite of coals ranging in rank from lignite to low-volatile (lv) bituminous coal under combustion conditions similar to those found in commercial-scale boilers. Experimental measurements are described that utilize identical particle sizing characteristics to determine initial and final size distributions. Mechanistic interpretation of the data suggest that coal fragmentation is an insignificant event and that char fragmentation is controlled by char structure. Chars forming cenospheres fragment more extensively than solid chars. Among the chars that fragment, large particles produce more fine material than small particles. In all cases, coal and char fragmentation are seen to be sufficiently minor as to be relatively insignificant factors influencing fly ash size distribution, particle loading, and char burnout.

  20. Mechanisms in Impact Fragmentation

    OpenAIRE

    Wittel, Falk K.; Carmona, Humberto A.; Kun, Ferenc; Herrmann, Hans J.

    2015-01-01

    The brittle fragmentation of spheres is studied numerically by a 3D Discrete Element Model. Large scale computer simulations are performed with models that consist of agglomerates of many spherical particles, interconnected by beam-truss elements. We focus on a detailed description of the fragmentation process and study several fragmentation mechanisms involved. The evolution of meridional cracks is studied in detail. These cracks are found to initiate in the inside of the specimen with quasi...

  1. Habitat fragmentation causes rapid genetic differentiation and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... differentiation and homogenization in natural plant populations – A ... The effects of habitat fragmentations on the forage grass Leymus thinness (Trin.) Tzvel, which ... selection etc, combined together with ecological factors.

  2. FOREST FRAGMENTATION AS AN ECONOMIC INDICATOR

    Science.gov (United States)

    Despite concern over the ecological consequences of conversion of land from natural cover to anthropogenic uses, there are few studies that show a quantitative relationship between fragmentation and economic factors. For the southside economic region of Virginia, we generated a ...

  3. Risk factors connected to gastrointestinal parasites in mantled Alouatta palliata mexicana and black howler monkeys Alouatta pigra living in continuous and in fragmented rainforests in Mexico

    Directory of Open Access Journals (Sweden)

    Genoveva TREJO-MACÍAS, Alejandro ESTRADA

    2012-06-01

    Full Text Available In this study we document the prevalence of gastrointestinal parasites (helminths and protozoans found in fecal samples of populations of Alouatta palliata mexicana and of A. pigra in Los Tuxtlas and in Palenque, southeast Mexico, and its relation to habitat condition, sex/age and season. Nineteen parasite morphotypes were detected in the fecal samples from populations of the two howler monkeys, of which 58% were shared by both species. When considering all parasite species, populations of the two howler species were more likely to be parasitized in fragmented habitat compared to continuous habitat. Individuals of both howler monkey species that lived in fragmented habitat had a higher prevalence of Controrchis biliophilus. A. p. mexicana individuals had a higher prevalence of Trypanoxyuris minutus than A. pigra, probably the result of the larger group sizes found in the former species, and T. minutus was more likely to be found in A. palliata individuals that lived in fragmented habitat. Adult A. p. mexicana males had a higher risk of being parasitized compared to adult females, but these differences were not detected in A. pigra. Parasite species such as Entamoeba sp., Nematoda sp. 28, Nematoda sp. B and Parabronema sp. where only found during the wet season in both howler monkey species. Populations of both howler monkey species had a higher prevalence of Nematoda sp. A in the wet season and Ascaridae eggs were only detected during the wet season in A. pigra. Other parasites detected displayed no clear seasonal pattern [Current Zoology 58 (3: 375-383, 2012].

  4. Risk factors connected to gastrointestinal parasites in mantled Alouatta palliata mexicana and black howler monkeys Alouatta pigra living in continuous and in fragmented rainforests in Mexico

    Institute of Scientific and Technical Information of China (English)

    Genoveva TREJO-MAC(I)AS; Alejandro ESTRADA

    2012-01-01

    In this study we document the prevalence of gastrointestinal parasites (helminths and protozoans) found in fecal samples of populations of Alouatta palliata mexicana and of A.pigra in Los Tuxtlas and in Palenque,southeast Mexico,and its relation to habitat condition,sex/age and season.Nineteen parasite morphotypes were detected in the fecal samples from populations of the two howler monkeys,of which 58% were shared by both species.When considering all parasite species,populations of the two howler species were more likely to be parasitized in fragmented habitat compared to continuous habitat.Individuals of both howler monkey species that lived in fragmented habitat had a higher prevalence of Controrchis biliophilus.A.p.mexicana individuals had a higher prevalence of Trypanoxyuris minutus than A.pigra,probably the result of the larger group sizes found in the former species,and T.minutus was more likely to be found in A.palliata individuals that lived in fragmented habitat.Adult A.p.mexicana males had a higher risk of being parasitized compared to adult females,but these differences were not detected in A.pigra.Parasite species such as Entamoeba sp.,Nematoda sp.28.Nematoda sp.B and Parabronema sp.where only found during the wet season m both howler monkey species.Populations of both howler monkey species had a higher prevalence of Nematoda sp.A in the wet season and Ascaridae eggs were only detected during the wet season in A.pigra.Other parasites detected displayed no clear seasonal pattern.

  5. Microscopic factors that control beta-sheet registry in amyloid fibrils formed by fragment 11-25 of amyloid beta peptide: insights from computer simulations.

    Science.gov (United States)

    Negureanu, Lacramioara; Baumketner, Andrij

    2009-06-26

    Short fragments of amyloidogenic proteins are widely used as model systems in studies of amyloid formation. Fragment 11-25 of the amyloid beta protein involved in Alzheimer's disease (Abeta11-25) was recently shown to form amyloid fibrils composed of anti-parallel beta-sheets. Interestingly, fibrils grown under neutral and acidic conditions were seen to possess different registries of their inter-beta-strand hydrogen bonds. In an effort to explain the microscopic origin of this pH dependence, we studied Abeta11-25 fibrils using methods of theoretical modeling. Several structural models were built for fibrils at low and neutral pH levels and these were examined in short molecular dynamics simulations in explicit water. The models that displayed the lowest free energy, as estimated using an implicit solvent model, were selected as representative of the true fibrillar structure. It was shown that the registry of these models agrees well with the experimental results. At neutral pH, the main contribution to the free energy difference between the two registries comes from the electrostatic interactions. The charge group of the carboxy terminus makes a large contribution to these interactions and thus appears to have a critical role in determining the registry.

  6. Neuroprotective effects of cerebrolysin, a combination of different active fragments of neurotrophic factors and peptides on the whole body hyperthermia-induced neurotoxicity: modulatory roles of co-morbidity factors and nanoparticle intoxication.

    Science.gov (United States)

    Sharma, Hari Shanker; Sharma, Aruna; Mössler, Herbert; Muresanu, Dafin Fior

    2012-01-01

    Military personals are often exposed to adverse environmental circumstances, for example, heat stress during peacekeeping or combat operations in summer months or in desert areas leading to disturbed mental functions. The suitable therapeutic strategies to treat heat-induced mental anomalies are still not worked out. Thus, exploration of suitable therapeutic strategies to minimize heat-induced abnormal brain function is needed in suitable animal models. Previous works from our laboratory show that rats exposed to whole body hyperthermia (WBH) for 4 h at 38 °C exhibited profound neuronal, glial, and axonal damages in the cerebral cortex, hippocampus, cerebellum, thalamus, and hypothalamus in a specific manner at light microscopy. Electron microscopy further revealed endothelial cell membrane damage, that is, breakdown of the blood-brain barrier (BBB) after WBH in the brain areas showing cellular damages. These observations indicate that breakdown of the BBB is instrumental in hyperthermia-induced brain injury. Pretreatment with cerebrolysin (2.5 ml or 5 ml/kg, i.v. 30 min before WBH), a mixture of various neurotropic factors and active peptide fragments significantly attenuated BBB disruption and brain damage following heat exposure in a dose-dependent manner. Furthermore, repeated administration of cerebrolysin (5 ml/kg, i.v.) starting from 30 min to 1h after but not after 1.5 or 2 h WBH markedly reduced the BBB disruption and neurotoxicity. Taken together our observations suggest that cerebrolysin if administered within 1 h after WBH in suitable doses induce marked reduction in neurotoxicity. This indicated that cerebrolysin has potential therapeutic value to treat heat stress victims to prevent mental dysfunction in future clinical settings.

  7. Chromatin Collapse during Caspase-dependent Apoptotic Cell Death Requires DNA Fragmentation Factor, 40-kDa Subunit-/Caspase-activated Deoxyribonuclease-mediated 3′-OH Single-strand DNA Breaks*

    Science.gov (United States)

    Iglesias-Guimarais, Victoria; Gil-Guiñon, Estel; Sánchez-Osuna, María; Casanelles, Elisenda; García-Belinchón, Mercè; Comella, Joan X.; Yuste, Victor J.

    2013-01-01

    Apoptotic nuclear morphology and oligonucleosomal double-strand DNA fragments (also known as DNA ladder) are considered the hallmarks of apoptotic cell death. From a classic point of view, these two processes occur concomitantly. Once activated, DNA fragmentation factor, 40-kDa subunit (DFF40)/caspase-activated DNase (CAD) endonuclease hydrolyzes the DNA into oligonucleosomal-size pieces, facilitating the chromatin package. However, the dogma that the apoptotic nuclear morphology depends on DNA fragmentation has been questioned. Here, we use different cellular models, including MEF CAD−/− cells, to unravel the mechanism by which DFF40/CAD influences chromatin condensation and nuclear collapse during apoptosis. Upon apoptotic insult, SK-N-AS cells display caspase-dependent apoptotic nuclear alterations in the absence of internucleosomal DNA degradation. The overexpression of a wild-type form of DFF40/CAD endonuclease, but not of different catalytic-null mutants, restores the cellular ability to degrade the chromatin into oligonucleosomal-length fragments. We show that apoptotic nuclear collapse requires a 3′-OH endonucleolytic activity even though the internucleosomal DNA degradation is impaired. Moreover, alkaline unwinding electrophoresis and In Situ End-Labeling (ISEL)/In Situ Nick Translation (ISNT) assays reveal that the apoptotic DNA damage observed in the DNA ladder-deficient SK-N-AS cells is characterized by the presence of single-strand nicks/breaks. Apoptotic single-strand breaks can be impaired by DFF40/CAD knockdown, abrogating nuclear collapse and disassembly. In conclusion, the highest order of chromatin compaction observed in the later steps of caspase-dependent apoptosis relies on DFF40/CAD-mediated DNA damage by generating 3′-OH ends in single-strand rather than double-strand DNA nicks/breaks. PMID:23430749

  8. Tissue Factor Structure and Function

    Directory of Open Access Journals (Sweden)

    Saulius Butenas

    2012-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein that is essential to life. It is a component of the factor VIIa-TF complex enzyme and plays a primary role in both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed to blood and binds plasma factor VIIa, and the resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing. Many cells, both healthy, and tumor cells, produce detectable amounts of TF, especially when they are stimulated by various agents. Despite the relative simplicity and small size of TF, there are numerous contradictory reports about the synthesis and presentation of TF on blood cells and circulation in normal blood either on microparticles or as a soluble protein. Another subject of controversy is related to the structure/function of TF. It has been almost commonly accepted that cell-surface-associated TF has low (if any activity, that is, is “encrypted” and requires specific conditions/reagents to become active, that is, “decrypted.” However there is a lack of agreement related to the mechanism and processes leading to alterations in TF function. In this paper TF structure, presentation, and function, and controversies concerning these features are discussed.

  9. String fragmentation; La fragmentation des cordes

    Energy Technology Data Exchange (ETDEWEB)

    Drescher, H.J.; Werner, K. [Laboratoire de Physique Subatomique et des Technologies Associees - SUBATECH, Centre National de la Recherche Scientifique, 44 - Nantes (France)

    1997-10-01

    The classical string model is used in VENUS as a fragmentation model. For the soft domain simple 2-parton strings were sufficient, whereas for higher energies up to LHC, the perturbative regime of the QCD gives additional soft gluons, which are mapped on the string as so called kinks, energy singularities between the leading partons. The kinky string model is chosen to handle fragmentation of these strings by application of the Lorentz invariant area law. The `kinky strings` model, corresponding to the perturbative gluons coming from pQCD, takes into consideration this effect by treating the partons and gluons on the same footing. The decay law is always the Artru-Menessier area law which is the most realistic since it is invariant to the Lorentz and gauge transformations. For low mass strings a manipulation of the rupture point is necessary if the string corresponds already to an elementary particle determined by the mass and the flavor content. By means of the fragmentation model it will be possible to simulate the data from future experiments at LHC and RHIC 3 refs.

  10. Fragmentation trees reloaded.

    Science.gov (United States)

    Böcker, Sebastian; Dührkop, Kai

    2016-01-01

    Untargeted metabolomics commonly uses liquid chromatography mass spectrometry to measure abundances of metabolites; subsequent tandem mass spectrometry is used to derive information about individual compounds. One of the bottlenecks in this experimental setup is the interpretation of fragmentation spectra to accurately and efficiently identify compounds. Fragmentation trees have become a powerful tool for the interpretation of tandem mass spectrometry data of small molecules. These trees are determined from the data using combinatorial optimization, and aim at explaining the experimental data via fragmentation cascades. Fragmentation tree computation does not require spectral or structural databases. To obtain biochemically meaningful trees, one needs an elaborate optimization function (scoring). We present a new scoring for computing fragmentation trees, transforming the combinatorial optimization into a Maximum A Posteriori estimator. We demonstrate the superiority of the new scoring for two tasks: both for the de novo identification of molecular formulas of unknown compounds, and for searching a database for structurally similar compounds, our method SIRIUS 3, performs significantly better than the previous version of our method, as well as other methods for this task. SIRIUS 3 can be a part of an untargeted metabolomics workflow, allowing researchers to investigate unknowns using automated computational methods.Graphical abstractWe present a new scoring for computing fragmentation trees from tandem mass spectrometry data based on Bayesian statistics. The best scoring fragmentation tree most likely explains the molecular formula of the measured parent ion.

  11. Cloning and expression analysis of a protease maturation factor gene fragment from Beauveria bassiana%球孢白僵菌蛋白酶成熟因子基因片段的克隆及其表达分析

    Institute of Scientific and Technical Information of China (English)

    张军; 谢翎; 孟慧敏; 汪章勋; 黄勃

    2012-01-01

    The fragment of a protease maturation factor gene from Beauveria bassiana was cloned using DDRT-PCR (differential display reverse transcription polymerase chain reaction) . The length of the cloned specific fragment was 295 bp. Analysis of the amino acid sequences indicated that the protease maturation factor from Beauveria bassiana was highly homologous to Aspergillus oryzae (94.44%). The expression of the protease maturation factor gene from Beauveria bassiana under different induced conditions was detected using Realtime PCR. We found that the expression of protease maturation factor gene for cuticle of cicada induced was significantly higher than that in control (nearly 8 times of control). It can be inferred that the protease maturation factor gene in Beauveria bassiana may has important application value in construction of genetic engineering strain with high toxicity.%通过mRNA差异显示技术,从蝉脱诱导培养的球孢白僵菌中分离获得了长度295 bp一种蛋白酶成熟因子的基因片段.该片段编码多肽序列与米曲霉的蛋白酶成熟因子编码氨基酸序列同源性较高,达94.44%.Realtime-PCR检测结果表明,蝉蜕诱导条件下该基因的表达量为对照的8倍左右.诱导下蛋白酶成熟因子的高效表达,表明其在白僵菌毒力相关重组菌株构建研究中可能具有重要的应用价值.

  12. Embedded Fragments Registry (EFR)

    Data.gov (United States)

    Department of Veterans Affairs — In 2009, the Department of Defense estimated that approximately 40,000 service members who served in OEF/OIF may have embedded fragment wounds as the result of small...

  13. Fragmentation in Biaxial Tension

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, G H; Archbold, G C; Hurricane, O A; Miller, P L

    2006-06-13

    We have carried out an experiment that places a ductile stainless steel in a state of biaxial tension at a high rate of strain. The loading of the ductile metal spherical cap is performed by the detonation of a high explosive layer with a conforming geometry to expand the metal radially outwards. Simulations of the loading and expansion of the metal predict strain rates that compare well with experimental observations. A high percentage of the HE loaded material was recovered through a soft capture process and characterization of the recovered fragments provided high quality data, including uniform strain prior to failure and fragment size. These data were used with a modified fragmentation model to determine a fragmentation energy.

  14. DNA fragmentation in spermatozoa

    DEFF Research Database (Denmark)

    Rex, A S; Aagaard, J.; Fedder, J

    2017-01-01

    Sperm DNA Fragmentation has been extensively studied for more than a decade. In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the DNA was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated....... In the seventies, the impact of induced DNA damage was investigated. In the 1980s the concept of sperm DNA fragmentation as related to infertility was introduced as well as the first DNA fragmentation test: the Sperm Chromatin Structure Assay (SCSA). The terminal deoxynucleotidyl transferase nick end labelling...... (TUNEL) test followed by others was introduced in the nineties. The association between DNA fragmentation in spermatozoa and pregnancy loss has been extensively investigated spurring the need for a therapeutic tool for these patients. This gave rise to an increased interest in the aetiology of DNA damage...

  15. Fragmentation Main Model

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The fragmentation model combines patch size and patch continuity with diversity of vegetation types per patch and rarity of vegetation types per patch. A patch was...

  16. Thermodynamics of fragment binding.

    Science.gov (United States)

    Ferenczy, György G; Keserű, György M

    2012-04-23

    The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, polar, water-soluble fragments. In order to understand this phenomenon, we analyzed high resolution X-ray data of protein-ligand complexes from the Protein Data Bank and found that fragments bind to proteins with two near optimal geometry H-bonds on average. The linear extent of the fragment binding site was found not to be larger than 10 Å, and the H-bonding region was found to be restricted to about 5 Å on average. The number of conserved H-bonds in proteins cocrystallized with multiple different fragments is also near to 2. These fragment binding sites that are able to form limited number of strong H-bonds in a hydrophobic environment are identified as hot spots. An estimate of the free-energy gain of H-bond formation versus apolar desolvation supports that fragment sized compounds need H-bonds to achieve detectable binding. This suggests that fragment binding is mostly enthalpic that is in line with their observed binding thermodynamics documented in Isothermal Titration Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment based approaches. The binding of larger compounds tends to more rely on apolar desolvation with a corresponding increase of the entropy content of their binding free-energy. These findings explain the reported size-dependence of maximal available affinity and ligand efficiency both behaving differently in the small molecule region featured by strong H-bond formation and in the larger molecule region featured by apolar desolvation.

  17. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Münster, A M; Marckmann, P

    2000-01-01

    for triglycerides, activated FVII (FVIIa), FVII protein concentration (FVII:Ag), prothrombin fragment 1+2 (F1+2), and soluble fibrin. Triglyceride levels increased from fasting levels on both diets, but they increased most markedly on the high-fat diet. FVIIa and FVIIa/FVII:Ag increased with the high-fat diet...... and decreased with the low-fat diet. For both diets, FVII:Ag and F1+2 decreased slightly. No postprandial changes were observed for soluble fibrin. Postprandial mean values of triglycerides, FVIIa, FVII:Ag, and FVIIa/FVII:Ag were significantly higher for the high-fat diet than for the low-fat diet. Our findings...... confirm that high-fat meals cause immediate activation of FVII. The clinical implication is debatable because FVII activation was not accompanied by an increase in plasma F1+2 concentrations in patients with severe atherosclerosis. However, a local thrombin generation on the plaque surface cannot...

  18. 前牙冠折断端再接粘接效果的影响因素%Factors in bonding effects of reattachments of anterior tooth fragments

    Institute of Scientific and Technical Information of China (English)

    黄晓; 汪俊

    2015-01-01

    前牙冠折是儿童及青少年牙外伤的常见类型。随着树脂粘接技术的发展,冠折断端再接作为上前牙外伤冠折后过渡性甚至是最终的修复方法已被广大口腔医生接受并应用于临床。本文将对其影响因素作一综述。%Crown fractures of the anterior teeth are the most frequent form of traumatic dental injury and mainly affect children and adolescents. Given the development of adhesive materials, the reattachment of tooth fragments is now widely accepted by dentists as a transitional or even final restoration method and used clinically. This article briefly reviews the factors that affect the bonding effect of reattaching anterior tooth fragments.

  19. Recombinant factor VII (NovoSeven in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Novak Vesna

    2007-01-01

    Full Text Available Background. Cerebral arteriovenous (AV malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven significantly reduce complications during surgical treatment. Case report. We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scale, in the brain. Due to a possible heavy bleeding we used a apparatus for intrasurgical blood recovery, Cell Saver, Sequestra 1 000, Medtronic, U.S.A., and recombinant human factor VIIa (rFVIIa - NovoSeven, NovoNordisk, Denmark to control bleeding and restore an adequate hemostasis. Conclusion. The use of an apparatus for intraoperative blood saving, as well as the NovoSeven preparation in the management of AV malformation of IV stage, showed to be successful.

  20. Fluctuations of fragment observables

    CERN Document Server

    Gulminelli, F

    2006-01-01

    This contribution presents a review of our present theoretical as well as experimental knowledge of different fluctuation observables relevant to nuclear multifragmentation. The possible connection between the presence of a fluctuation peak and the occurrence of a phase transition or a critical phenomenon is critically analyzed. Many different phenomena can lead both to the creation and to the suppression of a fluctuation peak. In particular, the role of constraints due to conservation laws and to data sorting is shown to be essential. From the experimental point of view, a comparison of the available fragmentation data reveals that there is a good agreement between different data sets of basic fluctuation observables, if the fragmenting source is of comparable size. This compatibility suggests that the fragmentation process is largely independent of the reaction mechanism (central versus peripheral collisions, symmetric versus asymmetric systems, light ions versus heavy ion induced reactions). Configurationa...

  1. Tropical Forest Landscape Fragmentation in Batang Toru Watershed, North Sumatra

    OpenAIRE

    Samsuri Samsuri; I Nengah Surati Jaya; Cecep Kusmana; Kukuh Murtilaksono

    2014-01-01

    Timber-based forest management is now shifting to as broader scope including ecosystem-based management. Timber-oriented forest management frequently affects the fragmentation of forest landscape. This paper defines the degree of forest landscape fragmentation in Batang Toru watershed, North Sumatra through indentification of correlation between forest landscape fragmentation and driving factors including biophysical and anthropogenic factors. Identification structure, pattern, and fragmentat...

  2. Fragments of Time

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    Time travel films necessarily fragment linear narratives, as scenes are revisited with differences from the first time we saw it. Popular films such as Back to the Future mine comedy from these visitations, but there are many different approaches. One extreme is Chris Marker's La Jetée - a film...... made almost completely of still images, recounting the end of the world. These stills can be viewed as fragments that have survived the end of the world and now provide the only access to the events that occured. Shane Carruth's Primer has a different approach to time travel, the narrative diegesis...

  3. The Serendipity of Fragmentation

    DEFF Research Database (Denmark)

    Leixnering, Stephan; Meyer, Renate E.

    , it was the central government’s task to coordinate, steer and control the newly emerged decentralized organizations. This raises questions about the overall design of the public sector at present. Our paper engages with the prevalent public governance phenomenon of fragmentation from a design perspective in order...... form of organizing between networks and formal organization: lacking a single center and featuring multiplex and multifaceted relations within the politico-administrative apparatus and between government and PSOs, high fragmentation, local and robust action, but latent structures of significant formal...

  4. IMPACT fragmentation model developments

    Science.gov (United States)

    Sorge, Marlon E.; Mains, Deanna L.

    2016-09-01

    The IMPACT fragmentation model has been used by The Aerospace Corporation for more than 25 years to analyze orbital altitude explosions and hypervelocity collisions. The model is semi-empirical, combining mass, energy and momentum conservation laws with empirically derived relationships for fragment characteristics such as number, mass, area-to-mass ratio, and spreading velocity as well as event energy distribution. Model results are used for several types of analysis including assessment of short-term risks to satellites from orbital altitude fragmentations, prediction of the long-term evolution of the orbital debris environment and forensic assessments of breakup events. A new version of IMPACT, version 6, has been completed and incorporates a number of advancements enabled by a multi-year long effort to characterize more than 11,000 debris fragments from more than three dozen historical on-orbit breakup events. These events involved a wide range of causes, energies, and fragmenting objects. Special focus was placed on the explosion model, as the majority of events examined were explosions. Revisions were made to the mass distribution used for explosion events, increasing the number of smaller fragments generated. The algorithm for modeling upper stage large fragment generation was updated. A momentum conserving asymmetric spreading velocity distribution algorithm was implemented to better represent sub-catastrophic events. An approach was developed for modeling sub-catastrophic explosions, those where the majority of the parent object remains intact, based on estimated event energy. Finally, significant modifications were made to the area-to-mass ratio distribution to incorporate the tendencies of different materials to fragment into different shapes. This ability enabled better matches between the observed area-to-mass ratios and those generated by the model. It also opened up additional possibilities for post-event analysis of breakups. The paper will discuss

  5. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis : The RAMSES Study

    NARCIS (Netherlands)

    Reinhart, K; Menges, T; Gardlund, B; Zwaveling, JH; Smithes, M; Vincent, JL; Tellado, JM; Salgado-Remigio, A; Zimlichman, R; Withington, S; Tschaikowsky, K; Brase, R; Damas, P; Kupper, H; Kempeni, J; Eiselstein, J; Kaul, M

    Objective: This study investigated whether treatment with the anti-tumor necrosis factor-or monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/ml, Design: Multicenter, double-blind, randomized, placebo-controlled study.

  6. Peri/nuclear localization of intact insulin-like growth factor binding protein-2 and a distinct carboxyl-terminal IGFBP-2 fragment in vivo

    NARCIS (Netherlands)

    Hoeflich, A; Reisinger, R; Schuett, BS; Elmlinger, MW; Russo, VC; Vargas, GA; Jehle, PM; Lahm, H; Renner-Muller, [No Value; Wolf, E

    2004-01-01

    Insulin-like growth factor binding protein-2 (IGFBP-2) as one of the most important IGFBPs has never been assessed in the intracellular compartment in vivo. Since there is evidence for novel intracellular functions of distinct IGFBPs, we investigated the presence of IGFBP-2 inside the cell. In

  7. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis : The RAMSES Study

    NARCIS (Netherlands)

    Reinhart, K; Menges, T; Gardlund, B; Zwaveling, JH; Smithes, M; Vincent, JL; Tellado, JM; Salgado-Remigio, A; Zimlichman, R; Withington, S; Tschaikowsky, K; Brase, R; Damas, P; Kupper, H; Kempeni, J; Eiselstein, J; Kaul, M

    2001-01-01

    Objective: This study investigated whether treatment with the anti-tumor necrosis factor-or monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/ml, Design: Multicenter, double-blind, randomized, placebo-controlled study. S

  8. Peri/nuclear localization of intact insulin-like growth factor binding protein-2 and a distinct carboxyl-terminal IGFBP-2 fragment in vivo

    NARCIS (Netherlands)

    Hoeflich, A; Reisinger, R; Schuett, BS; Elmlinger, MW; Russo, VC; Vargas, GA; Jehle, PM; Lahm, H; Renner-Muller, [No Value; Wolf, E

    2004-01-01

    Insulin-like growth factor binding protein-2 (IGFBP-2) as one of the most important IGFBPs has never been assessed in the intracellular compartment in vivo. Since there is evidence for novel intracellular functions of distinct IGFBPs, we investigated the presence of IGFBP-2 inside the cell. In peri/

  9. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Münster, A M; Marckmann, P

    2000-01-01

    tissue factor, the cofactor of FVII, to circulating blood; therefore, thrombin formation in response to FVII activation is more likely to occur in such patients. This hypothesis was tested in a randomized crossover study of 30 patients (aged 43 to 70 years) with stable angina pectoris...

  10. Land fragmentation and its driving forces in China

    NARCIS (Netherlands)

    Tan, S.; Heerink, N.; Qu, F.

    2006-01-01

    Fragmentation of landholdings is commonly regarded as a major obstacle to agricultural production growth in China. This study analyses the factors contributing to land fragmentation, and uses household- and village-level data from 11 villages in Jiangxi Province to test these factors empirically.

  11. Fragmented Work Stories

    DEFF Research Database (Denmark)

    Humle, Didde Maria; Reff Pedersen, Anne

    2015-01-01

    by exploring how different types of fragmentation create meanings. This is done by studying the work stories of job and personnel consultants and by drawing on the results of a narrative, ethnographic study of a consultancy. The analysis demonstrates how work stories are social practices negotiated, retold...

  12. Picking Up (On) Fragments

    NARCIS (Netherlands)

    Ellis, Phil

    2015-01-01

    abstractThis article discusses the implications for archival and media archaeological research and reenactment artwork relating to a recent arts practice project: reenacttv: 30 lines / 60 seconds. It proposes that archival material is unstable but has traces and fragments that are full of creative p

  13. Fragments of the Past

    Directory of Open Access Journals (Sweden)

    Peter Szende

    2016-10-01

    Full Text Available With travel being made more accessible throughout the decades, the hospitality industry constantly evolved their practices as society and technology progressed. Hotels looked for news ways up service their customers, which led to the invention of the Servidor in 1918. Once revolutionary innovations have gone extinct, merely becoming fragments of the past.

  14. Cryobiology of coral fragments.

    Science.gov (United States)

    Hagedorn, Mary; Farrell, Ann; Carter, Virginia L

    2013-02-01

    Around the world, coral reefs are dying due to human influences, and saving habitat alone may not stop this destruction. This investigation focused on the biological processes that will provide the first steps in understanding the cryobiology of whole coral fragments. Coral fragments are a partnership of coral tissue and endosymbiotic algae, Symbiodinium sp., commonly called zooxanthellae. These data reflected their separate sensitivities to chilling and a cryoprotectant (dimethyl sulfoxide) for the coral Pocillopora damicornis, as measured by tissue loss and Pulse Amplitude Modulated fluorometry 3weeks post-treatment. Five cryoprotectant treatments maintained the viability of the coral tissue and zooxanthellae at control values (1M dimethyl sulfoxide at 1.0, 1.5 and 2.0h exposures, and 1.5M dimethyl sulfoxide at 1.0 and 1.5h exposures, P>0.05, ANOVA), whereas 2M concentrations did not (Pcoral tissue, but not in the zooxanthellae. During the winter when the fragments were chilled, the coral tissue remained relatively intact (∼25% loss) post-treatment, but the zooxanthellae numbers in the tissue declined after 5min of chilling (Pcoral tissue (∼75% loss) and zooxanthellae numbers declined in response to chilling alone (Pcoral against tissue loss after 45min of cryoprotectant exposure (P>0.05, ANOVA), but it did not protect against the loss of zooxanthellae (Pcoral fragment complex and future cryopreservation protocols must be guided by their greater sensitivity. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Picking Up (On) Fragments

    NARCIS (Netherlands)

    Ellis, Phil

    2015-01-01

    abstractThis article discusses the implications for archival and media archaeological research and reenactment artwork relating to a recent arts practice project: reenacttv: 30 lines / 60 seconds. It proposes that archival material is unstable but has traces and fragments that are full of creative p

  16. Wildlife habitat fragmentation.

    Science.gov (United States)

    John. Lehmkuhl

    2005-01-01

    A primary issue in forest wildlife management is habitat fragmentation and its effects on viability, which is the "bottom line" for plant and animal species of conservation concern. Population viability is the likelihood that a population will be able to maintain itself (remain viable) over a long period of time-usually 100 years or more. Though it is true...

  17. Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.

    Science.gov (United States)

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Wenyue; Yang, Jun

    2016-05-01

    Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin.

  18. DNA fragmentation status in patients with necrozoospermia.

    Science.gov (United States)

    Brahem, Sonia; Jellad, Sonia; Ibala, Samira; Saad, Ali; Mehdi, Meriem

    2012-12-01

    The aim of this study was to determine if a relationship exists between the levels of sperm DNA fragmentation and necrospermia in infertile men. Semen samples obtained from 70 men consulting for infertility evaluation were analyzed according to World Health Organization (WHO) guidelines. Patients were subdivided into three groups according to the percentage of necrotic spermatozoa: normozoospermia (80%; n = 20). DNA fragmentation was detected by the terminal desoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) assay. The sperm DNA fragmentation index (DFI) was 9.28 ± 2.98% in patients with a normal level of necrotic spermatozoa, 20.25 ± 3.21% in patients with moderate necrozoospermia, and 35.31 ± 5.25% in patients with severe necrozoospermia. There was a statistically significant increase of DNA fragmentation in the necrozoospermic group (P DNA fragmentation. We concluded that patients with necrozoospermia showed a high level of DNA fragmentation compared to normozoospermic men. Severe necrozoospermia (>80%) is a predictive factor for increased sperm DNA damage.

  19. Electroeluting DNA fragments.

    Science.gov (United States)

    Zarzosa-Alvarez, Ana L; Sandoval-Cabrera, Antonio; Torres-Huerta, Ana L; Bermudez-Cruz, Rosa M

    2010-09-05

    Purified DNA fragments are used for different purposes in Molecular Biology and they can be prepared by several procedures. Most of them require a previous electrophoresis of the DNA fragments in order to separate the band of interest. Then, this band is excised out from an agarose or acrylamide gel and purified by using either: binding and elution from glass or silica particles, DEAE-cellulose membranes, "crush and soak method", electroelution or very often expensive commercial purification kits. Thus, selecting a method will depend mostly of what is available in the laboratory. The electroelution procedure allows one to purify very clean DNA to be used in a large number of applications (sequencing, radiolabeling, enzymatic restriction, enzymatic modification, cloning etc). This procedure consists in placing DNA band-containing agarose or acrylamide slices into sample wells of the electroeluter, then applying current will make the DNA fragment to leave the agarose and thus be trapped in a cushion salt to be recovered later by ethanol precipitation.

  20. Dihadron Fragmentation Functions and Transversity

    CERN Document Server

    Radici, Marco; Bacchetta, Alessandro

    2014-01-01

    We present preliminary results for an updated extraction of the transversity parton distribution based on the analysis of pion-pair production in deep-inelastic scattering off transversely polarized targets in collinear factorization. Data for proton and deuteron targets by HERMES and COMPASS allow for a flavor separation of the valence components of transversity, while di-hadron fragmentation functions are taken from the semi-inclusive production of two pion pairs in back-to-back jets in $e^+ e^-$ annihilation. The latter data from Belle have been reanalyzed using the replica method and a more realistic estimate of the uncertainties on the chiral-odd interference fragmentation function has been obtained. After encoding this piece of information into the deep-inelastic scattering cross section, the transversity has been re-extracted by using the most recent and more precise COMPASS data for proton target. This picture represents the current most realistic estimate of the uncertainties on our knowledge of tran...

  1. Dihadron Fragmentation Functions and Transversity

    Directory of Open Access Journals (Sweden)

    Radici Marco

    2015-01-01

    Full Text Available We present preliminary results for an updated extraction of the transversity parton distribution based on the analysis of pion-pair production in deep-inelastic scattering off transversely polarized targets in collinear factorization. Data for proton and deuteron targets by HERMES and COMPASS allow for a flavor separation of the valence components of transversity, while di-hadron fragmentation functions are taken from the semi-inclusive production of two pion pairs in back-to-back jets in e+e− annihilation. The latter data from Belle have been reanalyzed using the replica method and a more realistic estimate of the uncertainties on the chiral-odd interference fragmentation function has been obtained. After encoding this piece of information into the deep-inelastic scattering cross section, the transversity has been re-extracted by using the most recent and more precise COMPASS data for proton target. This picture represents the current most realistic estimate of the uncertainties on our knowledge of transversity. The preliminary results indicate that the valence up component seems smaller and with a narrower error band than in previous extraction.

  2. Heavy meson fragmentation at LHC

    Directory of Open Access Journals (Sweden)

    M. A. Gomshi Nobary

    2003-06-01

    Full Text Available   Large Hadron Collider (LHC at CERN will provide excellent opportunity to study the production and decay of heavy mesons and baryons with high statistics. We aim at the heavy mesons in this work and calculate their fragmentation functions consistent with this machine and present their total fragmentation probabilities and average fragmentation parameters.

  3. SCALING AND 4-QUARK FRAGMENTATION

    NARCIS (Netherlands)

    SCHOLTEN, O; BOSVELD, GD

    1991-01-01

    The conditions for a scaling behaviour from the fragmentation process leading to slow protons are discussed- The scaling referred to implies that the fragmentation functions depend on the light-cone momentum fraction only. It is shown that differences in the fragmentation functions for valence- and

  4. Improved Empirical Parametrization of Fragmentation Cross Sections

    CERN Document Server

    Sümmerer, Klaus

    2012-01-01

    A new version is proposed for the universal empirical formula, EPAX, which describes fragmentation cross sections in high-energy heavy-ion reactions. The new version, EPAX 3, can be shown to yield cross sections that are in better agreement with experimental data for the most neutron-rich fragments than the previous version. At the same time, the very good agreement of EPAX 2 with data on the neutron-deficient side has been largely maintained. Comparison with measured cross sections show that the bulk of the data is reproduced within a factor of about 2, for cross sections down to the pico-barn range.

  5. Angular Momentum Population in Projectile Fragmentation

    Science.gov (United States)

    Podolyák, Zs.; Gladnishki, K. A.; Gerl, J.; Hellström, M.; Kopatch, Y.; Mandal, S.; Górska, M.; Regan, P. H.; Wollersheim, H. J.; Schmidt, K.-H.; Gsi-Isomer Collaboration

    2004-02-01

    Isomeric states in neutron-deficient nuclei around A ≈190 have been identified following the projectile fragmentation of a relativistic energy 238U beam. The deduced isomeric ratios are compared with a model based on the abrasion-ablation description. The experimental isomeric ratios are lower by a factor of ≈2 than the calculated ones assuming the `sharp cutoff' approximation. The observation of the previously reported isomeric Iπ=43/2- state in 215Ra represents the current record for the highest discrete spin state observed following a projectile fragmentation reaction.

  6. Picking Up (On Fragments

    Directory of Open Access Journals (Sweden)

    Phil Ellis

    2015-09-01

    Full Text Available This article discusses the implications for archival and media archaeological research and reenactment artwork relating to a recent arts practice project: reenacttv: 30 lines / 60 seconds. It proposes that archival material is unstable but has traces and fragments that are full of creative potential to re-think and re-examine past media historical events through a media archaeological approach to reenactment. The article contains images and links to videos from the final reenactment artworks as well as from rehearsals in Vienna and Bradford.

  7. An Archeology of Fragments

    Directory of Open Access Journals (Sweden)

    Gerald L. Bruns

    2014-10-01

    Full Text Available This is a short (fragmentary history of fragmentary writing from the German Romantics (F. W. Schlegel, Friedrich Hölderlin to modern and contemporary concrete or visual poetry. Such writing is (often deliberately a critique of the logic of subsumption that tries to assimilate whatever is singular and irreducible into totalities of various categorical or systematic sorts. Arguably, the fragment (parataxis is the distinctive feature of literary Modernism, which is a rejection, not of what precedes it, but of what Max Weber called “the rationalization of the world” (or Modernity whose aim is to keep everything, including all that is written, under surveillance and control.

  8. Generic behaviours in impact fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Sator, N.; Mechkov, S.; Sausset, F. [Paris-6 Univ. Pierre et Marie Curie, Lab. de Physique Theorique de la Matiere Condensee, UMR CNRS 7600, 75 - Paris (France); Mechkov, S. [Ecole Normale Superieure, Lab. de Physique Statistique, 75 - Paris (France)

    2008-02-15

    From atomic nuclei to supernovae, including plates and rocks, every cohesive system can be broken into fragments, provided that the deposited energy is sufficiently large compared to its cohesive energy. We present a simple numerical model for investigating the general properties of fragmentation. By use of molecular dynamics simulations, we study the impact fragmentation of a solid disk of interacting particles with a wall. Regardless of the particular form of the interaction potential, the fragment size distribution exhibits a power law behaviour with an exponent that increases logarithmically with the energy deposited in the system, in agreement with experiments. We expect this behaviour to be generic in fragmentation phenomena. (authors)

  9. Rock fragmentation control in opencast blasting

    Directory of Open Access Journals (Sweden)

    P.K. Singh

    2016-04-01

    Full Text Available The blasting operation plays a pivotal role in the overall economics of opencast mines. The blasting sub-system affects all the other associated sub-systems, i.e. loading, transport, crushing and milling operations. Fragmentation control through effective blast design and its effect on productivity are the challenging tasks for practicing blasting engineer due to inadequate knowledge of actual explosive energy released in the borehole, varying initiation practice in blast design and its effect on explosive energy release characteristic. This paper describes the result of a systematic study on the impact of blast design parameters on rock fragmentation at three mines in India. The mines use draglines and shovel–dumper combination for removal of overburden. Despite its pivotal role in controlling the overall economics of a mining operation, the expected blasting performance is often judged almost exclusively on the basis of poorly defined parameters such as powder factor and is often qualitative which results in very subjective assessment of blasting performance. Such an approach is very poor substitutes for accurate assessment of explosive and blasting performance. Ninety one blasts were conducted with varying blast designs and charging patterns, and their impacts on the rock fragmentation were documented. A high-speed camera was deployed to record the detonation sequences of the blasts. The efficiency of the loading machines was also correlated with the mean fragment size obtained from the fragmentation analyses.

  10. Relativistic correction to gluon fragmentation function into pseudoscalar quarkonium

    CERN Document Server

    Gao, Xiangrui; Li, LiuJi; Xiong, Xiaonu

    2016-01-01

    Inspired by the recent measurements of the $\\eta_c$ meson production at LHC, we investigate the relativistic correction effect for the fragmentation function of the gluon into $\\eta_c$, which constitutes the crucial nonperturbative elements to understand $\\eta_c$ production at high $p_T$. Employing three distinct methods, we calculate the leading relativistic correction to the $g\\to\\eta_c$ fragmentation function in the NRQCD factorization framework, as well as verify the existing NLO result for the $c\\to \\eta_c$ fragmentation function. We also study the evolution behavior of these fragmentation functions with the aid of DGLAP equation.

  11. Forest Fragmentation and Driving Forces in Yingkou, Northeastern China

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2017-03-01

    Full Text Available Forest fragmentation, the process of changing original large and intact forest patches into smaller and isolated areas, significantly influences the balance of surface physical environment, biodiversity, and species richness. Sufficient knowledge of forest fragmentation is necessary to maintain ecological balance and promote sustainable resource utilization. This study combines remote sensing, geographical information systems, and landscape metrics to assess forest fragmentation at landscape and pixel levels during different time periods (2000–2005, 2005–2010, and 2010–2015 in the Yingkou region. Spatial statistical analysis is also used to analyze the relationship between forest landscape fragmentation and its determinants (e.g., natural factors, socioeconomic factors, and proximity factors. Results show that forest patches became smaller, subdivided, and isolated during 2010–2015 at the total landscape level. Local changes occurred in the southwest of the study region or around the development area. Our data also indicate that shrinkage and subdivision were the main forest fragmentation processes during three times, and attrition became the main forest fragmentation process from 2010 to 2015. These changes were significantly influenced by natural factors (e.g., elevation and slope, proximity factors (e.g., distance to city and distance to province roads, and socioeconomic factors (e.g., gross domestic product. Results presented in this study provide valuable insights into the pattern and processes of forest fragmentation and present direct implications for the protection and reasonable utilization of forest resources.

  12. Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-alpha-like effector A, in rat interscapular brown adipose tissue by sympathetically activated beta3-adrenoreceptors.

    Science.gov (United States)

    Shimizu, Takahiro; Yokotani, Kunihiko

    2009-09-18

    The thermogenic activity of brown adipose tissue (BAT) largely depends on the mitochondrial uncoupling protein 1 (UCP1), which is up-regulated by environmental alterations such as cold. Recently, CIDEA (cell death-inducing DNA fragmentation factor-alpha-like effector A) has also been shown to be expressed at high levels in the mitochondria of BAT. Here we examined the effect of cold on the mRNA and protein levels of CIDEA in interscapular BAT of conscious rats with regard to the sympathetic nervous system. Cold exposure (4 degrees C for 3h) elevated the plasma norepinephrine level and increased norepinephrine turnover in BAT. Cold exposure resulted in down-regulation of the mRNA and protein levels of CIDEA in BAT, accompanied by up-regulation of mRNA and protein levels of UCP1. The cold exposure-induced changes of CIDEA and UCP1 were attenuated by intraperitoneal pretreatment with propranolol (a non-selective beta-adrenoreceptor antagonist) (2mg/animal) or SR59230A (a selective beta(3)-adrenoreceptor antagonist) (2mg/animal), respectively. These results suggest that acute cold exposure resulted in down-regulation of CIDEA in interscapular BAT by sympathetically activated beta(3)-adrenoreceptor-mediated mechanisms in rats.

  13. Co-expression of Dsb proteins enables soluble expression of a single-chain variable fragment (scFv) against human type 1 insulin-like growth factor receptor (IGF-1R) in E. coli.

    Science.gov (United States)

    Sun, Xue-Wen; Wang, Xiao-Hua; Yao, Yan-Bing

    2014-12-01

    Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb.

  14. Nuclear Fragmentation in Clinical Heavy Ion Beams, Should We Worry?

    DEFF Research Database (Denmark)

    Bassler, Niels; Hansen, David Christoffer; Toftegaard, Jakob

    fragmentation of the primary ions. Even if patient treatment with heavy ions has been established, the influence of nuclear fragmentation is yet to be fully quantified. The fragmentation spectrum of ions is relevant for particle therapy in numerous ways: 1. Dose distribution: A distinct tail of secondary...... on the secondary particle spectrum from fragmentation. b. In addition hereto, fluence correction factors can be calculated which take this effect into account, which are directly a result of nuclear fragmentation in the medium. 3. Radiobiology: Physical dose is not sufficient to describe the outcome of a treatment...... the sensitivity on the three fields mentioned above, including: turning off nuclear fragmentation entirely, changing all ineleastic cross sections +/- 20%, changing key parameters in the Fermi-Breakup (FB) model. Results show nuclear effects have their largest impact on the dose distribution. Stopping power...

  15. The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of factor H reveal partially folded-back solution structures and different self-associative properties.

    Science.gov (United States)

    Okemefuna, Azubuike I; Gilbert, Hannah E; Griggs, Kim M; Ormsby, Rebecca J; Gordon, David L; Perkins, Stephen J

    2008-01-04

    Factor H (FH) is a plasma glycoprotein that plays a central role in regulation of the alternative pathway of complement. It is composed of 20 short complement regulator (SCR) domains. The SCR-1/5 fragment is required for decay acceleration and cofactor activity, while the SCR-16/20 fragment possesses binding sites for complement C3d and heparin. X-ray scattering and analytical ultracentrifugation showed that SCR-1/5 was monomeric, while SCR-16/20 formed dimers. The Guinier radius of gyration R(G) of 4.3 nm for SCR-1/5 and those of 4.7 nm and about 7.8 nm for monomeric and dimeric SCR-16/20, respectively, showed that their structures are partially folded back and bent. The distance distribution function P(r) showed that SCR-1/5 has a maximum dimension of 15 nm while monomeric and dimeric SCR-16/20 are 17 nm and about 27 nm long, respectively. The sedimentation coefficient of 2.4 S for SCR-1/5 showed no concentration-dependence, while that for SCR-16/20 was 2.8 S for the monomer and 3.9 S for the dimer. Sedimentation equilibrium data showed that SCR-1/5 is monomeric while SCR-16/20 exhibited a weak monomer-dimer equilibrium with a dissociation constant of 16 microM. The constrained scattering and sedimentation modelling of SCR-1/5 and SCR-16/20 showed that partially folded-back and bent flexible SCR arrangements fitted both data sets better than extended linear arrangements, and that the dimer was best modelled in the SCR-16/20 model by an end-to-end association of two SCR-20 domains. The SCR-1/5 and SCR-16/20 models were conformationally similar to the previously determined partially folded-back structure for intact wild-type FH, hence suggesting a partial explanation of the intact FH structure. Comparison of the SCR-16/20 model with the crystal structure of C3b clarified reasons for the distribution of mutations leading to atypical haemolytic uraemic syndrome.

  16. Purification optimization for a recombinant single-chain variable fragment against type 1 insulin-like growth factor receptor (IGF-1R) by using design of experiment (DoE).

    Science.gov (United States)

    Song, Yong-Hong; Sun, Xue-Wen; Jiang, Bo; Liu, Ji-En; Su, Xian-Hui

    2015-12-01

    Design of experiment (DoE) is a statistics-based technique for experimental design that could overcome the shortcomings of traditional one-factor-at-a-time (OFAT) approach for protein purification optimization. In this study, a DoE approach was applied for optimizing purification of a recombinant single-chain variable fragment (scFv) against type 1 insulin-like growth factor receptor (IGF-1R) expressed in Escherichia coli. In first capture step using Capto L, a 2-level fractional factorial analysis and successively a central composite circumscribed (CCC) design were used to identify the optimal elution conditions. Two main effects, pH and trehalose, were identified, and high recovery (above 95%) and low aggregates ratio (below 10%) were achieved at the pH range from 2.9 to 3.0 with 32-35% (w/v) trehalose added. In the second step using cation exchange chromatography, an initial screening of media and elution pH and a following CCC design were performed, whereby the optimal selectivity of the scFv was obtained on Capto S at pH near 6.0, and the optimal conditions for fulfilling high DBC and purity were identified as pH range of 5.9-6.1 and loading conductivity range of 5-12.5 mS/cm. Upon a further gel filtration, the final purified scFv with a purity of 98% was obtained. Finally, the optimized conditions were verified by a 20-fold scale-up experiment. The purities and yields of intermediate and final products all fell within the regions predicted by DoE approach, suggesting the robustness of the optimized conditions. We proposed that the DoE approach described here is also applicable in production of other recombinant antibody constructs.

  17. Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study.

    Directory of Open Access Journals (Sweden)

    Thomas Meyer

    Full Text Available The role of endothelin-1 (ET-1 in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1 is linked to anxiety.Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2% who had completed the Hospital Anxiety and Depression Scale (HADS questionnaire.Among the total study cohort (n = 1,410, there were 118 subjects (8.4% with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013. In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β = 0.247, 95%-confidence interval [95%-CI] = 0.067-0.914, p = 0.036. Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β = 0.114, 95%-CI = 0.023-0.566, p = 0.008.Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.

  18. Stone fragmentation by ultrasound

    Indian Academy of Sciences (India)

    S K Shrivastava; Kailash

    2004-08-01

    The presence of kidney stone in the kidney causes discomfort to patients. Hence, removal of such stones is important which is commonly done these days, non-destructively, with lithotripters without surgery. Commercially, lithotripters like extra-corporeal shock wave lithotripters (ESWL) made by Siemens etc are in routine use. These methods are very cumbersome and expensive. Treatment of the patients also takes comparatively more time because of more number of sittings. Some delicate nerves and fibres in the surrounding areas of the stones present in the kidney are also damaged by high ultrasonic intensity used in such systems. In the present work, enhancement of the kidney stone fragmentation by using ultrasound is studied. The cavitation bubbles are found to implode faster, with more disintegration efficiency of the lithotripters, which give better treatment to the patients.

  19. Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry

    DEFF Research Database (Denmark)

    Song, Hongjian; Olsen, Ole H; Persson, Egon;

    2014-01-01

    enhancement remain elusive. Here we have applied hydrogen/deuterium exchange mass spectrometry coupled to electron transfer dissociation to pinpoint individual residues in the heavy chain of FVIIa whose conformation and/or local interaction pattern changes when the enzyme transitions to the active form...

  20. Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) - a review of a new treatment paradigm

    DEFF Research Database (Denmark)

    Heslet, Lars; Nielsen, Jørn Dalsgaard; Nepper-Christensen, Steen

    2012-01-01

    Diffuse alveolar hemorrhage (DAH) is a clinical syndrome with typical symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in some cases with acute catastrophic hemoptysis, while other patients present low grade alveolar bleeding with a need of chronic transfusion as in pu...

  1. The origins of enhanced activity in factor VIIa analogs and the interplay between key allosteric sites revealed by hydrogen exchange mass spectrometry

    DEFF Research Database (Denmark)

    Rand, Kasper D; Andersen, Mette D; Olsen, Ole H;

    2008-01-01

    to investigate the conformational effects of site-directed mutagenesis at key positions in FVIIa and the origins of enhanced intrinsic activity of FVIIa analogs. The differences in hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY), imply that enhanced catalytic efficiency was attained...

  2. Critical Features of Fragment Libraries for Protein Structure Prediction.

    Science.gov (United States)

    Trevizani, Raphael; Custódio, Fábio Lima; Dos Santos, Karina Baptista; Dardenne, Laurent Emmanuel

    2017-01-01

    The use of fragment libraries is a popular approach among protein structure prediction methods and has proven to substantially improve the quality of predicted structures. However, some vital aspects of a fragment library that influence the accuracy of modeling a native structure remain to be determined. This study investigates some of these features. Particularly, we analyze the effect of using secondary structure prediction guiding fragments selection, different fragments sizes and the effect of structural clustering of fragments within libraries. To have a clearer view of how these factors affect protein structure prediction, we isolated the process of model building by fragment assembly from some common limitations associated with prediction methods, e.g., imprecise energy functions and optimization algorithms, by employing an exact structure-based objective function under a greedy algorithm. Our results indicate that shorter fragments reproduce the native structure more accurately than the longer. Libraries composed of multiple fragment lengths generate even better structures, where longer fragments show to be more useful at the beginning of the simulations. The use of many different fragment sizes shows little improvement when compared to predictions carried out with libraries that comprise only three different fragment sizes. Models obtained from libraries built using only sequence similarity are, on average, better than those built with a secondary structure prediction bias. However, we found that the use of secondary structure prediction allows greater reduction of the search space, which is invaluable for prediction methods. The results of this study can be critical guidelines for the use of fragment libraries in protein structure prediction.

  3. Critical Features of Fragment Libraries for Protein Structure Prediction

    Science.gov (United States)

    dos Santos, Karina Baptista

    2017-01-01

    The use of fragment libraries is a popular approach among protein structure prediction methods and has proven to substantially improve the quality of predicted structures. However, some vital aspects of a fragment library that influence the accuracy of modeling a native structure remain to be determined. This study investigates some of these features. Particularly, we analyze the effect of using secondary structure prediction guiding fragments selection, different fragments sizes and the effect of structural clustering of fragments within libraries. To have a clearer view of how these factors affect protein structure prediction, we isolated the process of model building by fragment assembly from some common limitations associated with prediction methods, e.g., imprecise energy functions and optimization algorithms, by employing an exact structure-based objective function under a greedy algorithm. Our results indicate that shorter fragments reproduce the native structure more accurately than the longer. Libraries composed of multiple fragment lengths generate even better structures, where longer fragments show to be more useful at the beginning of the simulations. The use of many different fragment sizes shows little improvement when compared to predictions carried out with libraries that comprise only three different fragment sizes. Models obtained from libraries built using only sequence similarity are, on average, better than those built with a secondary structure prediction bias. However, we found that the use of secondary structure prediction allows greater reduction of the search space, which is invaluable for prediction methods. The results of this study can be critical guidelines for the use of fragment libraries in protein structure prediction. PMID:28085928

  4. Thermodynamical string fragmentation

    Science.gov (United States)

    Fischer, Nadine; Sjöstrand, Torbjörn

    2017-01-01

    The observation of heavy-ion-like behaviour in pp collisions at the LHC suggests that more physics mechanisms are at play than traditionally assumed. The introduction e.g. of quark-gluon plasma or colour rope formation can describe several of the observations, but as of yet there is no established paradigm. In this article we study a few possible modifications to the Pythia event generator, which describes a wealth of data but fails for a number of recent observations. Firstly, we present a new model for generating the transverse momentum of hadrons during the string fragmentation process, inspired by thermodynamics, where heavier hadrons naturally are suppressed in rate but obtain a higher average transverse momentum. Secondly, close-packing of strings is taken into account by making the temperature or string tension environment-dependent. Thirdly, a simple model for hadron rescattering is added. The effect of these modifications is studied, individually and taken together, and compared with data mainly from the LHC. While some improvements can be noted, it turns out to be nontrivial to obtain effects as big as required, and further work is called for.

  5. Thermodynamical String Fragmentation

    CERN Document Server

    Fischer, Nadine

    2016-01-01

    The observation of heavy-ion-like behaviour in pp collisions at the LHC suggests that more physics mechanisms are at play than traditionally assumed. The introduction e.g. of quark-gluon plasma or colour rope formation can describe several of the observations, but as of yet there is no established paradigm. In this article we study a few possible modifications to the Pythia event generator, which describes a wealth of data but fails for a number of recent observations. Firstly, we present a new model for generating the transverse momentum of hadrons during the string fragmentation process, inspired by thermodynamics, where heavier hadrons naturally are suppressed in rate but obtain a higher average transverse momentum. Secondly, close-packing of strings is taken into account by making the temperature or string tension environment-dependent. Thirdly, a simple model for hadron rescattering is added. The effect of these modifications is studied, individually and taken together, and compared with data mainly from...

  6. Fragmentation Considered Poisonous

    CERN Document Server

    Herzberg, Amir

    2012-01-01

    We present practical poisoning and name-server block- ing attacks on standard DNS resolvers, by off-path, spoofing adversaries. Our attacks exploit large DNS responses that cause IP fragmentation; such long re- sponses are increasingly common, mainly due to the use of DNSSEC. In common scenarios, where DNSSEC is partially or incorrectly deployed, our poisoning attacks allow 'com- plete' domain hijacking. When DNSSEC is fully de- ployed, attacker can force use of fake name server; we show exploits of this allowing off-path traffic analy- sis and covert channel. When using NSEC3 opt-out, attacker can also create fake subdomains, circumvent- ing same origin restrictions. Our attacks circumvent resolver-side defenses, e.g., port randomisation, IP ran- domisation and query randomisation. The (new) name server (NS) blocking attacks force re- solver to use specific name server. This attack allows Degradation of Service, traffic-analysis and covert chan- nel, and also facilitates DNS poisoning. We validated the attac...

  7. An Algebra for Program Fragments

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    1985-01-01

    Program fragments are described either by strings in the concrete syntax or by constructor applications in the abstract syntax. By defining conversions between these forms, both may be intermixed. Program fragments are constructed by terminal and nonterminal symbols from the grammar and by variab...

  8. Complete axiomatizations for XPath fragments

    NARCIS (Netherlands)

    ten Cate, B.; Litak, T.; Marx, M.

    2010-01-01

    We provide complete axiomatizations for several fragments of Core XPath, the navigational core of XPath 1.0 introduced by Gottlob, Koch and Pichler. A complete axiomatization for a given fragment is a set of equivalences from which every other valid equivalence is derivable; equivalences can be thou

  9. Water cluster fragmentation probed by pickup experiments

    Science.gov (United States)

    Huang, Chuanfu; Kresin, Vitaly V.; Pysanenko, Andriy; Fárník, Michal

    2016-09-01

    Electron ionization is a common tool for the mass spectrometry of atomic and molecular clusters. Any cluster can be ionized efficiently by sufficiently energetic electrons, but concomitant fragmentation can seriously obstruct the goal of size-resolved detection. We present a new general method to assess the original neutral population of the cluster beam. Clusters undergo a sticking collision with a molecule from a crossed beam, and the velocities of neat and doped cluster ion peaks are measured and compared. By making use of longitudinal momentum conservation, one can reconstruct the sizes of the neutral precursors. Here this method is applied to H2O and D2O clusters in the detected ion size range of 3-10. It is found that water clusters do fragment significantly upon electron impact: the deduced neutral precursor size is ˜3-5 times larger than the observed cluster ions. This conclusion agrees with beam size characterization by another experimental technique: photoionization after Na-doping. Abundant post-ionization fragmentation of water clusters must therefore be an important factor in the interpretation of experimental data; interestingly, there is at present no detailed microscopic understanding of the underlying fragmentation dynamics.

  10. Physical laws of cholesterol gallstone fragmentation.

    Science.gov (United States)

    Neubrand, M; Greinwald, I; Lobentanzer, H; Paumgartner, G; Hermeking, H; Sauerbruch, T

    1997-03-01

    Efficient fragmentation is the most important prerequisite for successful treatment of gallstones by extracorporeally induced shock waves. No data are available on the amount of energy necessary for stone disintegration and on the threshold energy below which no further fragmentation occurs. We therefore performed an in vitro investigation on human cholesterol gallstones to elucidate physical laws governing shock-wave lithotripsy. First, the focal pressure of the lithotripter was measured to calculate the energy traversing a stone. Second, 96 gallstones from 16 gall bladders were analysed with respect to physicochemical composition, radiological features and ultrasound before fragmentation was performed. Energy for stone disintegration was constant within each stone family but varied between 4.6 mL-1 and 36.8J mL-1 in different families. This energy correlated linearly with stone volume. None of the radiological and physicochemical factors revealed a clear-cut correlation of the different energies necessary for similar stone disintegration. The threshold energy differed between 0.26 mJ and 1.04 mJ per pulse. In conclusion, stone volume was the best parameter predicting stone fragmentation. However, in cholesterol stones with a similar composition the required energy per volume varies considerably together with the threshold energy. Radiological and ultrasound parameters appear to be of minor importance in explaining these differences.

  11. Fragmentation of a Jet with Small Radius

    CERN Document Server

    Dai, Lin; Leibovich, Adam K

    2016-01-01

    In this paper we consider the fragmentation of a parton into a jet with small jet radius $R$. Perturbatively, logarithms of $R$ can appear, which for narrow jets can lead to large corrections. Using soft-collinear effective theory (SCET), we introduce the jet fragmentation function (JFF), which describes the fragmentation of a parton into a jet. We discuss how these objects are related to the standard jet functions. Calculating the JFF to next-to-leading order, we show that these objects satisfy the standard DGLAP evolution equations, with a natural scale that depends upon $R$. By using standard renormalization group evolution, we can therefore resum logarithms of $R$. We further use SCET to prove a factorization theorem where the JFFs naturally appear, for the fragmentation of a hadron within a jet with small $R$. Finally, we also show how this formalism can be used to resum the ratio of jet radii for a subjet to be emitted from within a fat jet.

  12. Driven fragmentation of granular gases.

    Science.gov (United States)

    Cruz Hidalgo, Raúl; Pagonabarraga, Ignacio

    2008-06-01

    The dynamics of homogeneously heated granular gases which fragment due to particle collisions is analyzed. We introduce a kinetic model which accounts for correlations induced at the grain collisions and analyze both the kinetics and relevant distribution functions these systems develop. The work combines analytical and numerical studies based on direct simulation Monte Carlo calculations. A broad family of fragmentation probabilities is considered, and its implications for the system kinetics are discussed. We show that generically these driven materials evolve asymptotically into a dynamical scaling regime. If the fragmentation probability tends to a constant, the grain number diverges at a finite time, leading to a shattering singularity. If the fragmentation probability vanishes, then the number of grains grows monotonously as a power law. We consider different homogeneous thermostats and show that the kinetics of these systems depends weakly on both the grain inelasticity and driving. We observe that fragmentation plays a relevant role in the shape of the velocity distribution of the particles. When the fragmentation is driven by local stochastic events, the long velocity tail is essentially exponential independently of the heating frequency and the breaking rule. However, for a Lowe-Andersen thermostat, numerical evidence strongly supports the conjecture that the scaled velocity distribution follows a generalized exponential behavior f(c) approximately exp(-cn) , with n approximately 1.2 , regarding less the fragmentation mechanisms.

  13. The spectroscopy of fission fragments

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, W.R. [Department of Physics and Astronomy, University of Manchester, Manchester, M13 9PL (United Kingdom); Collaboration: La Direction des Sciences de la Matiere du CEA (FR); Le Fonds National de la Recherche Scientifique de Belgique (BE)

    1998-12-31

    High-resolution measurements on {gamma} rays from fission fragments have provided a rich source of information, unobtainable at the moment in any other way, on the spectroscopy of neutron-rich nuclei. In recent years important data have been obtained on the yrast- and near yrast-structure of neutron-rich fission fragments. We discuss the scope of measurements which can be made on prompt gamma rays from secondary fission fragments, the techniques used in the experiments and some results recently obtained. (author) 24 refs., 8 figs., 1 tab.

  14. Increased Abundance of Native and Non-Native Spiders With Habitat Fragmentation

    OpenAIRE

    Bolger, Douglas T.; Beard, Karen H.; Suarez, Andrew; Case, Ted

    2008-01-01

    Habitat fragmentation and invasive species often contribute to the decline of native taxa. Since the penetration of non-native species into natural habitat may be facilitated by habitat fragmentation, it is important to examine how these two factors interact. Previous research documented that, in contrast to most other arthropod taxa, spiders increased in density and morphospecies richness with decreasing fragment area and increasing fragment age (time since insularization) in urban habitat f...

  15. Release and characteristics of fungal fragments in various conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mensah-Attipoe, Jacob [Department of Environmental Science, University of Eastern Finland, Yliopistonranta 1D, P. O. Box 1627, FI-70211 Kuopio (Finland); Saari, Sampo [Department of Physics, Tampere University of Technology, Korkeakoulunkatu 3, 33720 Tampere (Finland); Veijalainen, Anna-Maria; Pasanen, Pertti [Department of Environmental Science, University of Eastern Finland, Yliopistonranta 1D, P. O. Box 1627, FI-70211 Kuopio (Finland); Keskinen, Jorma [Department of Physics, Tampere University of Technology, Korkeakoulunkatu 3, 33720 Tampere (Finland); Leskinen, Jari T.T. [SIB Labs, University of Eastern Finland, Yliopistonranta 1E, P. O. Box 1627, FI-70211, Kuopio (Finland); Reponen, Tiina, E-mail: reponeta@ucmail.uc.edu [Department of Environmental Science, University of Eastern Finland, Yliopistonranta 1D, P. O. Box 1627, FI-70211 Kuopio (Finland); Department of Environmental Health, University of Cincinnati, P.O. Box 670056, Cincinnati, OH 45267-0056 (United States)

    2016-03-15

    Intact spores and submicrometer size fragments are released from moldy building materials during growth and sporulation. It is unclear whether all fragments originate from fungal growth or if small pieces of building materials are also aerosolized as a result of microbial decomposition. In addition, particles may be formed through nucleation from secondary metabolites of fungi, such as microbial volatile organic compounds (MVOCs). In this study, we used the elemental composition of particles to characterize the origin of submicrometer fragments released from materials contaminated by fungi. Particles from three fungal species (Aspergillus versicolor, Cladosporium cladosporioides and Penicillium brevicompactum), grown on agar, wood and gypsum board were aerosolized using the Fungal Spore Source Strength Tester (FSSST) at three air velocities (5, 16 and 27 m/s). Released spores (optical size, d{sub p} ≥ 0.8 μm) and fragments (d{sub p} ≤ 0.8 μm) were counted using direct-reading optical aerosol instruments. Particles were also collected on filters, and their morphology and elemental composition analyzed using scanning electron microscopes (SEMs) coupled with an Energy-Dispersive X-ray spectroscopy (EDX). Among the studied factors, air velocity resulted in the most consistent trends in the release of fungal particles. Total concentrations of both fragments and spores increased with an increase in air velocity for all species whereas fragment–spore (F/S) ratios decreased. EDX analysis showed common elements, such as C, O, Mg and Ca, for blank material samples and fungal growth. However, N and P were exclusive to the fungal growth, and therefore were used to differentiate biological fragments from non-biological ones. Our results indicated that majority of fragments contained N and P. Because we observed increased release of fragments with increased air velocities, nucleation of MVOCs was likely not a relevant process in the formation of fungal fragments. Based

  16. Effects of forest fragmentation on nocturnal Asian birds: A case study from Xishuangbanna, China.

    Science.gov (United States)

    K Dayananda, Salindra; Goodale, Eben; Lee, Myung-Bok; Liu, Jia-Jia; Mammides, Christos; O Pasion, Bonifacio; Quan, Rui-Chang; W Ferry Slik, J; Sreekar, Rachakonda; W Tomlinson, Kyle; Yasuda, Mika

    2016-05-18

    Owls have the potential to be keystone species for conservation in fragmented landscapes, as the absence of these predators could profoundly change community structure. Yet few studies have examined how whole communities of owls respond to fragmentation, especially in the tropics. When evaluating the effect of factors related to fragmentation, such as fragment area and distance to the edge, on these birds, it is also important in heterogeneous landscapes to ask how 'location factors' such as the topography, vegetation and soil of the fragment predict their persistence. In Xishuangbanna, southwest China, we established 43 transects (200 m×60 m) within 20 forest fragments to sample nocturnal birds, both visually and aurally. We used a multimodel inference approach to identify the factors that influence owl species richness, and generalized linear mixed models to predict the occurrence probabilities of each species. We found that fragmentation factors dominated location factors, with larger fragments having more species, and four of eight species were significantly more likely to occur in large fragments. Given the potential importance of these birds on regulating small mammal and other animal populations, and thus indirectly affecting seed dispersal, we suggest further protection of large fragments and programs to increase their connectivity to the remaining smaller fragments.

  17. Biomechanical evaluation of fixation degree of fragments by periosteal osteosynthesis

    Directory of Open Access Journals (Sweden)

    Barabash Yu.A.

    2010-09-01

    Full Text Available Expansion of indications for surgery and plate osteosynthesis of long bones points to increased number of complications caused by instability of fragments, that can be associated in their turn with constructive features or iatrogenic factors. Insufficient rigidity of fragment fixation is due to incorrect technical treatment and wrong choice of fixator. Biomechanical parameters of periosteal fixation rigidity have been experimentally proved, depending on fixator lever

  18. Fragment Driven Magnetic Reconnection

    CERN Document Server

    Galsgaard, K

    2004-01-01

    In this paper, we investigate a simple model where two, initially unconnected, flux systems are forced to interact in response to the imposed boundary driving by solving the non-ideal 3D MHD equations numerically. The reconnection rate of the dynamical process is determined and compared with the corresponding rate for the potential evolution of the magnetic field. This shows that the dynamic reconnection rate is about a factor of two smaller than the potential (perfect, instantaneous) rate for realistic solar driving velocities demonstrating that this three-dimensional magnetic reconnection process is fast. The energy input for a fixed advection distance is found to be independent of the driving velocity. The Joule dissipation associated with the reconnection process is also found to be basically dependent on the advection distance rather than driving velocity. This implies that the timescale for the event determines the effect the heating has on the temperature increase. Finally, the numerical experiments in...

  19. Vapor film collapse triggered by external pressure pulse and the fragmentation of melt droplet in FCIs

    Institute of Scientific and Technical Information of China (English)

    LIN Qian; TONG Lili; CAO Xuewu; KRIVENTSEV Vladimir

    2008-01-01

    The fragmentation process of high-temperature molten drop is a key factor to determine the ratio heat transferred to power in FCIs,which estimates the possible damage degree during the hypothetical severe accident in the nuclear reactors.In this paper,the fragmentation process of melt droplet in FCIs is investigated by theoretic analysis.The fragmentation mechanism is studied when an external pressure pulse applied to a melt droplet,which is surrounded by vapor film.The vapor film collapse which induces fragmentation of melt droplet is analyzed and modeled.And then the generated pressure is calculated.The vapor film collapse model is introduced to fragmentation correlation,and the predicted fragment size is calculated and compared with experimental data.The result shows that the developed model can predict the diameter of fragments and can be used to calculate the fragmentation process appreciatively.

  20. DNA fragmentation in spermatozoa and its relationship with impaired spermatogenesis

    Directory of Open Access Journals (Sweden)

    S. A. Rudneva

    2014-01-01

    Full Text Available Sperm cells DNA fragmentation is one of the factors of male sub-/infertility discovered recently. At present, pathophysiological mechanisms that cause DNA fragmentation have not been studied completely. It is suggested that they may be caused with defects of chromatin remodeling, apoptosis, and oxidative stress. Spermiological examination was performed in 461 infertile men. With 23 % of the patients examined, the frequency of sperm cells DNA fragmentation comprises over 15 %, with that, 18 % of the patients demonstrated its range from 15.1 to 30 %, and with 5 % of patients, it exceeded 30 %. We found that the amount of sperm cells with fragmented DNA with severe forms of pathozoospermia is higher that with less manifested disturbances of spermatogenesis. Negative dynamics was revealed regarding the change in sperm concentration in men that have increased frequency of DNA fragmentation. Obtained results confirm the suggestion of the correlation between some semen parameters (concentration, motility, and morphology and sperm DNA fragmentation. Thus, one can state that the DNA fragmentation parameter of sperm cells has a certain diagnostic and forecasting value for married couples with reproduction disorders.

  1. Nuclear energy release from fragmentation

    CERN Document Server

    Li, Cheng; Tsang, M B; Zhang, Feng-Shou

    2015-01-01

    Nuclear energy released by splitting Uranium and Thorium isotopes into two, three, four, up to eight fragments with nearly equal size are studied. We found that the energy released come from equally splitting the $^{235,238}$U and $^{230,232}$Th nuclei into to three fragments is largest. The statistical multifragmentation model is employed to calculate the probability of different breakup channels for the excited nuclei. Weighing the the probability distributions of fragments multiplicity at different excitation energies for the $^{238}$U nucleus, we found that an excitation energy between 1.2 and 2 MeV/u is optimal for the $^{235}$U, $^{238}$U, $^{230}$Th and $^{232}$Th nuclei to release nuclear energy of about 0.7-0.75 MeV/u.

  2. Hands as markers of fragmentation

    Directory of Open Access Journals (Sweden)

    A. Barnard

    2005-07-01

    Full Text Available Margaret Atwood is an internationally read, translated, and critiqued writer whose novels have established her as one of the most esteemed authors in English (McCombs & Palmer, 1991:1. Critical studies of her work deal mainly with notions of identity from psychoanalytical perspectives. This study has identified a gap in current critical studies on Atwood’s works, namely the challenging of textual unity which is paralleled in the challenging of the traditional (single narrative voice. The challenging of textual unity and the single narrative voice brings about the fragmentation of both. This article will focus on the role that hands play as markers of fragmentation in “The Blind Assassin” (2000. In the novel, the writing hand destabilises the narrative voice, since it is not connected to the voice of a single author. If the author of the text – the final signified – is eliminated, the text becomes fragmentary and open, inviting the reader to contribute to the creation of meaning. Hands play a signficant role in foregrounding the narrator’s fragmented identity, and consequently, the fragmentation of the text. We will investigate this concept in the light of Roland Barthes’ notion of the scriptor, whose hand is metaphorically severed from his or her “voice”. Instead of the text being a unified entity, it becomes unstable and it displays the absence of hierarchical textual levels. Based mainly on Barthes’ writings, this article concludes that hands foreground the narrator’s fragmented identity, which is paralleled in the fragmented text.

  3. Phenomenology of Dihadron Fragmentation Function

    CERN Document Server

    Courtoy, A

    2016-01-01

    We report on the phenomenological results obtained through Dihadron Fragmentation Functions related processes. In 2015, an update on the fitting techniques for the Dihadron Fragmentation Functions has led to an improved extraction of the transversity PDF and, as a consequence, the nucleon tensor charge. We discuss the impact of the determination of the latter on search for physics Beyond the Standard Model, focusing on the error treatment. We also comment on the future of the extraction of the subleading-twist PDF $e(x)$ from JLab soon-to-be-released Beam Spin Asymmetry data.

  4. Transversity and dihadron fragmentation functions

    CERN Document Server

    Bacchetta, A; Bacchetta, Alessandro; Radici, Marco

    2005-01-01

    The observation of the quark transversity distribution requires another soft object sensitive to the quark's transverse spin. Dihadron fragmentation functions represent a convenient tool to analyze partonic spin, which can influence the angular distribution of the two hadrons. In particular, the so-called interference fragmentation functions can be used to probe transversity both in semi-inclusive deep inelastic scattering as well as proton-proton collisions. We discuss two single-spin asymmetries sensitive to transversity in the these two processes, at leading twist and leading order in alpha_S.

  5. RIA Fragmentation Line Beam Dumps

    Energy Technology Data Exchange (ETDEWEB)

    Stein, W

    2003-08-08

    The Rare Isotope Accelerator project involves generating heavy-element ion beams for use in a fragmentation target line to produce beams for physics research. The main beam, after passing through the fragmentation target, may be dumped into a beam dump located in the vacuum cavity of the first dipole magnet. For a dump beam power of 100 kW, cooling is required to avoid excessive high temperatures. The proposed dump design involves rotating cylinders to spread out the energy deposition and turbulent subcooled water flow through internal water cooling passages to obtain high, nonboiling, cooling rates.

  6. Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae

    Science.gov (United States)

    Michaillat, Lydie; Mayer, Andreas

    2013-01-01

    The equilibrium of membrane fusion and fission influences the volume and copy number of organelles. Fusion of yeast vacuoles has been well characterized but their fission and the mechanisms determining vacuole size and abundance remain poorly understood. We therefore attempted to systematically characterize factors necessary for vacuole fission. Here, we present results of an in vivo screening for deficiencies in vacuolar fragmentation activity of an ordered collection deletion mutants, representing 4881 non-essential genes of the yeast Saccharomyces cerevisiae. The screen identified 133 mutants with strong defects in vacuole fragmentation. These comprise numerous known fragmentation factors, such as the Fab1p complex, Tor1p, Sit4p and the V-ATPase, thus validating the approach. The screen identified many novel factors promoting vacuole fragmentation. Among those are 22 open reading frames of unknown function and three conspicuous clusters of proteins with known function. The clusters concern the ESCRT machinery, adaptins, and lipases, which influence the production of diacylglycerol and phosphatidic acid. A common feature of these factors of known function is their capacity to change membrane curvature, suggesting that they might promote vacuole fragmentation via this property. PMID:23383298

  7. Policing, Community Fragmentation, and Public Health: Observations from Baltimore.

    Science.gov (United States)

    Gomez, Marisela B

    2016-04-01

    Studies show that policing, when violent, and community fragmentation have a negative impact on health outcomes. This current study investigates the connection of policing and community fragmentation and public health. Using an embedded case study analysis, semi-structured interviews were conducted with 21 African-American female and male residents, ages 21-64 years of various neighborhoods of high arrest rates and health and socioeconomic depravation in Baltimore City, MD. Baltimore residents' perceptions of policing, stress, community fragmentation, and solutions are presented. Analysis of the perceptions of these factors suggests that violent policing increases community fragmentation and is a public health threat. Approaches to address this public health threat are discussed.

  8. Simulation of the mixing process in FCIs with hydrodynamic fragmentation model

    Institute of Scientific and Technical Information of China (English)

    LIN Qian; CAO Xuewu

    2007-01-01

    Fuel Coolant Interactions (FCIs) are important issues in nuclear reactor severe accident analysis. In FCIs,fragmentation model of molten droplets is a key factor to estimate degree of possible damage. In this paper, the mixing process in FCIs is studied by the simulation of MIXA experiment with hydrodynamic fragmentation model. The result shows that hydrodynamic fragmentation model underestimates the fragmentation rate of high temperature molten droplets under the condition of low Weber numbers. It is concluded that models based on thermal fragmentation mechanism should be adopted to analyze the FCI process and its consequence.

  9. Life history strategy influences parasite responses to habitat fragmentation.

    Science.gov (United States)

    Froeschke, Götz; van der Mescht, Luther; McGeoch, Melodie; Matthee, Sonja

    2013-12-01

    Anthropogenic habitat use is a major threat to biodiversity and is known to increase the abundance of generalist host species such as rodents, which are regarded as potential disease carriers. Parasites have an intimate relationship with their host and the surrounding environment and it is expected that habitat fragmentation will affect parasite infestation levels. We investigated the effect of habitat fragmentation on the ecto- and endoparasitic burdens of a broad niche small mammal, Rhabdomys pumilio, in the Western Cape Province, South Africa. Our aim was to look at the effects of fragmentation on different parasite species with diverse life history characteristics and to determine whether general patterns can be found. Sampling took place within pristine lowland (Fynbos/Renosterveld) areas and at fragmented sites surrounded and isolated by agricultural activities. All arthropod ectoparasites and available gastrointestinal endoparasites were identified. We used conditional autoregressive models to investigate the effects of habitat fragmentation on parasite species richness and abundance of all recovered parasites. Host density and body size were larger in the fragments. Combined ecto- as well as combined endoparasite taxa showed higher parasite species richness in fragmented sites. Parasite abundance was generally higher in the case of R. pumilio individuals in fragmented habitats but it appears that parasites that are more permanently associated with the host's body and those that are host-specific show the opposite trend. Parasite life history is an important factor that needs to be considered when predicting the effects of habitat fragmentation on parasite and pathogen transmission. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  10. A thermodynamic theory of dynamic fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Yew, Ching H. [Texas Univ., Austin, TX (United States); Taylor, P.A. [Sandia National Labs., Albuquerque, NM (United States)

    1993-08-01

    We present a theory of dynamic fragmentation of brittle materials based on thermodynamic arguments. We recover the expressions for average fragment size and number as originally derived by Grady. We extend the previous work by obtaining descriptions of fragment size distribution and compressibility change due to the fragmentation process. The size distribution is assumed to be proportional to the spectral power of the strain history and a sample distribution is presented for a fragmentation process corresponding to a constant rate strain history. The description of compressibility change should be useful in computational studies of fragmentation. These results should provide insight into the process of fragmentation of brittle materials from hypervelocity impact.

  11. Population pressure and farm fragmentation:

    African Journals Online (AJOL)

    user

    small but farms are further fragmented into diminutive size fields due to ... terms of household characteristics; land use and performance indicators; technology adoption .... 'best' unit of measurement of farm size, and size of enterprises within farms will ..... less common, accounting for 18 percent (3 percent) and 10 percent (7.

  12. Nuclear energy release from fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Cheng [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Souza, S.R. [Instituto de Física, Universidade Federal do Rio de Janeiro Cidade Universitária, Caixa Postal 68528, 21945-970 Rio de Janeiro (Brazil); Tsang, M.B. [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); National Superconducting Cyclotron Laboratory and Physics and Astronomy Department, Michigan State University, East Lansing, MI 48824 (United States); Zhang, Feng-Shou, E-mail: fszhang@bnu.edu.cn [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Center of Theoretical Nuclear Physics, National Laboratory of Heavy Ion Accelerator of Lanzhou, Lanzhou 730000 (China)

    2016-08-15

    It is well known that binary fission occurs with positive energy gain. In this article we examine the energetics of splitting uranium and thorium isotopes into various numbers of fragments (from two to eight) with nearly equal size. We find that the energy released by splitting {sup 230,232}Th and {sup 235,238}U into three equal size fragments is largest. The statistical multifragmentation model (SMM) is applied to calculate the probability of different breakup channels for excited nuclei. By weighing the probability distributions of fragment multiplicity at different excitation energies, we find the peaks of energy release for {sup 230,232}Th and {sup 235,238}U are around 0.7–0.75 MeV/u at excitation energy between 1.2 and 2 MeV/u in the primary breakup process. Taking into account the secondary de-excitation processes of primary fragments with the GEMINI code, these energy peaks fall to about 0.45 MeV/u.

  13. Nuclear energy release from fragmentation

    Science.gov (United States)

    Li, Cheng; Souza, S. R.; Tsang, M. B.; Zhang, Feng-Shou

    2016-08-01

    It is well known that binary fission occurs with positive energy gain. In this article we examine the energetics of splitting uranium and thorium isotopes into various numbers of fragments (from two to eight) with nearly equal size. We find that the energy released by splitting 230,232Th and 235,238U into three equal size fragments is largest. The statistical multifragmentation model (SMM) is applied to calculate the probability of different breakup channels for excited nuclei. By weighing the probability distributions of fragment multiplicity at different excitation energies, we find the peaks of energy release for 230,232Th and 235,238U are around 0.7-0.75 MeV/u at excitation energy between 1.2 and 2 MeV/u in the primary breakup process. Taking into account the secondary de-excitation processes of primary fragments with the GEMINI code, these energy peaks fall to about 0.45 MeV/u.

  14. The Fragmentation of Literary Theory

    Science.gov (United States)

    Howard, Jennifer

    2005-01-01

    Syllabi from some 20 colleges and universities were reviewed with prominent English and literature departments and a discussion was held with a number of professors who teach literary theory. It is suggested that devolution and fragmentation of theory might be a survival strategy, an adaptation to the new realties of academic institutions.

  15. Fragmented nature : consequences for biodiversity

    NARCIS (Netherlands)

    Olff, Han; Ritchie, Mark E.

    2002-01-01

    We discuss how fragmentation of resources and habitat operate differently on species diversity across spatial scales, ranging from positive effects on local species coexistence to negative effect on intermediate spatial scales, to again positive effects on large spatial and temporal scales. Species

  16. Fragmented nature: consequences for biodiversity

    NARCIS (Netherlands)

    Olff, H.; Ritchie, M.E.

    2002-01-01

    We discuss how fragmentation of resources and habitat operate differently on species diversity across spatial scales, ranging from positive effects on local species coexistence to negative effect on intermediate spatial scales, to again positive effects on large spatial and temporal scales. Species

  17. Fragmented nature : consequences for biodiversity

    NARCIS (Netherlands)

    Olff, Han; Ritchie, Mark E.

    2002-01-01

    We discuss how fragmentation of resources and habitat operate differently on species diversity across spatial scales, ranging from positive effects on local species coexistence to negative effect on intermediate spatial scales, to again positive effects on large spatial and temporal scales. Species

  18. Fragmented nature: consequences for biodiversity

    NARCIS (Netherlands)

    Olff, H.; Ritchie, M.E.

    2002-01-01

    We discuss how fragmentation of resources and habitat operate differently on species diversity across spatial scales, ranging from positive effects on local species coexistence to negative effect on intermediate spatial scales, to again positive effects on large spatial and temporal scales. Species

  19. Investigation of Nuclear Fragmentation in Relativistic Heavy Ion Collisions Using Plastic - Nuclear - Track Detectors

    CERN Multimedia

    2002-01-01

    In this experiment CR39 plastic nuclear track detectors will be used which are sensitive to detect relativistic nuclear fragments with charges Z@$>$5. They will be analyzed using an automatic track measuring system which was developed at the University of Siegen.\\\\ \\\\ This allows to measure large quantities of tracks in these passive detectors and to perform high statistics experiments. We intend to measure cross sections for the production of nuclear fragments from heavy ion beams at the SPS. \\\\ \\\\ The energy independence of the cross sections predicted by the idea of limiting fragmentation will be tested at high energies. In exposures with different targets we plan to analyze the factorization of the fragmentation cross sections into a target depending factor and a factor depending on the beam particle and the fragment. The cross sections for one proton remov Coulomb dissociation. \\\\ \\\\ We plan to investigate Coulomb dissociation for different targets and different energies. Fragment and projectile charges ...

  20. Dung beetle (Coleoptera, Scarabaeidae assemblage of a highly fragmented landscape of Atlantic forest: from small to the largest fragments of northeastern Brazilian region

    Directory of Open Access Journals (Sweden)

    Renato P. Salomão

    2015-06-01

    Full Text Available Human activities in tropical forests are the main causes of forest fragmentation. According to historical factor in deforestation processes, forest remnants exhibit different sizes and shapes. The aim of the present study was to evaluate the dung beetle assemblage on fragments of different degree of sizes. Sampling was performed during rainy and dry season of 2010 in six fragments of Atlantic forest, using pitfall traps baited with excrement and carrion. Also, we used two larger fragments as control. We used General Linear Models to determine whether the fragments presented distinguished dung beetle abundance and richness. Analysis of Similarities and Non-Metric Multidimensional Scaling were used to determine whether the dung beetle assemblage was grouped according to species composition. A total of 3352 individuals were collected and 19 species were identified in the six fragments sampled. Dung beetle abundance exhibited a shift according to fragment size; however, richness did not change among fragments evaluated. Also, fragments sampled and the two controls exhibited distinct species composition. The distinction on abundance of dung beetles among fragments may be related to different amount of resource available in each one. It is likely that the dung beetle richness did not distinguish among the different fragments due to the even distribution of the mammal communities in these patches, and consequent equal dung diversity. We conclude that larger fragments encompass higher abundance of dung beetle and distinct species. However, for a clearer understanding of effects of fragmentation on dung beetles in Atlantic forest, studies evaluating narrower variations of larger fragments should be conducted.

  1. The VERDI fission fragment spectrometer

    Science.gov (United States)

    Frégeau, M. O.; Bryś, T.; Gamboni, Th.; Geerts, W.; Oberstedt, S.; Oberstedt, A.; Borcea, R.

    2013-12-01

    The VERDI time-of-flight spectrometer is dedicated to measurements of fission product yields and of prompt neutron emission data. Pre-neutron fission-fragment masses will be determined by the double time-of-flight (TOF) technique. For this purpose an excellent time resolution is required. The time of flight of the fragments will be measured by electrostatic mirrors located near the target and the time signal coming from silicon detectors located at 50 cm on both sides of the target. This configuration, where the stop detector will provide us simultaneously with the kinetic energy of the fragment and timing information, significantly limits energy straggling in comparison to legacy experimental setup where a thin foil was usually used as a stop detector. In order to improve timing resolution, neutron transmutation doped silicon will be used. The high resistivity homogeneity of this material should significantly improve resolution in comparison to standard silicon detectors. Post-neutron fission fragment masses are obtained form the time-of-flight and the energy signal in the silicon detector. As an intermediary step a diamond detector will also be used as start detector located very close to the target. Previous tests have shown that poly-crystalline chemical vapour deposition (pCVD) diamonds provides a coincidence time resolution of 150 ps not allowing complete separation between very low-energy fission fragments, alpha particles and noise. New results from using artificial single-crystal diamonds (sCVD) show similar time resolution as from pCVD diamonds but also sufficiently good energy resolution.

  2. The VERDI fission fragment spectrometer

    Directory of Open Access Journals (Sweden)

    Frégeau M.O.

    2013-12-01

    Full Text Available The VERDI time-of-flight spectrometer is dedicated to measurements of fission product yields and of prompt neutron emission data. Pre-neutron fission-fragment masses will be determined by the double time-of-flight (TOF technique. For this purpose an excellent time resolution is required. The time of flight of the fragments will be measured by electrostatic mirrors located near the target and the time signal coming from silicon detectors located at 50 cm on both sides of the target. This configuration, where the stop detector will provide us simultaneously with the kinetic energy of the fragment and timing information, significantly limits energy straggling in comparison to legacy experimental setup where a thin foil was usually used as a stop detector. In order to improve timing resolution, neutron transmutation doped silicon will be used. The high resistivity homogeneity of this material should significantly improve resolution in comparison to standard silicon detectors. Post-neutron fission fragment masses are obtained form the time-of-flight and the energy signal in the silicon detector. As an intermediary step a diamond detector will also be used as start detector located very close to the target. Previous tests have shown that poly-crystalline chemical vapour deposition (pCVD diamonds provides a coincidence time resolution of 150 ps not allowing complete separation between very low-energy fission fragments, alpha particles and noise. New results from using artificial single-crystal diamonds (sCVD show similar time resolution as from pCVD diamonds but also sufficiently good energy resolution.

  3. Fragmentation

    Science.gov (United States)

    K.H. Riitters

    2009-01-01

    Effective resource management takes into account the administrative and biophysical settings within which natural resources occur. A setting may be described in many ways; for example, by forest land ownership, by reserved and roadless designation, or by the distribution of human populations in relation to forest (chapter 3). The physical arrangement of forest in a...

  4. [The fragmentation of representational space in schizophrenia].

    Science.gov (United States)

    Plagnol, A; Oïta, M; Montreuil, M; Granger, B; Lubart, T

    2003-01-01

    compatible with numerous etiological factors. Multiple clinical forms can be differentiated in accordance with the persistence of parasitic areas, the degree of fragmentation, and the formation of sutures. We use this approach to account for an empirical study concerning the analysis of analogical representations in schizophrenia. We used the Parallel Visual Information Processing Test (PVIPT) which assesses the analysis of interfering visual information. Subjects were asked to connect several small geometric figures printed on a transparency. The transparency was displayed above four photographs which were the interfering material. Then, subjects completed three tasks concerning the photographs: a recognition task, a recall task, and an affective qualification task. Using a case-by-case study, this test allows us to access the defense processes of the subjects, which is not possible with the usual methods in cognitive psychopathology. Twelve clinically-stable schizophrenic subjects participated in the study which also included a self-assessment of alexithymia by the Toronto Alexithymia Scale. We obtained 2 main results: (a) creation of items in recall or false recognition by 8 subjects, and (b) lack of the usual -negative correlations between the alexithymia score and the recall, recognition and affective qualification scores in the PVIPT. These 2 results contrast with what has been previously observed for alexithymia using the same methodology. The result (a) confirms an interfering activation in schizophrenic memory, which can be interpreted in our framework as indicative of parasitic areas. The creation of items suggests the formation of sutures between the semantic content of photographs and some delusional fragments. The result (b) suggests that the apparent alexithymia in schizophrenia is a defense against interfering activation in parasitic areas. We underline the interest of individual protocols to exhibit the dynamic interplay between an interfering activity in

  5. Efficient and accurate fragmentation methods.

    Science.gov (United States)

    Pruitt, Spencer R; Bertoni, Colleen; Brorsen, Kurt R; Gordon, Mark S

    2014-09-16

    Conspectus Three novel fragmentation methods that are available in the electronic structure program GAMESS (general atomic and molecular electronic structure system) are discussed in this Account. The fragment molecular orbital (FMO) method can be combined with any electronic structure method to perform accurate calculations on large molecular species with no reliance on capping atoms or empirical parameters. The FMO method is highly scalable and can take advantage of massively parallel computer systems. For example, the method has been shown to scale nearly linearly on up to 131 000 processor cores for calculations on large water clusters. There have been many applications of the FMO method to large molecular clusters, to biomolecules (e.g., proteins), and to materials that are used as heterogeneous catalysts. The effective fragment potential (EFP) method is a model potential approach that is fully derived from first principles and has no empirically fitted parameters. Consequently, an EFP can be generated for any molecule by a simple preparatory GAMESS calculation. The EFP method provides accurate descriptions of all types of intermolecular interactions, including Coulombic interactions, polarization/induction, exchange repulsion, dispersion, and charge transfer. The EFP method has been applied successfully to the study of liquid water, π-stacking in substituted benzenes and in DNA base pairs, solvent effects on positive and negative ions, electronic spectra and dynamics, non-adiabatic phenomena in electronic excited states, and nonlinear excited state properties. The effective fragment molecular orbital (EFMO) method is a merger of the FMO and EFP methods, in which interfragment interactions are described by the EFP potential, rather than the less accurate electrostatic potential. The use of EFP in this manner facilitates the use of a smaller value for the distance cut-off (Rcut). Rcut determines the distance at which EFP interactions replace fully quantum

  6. Gravity or turbulence? -III. Evidence of pure thermal Jeans fragmentation at ~0.1 pc scales

    CERN Document Server

    Palau, Aina; Vazquez-Semadeni, Enrique; Sanchez-Monge, Alvaro; Estalella, Robert; Fall, S Michael; Zapata, Luis A; Camacho, Vianey; Gomez, Laura; Naranjo-Romero, Raul; Busquet, Gemma; Fontani, Francesco

    2015-01-01

    We combine previously published interferometric and single-dish data of relatively nearby massive dense cores that are actively forming stars to test whether their `fragmentation level' is controlled by turbulent or thermal support. We find no clear correlation between the fragmentation level and velocity dispersion, nor between the observed number of fragments and the number of fragments expected when the gravitationally unstable mass is calculated including various prescriptions for `turbulent support'. On the other hand, the best correlations are found for the case of pure thermal Jeans fragmentation, for which we infer a core formation efficiency in the range 12-34%, consistent with previous works. We conclude that the dominant factor determining the fragmentation level of star-forming massive dense cores seems to be thermal Jeans fragmentation.

  7. Combinatorial Labeling Method for Improving Peptide Fragmentation in Mass Spectrometry

    Science.gov (United States)

    Kuchibhotla, Bhanuramanand; Kola, Sankara Rao; Medicherla, Jagannadham V.; Cherukuvada, Swamy V.; Dhople, Vishnu M.; Nalam, Madhusudhana Rao

    2017-06-01

    Annotation of peptide sequence from tandem mass spectra constitutes the central step of mass spectrometry-based proteomics. Peptide mass spectra are obtained upon gas-phase fragmentation. Identification of the protein from a set of experimental peptide spectral matches is usually referred as protein inference. Occurrence and intensity of these fragment ions in the MS/MS spectra are dependent on many factors such as amino acid composition, peptide basicity, activation mode, protease, etc. Particularly, chemical derivatizations of peptides were known to alter their fragmentation. In this study, the influence of acetylation, guanidinylation, and their combination on peptide fragmentation was assessed initially on a lipase (LipA) from Bacillus subtilis followed by a bovine six protein mix digest. The dual modification resulted in improved fragment ion occurrence and intensity changes, and this resulted in the equivalent representation of b- and y-type fragment ions in an ion trap MS/MS spectrum. The improved representation has allowed us to accurately annotate the peptide sequences de novo. Dual labeling has significantly reduced the false positive protein identifications in standard bovine six peptide digest. Our study suggests that the combinatorial labeling of peptides is a useful method to validate protein identifications for high confidence protein inference. [Figure not available: see fulltext.

  8. High Efficiency Hydrodynamic DNA Fragmentation in a Bubbling System

    Science.gov (United States)

    Li, Lanhui; Jin, Mingliang; Sun, Chenglong; Wang, Xiaoxue; Xie, Shuting; Zhou, Guofu; van den Berg, Albert; Eijkel, Jan C. T.; Shui, Lingling

    2017-01-01

    DNA fragmentation down to a precise fragment size is important for biomedical applications, disease determination, gene therapy and shotgun sequencing. In this work, a cheap, easy to operate and high efficiency DNA fragmentation method is demonstrated based on hydrodynamic shearing in a bubbling system. We expect that hydrodynamic forces generated during the bubbling process shear the DNA molecules, extending and breaking them at the points where shearing forces are larger than the strength of the phosphate backbone. Factors of applied pressure, bubbling time and temperature have been investigated. Genomic DNA could be fragmented down to controllable 1-10 Kbp fragment lengths with a yield of 75.30-91.60%. We demonstrate that the ends of the genomic DNAs generated from hydrodynamic shearing can be ligated by T4 ligase and the fragmented DNAs can be used as templates for polymerase chain reaction. Therefore, in the bubbling system, DNAs could be hydrodynamically sheared to achieve smaller pieces in dsDNAs available for further processes. It could potentially serve as a DNA sample pretreatment technique in the future.

  9. Fragmentation in the biopharmaceutical industry.

    Science.gov (United States)

    Goldsmith, Andrew D; Varela, Francisco E

    2017-02-01

    The large number of biopharmaceutical mergers and acquisitions (M&A) that occurred over the past decade has generated questions about whether the industry is consolidating around too-few players, negatively impacting both the number of medicines developed and overall innovation. However, closer examination of the level of biopharmaceutical consolidation by prescription sales shows that the industry was more fragmented in 2015 than in 2003. The trend towards increasing fragmentation is also observed across noncommercial and independent metrics over the same time period. The number and size of M&A deals has masked an active and competitive marketplace in which market growth and the number of companies entering the market exceeded the apparent reduction in the number of players caused by acquisitions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Fragment separator momentum compression schemes

    Energy Technology Data Exchange (ETDEWEB)

    Bandura, Laura, E-mail: bandura@anl.gov [Facility for Rare Isotope Beams (FRIB), 1 Cyclotron, East Lansing, MI 48824-1321 (United States); National Superconducting Cyclotron Lab, Michigan State University, 1 Cyclotron, East Lansing, MI 48824-1321 (United States); Erdelyi, Bela [Argonne National Laboratory, Argonne, IL 60439 (United States); Northern Illinois University, DeKalb, IL 60115 (United States); Hausmann, Marc [Facility for Rare Isotope Beams (FRIB), 1 Cyclotron, East Lansing, MI 48824-1321 (United States); Kubo, Toshiyuki [RIKEN Nishina Center, RIKEN, Wako (Japan); Nolen, Jerry [Argonne National Laboratory, Argonne, IL 60439 (United States); Portillo, Mauricio [Facility for Rare Isotope Beams (FRIB), 1 Cyclotron, East Lansing, MI 48824-1321 (United States); Sherrill, Bradley M. [National Superconducting Cyclotron Lab, Michigan State University, 1 Cyclotron, East Lansing, MI 48824-1321 (United States)

    2011-07-21

    We present a scheme to use a fragment separator and profiled energy degraders to transfer longitudinal phase space into transverse phase space while maintaining achromatic beam transport. The first order beam optics theory of the method is presented and the consequent enlargement of the transverse phase space is discussed. An interesting consequence of the technique is that the first order mass resolving power of the system is determined by the first dispersive section up to the energy degrader, independent of whether or not momentum compression is used. The fragment separator at the Facility for Rare Isotope Beams is a specific application of this technique and is described along with simulations by the code COSY INFINITY.

  11. Fragment separator momentum compression schemes.

    Energy Technology Data Exchange (ETDEWEB)

    Bandura, L.; Erdelyi, B.; Hausmann, M.; Kubo, T.; Nolen, J.; Portillo, M.; Sherrill, B.M. (Physics); (MSU); (Northern Illinois Univ.); (RIKEN)

    2011-07-21

    We present a scheme to use a fragment separator and profiled energy degraders to transfer longitudinal phase space into transverse phase space while maintaining achromatic beam transport. The first order beam optics theory of the method is presented and the consequent enlargement of the transverse phase space is discussed. An interesting consequence of the technique is that the first order mass resolving power of the system is determined by the first dispersive section up to the energy degrader, independent of whether or not momentum compression is used. The fragment separator at the Facility for Rare Isotope Beams is a specific application of this technique and is described along with simulations by the code COSY INFINITY.

  12. Fragment correlations from NAUTILUS multidetector

    Energy Technology Data Exchange (ETDEWEB)

    Bizard, G. [Caen Univ., 14 (France). Lab. de Physique Corpusculaire

    1995-12-31

    It is shown on a few examples how heavy fragment correlations, induced either by conservation laws or by Coulomb interaction can bring physical information on nuclear reactions. All the experimental data discussed have been obtained at GANIL using the NAUTILUS gaseous multi detectors DELF and XYZT, which - due to their good spatial and time resolution and their large solid angle coverage - have proved to be efficient tools for multifragment correlation studies. Different reactions of Ar, Kr, Xe, and Pb beams on Au targets are discussed. It is shown that velocity and angular correlations between fragments provide a powerful clock to scrutinize the details of the hot nuclei decay history. (K.A.). 18 refs., 6 figs.

  13. Fragmentation in filamentary molecular clouds

    CERN Document Server

    Contreras, Yanett; Rathborne, Jill M; Sanhueza, Patricio

    2015-01-01

    Recent surveys of dust continuum emission at sub-mm wavelengths have shown that filamentary molecular clouds are ubiquitous along the Galactic plane. These structures are inhomogeneous, with over-densities that are sometimes associated with infrared emission and active of star formation. To investigate the connection between filaments and star formation, requires an understanding of the processes that lead to the fragmentation of filaments and a determination of the physical properties of the over-densities (clumps). In this paper, we present a multi-wavelength study of five filamentary molecular clouds, containing several clumps in different evolutionary stages of star formation. We analyse the fragmentation of the filaments and derive the physical properties of their clumps. We find that the clumps in all filaments have a characteristic spacing consistent with the prediction of the `sausage' instability theory, regardless of the complex morphology of the filaments or their evolutionary stage. We also find t...

  14. Fragmentering og korridorer i landskabet

    DEFF Research Database (Denmark)

    Hammershøj, M.; Madsen, A. B.

    , at fragmentering af habitater resulterer i en reduktion og isolering af mange plante- og dyrepopulationer. Det er desuden vist, at korridorer har en funktion som habitater, hvilket er medvirkende til, at et område med korridorer kan huse flere arter og individer end et tilsvarende område uden korridorer. Der......Rapporten indeholder en litteraturudredning, der er baseret på en bearbejdning af den tilgængelige nationale og internationale litteratur omhandlende fragmentering og korridorer på det botaniske og zoologiske område. I alt 1.063 titler ligger til grund for udredningen. Udredningen har vist...... mangler dog entydige beviser for, at korridorer kan være af afgørende betydning for rekolonisering af habitater, i hvilke en given art er forsvundet. Afslutningsvis gives en liste med forskningsbehov samt en række anbefalinger....

  15. Asymmetry effects in fragment production

    Science.gov (United States)

    Kaur, Manpreet; Kaur, Varinderjit

    2016-05-01

    The production of different fragments has been studied by taking into account the mass asymmetry of the reaction and employing the momentum dependent interactions. Two different set of asymmetric reactions have been analyzed while keeping Atotal fixed using soft momentum dependent equation of state. Our results indicate that the impact of momentum dependent interactions is different in lighter projectile systems as compared to heavier ones. The comparative analysis of IQMD simulations with the experimental data in case of heavier projectile and lighter target system for the reaction of 197Au+27Al (η = 0.7) at E = 600 MeV/nucleon shows that with the inclusion of MDI we are able, upto some extent, to reproduce the experimental universality of rise and fall of intermediate mass fragments (IMFs).

  16. The fragmentation of Kosmos 2163

    Science.gov (United States)

    1992-01-01

    On 6 Dec. 1991 Kosmos 2163, a maneuverable Soviet spacecraft which had been in orbit for 58 days, experienced a major breakup at an altitude of approximately 210 km. Although numerous pieces of debris were created, the fragments decayed rapidly leaving no long-term impact on the near-Earth environment. The assessed cause of the event is the deliberate detonation of an explosive device. Details of this event are presented.

  17. Modeling of Fragmentation of Asteroids

    Science.gov (United States)

    Agrawal, Parul; Prabhu, Dinesh K.; Carlozzi, Alexander; Hart, Kenneth; Bryson, Katie; Sears, Derek

    2015-01-01

    The objective of this study is to understand fragmentation and fracture of a given asteroid and mechanisms of break-up. The focus of the present work is to develop modeling techniques for stony asteroids in 10m-100m range to answer two questions: 1) What is the role of material makeup of an asteroid in the stress distribution? 2)How is stress distribution altered in the presence of pre-existing defects?

  18. Fragmentation measurement using image processing

    Directory of Open Access Journals (Sweden)

    Farhang Sereshki

    2016-12-01

    Full Text Available In this research, first of all, the existing problems in fragmentation measurement are reviewed for the sake of its fast and reliable evaluation. Then, the available methods used for evaluation of blast results are mentioned. The produced errors especially in recognizing the rock fragments in computer-aided methods, and also, the importance of determination of their sizes in the image analysis methods are described. After reviewing the previous work done, an algorithm is proposed for the automated determination of rock particles’ boundary in the Matlab software. This method can determinate automatically the particles boundary in the minimum time. The results of proposed method are compared with those of Split Desktop and GoldSize software in two automated and manual states. Comparing the curves extracted from different methods reveals that the proposed approach is accurately applicable in measuring the size distribution of laboratory samples, while the manual determination of boundaries in the conventional software is very time-consuming, and the results of automated netting of fragments are very different with the real value due to the error in separation of the objects.

  19. Residual Fragments after Percutaneous Nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Kaan Özdedeli

    2012-09-01

    Full Text Available Clinically insignificant residual fragments (CIRFs are described as asymptomatic, noninfectious and nonobstructive stone fragments (≤4 mm remaining in the urinary system after the last session of any intervention (ESWL, URS or PCNL for urinary stones. Their insignificance is questionable since CIRFs could eventually become significant, as their presence may result in recurrent stone growth and they may cause pain and infection due to urinary obstruction. They may become the source of persistent infections and a significant portion of the patients will have a stone-related event, requiring auxilliary interventions. CT seems to be the ultimate choice of assessment. Although there is no concensus about the timing, recent data suggests that it may be performed one month after the procedure. However, imaging can be done in the immediate postoperative period, if there are no tubes blurring the assessment. There is some evidence indicating that selective medical therapy may have an impact on decreasing stone formation rates. Retrograde intrarenal surgery, with its minimally invasive nature, seems to be the best way to deal with residual fragments.

  20. Preliminary insights into a model for mafic magma fragmentation

    Science.gov (United States)

    Edwards, Matt; Pioli, Laura; Andronico, Daniele; Cristaldi, Antonio; Scollo, Simona

    2017-04-01

    Fragmentation of mafic magmas remains a poorly understood process despite the common occurrence of low viscosity explosive eruptions. In fact, it has been commonly overlooked based on the assumption that low viscosity magmas have very limited explosivity and low potential to undergo brittle fragmentation. However, it is now known that highly explosive, ash forming eruptions can be relatively frequent at several mafic volcanoes. Three questions arise due to this - What is the specific fragmentation mechanism occuring in these eruptions? What are the primary factors controlling fragmentation efficiency? Can a link between eruption style and fragmentation efficiency be quantified? We addressed these questions by coupling theoretical observations and field analysis of the recent May 2016 eruption at Mount Etna volcano. Within this complex 10-day event three paroxysmal episodes of pulsating basaltic lava jets alternating with small lava flows were recorded from a vent within the Voragine crater. The associated plumes which were produced deposited tephra along narrow axes to the east and south east. Sampling was done on the deposits associated with the first two plumes and the third one. We briefly characterise the May 2016 eruption by assessing plume height, eruption phases, total erupted masses and fallout boundaries and comparing them to previous eruptions. We also analyse the total grainsize distribution (TGSD) of the scoria particles formed in the jets. Conventional methods for obtaining grainsize and total distributions of an eruption are based on mass and provide limited information on fragmentation though. For this reason, the TGSD was assessed by coupling particle analyser data and conventional sieving data to assess both particle size and number of particle distributions with better precision. This allowed for more accurate testing of several existing models describing the shape of the TGSD. Coupled further with observations on eruption dynamics and eruption

  1. Habitat fragmentation, tree diversity, and plant invasion interact to structure forest caterpillar communities.

    Science.gov (United States)

    Stireman, John O; Devlin, Hilary; Doyle, Annie L

    2014-09-01

    Habitat fragmentation and invasive species are two of the most prominent threats to terrestrial ecosystems. Few studies have examined how these factors interact to influence the diversity of natural communities, particularly primary consumers. Here, we examined the effects of forest fragmentation and invasion of exotic honeysuckle (Lonicera maackii, Caprifoliaceae) on the abundance and diversity of the dominant forest herbivores: woody plant-feeding Lepidoptera. We systematically surveyed understory caterpillars along transects in 19 forest fragments over multiple years in southwestern Ohio and evaluated how fragment area, isolation, tree diversity, invasion by honeysuckle and interactions among these factors influence species richness, diversity and abundance. We found strong seasonal variation in caterpillar communities, which responded differently to fragmentation and invasion. Abundance and richness increased with fragment area, but these effects were mitigated by high levels of honeysuckle, tree diversity, landscape forest cover, and large recent changes in area. Honeysuckle infestation was generally associated with decreased caterpillar abundance and diversity, but these effects were strongly dependent on other fragment traits. Effects of honeysuckle on abundance were moderated when fragment area, landscape forest cover and tree diversity were high. In contrast, negative effects of honeysuckle invasion on caterpillar diversity were most pronounced in fragments with high tree diversity and large recent increases in area. Our results illustrate the complex interdependencies of habitat fragmentation, plant diversity and plant invasion in their effects on primary consumers and emphasize the need to consider these processes in concert to understand the consequences of anthropogenic habitat change for biodiversity.

  2. Augmenting Tractable Fragments of Abstract Argumentation

    CERN Document Server

    Ordyniak, Sebastian

    2011-01-01

    We present a new and compelling approach to the efficient solution of important computational problems that arise in the context of abstract argumentation. Our approach makes known algorithms defined for restricted fragments generally applicable, at a computational cost that scales with the distance from the fragment. Thus, in a certain sense, we gradually augment tractable fragments. Surprisingly, it turns out that some tractable fragments admit such an augmentation and that others do not. More specifically, we show that the problems of credulous and skeptical acceptance are fixed-parameter tractable when parameterized by the distance from the fragment of acyclic argumentation frameworks. Other tractable fragments such as the fragments of symmetrical and bipartite frameworks seem to prohibit an augmentation: the acceptance problems are already intractable for frameworks at distance 1 from the fragments. For our study we use a broad setting and consider several different semantics. For the algorithmic results...

  3. Energy-loss distributions of fission fragments

    Energy Technology Data Exchange (ETDEWEB)

    Demidovich, N.N.; Nakhutin, I.E.; Shatunov, V.G.

    1976-03-05

    The f-f coincidence method was used to investigate the change in the form of the energy-loss distributions of Cf/sup 252/ fission fragments in air, down to fragment energies approx.0.8 MeV. A theoretical model is considered for the estimate of the mean-squared deviations of the fragment energy-loss distributions. (AIP)

  4. Self-organized criticality in fragmenting

    DEFF Research Database (Denmark)

    Oddershede, L.; Dimon, P.; Bohr, J.

    1993-01-01

    The measured mass distributions of fragments from 26 fractured objects of gypsum, soap, stearic paraffin, and potato show evidence of obeying scaling laws; this suggests the possibility of self-organized criticality in fragmenting. The probability of finding a fragment scales inversely to a power...

  5. Low pressure microfluidic-based DNA fragmentation

    NARCIS (Netherlands)

    Shui, Lingling; Sparreboom, Wouter; Bomer, Johan G.; Jin, Mingliang; Carlen, Edwin; van den Berg, Albert

    2011-01-01

    We report a low-pressure microfluidic deoxyribonucleic acid (DNA) fragmentation device based on a combination of me-chanical hydrodynamic shearing and low temperature sample heating. Conventional DNA fragmentation based on hydrody-namic shearing is capable of achieving fragment lengths (FL) < 10k bp

  6. Scaling and four-quark fragmentation

    NARCIS (Netherlands)

    Scholten, O.; Bosveld, G. D.

    1991-01-01

    The conditions for a scaling behaviour from the fragmentation process leading to slow protons are discussed. The scaling referred to implies that the fragmentation functions depend on the light-cone momentum fraction only. It is shown that differences in the fragmentation functions for valence- and

  7. A linear relationship between crystal size and fragment binding time observed crystallographically: implications for fragment library screening using acoustic droplet ejection.

    Directory of Open Access Journals (Sweden)

    Krystal Cole

    Full Text Available High throughput screening technologies such as acoustic droplet ejection (ADE greatly increase the rate at which X-ray diffraction data can be acquired from crystals. One promising high throughput screening application of ADE is to rapidly combine protein crystals with fragment libraries. In this approach, each fragment soaks into a protein crystal either directly on data collection media or on a moving conveyor belt which then delivers the crystals to the X-ray beam. By simultaneously handling multiple crystals combined with fragment specimens, these techniques relax the automounter duty-cycle bottleneck that currently prevents optimal exploitation of third generation synchrotrons. Two factors limit the speed and scope of projects that are suitable for fragment screening using techniques such as ADE. Firstly, in applications where the high throughput screening apparatus is located inside the X-ray station (such as the conveyor belt system described above, the speed of data acquisition is limited by the time required for each fragment to soak into its protein crystal. Secondly, in applications where crystals are combined with fragments directly on data acquisition media (including both of the ADE methods described above, the maximum time that fragments have to soak into crystals is limited by evaporative dehydration of the protein crystals during the fragment soak. Here we demonstrate that both of these problems can be minimized by using small crystals, because the soak time required for a fragment hit to attain high occupancy depends approximately linearly on crystal size.

  8. A linear relationship between crystal size and fragment binding time observed crystallographically: implications for fragment library screening using acoustic droplet ejection.

    Science.gov (United States)

    Cole, Krystal; Roessler, Christian G; Mulé, Elizabeth A; Benson-Xu, Emma J; Mullen, Jeffrey D; Le, Benjamin A; Tieman, Alanna M; Birone, Claire; Brown, Maria; Hernandez, Jesus; Neff, Sherry; Williams, Daniel; Allaire, Marc; Orville, Allen M; Sweet, Robert M; Soares, Alexei S

    2014-01-01

    High throughput screening technologies such as acoustic droplet ejection (ADE) greatly increase the rate at which X-ray diffraction data can be acquired from crystals. One promising high throughput screening application of ADE is to rapidly combine protein crystals with fragment libraries. In this approach, each fragment soaks into a protein crystal either directly on data collection media or on a moving conveyor belt which then delivers the crystals to the X-ray beam. By simultaneously handling multiple crystals combined with fragment specimens, these techniques relax the automounter duty-cycle bottleneck that currently prevents optimal exploitation of third generation synchrotrons. Two factors limit the speed and scope of projects that are suitable for fragment screening using techniques such as ADE. Firstly, in applications where the high throughput screening apparatus is located inside the X-ray station (such as the conveyor belt system described above), the speed of data acquisition is limited by the time required for each fragment to soak into its protein crystal. Secondly, in applications where crystals are combined with fragments directly on data acquisition media (including both of the ADE methods described above), the maximum time that fragments have to soak into crystals is limited by evaporative dehydration of the protein crystals during the fragment soak. Here we demonstrate that both of these problems can be minimized by using small crystals, because the soak time required for a fragment hit to attain high occupancy depends approximately linearly on crystal size.

  9. Imaging Systems for Size Measurements of Debrisat Fragments

    Science.gov (United States)

    Shiotani, B.; Scruggs, T.; Toledo, R.; Fitz-Coy, N.; Liou, J. C.; Sorge, M.; Huynh, T.; Opiela, J.; Krisko, P.; Cowardin, H.

    2017-01-01

    The overall objective of the DebriSat project is to provide data to update existing standard spacecraft breakup models. One of the key sets of parameters used in these models is the physical dimensions of the fragments (i.e., length, average-cross sectional area, and volume). For the DebriSat project, only fragments with at least one dimension greater than 2 mm are collected and processed. Additionally, a significant portion of the fragments recovered from the impact test are needle-like and/or flat plate-like fragments where their heights are almost negligible in comparison to their other dimensions. As a result, two fragment size categories were defined: 2D objects and 3D objects. While measurement systems are commercially available, factors such as measurement rates, system adaptability, size characterization limitations and equipment costs presented significant challenges to the project and a decision was made to develop our own size characterization systems. The size characterization systems consist of two automated image systems, one referred to as the 3D imaging system and the other as the 2D imaging system. Which imaging system to use depends on the classification of the fragment being measured. Both imaging systems utilize point-and-shoot cameras for object image acquisition and create representative point clouds of the fragments. The 3D imaging system utilizes a space-carving algorithm to generate a 3D point cloud, while the 2D imaging system utilizes an edge detection algorithm to generate a 2D point cloud. From the point clouds, the three largest orthogonal dimensions are determined using a convex hull algorithm. For 3D objects, in addition to the three largest orthogonal dimensions, the volume is computed via an alpha-shape algorithm applied to the point clouds. The average cross-sectional area is also computed for 3D objects. Both imaging systems have automated size measurements (image acquisition and image processing) driven by the need to quickly

  10. Mechanical heterogeneity favors fragmentation of strained actin filaments.

    Science.gov (United States)

    De La Cruz, Enrique M; Martiel, Jean-Louis; Blanchoin, Laurent

    2015-05-05

    We present a general model of actin filament deformation and fragmentation in response to compressive forces. The elastic free energy density along filaments is determined by their shape and mechanical properties, which were modeled in terms of bending, twisting, and twist-bend coupling elasticities. The elastic energy stored in filament deformation (i.e., strain) tilts the fragmentation-annealing reaction free-energy profile to favor fragmentation. The energy gradient introduces a local shear force that accelerates filament intersubunit bond rupture. The severing protein, cofilin, renders filaments more compliant in bending and twisting. As a result, filaments that are partially decorated with cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric shape deformations and energy profiles distinct from mechanically homogenous (i.e., uniform), bare actin, or saturated cofilactin filaments. The local buckling strain depends on the relative size of the compliant segment as well as the bending and twisting rigidities of flanking regions. Filaments with a single bare/cofilin-decorated boundary localize energy and force adjacent to the boundary, within the compliant cofilactin segment. Filaments with small cofilin clusters were predicted to fragment within the compliant cofilactin rather than at boundaries. Neglecting contributions from twist-bend coupling elasticity underestimates the energy density and gradients along filaments, and thus the net effects of filament strain to fragmentation. Spatial confinement causes compliant cofilactin segments and filaments to adopt higher deformation modes and store more elastic energy, thereby promoting fragmentation. The theory and simulations presented here establish a quantitative relationship between actin filament fragmentation thermodynamics and elasticity, and reveal how local discontinuities in filament mechanical properties introduced by regulatory proteins can modulate both the severing efficiency

  11. Isoscaling of projectile-like fragments

    Institute of Scientific and Technical Information of China (English)

    Zhong Chen; Chen Jin-Hui; Guo Wei; Ma Chun-Wang; Ma Guo-Liang; Su Qian-Min; Yan Ting-Zhi; Zuo Jia-Xu; Ma Yu-Gang; Fang De-Qing; Cai Xiang-Zhou; Chen Jin-Gen; Shen Wen-Qing; Tian Wen-Dong; Wang Kun; Wei Yi-Bin

    2006-01-01

    In this paper, the isotopic and isotonic distributions of projectile fragmentation products have been simulated by a modified statistical abrasion-ablation model and the isoscaling behaviour of projectile-like fragments has been discussed. The isoscaling parameters α andβ have been extracted respectively, for hot fragments before evaporation and cold fragments after evaporation. It looks that the evaporation has stronger effect on α than β. For cold fragments,a monotonic increase of α and |β| with the increase of Z and N is observed. The relation between isoscaling parameter and the change of isospin content is discussed.

  12. [Sperm DNA fragmentation: association with semen parameters in young men].

    Science.gov (United States)

    Osadchuk, L V; Tataru, D A; Kuznetsova, N N; Kleshev, M A; Markova, E V; Svetlakov, A V

    2016-12-01

    Abnormal sperm DNA integrity is an important risk factor for male infertility. The aim of this work was to examine sperm DNA fragmentation in a cohort of young male volunteers (n=111; age 21.0+/-0.2 years) from the general population and establish the association between the level of sperm DNA fragmentation and sperm functional parameters. Sperm DNA fragmentation index (DFI) was determined by SCSA (sperm chromatin structure assay) using flow cytometry. Standard semen parameters (concentration, motility, and morphology) were evaluated according to the WHO guidelines (2010). and conclusions. In the study cohort, 79.0%, 12.4% and 8.6% of men had normal (DFIfragmentation, respectively. Men with impaired spermatogenesis had greater IDF values (14.53+/-1.43%) than men with normal semen parameters (8.88+/-0.77%, pfragmentation using SCSA technique can be employed in epidemiological studies of male fertility.

  13. Analysis of Transmissions Scheduling with Packet Fragmentation

    Directory of Open Access Journals (Sweden)

    Nir Menakerman

    2001-12-01

    Full Text Available We investigate a scheduling problem in which packets, or datagrams, may be fragmented. While there are a few applications to scheduling with datagram fragmentation, our model of the problem is derived from a scheduling problem present in data over CATV networks. In the scheduling problem datagrams of variable lengths must be assigned (packed into fixed length time slots. One of the capabilities of the system is the ability to break a datagram into several fragments. When a datagram is fragmented, extra bits are added to the original datagram to enable the reassembly of all the fragments. We convert the scheduling problem into the problem of bin packing with item fragmentation, which we define in the following way: we are asked to pack a list of items into a minimum number of unit capacity bins. Each item may be fragmented in which case overhead units are added to the size of every fragment. The cost associated with fragmentation renders the problem NP-hard, therefore an approximation algorithm is needed. We define a version of the well-known Next-Fit algorithm, capable of fragmenting items, and investigate its performance. We present both worst case and average case results and compare them to the case where fragmentation is not allowed.

  14. Impact of numerical models on fragmentation processes

    Science.gov (United States)

    Renouf, Mathieu; Gezahengn, Belien; Abbas, Micheline; Bourgeois, Florent

    2013-06-01

    Simulated fragmentation process in granular assemblies is a challenging problem which date back the beginning of the 90'. If first approaches have focus on the fragmentation on a single particle, with the development of robust, fast numerical method is is possible today to simulated such process in a large collection of particles. But the question of the fragmentation problem is still open: should the fragmentation be done dynamically (one particle becoming two fragments) and according which criterion or should the fragment paths be defined initially and which is the impact of the discretization and the model of fragments? The present contribution proposes to investigate the second aspect i.e. the impact of fragment modeling on the fragmentation processes. First to perform such an analysis, the geometry of fragments (disks/sphere or polygon/polyhedra), their behavior (rigid/deformable) and the law governing their interactions are investigated. Then such model will be used in a grinding application where the evolution of fragments and impact on the behavior of the whole packing are investigate.

  15. The formation of planets by disc fragmentation

    Directory of Open Access Journals (Sweden)

    Stamatellos Dimitris

    2013-04-01

    Full Text Available I discuss the role that disc fragmentation plays in the formation of gas giant and terrestrial planets, and how this relates to the formation of brown dwarfs and low-mass stars, and ultimately to the process of star formation. Protostellar discs may fragment, if they are massive enough and can cool fast enough, but most of the objects that form by fragmentation are brown dwarfs. It may be possible that planets also form, if the mass growth of a proto-fragment is stopped (e.g. if this fragment is ejected from the disc, or suppressed and even reversed (e.g by tidal stripping. I will discuss if it is possible to distinguish whether a planet has formed by disc fragmentation or core accretion, and mention of a few examples of observed exoplanets that are suggestive of formation by disc fragmentation.

  16. Reframing landscape fragmentation's effects on ecosystem services.

    Science.gov (United States)

    Mitchell, Matthew G E; Suarez-Castro, Andrés F; Martinez-Harms, Maria; Maron, Martine; McAlpine, Clive; Gaston, Kevin J; Johansen, Kasper; Rhodes, Jonathan R

    2015-04-01

    Landscape structure and fragmentation have important effects on ecosystem services, with a common assumption being that fragmentation reduces service provision. This is based on fragmentation's expected effects on ecosystem service supply, but ignores how fragmentation influences the flow of services to people. Here we develop a new conceptual framework that explicitly considers the links between landscape fragmentation, the supply of services, and the flow of services to people. We argue that fragmentation's effects on ecosystem service flow can be positive or negative, and use our framework to construct testable hypotheses about the effects of fragmentation on final ecosystem service provision. Empirical efforts to apply and test this framework are critical to improving landscape management for multiple ecosystem services.

  17. Extraction of 16th Century Calender Fragments

    DEFF Research Database (Denmark)

    Holck, Jakob Povl; Etheridge, Christian

    at the Cultural Heritage & Archaeometric Research Team, SDU. Upon finding medieval manuscript fragments in the university library’s special collections, scholars at the Centre for Medieval Literature are consulted. In most cases, digital pictures of the finds will circulate in the international community...... of medieval scholars. Thousands of 16th and 17th Century books are stored in the University Library of Southern Denmark. One out of five of these books is expected to contain medieval manuscript fragments or fragments of rare prints, e.g. incunabula....... fragments may require extensive use of Big Data and other forms of analysis in order to be identified. Usually, the university library prefers not to remove the fragments from their “fragment carriers”. In order to read fragments that are only partially visible or invisible, x-ray technology may be deployed...

  18. Di-hadron fragmentation and mapping of the nucleon structure

    CERN Document Server

    Pisano, Silvia

    2015-01-01

    The fragmentation of a colored parton directly into a pair of colorless hadrons is a non-perturbative mechanism that offers important insights into the nucleon structure. Di-hadron fragmentation functions can be extracted from semi-inclusive electron-positron annihilation data. They also appear in observables describing the semi-inclusive production of two hadrons in deep-inelastic scattering of leptons off nucleons or in hadron-hadron collisions. When a target nucleon is transversely polarized, a specific chiral-odd di-hadron fragmentation function can be used as the analyzer of the net density of transversely polarized quarks in a transversely polarized nucleon, the so-called transversity distribution. The latter can be extracted through suitable single-spin asymmetries in the framework of collinear factorization, thus in a much simpler framework with respect to the traditional one in single-hadron fragmentation. At subleading twist, the same chiral-odd di-hadron fragmentation function provides the cleanest...

  19. Sperm DNA fragmentation affects epigenetic feature in human male pronucleus.

    Science.gov (United States)

    Rajabi, H; Mohseni-Kouchesfehani, H; Eslami-Arshaghi, T; Salehi, M

    2017-03-06

    To evaluate whether the sperm DNA fragmentation affects male pronucleus epigenetic factors, semen analysis was performed and DNA fragmentation was assessed by the method of sperm chromatin structure assay (SCSA). Human-mouse interspecies fertilisation was used to create human male pronucleus. Male pronucleus DNA methylation and H4K12 acetylation were evaluated by immunostaining. Results showed a significant positive correlation between the level of sperm DNA fragmentation and DNA methylation in male pronuclei. In other words, an increase in DNA damage caused an upsurge in DNA methylation. In the case of H4K12 acetylation, no correlation was detected between DNA damage and the level of histone acetylation in the normal group, but results for the group in which male pronuclei were derived from sperm cells with DNA fragmentation, increased DNA damage led to a decreased acetylation level. Sperm DNA fragmentation interferes with the active demethylation process and disrupts the insertion of histones into the male chromatin in the male pronucleus, following fertilisation. © 2017 Blackwell Verlag GmbH.

  20. The effects of amino acid composition of glutamine-rich domains on amyloid formation and fragmentation.

    Directory of Open Access Journals (Sweden)

    Alexander I Alexandrov

    Full Text Available Fragmentation of amyloid polymers by the chaperone Hsp104 allows them to propagate as prions in yeast. The factors which determine the frequency of fragmentation are unclear, though it is often presumed to depend on the physical strength of prion polymers. Proteins with long polyglutamine stretches represent a tractable model for revealing sequence elements required for polymer fragmentation in yeast, since they form poorly fragmented amyloids. Here we show that interspersion of polyglutamine stretches with various amino acid residues differentially affects the in vivo formation and fragmentation of the respective amyloids. Aromatic residues tyrosine, tryptophan and phenylalanine strongly stimulated polymer fragmentation, leading to the appearance of oligomers as small as dimers. Alanine, methionine, cysteine, serine, threonine and histidine also enhanced fragmentation, while charged residues, proline, glycine and leucine inhibited polymerization. Our data indicate that fragmentation frequency primarily depends on the recognition of fragmentation-promoting residues by Hsp104 and/or its co-chaperones, rather than on the physical stability of polymers. This suggests that differential exposure of such residues to chaperones defines prion variant-specific differences in polymer fragmentation efficiency.

  1. Disentangling fragmentation effects on herbivory in understory plants of longleaf pine savanna.

    Science.gov (United States)

    Levey, Douglas J; Caughlin, T Trevor; Brudvig, Lars A; Haddad, Nick M; Damschen, Ellen I; Tewksbury, Joshua J; Evans, Daniel M

    2016-09-01

    Habitat fragmentation affects species and their interactions through intertwined mechanisms that include changes to fragment area, shape, connectivity and distance to edge. Disentangling these pathways is a fundamental challenge of landscape ecology and will help identify ecological processes important for management of rare species or restoration of fragmented habitats. In a landscape experiment that manipulated connectivity, fragment shape, and distance to edge while holding fragment area constant, we examined how fragmentation impacts herbivory and growth of nine plant species in longleaf pine savanna. Probability of herbivory in open habitat was strongly dependent on proximity to forest edge for every species, increasing with distance to edge in six species (primarily grasses and annual forbs) and decreasing in three species (perennial forbs and a shrub). In the two species of perennial forbs, these edge effects were dependent on fragment shape; herbivory strongly decreased with distance to edge in fragments of two shapes, but not in a third shape. For most species, however, probability of herbivory was unrelated to connectivity or fragment shape. Growth was generally determined more strongly by leaf herbivory than by distance to edge, fragment shape, or connectivity. Taken together, these results demonstrate consistently strong edge effects on herbivory, one of the most important biotic factors determining plant growth and demography. Our results contrast with the generally inconsistent results of observational studies, likely because our experimental approach enabled us to tease apart landscape processes that are typically confounded.

  2. Single chain Fab (scFab fragment

    Directory of Open Access Journals (Sweden)

    Brenneis Mariam

    2007-03-01

    Full Text Available Abstract Background The connection of the variable part of the heavy chain (VH and and the variable part of the light chain (VL by a peptide linker to form a consecutive polypeptide chain (single chain antibody, scFv was a breakthrough for the functional production of antibody fragments in Escherichia coli. Being double the size of fragment variable (Fv fragments and requiring assembly of two independent polypeptide chains, functional Fab fragments are usually produced with significantly lower yields in E. coli. An antibody design combining stability and assay compatibility of the fragment antigen binding (Fab with high level bacterial expression of single chain Fv fragments would be desirable. The desired antibody fragment should be both suitable for expression as soluble antibody in E. coli and antibody phage display. Results Here, we demonstrate that the introduction of a polypeptide linker between the fragment difficult (Fd and the light chain (LC, resulting in the formation of a single chain Fab fragment (scFab, can lead to improved production of functional molecules. We tested the impact of various linker designs and modifications of the constant regions on both phage display efficiency and the yield of soluble antibody fragments. A scFab variant without cysteins (scFabΔC connecting the constant part 1 of the heavy chain (CH1 and the constant part of the light chain (CL were best suited for phage display and production of soluble antibody fragments. Beside the expression system E. coli, the new antibody format was also expressed in Pichia pastoris. Monovalent and divalent fragments (DiFabodies as well as multimers were characterised. Conclusion A new antibody design offers the generation of bivalent Fab derivates for antibody phage display and production of soluble antibody fragments. This antibody format is of particular value for high throughput proteome binder generation projects, due to the avidity effect and the possible use of

  3. Fluid fragmentation from hospital toilets

    CERN Document Server

    Traverso, G; Lu, C -C; Maa, R; Langer, R; Bourouiba, L

    2013-01-01

    Hospital-acquired infections represent significant health and financial burdens to society. Clostridium difficile (C. difficile) is a particularly challenging bacteria with the potential to cause severe diarrhea and death. One mode of transmission for C. difficile, as well as other pathogens, which has received little attention is the potential air contamination by pathogen-bearing droplets emanating from toilets. In the fluid dynamics video submitted to the APS DFD Gallery of Fluid Motion 2013, we present flow visualizations via high-speed recordings showing the capture of the product of the fluid fragmentation generated by hospital toilet high-pressure flushes. Important quantities of both large and small droplets are observed. We illustrate how high-pressure flushes and cleaning products currently used in hospital toilets result in aggravating, rather than alleviating, the suspension and recirculation of tenacious airborne pathogen-bearing droplets.

  4. Fragmentation in Carbon Therapy Beams

    CERN Document Server

    Charara, Y M

    2010-01-01

    The state of the art Monte Carlo code HETC-HEDS was used to simulate spallation products, secondary neutron, and secondary proton production in A-150 Tissue Equivalent Plastic phantoms to investigate fragmentation of carbon therapy beams. For a 356 MeV/Nucleon carbon ion beam, production of charged particles heavier than protons was 0.24 spallation products per incident carbon ion with atomic numbers ranging from 1 through 5 (hydrogen to boron). In addition, there were 4.73 neutrons and 2.95 protons produced per incident carbon ion. Furthermore, as the incident energy increases, the neutron production rate increases at a rate of 20% per 10 MeV/nucleon. Secondary protons were created at a rate between 2.62-2.87 per carbon ion, while spallation products were created at a rate between 0.20-0.24 per carbon ion.

  5. Nonlinear Inflaton Fragmentation after Preheating

    CERN Document Server

    Felder, G N; Felder, Gary N.; Kofman, Lev

    2007-01-01

    We consider the nonlinear dynamics of inflaton fragmentation during and after preheating in the simplest model of chaotic inflation. While the earlier regime of parametric resonant particle production and the later turbulent regime of interacting fields evolving towards equilibrium are well identified and understood, the short intermediate stage of violent nonlinear dynamics remains less explored. Lattice simulations of fully nonlinear preheating dynamics show specific features of this intermediate stage: occupation numbers of the scalar particles are peaked, scalar fields become significantly non-gaussian and the field dynamics become chaotic and irreversible. Visualization of the field dynamics in configuration space reveals that nonlinear interactions generate non-gaussian inflaton inhomogeneities with very fast growing amplitudes. The peaks of the inflaton inhomogeneities coincide with the peaks of the scalar field(s) produced by parametric resonance. When the inflaton peaks reach their maxima, they stop ...

  6. High yield DNA fragmentation using cyclical hydrodynamic shearing

    NARCIS (Netherlands)

    Shui, Lingling; Sparreboom, Wouter; Spang, Peter; Roeser, Tina; Nieto, Benjamin; Guasch, Francesc; Corbera, Antoni Homs; van den Berg, Albert; Carlen, Edwin

    2013-01-01

    We report a new DNA fragmentation technique that significantly simplifies conventional hydrodynamic shearing fragmentation by eliminating the need for sample recirculation while maintaining high fragmentation yield and low fragment length variation, and therefore, reduces instrument complexity and c

  7. High yield DNA fragmentation using cyclical hydrodynamic shearing

    NARCIS (Netherlands)

    Shui, Lingling; Sparreboom, Wouter; Spang, Peter; Roeser, Tina; Nieto, Benjamin; Guasch, Francesc; Corbera, Antoni Homs; van den Berg, Albert; Carlen, Edwin

    2013-01-01

    We report a new DNA fragmentation technique that significantly simplifies conventional hydrodynamic shearing fragmentation by eliminating the need for sample recirculation while maintaining high fragmentation yield and low fragment length variation, and therefore, reduces instrument complexity and

  8. Generalized fragmentation functions for fractal jet observables

    Science.gov (United States)

    Elder, Benjamin T.; Procura, Massimiliano; Thaler, Jesse; Waalewijn, Wouter J.; Zhou, Kevin

    2017-06-01

    We introduce a broad class of fractal jet observables that recursively probe the collective properties of hadrons produced in jet fragmentation. To describe these collinear-unsafe observables, we generalize the formalism of fragmentation functions, which are important objects in QCD for calculating cross sections involving identified final-state hadrons. Fragmentation functions are fundamentally nonperturbative, but have a calculable renormalization group evolution. Unlike ordinary fragmentation functions, generalized fragmentation functions exhibit nonlinear evolution, since fractal observables involve correlated subsets of hadrons within a jet. Some special cases of generalized fragmentation functions are reviewed, including jet charge and track functions. We then consider fractal jet observables that are based on hierarchical clustering trees, where the nonlinear evolution equations also exhibit tree-like structure at leading order. We develop a numeric code for performing this evolution and study its phenomenological implications. As an application, we present examples of fractal jet observables that are useful in discriminating quark jets from gluon jets.

  9. 诱导细胞死亡的DFF45样效应因子-B在宫颈癌组织中的表达及意义%Expression and Significance of Cell-death-inducing DNA- fragmentation-factor-like Effector-B in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    温冬雪; 鲁艳明; 李海霞; 张淑兰

    2009-01-01

    目的 检测诱导细胞死亡的DFF45样效应因子-B(the cell-death-inducing DNA-fragmentation-factor-like effector-B,CIDE-B)在人宫颈癌组织中的表达,探讨其与宫颈癌发生发展的关系.方法 采用免疫组化技术检测45例宫颈癌、33例癌前病变和10例正常宫颈组织中CIDE-B的表达.结果 CIDE-B蛋白在宫颈癌组织中的表达高于癌前病变及正常宫颈组织(P0.05).结论 CIDE-B蛋白高表达可能与宫颈癌的发生发展有关.

  10. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

    DEFF Research Database (Denmark)

    Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

    2004-01-01

    in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

  11. Shape Distribution of Fragments from Microsatellite Impact Tests

    Science.gov (United States)

    Liou, J.C.; Hanada, T.

    2009-01-01

    Fragment shape is an important factor for conducting reliable orbital debris damage assessments for critical space assets, such as the International Space Station. To date, seven microsatellite impact tests have been completed as part of an ongoing collaboration between Kyushu University and the NASA Orbital Debris Program Office. The target satellites ranged in size from 15 cm 15 cm 15 cm to 20 cm 20 cm 20 cm. Each target satellite was equipped with fully functional electronics, including circuits, battery, and transmitter. Solar panels and multi-layer insulation (MLI) were added to the target satellites of the last two tests. The impact tests were carried out with projectiles of different sizes and impact speeds. All fragments down to about 2 mm in size were collected and analyzed based on their three orthogonal dimensions, x, y, and z, where x is the longest dimension, y is the longest dimension in the plane perpendicular to x, and z is the longest dimension perpendicular to both x and y. Each fragment was also photographed and classified by shape and material composition. This data set serves as the basis of our effort to develop a fragment shape distribution. Two distinct groups can be observed in the x/y versus y/z distribution of the fragments. Objects in the first group typically have large x/y values. Many of them are needle-like objects originating from the fragmentation of carbon fiber reinforced plastic materials used to construct the satellites. Objects in the second group tend to have small x/y values, and many of them are box-like or plate-like objects, depending on their y/z values. Each group forms the corresponding peak in the x/y distribution. However, only one peak can be observed in the y/z distribution. These distributions and how they vary with size, material type, and impact parameters will be described in detail within the paper.

  12. A mechanism of gene amplification driven by small DNA fragments.

    Directory of Open Access Journals (Sweden)

    Kuntal Mukherjee

    Full Text Available DNA amplification is a molecular process that increases the copy number of a chromosomal tract and often causes elevated expression of the amplified gene(s. Although gene amplification is frequently observed in cancer and other degenerative disorders, the molecular mechanisms involved in the process of DNA copy number increase remain largely unknown. We hypothesized that small DNA fragments could be the trigger of DNA amplification events. Following our findings that small fragments of DNA in the form of DNA oligonucleotides can be highly recombinogenic, we have developed a system in the yeast Saccharomyces cerevisiae to capture events of chromosomal DNA amplification initiated by small DNA fragments. Here we demonstrate that small DNAs can amplify a chromosomal region, generating either tandem duplications or acentric extrachromosomal DNA circles. Small fragment-driven DNA amplification (SFDA occurs with a frequency that increases with the length of homology between the small DNAs and the target chromosomal regions. SFDA events are triggered even by small single-stranded molecules with as little as 20-nt homology with the genomic target. A double-strand break (DSB external to the chromosomal amplicon region stimulates the amplification event up to a factor of 20 and favors formation of extrachromosomal circles. SFDA is dependent on Rad52 and Rad59, partially dependent on Rad1, Rad10, and Pol32, and independent of Rad51, suggesting a single-strand annealing mechanism. Our results reveal a novel molecular model for gene amplification, in which small DNA fragments drive DNA amplification and define the boundaries of the amplicon region. As DNA fragments are frequently found both inside cells and in the extracellular environment, such as the serum of patients with cancer or other degenerative disorders, we propose that SFDA may be a common mechanism for DNA amplification in cancer cells, as well as a more general cause of DNA copy number variation

  13. Levels of FSH, LH and testosterone, and sperm DNA fragmentation.

    Science.gov (United States)

    Wdowiak, Artur; Raczkiewicz, Dorota; Stasiak, Magdalena; Bojar, Iwona

    2014-01-01

    Having an offspring is the most important human biological goal, which is necessary for survival of the human species. Lack of offspring is a phenomenon concerning approximately 15% of married couples in Poland. In a half of the cases, a causative agent is the male factor infertility problem. There is evidence that certain male fertility problems are related with disorders of the process of spermatogenesis. The course of normal spermatogenesis depends on proper pituitary secretion of folliculostimulin (FSH), luteinizing hormone (LH), as well as testicular secretion of testosterone. It is considered that in approximately 20% of patients with idiopathic infertility an elevated level of sperm DNA fragmentation may be the cause of failure in reproduction. The objective of the present study was determination of the relationship between FSH, LH and testosterone levels, and the occurrence of sperm DNA fragmentation. The present study was conducted in the year 2012 in the Non-Public Health Care Unit 'Ovum Reproduction and Andrology' in Lublin, and covered 186 men treated for infertility. For inclusion into the study group we qualified males aged 25-35, who have been treated for infertility for more than 1 year, with no pathological features observed in the female partner. The structure of sperm chromatin was evaluated using the technique of flow cytometry-Sperm Chromatin Structure assay (SCSA). The result of the examination was a sperm DNA Fragmentation Index (DFI), i.e., the percentage of sperm with DNA lesions (DNA fragmentation). A morning blood sample (5 mL volume) was obtained and sent to an authorized laboratory to assess serum levels of testosterone, LH and FSH. An intensified sperm DNA fragmentation co-occurred with both extremely low and extremely high levels of FSH and LH. Sperm DNA fragmentation was negatively correlated with testosterone level.

  14. Genetic population structure of the wind-pollinated, dioecious shrub Juniperus communis in fragmented Dutch heathlands

    NARCIS (Netherlands)

    Oostermeijer, J.G.B.; de Knegt, B

    2004-01-01

    The wind-pollinated, dioecious shrub Juniperus communis L. is declining in Dutch heathlands, mainly because recruitment is scarce. Aside from ecological factors, inbreeding associated with reduced population size and isolation in the currently fragmented landscape might explain this decline.

  15. Fragmentation processes during explosion welding (review)

    Science.gov (United States)

    Grinberg, B. A.; Ivanov, M. A.; Rybin, V. V.; Elkina, O. A.; Patselov, A. M.; Antonova, O. V.; Inozemtsev, A. V.; Tolmachev, T. P.

    2013-10-01

    The fragmentation during explosion welding is briefly reviewed. Fragmentation of partitioning type (FPT), which consists in partitioning into particles that either fly away or join each other, is detected. FPT is an analog of the fragmentation during an explosion that was studied by Mott. In both cases, the flight of particles (fragments) takes place, and the integrity of the material is retained in FPT. FPT is a powerful channel for the dissipation of supplied energy, since the surface of flying particles has a large total area.

  16. Molecular energies from an incremental fragmentation method

    Science.gov (United States)

    Meitei, Oinam Romesh; Heßelmann, Andreas

    2016-02-01

    The systematic molecular fragmentation method by Collins and Deev [J. Chem. Phys. 125, 104104 (2006)] has been used to calculate total energies and relative conformational energies for a number of small and extended molecular systems. In contrast to the original approach by Collins, we have tested the accuracy of the fragmentation method by utilising an incremental scheme in which the energies at the lowest level of the fragmentation are calculated on an accurate quantum chemistry level while lower-cost methods are used to correct the low-level energies through a high-level fragmentation. In this work, the fragment energies at the lowest level of fragmentation were calculated using the random-phase approximation (RPA) and two recently developed extensions to the RPA while the incremental corrections at higher levels of the fragmentation were calculated using standard density functional theory (DFT) methods. The complete incremental fragmentation method has been shown to reproduce the supermolecule results with a very good accuracy, almost independent on the molecular type, size, or type of decomposition. The fragmentation method has also been used in conjunction with the DFT-SAPT (symmetry-adapted perturbation theory) method which enables a breakdown of the total nonbonding energy contributions into individual interaction energy terms. Finally, the potential problems of the method connected with the use of capping hydrogen atoms are analysed and two possible solutions are supplied.

  17. A Note on Convex Renorming and Fragmentability

    Indian Academy of Sciences (India)

    A K Mirmostafaee

    2005-05-01

    Using the game approach to fragmentability, we give new and simpler proofs of the following known results: (a) If the Banach space admits an equivalent Kadec norm, then its weak topology is fragmented by a metric which is stronger than the norm topology. (b) If the Banach space admits an equivalent rotund norm, then its weak topology is fragmented by a metric. (c) If the Banach space is weakly locally uniformly rotund, then its weak topology is fragmented by a metric which is stronger than the norm topology.

  18. Reduced Genetic Diversity and Increased Dispersal in Guigna (Leopardus guigna) in Chilean Fragmented Landscapes.

    Science.gov (United States)

    Napolitano, Constanza; Díaz, Diego; Sanderson, Jim; Johnson, Warren E; Ritland, Kermit; Ritland, Carol E; Poulin, Elie

    2015-01-01

    Landscape fragmentation is often a major cause of species extinction as it can affect a wide variety of ecological processes. The impact of fragmentation varies among species depending on many factors, including their life-history traits and dispersal abilities. Felids are one of the groups most threatened by fragmented landscapes because of their large home ranges, territorial behavior, and low population densities. Here, we model the impacts of habitat fragmentation on patterns of genetic diversity in the guigna (Leopardus guigna), a small felid that is closely associated with the heavily human-impacted temperate rainforests of southern South America. We assessed genetic variation in 1798 base pairs of mitochondrial DNA sequences, 15 microsatellite loci, and 2 sex chromosome genes and estimated genetic diversity, kinship, inbreeding, and dispersal in 38 individuals from landscapes with differing degrees of fragmentation on Chiloé Island in southern Chile. Increased fragmentation was associated with reduced genetic diversity, but not with increased kinship or inbreeding. However, in fragmented landscapes, there was a weaker negative correlation between pairwise kinship and geographic distance, suggesting increased dispersal distances. These results highlight the importance of biological corridors to maximize connectivity in fragmented landscapes and contribute to our understanding of the broader genetic consequences of habitat fragmentation, especially for forest-specialist carnivores.

  19. The relative influence of habitat loss and fragmentation: do tropical mammals meet the temperate paradigm?

    Science.gov (United States)

    Thornton, Daniel H; Branch, Lyn C; Sunquist, Melvin E

    2011-09-01

    The relative influence of habitat loss vs. habitat fragmentation per se (the breaking apart of habitat) on species distribution and abundance is a topic of debate. Although some theoretical studies predict a strong negative effect of fragmentation, consensus from empirical studies is that habitat fragmentation has weak effects compared with habitat loss and that these effects are as likely to be positive as negative. However, few empirical investigations of this issue have been conducted on tropical or wide-ranging species that may be strongly influenced by changes in patch size and edge that occur with increasing fragmentation. We tested the relative influence of habitat loss and fragmentation by examining occupancy of forest patches by 20 mid- and large-sized Neotropical mammal species in a fragmented landscape of northern Guatemala. We related patch occupancy of mammals to measures of habitat loss and fragmentation and compared the influence of these two factors while controlling for patch-level variables. Species responded strongly to both fragmentation and loss, and response to fragmentation generally was negative. Our findings support previous assumptions that conservation of large mammals in the tropics will require conservation strategies that go beyond prevention of habitat loss to also consider forest cohesion or other aspects of landscape configuration.

  20. Strategic rat control for restoring populations of native species in forest fragments.

    Science.gov (United States)

    Armstrong, Doug P; Gorman, Nic; Pike, Rhonda; Kreigenhofer, Brigitte; McArthur, Nikki; Govella, Susanne; Barrett, Paul; Richard, Yvan

    2014-06-01

    Forest fragments have biodiversity value that may be enhanced through management such as control of non-native predators. However, such efforts may be ineffective, and research is needed to ensure that predator control is done strategically. We used Bayesian hierarchical modeling to estimate fragment-specific effects of experimental rat control on a native species targeted for recovery in a New Zealand pastoral landscape. The experiment was a modified BACI (before-after-control-impact) design conducted over 6 years in 19 forest fragments with low-density subpopulations of North Island Robins (Petroica longipes). The aim was to identify individual fragments that not only showed clear benefits of rat control, but also would have a high probability of subpopulation growth even if they were the only fragment managed. We collected data on fecundity, adult and juvenile survival, and juvenile emigration, and modeled the data in an integrated framework to estimate the expected annual growth rate (λ) of each subpopulation with and without rat control. Without emigration, subpopulation growth was estimated as marginal (λ = 0.95-1.05) or negative (λ = 0.74-0.90) without rat control, but it was estimated as positive in all fragments (λ = 1.4-2.1) if rats were controlled. This reflected a 150% average increase in fecundity and 45% average increase in adult female survival. The probability of a juvenile remaining in its natal fragment was 0.37 on average, but varied with fragment connectivity. With juvenile emigration added, 6 fragments were estimated to have a high (>0.8) probability of being self-sustaining (λ > 1) with rat control. The key factors affecting subpopulation growth rates under rat control were low connectivity and stock fencing because these factors were associated with lower juvenile emigration and higher fecundity, respectively. However, there was also substantial random variation in adult survival among fragments, illustrating the importance of

  1. Is magnetic resonance imaging safe for patients with retained metal fragments from combat and terrorist attacks?

    Energy Technology Data Exchange (ETDEWEB)

    Eshed, Iris; Kushnir, Tamar; Shabshin, Noga; Konen, Eli (Dept. of Diagnostic Imaging, Sheba Medical center, Tel Hashomer, Sackler School of Medicine, Tel Aviv Univ., Tel Aviv (Israel)), e-mail: iris.eshed@sheba.health.gov.il

    2010-03-15

    Background: Increasing numbers of military confrontations and terrorist attacks have led to increasing reports of retained metal fragments among patients referred for magnetic resonance imaging (MRI). The potential hazard of retained metal fragments for patients undergoing MRI has been studied among patients with retained metal fragments from domestic violence but not from combat and terrorist attacks. Purpose: To retrospectively evaluate the safety of MRI in patients with subcutaneous warfare-metal fragments. Material and Methods: 10,322 consecutive metal screening forms of patients scheduled for 1.5 Tesla (T) MR examination were retrospectively reviewed. All patients reported to have retained metal fragments were contacted by telephone and asked to describe the event in which they were exposed to the fragments and for any adverse sequelae or sensations during and after MRI. Their radiographs were evaluated for the number and size of the fragments. The data were analyzed for correlations between these factors. Results: Seven of the 24 patients who reported retained metal fragments were excluded, since there was no validating evidence of their presence. Fragments in the remaining 17 patients (18 MRI examinations) were inflicted by military or terrorist attacks that occurred 2-39 years prior to the MRI. The fragment size ranged between 1 and 10 mm. One patient reported a superficial migration of a 10-mm fragment after MRI. No other adverse reactions were reported. Conclusion: Conducting 1.5T MRI examinations is safe in patients with retained metal fragments from combat and terrorist attacks not in the vicinity of vital organs. However, caution is advised.

  2. Governmental Fragmentation in Metropolitan Detroit

    Directory of Open Access Journals (Sweden)

    Davis, Kristal D.

    2012-01-01

    Full Text Available At its population peak in the 1950’s, Detroit, Michigan was inhabited by almost two million residents and served as the car capital of the country. Today, however, the population has dropped by more than fifty percent. With the loss of Detroit residents to surrounding cities and counties, the wedge between Detroit and the suburbs has grown wider. Detroit, once considered the crown jewel of the state of Michigan, is now treated as an immovable stain by its surrounding municipalities. What this means for the metro Detroit area is a high level of governmental fragmentation, preventing economic opportunities for both the city and its suburbs. This is especially unfortunate for the economy of the metro Detroit area because of the current economic crisis in the state of Michigan. With the state’s long tradition of home rule and pride in autonomous, municipal decision-making, municipalities in the metro Detroit area might better realize economic opportunities and the relief they can bring to their own local economies by not only collaborating with the city of Detroit, but with neighboring cities as well.

  3. On the fragmentation of biomolecules: fragmentation of alanine dipeptide along the polypeptide chain

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Yakubovich, Alexander; Solov'yov, Andrey

    2006-01-01

    . The fragmentation of dipeptide along the polypeptide chain, as well as the interaction between alanines, has been considered. The energy of the system has been analyzed as a function of the distance between fragments for all possible dipeptide fragmentation channels. Analysis of the energy barriers makes...... it possible to estimate the characteristic fragmentation times and to determine the degree of applicability of classical electrodynamics for describing the system energy....

  4. Modelling distribution functions and fragmentation functions

    CERN Document Server

    Rodrigues, J; Mulders, P J

    1995-01-01

    We present examples for the calculation of the distribution and fragmentation functions using the representation in terms of non-local matrix elements of quark field operators. As specific examples, we use a simple spectator model to estimate the leading twist quark distribution functions and the fragmentation functions for a quark into a nucleon or a pion.

  5. The Family Circle: A Study in Fragmentation

    Science.gov (United States)

    Bronfenbrenner, Urie

    1976-01-01

    Presents data describing the fragmentation of the family, suggests causes for the fragmentation, and offers suggestions for reversing the trend. The suggestions focus on day care, part-time employment practices, enhancing the position of women, and work and responsibility. (IRT)

  6. The Stellar IMF from turbulent fragmentation

    Science.gov (United States)

    Padoan, P.; Nordlund, A.

    2001-01-01

    In this paper they conclude that turbulent fragmentation is unavoidable in super-sonically turbulent molecular clouds, and given the success of the present model to predict the observed shape of the Stellar IMF, they conclude that turbulent fragmentation is essential to the origin of the stellar IMF.

  7. Baculovirus display of functional antibody Fab fragments.

    Science.gov (United States)

    Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

    2015-08-01

    The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

  8. Pollen and gene flow in fragmented habitats

    NARCIS (Netherlands)

    Kwak, Manja M.; Velterop, Odilia; van Andel, Jelte

    1998-01-01

    . Habitat fragmentation affects both plants and pollinators. Habitat fragmentation leads to changes in species richness, population number and size, density, and shape, thus to changes in the spatial arrangement of flowers. These changes influence the amount of food for flower-visiting insects and t

  9. Pollen and gene flow in fragmented habitats

    NARCIS (Netherlands)

    Kwak, Manja M.; Velterop, Odilia; van Andel, Jelte

    1998-01-01

    . Habitat fragmentation affects both plants and pollinators. Habitat fragmentation leads to changes in species richness, population number and size, density, and shape, thus to changes in the spatial arrangement of flowers. These changes influence the amount of food for flower-visiting insects and t

  10. INTERMITTENCY, A TEST FOR STRING FRAGMENTATION PROCESSES

    NARCIS (Netherlands)

    SCHOLTEN, O

    The Artru-Mennessier and the string fragmentation procedure as implemented in the code VENUS have been compared. The two fragmentation prescriptions predict a similar rapidity spectrum including its energy dependence and event multiplicities, but give rise to very different intermittency results.

  11. Fragmentation of eastern United States forest types

    Science.gov (United States)

    Kurt H. Riitters; John W. Coulston

    2013-01-01

    Fragmentation is a continuing threat to the sustainability of forests in the Eastern United States, where land use changes supporting a growing human population are the primary driver of forest fragmentation (Stein and others 2009). While once mostly forested, approximately 40 percent of the original forest area has been converted to other land uses, and most of the...

  12. DNA fragments assembly based on nicking enzyme system.

    Directory of Open Access Journals (Sweden)

    Rui-Yan Wang

    Full Text Available A couple of DNA ligation-independent cloning (LIC methods have been reported to meet various requirements in metabolic engineering and synthetic biology. The principle of LIC is the assembly of multiple overlapping DNA fragments by single-stranded (ss DNA overlaps annealing. Here we present a method to generate single-stranded DNA overlaps based on Nicking Endonucleases (NEases for LIC, the method was termed NE-LIC. Factors related to cloning efficiency were optimized in this study. This NE-LIC allows generating 3'-end or 5'-end ss DNA overlaps of various lengths for fragments assembly. We demonstrated that the 10 bp/15 bp overlaps had the highest DNA fragments assembling efficiency, while 5 bp/10 bp overlaps showed the highest efficiency when T4 DNA ligase was added. Its advantage over Sequence and Ligation Independent Cloning (SLIC and Uracil-Specific Excision Reagent (USER was obvious. The mechanism can be applied to many other LIC strategies. Finally, the NEases based LIC (NE-LIC was successfully applied to assemble a pathway of six gene fragments responsible for synthesizing microbial poly-3-hydroxybutyrate (PHB.

  13. Habitat Fragmentation Drives Plant Community Assembly Processes across Life Stages.

    Science.gov (United States)

    Hu, Guang; Feeley, Kenneth J; Yu, Mingjian

    2016-01-01

    Habitat fragmentation is one of the principal causes of biodiversity loss and hence understanding its impacts on community assembly and disassembly is an important topic in ecology. We studied the relationships between fragmentation and community assembly processes in the land-bridge island system of Thousand Island Lake in East China. We focused on the changes in species diversity and phylogenetic diversity that occurred between life stages of woody plants growing on these islands. The observed diversities were compared with the expected diversities from random null models to characterize assembly processes. Regression tree analysis was used to illustrate the relationships between island attributes and community assembly processes. We found that different assembly processes predominate in the seedlings-to-saplings life-stage transition (SS) vs. the saplings-to-trees transition (ST). Island area was the main attribute driving the assembly process in SS. In ST, island isolation was more important. Within a fragmented landscape, the factors driving community assembly processes were found to differ between life stage transitions. Environmental filtering had a strong effect on the seedlings-to-saplings life-stage transition. Habitat isolation and dispersal limitation influenced all plant life stages, but had a weaker effect on communities than area. These findings add to our understanding of the processes driving community assembly and species coexistence in the context of pervasive and widespread habitat loss and fragmentation.

  14. Long-term effects of fragmentation and fragment properties on bird species richness in Hawaiian forests

    Science.gov (United States)

    David J. Flaspohler; Christian P. Giardina; Gregory P. Asner; Patrick Hart; Jonathan Price; Cassie Ka’apu Lyons; Xeronimo. Castaneda

    2010-01-01

    Forest fragmentation is a common disturbance affecting biological diversity, yet the impacts of fragmentation on many forest processes remain poorly understood. Forest restoration is likely to be more successful when it proceeds with an understanding of how native and exotic vertebrates utilize forest patches of different size. We used a system of forest fragments...

  15. CLP-based protein fragment assembly

    CERN Document Server

    Palu', Alessandro Dal; Fogolari, Federico; Pontelli, Enrico; 10.1017/S1471068410000372

    2010-01-01

    The paper investigates a novel approach, based on Constraint Logic Programming (CLP), to predict the 3D conformation of a protein via fragments assembly. The fragments are extracted by a preprocessor-also developed for this work- from a database of known protein structures that clusters and classifies the fragments according to similarity and frequency. The problem of assembling fragments into a complete conformation is mapped to a constraint solving problem and solved using CLP. The constraint-based model uses a medium discretization degree Ca-side chain centroid protein model that offers efficiency and a good approximation for space filling. The approach adapts existing energy models to the protein representation used and applies a large neighboring search strategy. The results shows the feasibility and efficiency of the method. The declarative nature of the solution allows to include future extensions, e.g., different size fragments for better accuracy.

  16. The politics of municipal fragmentation in Ghana

    Directory of Open Access Journals (Sweden)

    Abdulai Kuyini Mohammed

    2015-06-01

    Full Text Available The scholarly debate over the rival merits of local government consolidation and fragmentation is an old but enduring one. However, in this debate very little attention has been focused on the political dimension of council amalgamation and fragmentation – yet political considerations play a central role in both the formulation and outcomes of de-concentration policy. The purpose of this article is to fill a gap in the literature by examining local government fragmentation in Ghana from 1988 to 2014. The article does this by identifying the key players and analysing their interests and gains, as well as the tensions arising from the fragmentation exercise. The implications from the Ghanaian case for more general theories of fragmentation are drawn out.

  17. First principles approach to ionicity of fragments

    Science.gov (United States)

    Pilania, Ghanshyam; Liu, Xiang-Yang; Valone, Steven M.

    2015-02-01

    We develop a first principles approach towards the ionicity of fragments. In contrast to the bond ionicity, the fragment ionicity refers to an electronic property of the constituents of a larger system, which may vary from a single atom to a functional group or a unit cell to a crystal. The fragment ionicity is quantitatively defined in terms of the coefficients of contributing charge states in a superposition of valence configurations of the system. Utilizing the constrained density functional theory-based computations, a practical method to compute the fragment ionicity from valence electron charge densities, suitably decomposed according to the Fragment Hamiltonian (FH) model prescription for those electron densities, is presented for the first time. The adopted approach is illustrated using BeO, MgO and CaO diatomic molecules as simple examples. The results are compared and discussed with respect to the bond ionicity scales of Phillips and Pauling.

  18. Exact Solutions of Fragmentation Equations with General Fragmentation Rates and Separable Particles Distribution Kernels

    Directory of Open Access Journals (Sweden)

    S. C. Oukouomi Noutchie

    2014-01-01

    Full Text Available We make use of Laplace transform techniques and the method of characteristics to solve fragmentation equations explicitly. Our result is a breakthrough in the analysis of pure fragmentation equations as this is the first instance where an exact solution is provided for the fragmentation evolution equation with general fragmentation rates. This paper is the key for resolving most of the open problems in fragmentation theory including “shattering” and the sudden appearance of infinitely many particles in some systems with initial finite particles number.

  19. Virtual fragment screening: an exploration of various docking and scoring protocols for fragments using Glide

    Science.gov (United States)

    Kawatkar, Sameer; Wang, Hongming; Czerminski, Ryszard; Joseph-McCarthy, Diane

    2009-08-01

    Fragment-based drug discovery approaches allow for a greater coverage of chemical space and generally produce high efficiency ligands. As such, virtual and experimental fragment screening are increasingly being coupled in an effort to identify new leads for specific therapeutic targets. Fragment docking is employed to create target-focussed subset of compounds for testing along side generic fragment libraries. The utility of the program Glide with various scoring schemes for fragment docking is discussed. Fragment docking results for two test cases, prostaglandin D2 synthase and DNA ligase, are presented and compared to experimental screening data. Self-docking, cross-docking, and enrichment studies are performed. For the enrichment runs, experimental data exists indicating that the docking decoys in fact do not inhibit the corresponding enzyme being examined. Results indicate that even for difficult test cases fragment docking can yield enrichments significantly better than random.

  20. Improved chemical shift based fragment selection for CS-Rosetta using Rosetta3 fragment picker

    Energy Technology Data Exchange (ETDEWEB)

    Vernon, Robert [Hospital for Sick Children, Program in Molecular Structure and Function (Canada); Shen, Yang [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Baker, David [University of Washington, Department of Biochemistry (United States); Lange, Oliver F., E-mail: oliver.lange@tum.de [Technische Universitaet Muenchen, Department Chemie, Biomolecular NMR and Munich Center for Integrated Protein Science (Germany)

    2013-10-15

    A new fragment picker has been developed for CS-Rosetta that combines beneficial features of the original fragment picker, MFR, used with CS-Rosetta, and the fragment picker, NNMake, that was used for purely sequence based fragment selection in the context of ROSETTA de-novo structure prediction. Additionally, the new fragment picker has reduced sensitivity to outliers and other difficult to match data points rendering the protocol more robust and less likely to introduce bias towards wrong conformations in cases where data is bad, missing or inconclusive. The fragment picker protocol gives significant improvements on 6 of 23 CS-Rosetta targets. An independent benchmark on 39 protein targets, whose NMR data sets were published only after protocol optimization had been finished, also show significantly improved performance for the new fragment picker (van der Schot et al. in J Biomol NMR, 2013)

  1. An Imaging System for Automated Characteristic Length Measurement of Debrisat Fragments

    Science.gov (United States)

    Moraguez, Mathew; Patankar, Kunal; Fitz-Coy, Norman; Liou, J.-C.; Sorge, Marlon; Cowardin, Heather; Opiela, John; Krisko, Paula H.

    2015-01-01

    The debris fragments generated by DebriSat's hypervelocity impact test are currently being processed and characterized through an effort of NASA and USAF. The debris characteristics will be used to update satellite breakup models. In particular, the physical dimensions of the debris fragments must be measured to provide characteristic lengths for use in these models. Calipers and commercial 3D scanners were considered as measurement options, but an automated imaging system was ultimately developed to measure debris fragments. By automating the entire process, the measurement results are made repeatable and the human factor associated with calipers and 3D scanning is eliminated. Unlike using calipers to measure, the imaging system obtains non-contact measurements to avoid damaging delicate fragments. Furthermore, this fully automated measurement system minimizes fragment handling, which reduces the potential for fragment damage during the characterization process. In addition, the imaging system reduces the time required to determine the characteristic length of the debris fragment. In this way, the imaging system can measure the tens of thousands of DebriSat fragments at a rate of about six minutes per fragment, compared to hours per fragment in NASA's current 3D scanning measurement approach. The imaging system utilizes a space carving algorithm to generate a 3D point cloud of the article being measured and a custom developed algorithm then extracts the characteristic length from the point cloud. This paper describes the measurement process, results, challenges, and future work of the imaging system used for automated characteristic length measurement of DebriSat fragments.

  2. Decomposition and fragmentation principles in computational chemistry

    Science.gov (United States)

    Mezey, Paul G.

    2015-12-01

    A common approach to the mathematical modeling of various objects and processes is the subdivision of the problem into smaller, (and, as hoped), more easily understandable entities. By modeling these smaller entities, which are often fragments of the whole, and eventually re-combining these smaller fragment models into a model of the whole, one may expect that a reasonably reliable modeling approach for the complete problem may be obtained. One crucial aspect of such an approach is the level of complexity of the interrelations between the fragments. If the interrelations are weak and relatively simple, than the fragmentation approach may succeed and provide satisfactory results. However, as often happens, the interrelations are complex and not well understood, and then the fragmentation approach may face difficulties and even fail. One field where the interrelations between potential fragments is strong, yet the fragment-based approach has proven to be successful, is the modelling of both small and large molecules, providing valuable lessons for some fields not directly linked to chemistry.

  3. On Disciplinary Fragmentation and Scientific Progress

    Science.gov (United States)

    Balietti, Stefano; Mäs, Michael; Helbing, Dirk

    2015-01-01

    Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i) signals received from the correct answer to the question; (ii) peer influence; and (iii) noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called “schools of thought”. We conducted two simulation experiments where we tested (A) whether the three forces foster or hamper progress, and (B) whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i) social interactions, and (ii) peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model’s implications for the design of social institutions fostering interdisciplinarity and participation in science. PMID:25790025

  4. New information on photon fragmentation functions

    CERN Document Server

    Klasen, M

    2014-01-01

    Thermal photons radiated in heavy-ion collisions represent an important signal for a recently discovered new state of matter, the deconfined quark-gluon plasma. However, a clean identification of this signal requires precise knowledge of the prompt photons produced simultaneously in hard collisions of quarks and gluons, mostly through their fragmentation. In this Letter, we demonstrate that PHENIX data on photons produced in proton-proton collisions with low transverse momenta allow to extract new information on this fragmentation process. In particular, these data favor one parameterization (BFG II) over the two other frequently used photon fragmentation functions (BFG I and GRV NLO).

  5. HETC-3STEP included fragmentation process

    Energy Technology Data Exchange (ETDEWEB)

    Shigyo, Nobuhiro; Iga, Kiminori; Ishibashi, Kenji [Kyushu Univ., Fukuoka (Japan). Faculty of Engineering

    1997-03-01

    High Energy Transport Code (HETC) based on the cascade-evaporation model is modified to calculate the fragmentation cross section. For the cascade process, nucleon-nucleon cross sections are used for collision computation; effective in-medium-corrected cross sections are adopted instead of the original free-nucleon collision. The exciton model is adopted for improvement of backward nucleon-emission cross section for low-energy nucleon-incident events. The fragmentation reaction is incorporated into the original HETC as a subroutine set by the use of the systematics of the reaction. The modified HETC (HETC-3STEP/FRG) reproduces experimental fragment yields to a reasonable degree. (author)

  6. Composite Overwrap Fragmentation Observations, Concerns, and Recommendations

    Science.gov (United States)

    Bangham, Mike; Hovater, Mary

    2017-01-01

    A series of test activities has raised some concerns about the generation of orbital debris caused by failures of composite overwrapped pressure vessels (COPVs). These tests have indicated that a large number of composite fragments can be produced by either pressure burst failures or by high-speed impacts. A review of prior high-speed tests with COPV indicates that other tests have produced large numbers of composite fragments. As was the case with the test referenced here, the tests tended to produce a large number of small composite fragments with relatively low velocities induced by the impact and or gas expansion.

  7. Vegetative propagation capacity of invasive alligator weed through small stolon fragments under different treatments

    Science.gov (United States)

    Peng, Xuemei; Li, Haiyan; Yang, Yunfei; Zhi, Heng; Li, Chengcheng; Guo, Jian

    2017-01-01

    The ability to propagate via small diaspores is crucial for the invasion of a clone plant that does not reproduce sexually in its introduced range. We investigated the effects of node and internode adjacent mode, fragment type, burial orientation and position of the node in relation to the soil surface on the sprouting and growth of alligator weed (Alternanthera philoxeroides (Martius) Griseb.). All the factors had effects and interaction effects on the sprouting rate and growth. As a whole fragment in all treatments, the fragments with basal node buried upward on the soil surface, exhibited the best above-ground growth and root growth. The one-node fragment with basal node buried downward above the soil surface and upward under the soil surface significantly decreased the above-ground growth and root growth compared to that of the two-node fragment. Therefore, the one-node fragments were more affected by environmental conditions than the two-node fragments. The results indicated that reducing the number of nodes of a fragment and burying the node under the soil or orienting it downward above the soil surface could be applied to control the invasion of alligator weed. PMID:28262788

  8. The Transverse Momentum Dependent Fragmentation Function at NNLO

    CERN Document Server

    Echevarria, Miguel G; Vladimirov, Alexey

    2016-01-01

    We calculate the unpolarized non-singlet transverse momentum dependent fragmentation function (TMDFF) at next-to-next-to-leading order (NNLO), evaluating separately TMD soft factor and TMD collinear correlator. For the first time the cancellation of spurious rapidity divergences in a properly defined individual TMD beyond the first non-trivial order is shown. This represents a strong check of the given TMD definition. We extract the matching coefficient necessary to perform the transverse momentum resummation at next-to-next-to-next-to-leading-logarithmic accuracy. The universal character of the soft function, which enters the definition of all (un)polarized TMD distribution/fragmentation functions, facilitates the future calculation of all the other TMDs and their coefficients at NNLO, pushing forward the accuracy of theoretical predictions for the current and next generation of high energy colliders.

  9. Regulation of mammalian horizontal gene transfer by apoptotic DNA fragmentation

    Science.gov (United States)

    Yan, B; Wang, H; Li, F; Li, C-Y

    2006-01-01

    Previously it was shown that horizontal DNA transfer between mammalian cells can occur through the uptake of apoptotic bodies, where genes from the apoptotic cells were transferred to neighbouring cells phagocytosing the apoptotic bodies. The regulation of this process is poorly understood. It was shown that the ability of cells as recipient of horizontally transferred DNA was enhanced by deficiency of p53 or p21. However, little is known with regard to the regulation of DNA from donor apoptotic cells. Here we report that the DNA fragmentation factor/caspase-activated DNase (DFF/CAD), which is the endonuclease responsible for DNA fragmentation during apoptosis, plays a significant role in regulation of horizontal DNA transfer. Cells with inhibited DFF/CAD function are poor donors for horizontal gene transfer (HGT) while their ability of being recipients of HGT is not affected. PMID:17146478

  10. Ultrasensitive, Stretchable Strain Sensors Based on Fragmented Carbon Nanotube Papers

    KAUST Repository

    Zhou, Jian

    2017-01-17

    The development of strain sensors featuring both ultra high sensitivity and high stretchability is still a challenge. We demonstrate that strain sensors based on fragmented single-walled carbon nanotube (SWCNT) paper embedded in poly(dimethylsiloxane) (PDMS) can sustain their sensitivity even at very high strain levels (with a gauge factor of over 10(7) at 50% strain). This record sensitivity is ascribed to the low initial electrical resistance (5-28 Omega) of the SWCNT paper and the wide change in resistance (up to 10(6) Omega) governed by the percolated network of SWCNT in the cracked region. The sensor response remains nearly unchanged after 10 000 strain cycles at 20% proving the robustness of this technology. This fragmentation based sensing system brings opportunities to engineer highly sensitive stretchable sensors.

  11. Cyclization of short DNA fragments

    Science.gov (United States)

    Lam, Pui-Man; Zhen, Yi

    2017-09-01

    From the per unit length free energy for DNA under tension, we have calculated an effective contour length dependent persistence length for short DNA. This effective persistence length results from the enhanced fluctuations in short DNA. It decreases for shorter DNA, making shorter DNA more flexible. The results of the J-factor calculated using this effective persistence length are in good agreement with experimental data.

  12. Oscillating Filaments: I - Oscillation and Geometrical Fragmentation

    CERN Document Server

    Gritschneder, Matthias; Burkert, Andreas

    2016-01-01

    We study the stability of filaments in equilibrium between gravity and internal as well as external pressure using the grid based AMR-code RAMSES. A homogeneous, straight cylinder below a critical line mass is marginally stable. However, if the cylinder is bent, e.g. with a slight sinusoidal perturbation, an otherwise stable configuration starts to oscillate, is triggered into fragmentation and collapses. This previously unstudied behavior allows a filament to fragment at any given scale, as long as it has slight bends. We call this process `geometrical fragmentation'. In our realization the spacing between the cores matches the wavelength of the sinusoidal perturbation, whereas up to now, filaments were thought to be only fragmenting on the characteristical scale set by the mass-to-line ratio. Using first principles, we derive the oscillation period as well as the collapse timescale analytically. To enable a direct comparison with observations, we study the line-of-sight velocity for different inclinations. ...

  13. Gravitational fragmentation of the Carina Flare supershell

    Science.gov (United States)

    Wünsch, Richard

    2015-03-01

    We study the gravitational fragmentation of a thick shell comparing the analytical theory to 3D hydrodynamic simulations and to observations of the Carina Flare supershell. We use both grid-based (AMR) and particle-based (SPH) codes to follow the idealised model of the fragmenting shell and found an excellent agreement between the two codes. Growth rates of fragments at different wavelength are well described by the pressure assisted gravitational instability (PAGI) - a new theory of the thick shell fragmentation. Using the APEX telescope we observe a part of the surface of the Carina Flare supershell (GSH287+04-17) in the 13CO(2-1) line. We apply a new clump-finding algorithm DENDROFIND to identify 50 clumps. We determine the clump mass function and we construct the minimum spanning tree connecting clumps positions to estimate the typical distance among clumps. We conclude that the observed masses and distances correspond well to the prediction of PAGI.

  14. Energy efficiency of consecutive fragmentation processes

    CERN Document Server

    Fontbona, Joaquin; Martinez, Servet

    2010-01-01

    We present a ?rst study on the energy required to reduce a unit mass fragment by consecutively using several devices, as it happens in the mining industry. Two devices are considered, which we represent as different stochastic fragmentation processes. Following the self-similar energy model introduced by Bertoin and Martinez, we compute the average energy required to attain a size x with this two-device procedure. We then asymptotically compare, as x goes to 0 or 1, its energy requirement with that of individual fragmentation processes. In particular, we show that for certain range of parameters of the fragmentation processes and of their energy cost-functions, the consecutive use of two devices can be asymptotically more efficient than using each of them separately, or conversely.

  15. The NJL Model for Quark Fragmentation Functions

    Energy Technology Data Exchange (ETDEWEB)

    T. Ito, W. Bentz, I. Cloet, A W Thomas, K. Yazaki

    2009-10-01

    A description of fragmentation functions which satisfy the momentum and isospin sum rules is presented in an effective quark theory. Concentrating on the pion fragmentation function, we first explain the reason why the elementary (lowest order) fragmentation process q → qπ is completely inadequate to describe the empirical data, although the “crossed” process π → qq describes the quark distribution functions in the pion reasonably well. Then, taking into account cascade-like processes in a modified jet-model approach, we show that the momentum and isospin sum rules can be satisfied naturally without introducing any ad-hoc parameters. We present numerical results for the Nambu-Jona-Lasinio model in the invariant mass regularization scheme, and compare the results with the empirical parametrizations. We argue that this NJL-jet model provides a very useful framework to calculate the fragmentation functions in an effective chiral quark theory.

  16. The NJL Model for Quark Fragmentation Functions

    Energy Technology Data Exchange (ETDEWEB)

    T. Ito, W. Bentz, I. Cloet, A W Thomas, K. Yazaki

    2009-10-01

    A description of fragmentation functions which satisfy the momentum and isospin sum rules is presented in an effective quark theory. Concentrating on the pion fragmentation function, we first explain the reason why the elementary (lowest order) fragmentation process q → qπ is completely inadequate to describe the empirical data, although the “crossed” process π → qq describes the quark distribution functions in the pion reasonably well. Then, taking into account cascade-like processes in a modified jet-model approach, we show that the momentum and isospin sum rules can be satisfied naturally without introducing any ad-hoc parameters. We present numerical results for the Nambu-Jona-Lasinio model in the invariant mass regularization scheme, and compare the results with the empirical parametrizations. We argue that this NJL-jet model provides a very useful framework to calculate the fragmentation functions in an effective chiral quark theory.

  17. An improved algorithm for MFR fragment assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kontaxis, Georg, E-mail: georg.kontaxis@univie.ac.at [University of Vienna, Max F. Perutz Laboratories, Department of Structural and Computational Biology, Centre for Molecular Biology (Austria)

    2012-06-15

    A method for generating protein backbone models from backbone only NMR data is presented, which is based on molecular fragment replacement (MFR). In a first step, the PDB database is mined for homologous peptide fragments using experimental backbone-only data i.e. backbone chemical shifts (CS) and residual dipolar couplings (RDC). Second, this fragment library is refined against the experimental restraints. Finally, the fragments are assembled into a protein backbone fold using a rigid body docking algorithm using the RDCs as restraints. For improved performance, backbone nuclear Overhauser effects (NOEs) may be included at that stage. Compared to previous implementations of MFR-derived structure determination protocols this model-building algorithm offers improved stability and reliability. Furthermore, relative to CS-ROSETTA based methods, it provides faster performance and straightforward implementation with the option to easily include further types of restraints and additional energy terms.

  18. Successfully introduce maize DNA fragments into rice

    Institute of Scientific and Technical Information of China (English)

    WANGKaizhi

    1994-01-01

    The maize DNA fragments was successfully incorporated into rice by Associate Prof WAN Wenju's research team at Hunan Agricultural College, Changsha, China. The new gene transferring rice is named Genetic Engineered Rice (GER) line.

  19. The Fragmentation of the College Mathematics Curriculum

    Science.gov (United States)

    Singleton, Cynthia

    2008-01-01

    The purpose of this paper examines to what extent and asking reason the fragmentation of college mathematics have attained the present development in the course of looking at the history of mathematics education. (Contains 1 table.)

  20. Anthropogenic Fragmentation in the western United States

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — We evaluated the fragmentation of the western United States by anthropogenic features. The addition of roads, railroads, and power lines to wildlands, and the...

  1. Emission of intermediate mass fragments during fission

    Science.gov (United States)

    Chen, S. L.; de Souza, R. T.; Cornell, E.; Davin, B.; Hamilton, T. M.; Hulbert, D.; Kwiatkowski, K.; Lou, Y.; Viola, V. E.; Korteling, R. G.; Wile, J. L.

    1996-11-01

    Ternary fission in the reaction 4He + 232Th at Elab=200 MeV has been observed. Intermediate mass fragments (IMF: 3fission. The widths of the energy spectra are relatively constant for neck fragments with Z>=4, suggesting little variability in the scission configurations. A linear dependence of on Z is observed for the neck IMFs. The observed trend is compared with a Coulomb trajectory model.

  2. Fragment Length of Circulating Tumor DNA.

    Directory of Open Access Journals (Sweden)

    Hunter R Underhill

    2016-07-01

    Full Text Available Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively. Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively. Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

  3. Fragment Length of Circulating Tumor DNA.

    Science.gov (United States)

    Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay

    2016-07-01

    Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

  4. Fragmentation of Care in Ectopic Pregnancy.

    Science.gov (United States)

    Stulberg, Debra B; Dahlquist, Irma; Jarosch, Christina; Lindau, Stacy T

    2016-05-01

    Ectopic pregnancy is an important cause of maternal morbidity and mortality. Women who experience fragmented care may undergo unnecessary delays to diagnosis and treatment. Based on ectopic pregnancy cases observed in clinical practice that raised our concern about fragmentation of care, we designed an exploratory study to describe the number, characteristics, and outcomes of fragmented care among patients with ectopic pregnancy at one urban academic hospital. Chart review with descriptive statistics. Fragmented care was defined as a patient being evaluated at an outside facility for possible ectopic pregnancy and transferred, referred, or discharged before receiving care at the study institution. Of 191 women seen for possible or definite ectopic pregnancy during the study period, 42 (22 %) met the study definition of fragmented care. The study was under-powered to observe statistically significant differences across groups, but we found concerning, non-significant trends: patients with fragmented care were more likely to be Medicaid recipients (65.9 vs. 58.8 %) and to experience a complication (23.8 vs. 18.1 %) compared to those with non-fragmented care. Most patients (n = 37) received no identifiable treatment prior to transfer and arrived to the study hospital with no communication to the receiving hospital from the outside provider (n = 34). Nine patients (21 %) presented with ruptured ectopic pregnancies. The fragmentation we observed in our study may contribute to previously identified socio-economic disparities in ectopic pregnancy outcomes. If future research confirms these findings, health information exchanges and regional coordination of care may be important strategies for reducing maternal mortality.

  5. Modified Empirical Parametrization of Fragmentation Cross Sections

    CERN Document Server

    Sümmerer, K

    2000-01-01

    New experimental data obtained mainly at the GSI/FRS facility allow to modify the empirical parametrization of fragmentation cross sections, EPAX. It will be shown that minor modifications of the parameters lead to a much better reproduction of measured cross sections. The most significant changes refer to the description of fragmentation yields close to the projectile and of the memory effect of neutron-deficient projectiles.

  6. Fragment-based approaches to enzyme inhibition

    OpenAIRE

    Ciulli, Alessio; Abell, Chris

    2007-01-01

    Fragment-based approaches have provided a new paradigm for small-molecule drug discovery. The methodology is complementary to high-throughput screening approaches, starting from fragments of low molecular complexity and high ligand efficiency, and building up to more potent inhibitors. The approach, which depends heavily on a number of biophysical techniques, is now being taken up by more groups in both industry and academia. This article describes key aspects of the process and highlights re...

  7. Observations of Titan IIIC Transtage Fragmentation Debris

    Science.gov (United States)

    Cowardin, Heather; Seitzer, P.; Abercromby, K.; Barker, E.; Buckalew, B.; Cardona, T.; Krisko, P.; Lederer, S.

    2013-01-01

    The fragmentation of a Titan IIIC Transtage (1968-081) on 21 February 1992 is one of only two known break-ups in or near geosynchronous orbit. The original rocket body and 24 pieces of debris are currently being tracked by the U. S. Space Surveillance Network (SSN). The rocket body (SSN# 3432) and several of the original fragments (SSN# 25000, 25001, 30000, and 33511) were observed in survey mode during 2004-2010 using the 0.6-m Michigan Orbital DEbris Survey Telescope (MODEST) in Chile using a broad R filter. This paper presents a size distribution for all calibrated magnitude data acquired on MODEST. Size distribution plots are also shown using historical models for small fragmentation debris (down to 10 cm) thought to be associated with the Titan Transtage break-up. In November 2010, visible broadband photometry (Johnson/Kron-Cousins BVRI) was acquired with the 0.9-m Small and Moderate Aperture Research Telescope System (SMARTS) at the Cerro Tololo Inter-American Observatory (CTIO) in Chile on several Titan fragments (SSN 25001, 33509, and 33510) and the parent rocket body (SSN 3432). Color index data are used to determine the fragment brightness distribution and how the data compares to spacecraft materials measured in the laboratory using similar photometric measurement techniques. In order to better characterize the break-up fragments, spectral measurements were acquired on three Titan fragments (one fragment observed over two different time periods) using the 6.5-m Magellan telescopes at Las Campanas Observatory in Chile. The telescopic spectra of SSN 25000 (May 2012 and January 2013), SSN 38690, and SSN 38699 are compared with laboratory acquired spectra of materials (e.g., aluminum and various paints) to determine the surface material.

  8. First principles approach to ionicity of fragments

    Energy Technology Data Exchange (ETDEWEB)

    Pilania, Ghanshyam, E-mail: gpilania@lanl.gov; Liu, Xiang-Yang; Valone, Steven M.

    2015-02-20

    Highlights: • A novel first principles approach towards the fragment ionicity. • Constrained DFT and valance charge density decomposition were employed. • Correct dissociation limit achieved for diatomics. • Ionicity is an input parameter for a new class of atomistic potentials. - Abstract: We develop a first principles approach towards the ionicity of fragments. In contrast to the bond ionicity, the fragment ionicity refers to an electronic property of the constituents of a larger system, which may vary from a single atom to a functional group or a unit cell to a crystal. The fragment ionicity is quantitatively defined in terms of the coefficients of contributing charge states in a superposition of valence configurations of the system. Utilizing the constrained density functional theory-based computations, a practical method to compute the fragment ionicity from valence electron charge densities, suitably decomposed according to the Fragment Hamiltonian (FH) model prescription for those electron densities, is presented for the first time. The adopted approach is illustrated using BeO, MgO and CaO diatomic molecules as simple examples. The results are compared and discussed with respect to the bond ionicity scales of Phillips and Pauling.

  9. Correlation measurements of fission-fragment properties

    Science.gov (United States)

    Oberstedt, S.; Belgya, T.; Billnert, R.; Borcea, R.; Cano-Ott, D.; Göök, A.; Hambsch, F.-J.; Karlsson, J.; Kis, Z.; Martinez, T.; Oberstedt, A.; Szentmiklosi, L.; Takác, K.

    2010-10-01

    For the development of future nuclear fission applications and for a responsible handling of nuclear waste the a-priori assessment of the fission-fragments' heat production and toxicity is a fundamental necessity. The success of an indispensable modelling of the fission process strongly depends on a good understanding of the particular mechanism of scission, the mass fragmentation and partition of excitation energy. Experimental observables are fission-fragment properties like mass- and energy-distributions, and the prompt neutron as well as γ-ray multiplicities and emission spectra. The latter quantities should preferably be known as a function of fragment mass and excitation energy. Those data are highly demanded as published by the OECD-NEA in its high priority data request list. With the construction of the double (v, E) spectrometer VERDI we aim at measuring pre- and post-neutron masses directly and simultaneously to avoid prompt neutron corrections. From the simultaneous measurement of pre- and post-neutron fission-fragment data the prompt neutron multiplicity may then be inferred fully correlated with fragment mass yield and total kinetic energy. Using an ultra-fast fission event trigger spectral prompt fission γ-ray measurements may be performed. For that purpose recently developed lanthanum-halide detectors, with excellent timing characteristics, were coupled to the VERDI spectrometer allowing for a very good discrimination of fission γ-rays and prompt neutrons due to their different time-of-flight.

  10. Disciplinary Fragmentation in Comprehensive Issues

    DEFF Research Database (Denmark)

    Lauridsen, Erik Hagelskjær

    2004-01-01

    The geographical and spatial proximity of the activities in the Songkhla Lake Bassin ties the region together trough the common use of the lake waters as a resource or a discharge media as well as a regional economy, the capacities of a common workforce, local demographic features and the social...... to social and economic factors are not subjects of specific analysis in the literature. They can to some extent be derived from the assumptions of the articles on environmental planning: Socio-economic data are available as statistics for the area, but they are not related to the concrete sources...

  11. Collins fragmentation function for pions and kaons in a spectator model

    Energy Technology Data Exchange (ETDEWEB)

    Bacchetta, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Gamberg, L.P. [Penn State Univ., Berks, PA (United States). Dept. of Physics; Goldstein, G.R. [Tufts Univ., Medford, MA (United States). Dept. of Physics and Astronomy; Mukherjee, A. [Indian Institute of Technology Bombay, Mumbai (India). Physics Dept.

    2007-07-15

    We calculate the Collins fragmentation function in the framework of a spectator model with pseudoscalar pion-quark coupling and a Gaussian form factor at the vertex. We determine the model parameters by fitting the unpolarized fragmentation function for pions and kaons. We show that the Collins function for the pions in this model is in reasonable agreement with recent parametrizations obtained by fits of the available data. In addition, we compute for the first time the Collins function for the kaons. (orig.)

  12. Natural fragmentation in river networks as a driver of speciation for freshwater fishes

    OpenAIRE

    Dias, Murilo S.; Cornu, Jean-François; Oberdorff, Thierry; Lasso, Carlos A.; Tedesco, Pablo A.

    2013-01-01

    Although habitat fragmentation fosters extinctions, it also increases the probability of speciation by promoting and maintaining divergence among isolated populations. Here we test for the effects of two isolation factors that may reduce population dispersal within river networks as potential drivers of freshwater fish speciation: 1) the position of subdrainages along the longitudinal river gradient, and 2) the level of fragmentation within subdrainages caused by natural waterfalls. The occur...

  13. Influence of atomic screening on fragmentation of ultrarelativistic lead ions in LHC collimators

    DEFF Research Database (Denmark)

    Baggesen, Jan C.; Sørensen, Allan H.

    2009-01-01

    When a lead beam is collimated in the CERN LHC some of the ions fragment in the collimators causing problems downstream. For design purposes the fragmentation probability needs to be assessed. At LHC energies ( γ 3000 ; the Lorentz-factor γ is the total energy of an ion in units of its rest energ...... case for various collimator materials and find a significant effect for tungsten, the heaviest candidate planned for use....

  14. Implications of promiscuous Pim-1 kinase fragment inhibitor hydrophobic interactions for fragment-based drug design.

    Science.gov (United States)

    Good, Andrew C; Liu, Jinyu; Hirth, Bradford; Asmussen, Gary; Xiang, Yibin; Biemann, Hans-Peter; Bishop, Kimberly A; Fremgen, Trisha; Fitzgerald, Maria; Gladysheva, Tatiana; Jain, Annuradha; Jancsics, Katherine; Metz, Markus; Papoulis, Andrew; Skerlj, Renato; Stepp, J David; Wei, Ronnie R

    2012-03-22

    We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.

  15. Fragment library design: using cheminformatics and expert chemists to fill gaps in existing fragment libraries.

    Science.gov (United States)

    Kutchukian, Peter S; So, Sung-Sau; Fischer, Christian; Waller, Chris L

    2015-01-01

    Fragment based screening (FBS) has emerged as a mainstream lead discovery strategy in academia, biotechnology start-ups, and large pharma. As a prerequisite of FBS, a structurally diverse library of fragments is desirable in order to identify chemical matter that will interact with the range of diverse target classes that are prosecuted in contemporary screening campaigns. In addition, it is also desirable to offer synthetically amenable starting points to increase the probability of a successful fragment evolution through medicinal chemistry. Herein we describe a method to identify biologically relevant chemical substructures that are missing from an existing fragment library (chemical gaps), and organize these chemical gaps hierarchically so that medicinal chemists can efficiently navigate the prioritized chemical space and subsequently select purchasable fragments for inclusion in an enhanced fragment library.

  16. Recombinant-activated factor VII in patients with uncontrolled bleeding: A retrospective observational analysis

    Directory of Open Access Journals (Sweden)

    Said D Abuhasna

    2012-01-01

    Full Text Available Background: Factor VIIa (recombinant has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Objective: The primary objective of this study was to assess the safety and effectiveness of factor VIIa (recombinant on blood transfusion requirements and coagulation parameters when used in patients whose bleeding was uncorrected by other means. The pharmacoeconomic impact for any discrepancy from our protocol was evaluated. Secondary outcomes included 4-hour and 28-day mortality, as well as safety of this agent in terms of thromboembolic complications. Materials and Methods: We retrospectively evaluated patients who received recombinant-activated factor VII (rFVIIa for uncontrolled bleeding from June 2008 to April 2011. The medical records of 33 patients were evaluated. Coagulation parameters and blood products were determined 24 hours before and 24 hours after administration of rFVIIa, and the results compared. Patients were also screened for any thromboembolic complications. Results: Administration of rFVIIa reduced blood transfusion requirements and improved coagulation parameters significantly (P<0.05. No thromboembolic complications were reported. Most of the dosing was consistent with those recommended in our institutional protocol, with discrepancies resulting in an average cost of $56 058. Moreover, pH was reported in only 67% of patients. All patients treated with rFVIIa survived up to 4 hours after receiving this agent, while the 28-day mortality was 24% (8/33. Conclusion: The use of rFVIIa appears to be safe and effective in promoting hemostasis, as evident from reducing transfusion requirements and improving the coagulation variables.

  17. The role of cell-death-inducing DNA-fragmentation-factor-like effector (CIDE)family in TG metabolism%DNA断裂因子相似蛋白(CIDE)家族在甘油三酯代谢中的作用

    Institute of Scientific and Technical Information of China (English)

    向梳瑕; 潘志雄; 李亮; 王继文

    2010-01-01

    DNA断裂因子相似蛋白(cell-death-inducing DNA-fragmentation-factor-like effector,CIDE)家族包括三个成员:CIDE-A、CIDE-B和CIDE-C.小鼠中CIDE-C被称为脂肪特异性蛋白27(fat special protein 27,FSP27),以前都作为细胞凋亡因子加以研究.近年来研究显示,敲除了CIDE-A、CIDE-B、FSP27的动物都表现出了能量释放增多,且能够抵抗食物导致的肥胖以及对胰岛素敏感性增强.CIDE家族定位于内质网、脂滴和线粒体,参与甘油三酯储存、降解以及分泌代谢,与肥胖、高血脂、糖尿病、脂肪肝等脂类代谢相关疾病也有着密切关系,在调控机体脂质代谢平衡方面扮演着重要的角色.该文对CIDE家族在甘油三酯代谢方面的作用及其调控的分子机制进行综述.

  18. Theory of cooperative fluorescence from products of reactions or collisions: Identical neutral atomic fragments

    Science.gov (United States)

    Kurizki, Gershon; Ben-Reuven, Abraham

    1987-07-01

    The time-resolved cooperative emission from a system of correlated neutral dissociation fragments, or molecular collision products in beams, is investigated. The investigation is focused on emission at large fragment separations (between 1 nm and a few emission wavelengths), exceeding the domain of short-range interactions within the reactive or collisional molecular complex. A master-equation approach is used to obtain a general expression for the cooperative emission rate, which consists of nonexponential decay factors multiplied by temporal ringing patterns. These features result from the time-dependent radiative coupling between the receding fragments; they depend in an essential manner on the initial electronic state of the parent molecular complex and its symmetry which determine the correlations between the fragments. In the model system of a pair of identical two-level fragments two cases are considered separately. (a) A single photon shared by the fragments, where the emission is initially superradiant or subradiant (radiation trapping), depending on the spin and inversion symmetry of the parent molecular system and of the nascent fragments. The ringing pattern depends on the electronic angular momentum state of the parent molecule and on the polarization of the emitted light. (Such a ringing has been observed recently by Grangier, Aspect, and Vigué [Phys. Rev. Lett. 54, 418 (1985)] in the emission of photodissociated Ca2.) (b) Two initially excited fragments, where the ringing pattern is of smaller amplitude, and is weakly dependent on the electronic angular momentum of the parent molecule. All the aforementioned cooperative features generally last until the fragments recede several radiation wavelengths away from each other. The application of this time-resolved analysis to various diagnostic problems is discussed, especially with regard to the identification of excited electronic states of the parent molecular complex, and the stereospecificity of the

  19. Shape Factor Modeling and Simulation

    Science.gov (United States)

    2016-06-01

    10 3. Shape Factor Distributions for Natural Fragments 12 3.1 Platonic Solids and Uniform Viewing from All Viewpoints 12 3.2 Natural Fragments from...12 Fig. 9 The 5 Platonic solids. ............................................................. 12 Fig. 10 Mean shape factor of...of the 5 Platonic solids............................................ 13 Table 3 Sequence of viewing angles in Icosahedron Gage

  20. Disciplinary Fragmentation in Comprehensive Issues

    DEFF Research Database (Denmark)

    Lauridsen, Erik Hagelskjær

    2004-01-01

    of environmental degradation of the lakes. Articles on environmental planning contain a more integrated understanding of the environmental degradation as a result of social activities. But also here the scope of the studies tend to be limited to the water related issues. The results of the literature survey...... welfare of the population at large. This paper suggests that The Lake Bassin must be described and analyzed as a comprehensive issue which integrates an understanding of the uplands of the lake as more than watersheds. A literature surevey was performed searching major international research databases...... to social and economic factors are not subjects of specific analysis in the literature. They can to some extent be derived from the assumptions of the articles on environmental planning: Socio-economic data are available as statistics for the area, but they are not related to the concrete sources...

  1. TMDs, universality and factorization

    CERN Document Server

    D'Alesio, Umberto

    2011-01-01

    We present a short overview on transverse momentum dependent parton distribution and fragmentation functions, giving their partonic interpretation and ways to access them. We then discuss the issue of their universality and its connection to factorization in perturbative QCD.

  2. 蓝花楹JaCBF1转录因子片段的序列分析及耐寒性功能验证%Sequence Analysis and Chilling Resistance about a New CBF-like Transcription Factor Fragment from Jacaranda acutifolia

    Institute of Scientific and Technical Information of China (English)

    周静; 张炜; 李大明; 张锡九; 陈其兵

    2013-01-01

    CBFs (CRT/DRE-binding factor) are key transcription factors regulating the chilling response in plants.A 457 bp CBF-like fragment was cloned from Jacaranda acutifolia.Sequence analysis showed that the fragment (named as JaCBF1) encoded a protein of 142 amino acids,and was highly homologous to many known CBF1-like transcription factors with the AP2 core domain that belongs to CBF gene family.The recombinant plasmid containing JaCBF1 sequence was introduced into Escherichia coli.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that JaCBF1 was translated into a 16 KDa protein.Expression pattern analysis indicated that JaCBF1 could be induced with different patterns and degrees by low temperature in roots,stems,and leaves of J.acutifolia.Southern blot revealed that the J.acutifolia genome contained at least two copies of JaCBF1.Ectopic transcription in Arabidopsis thaliana revealed that JaCBF1 functioned in the nuclei,and its expression could significantly improve the freezing resistance of transgenic A.thaliana.The results of study suggest that the novel JaCBF1 is a typical CBF-like transcription factor,and plays an important role responding to cold stress in J.acutifolia.%CBF类转录因子是调控植物冷害应答反应的关键因子.从蓝花楹中克隆到一个457 bp CBF类基因片段,序列分析表明其编码142氨基酸的片段,并与多个物种CBF1基因序列高度同源,且具有CBF家族的AP2核心结构域,因此将其命名为JaCBF1.原核表达的结果显示此基因片段编码16 kDa的蛋白,表达分析结果显示JaCBF1于低温条件下在蓝花楹根、茎、叶中有差异性转录.Southern杂交结果揭示JaCBF1在蓝花楹基因组中存在至少2个拷贝.通过脓杆菌介导方法将JaCBF1异源转录到拟南芥中,荧光共聚焦显微照相结果显示其编码的蛋白质定位于细胞核,冷处理实验发现转基因拟南芥植株的耐冷性得到了显著提高,表明此新片段具

  3. A fragment-based approach to the SAMPL3 Challenge

    Science.gov (United States)

    Kulp, John L.; Blumenthal, Seth N.; Wang, Qiang; Bryan, Richard L.; Guarnieri, Frank

    2012-05-01

    The success of molecular fragment-based design depends critically on the ability to make predictions of binding poses and of affinity ranking for compounds assembled by linking fragments. The SAMPL3 Challenge provides a unique opportunity to evaluate the performance of a state-of-the-art fragment-based design methodology with respect to these requirements. In this article, we present results derived from linking fragments to predict affinity and pose in the SAMPL3 Challenge. The goal is to demonstrate how incorporating different aspects of modeling protein-ligand interactions impact the accuracy of the predictions, including protein dielectric models, charged versus neutral ligands, ΔΔGs solvation energies, and induced conformational stress. The core method is based on annealing of chemical potential in a Grand Canonical Monte Carlo (GC/MC) simulation. By imposing an initially very high chemical potential and then automatically running a sequence of simulations at successively decreasing chemical potentials, the GC/MC simulation efficiently discovers statistical distributions of bound fragment locations and orientations not found reliably without the annealing. This method accounts for configurational entropy, the role of bound water molecules, and results in a prediction of all the locations on the protein that have any affinity for the fragment. Disregarding any of these factors in affinity-rank prediction leads to significantly worse correlation with experimentally-determined free energies of binding. We relate three important conclusions from this challenge as applied to GC/MC: (1) modeling neutral ligands—regardless of the charged state in the active site—produced better affinity ranking than using charged ligands, although, in both cases, the poses were almost exactly overlaid; (2) simulating explicit water molecules in the GC/MC gave better affinity and pose predictions; and (3) applying a ΔΔGs solvation correction further improved the ranking of the

  4. Okazaki fragment maturation: nucleases take centre stage

    Institute of Scientific and Technical Information of China (English)

    Li Zheng; Binghui Shen

    2011-01-01

    Completion of lagging strand DNA synthesis requires processing of up to 50 million Okazaki fragments per cell cycle in mammalian cells. Even in yeast, the Okazaki fragment maturation happens approximately a million times during a singte round of DNA replication. Therefore, efficient processing of Okazaki fragments is vital for DNA replication and cell proliferation. During this process,primase-synthesized RNA/DNA primers are removed, and Okazaki fragments are joined into an intact lagging strand DNA. The processing of RNA/DNA primers requires a group of structure-specific nucleases typified by flap endonuclease 1 (FEN1). Here, we summarize the distinct roles of these nucleases in different pathways for removal of RNA/DNA primers. Recent findings reveal that Okazaki fragment maturation is highly coordinated. The dynamic interactions of polymerase δ, FEN1 and DNA ligase I with proliferating cell nuclear antigen allow these enzymes to act sequentially during Okazaki fragment maturation. Such protein-protein interactions may be regulated by post-translational modifications. We also discuss studies using mutant mouse models that suggest two distinct cancer etiological mechanisms arising from defects in different steps of Okazaki fragment maturation.Mutations that affect the efficiency of RNA primer removal may result in accumulation of unligated nicks and DNA double-strand breaks. These DNA strand breaks can cause varying forms of chromosome aberrations, contributing to development of cancer that associates with aneuploidy and gross chromosomal rearrangement. On the other hand, mutations that impair editing out of polymerase o incorporation errors result in cancer displaying a strong mutator phenotype.

  5. Invariant Object Recognition Based on Extended Fragments

    Directory of Open Access Journals (Sweden)

    Evgeniy eBart

    2012-08-01

    Full Text Available Visual appearance of natural objects is profoundly affected by viewing conditions such as viewpoint and illumination. Human subjects can nevertheless compensate well for variations in these viewing conditions. The strategies that the visual system uses to accomplish this are largely unclear. Previous computational studies have suggested that in principle, certain types of object fragments (rather than whole objects can be used for invariant recognition. However, whether the human visual system is actually capable of using this strategy remains unknown. Here, we show that human observers can achieve illumination invariance by using object fragments that carry the relevant information. To determine this, we have used novel, but naturalistic, 3-D visual objects called ‘digital embryos’. Using novel instances of whole embryos, not fragments, we trained subjects to recognize individual embryos across illuminations. We then tested the illumination-invariant object recognition performance of subjects using fragments. We found that the performance was strongly correlated with the mutual information (MI of the fragments, provided that MI value took variations in illumination into consideration. This correlation was not attributable to any systematic differences in task difficulty between different fragments. These results reveal two important principles of invariant object recognition. First, the subjects can achieve invariance at least in part by compensating for the changes in the appearance of small local features, rather than of whole objects. Second, the subjects do not always rely on generic or pre-existing invariance of features (i.e., features whose appearance remains largely unchanged by variations in illumination, and are capable of using learning to compensate for appearance changes when necessary. These psychophysical results closely fit the predictions of earlier computational studies of fragment-based invariant object recognition.

  6. Invariant object recognition based on extended fragments.

    Science.gov (United States)

    Bart, Evgeniy; Hegdé, Jay

    2012-01-01

    Visual appearance of natural objects is profoundly affected by viewing conditions such as viewpoint and illumination. Human subjects can nevertheless compensate well for variations in these viewing conditions. The strategies that the visual system uses to accomplish this are largely unclear. Previous computational studies have suggested that in principle, certain types of object fragments (rather than whole objects) can be used for invariant recognition. However, whether the human visual system is actually capable of using this strategy remains unknown. Here, we show that human observers can achieve illumination invariance by using object fragments that carry the relevant information. To determine this, we have used novel, but naturalistic, 3-D visual objects called "digital embryos." Using novel instances of whole embryos, not fragments, we trained subjects to recognize individual embryos across illuminations. We then tested the illumination-invariant object recognition performance of subjects using fragments. We found that the performance was strongly correlated with the mutual information (MI) of the fragments, provided that MI value took variations in illumination into consideration. This correlation was not attributable to any systematic differences in task difficulty between different fragments. These results reveal two important principles of invariant object recognition. First, the subjects can achieve invariance at least in part by compensating for the changes in the appearance of small local features, rather than of whole objects. Second, the subjects do not always rely on generic or pre-existing invariance of features (i.e., features whose appearance remains largely unchanged by variations in illumination), and are capable of using learning to compensate for appearance changes when necessary. These psychophysical results closely fit the predictions of earlier computational studies of fragment-based invariant object recognition.

  7. DNA fragmentation in spermatozoa: a historical review.

    Science.gov (United States)

    Rex, A S; Aagaard, J; Fedder, J

    2017-07-01

    Sperm DNA Fragmentation has been extensively studied for more than a decade. In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the DNA was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated. In the seventies, the impact of induced DNA damage was investigated. In the 1980s the concept of sperm DNA fragmentation as related to infertility was introduced as well as the first DNA fragmentation test: the Sperm Chromatin Structure Assay (SCSA). The terminal deoxynucleotidyl transferase nick end labelling (TUNEL) test followed by others was introduced in the nineties. The association between DNA fragmentation in spermatozoa and pregnancy loss has been extensively investigated spurring the need for a therapeutic tool for these patients. This gave rise to an increased interest in the aetiology of DNA damage. The present decade continues within this research area. Some of the more novel methods recently submerging are sorting of cells with increased DNA fragmentation and hyaluronic acid (HA) binding techniques. The clinical value of these tests remains to be elucidated. In spite of half a century of research within the area, this analysis is not routinely implemented into the fertility clinics. The underlying causes are multiple. The abundance of methods has impeded the need for a clinical significant threshold. One of the most promising methods was commercialized in 2005 and has been reserved for larger licensed laboratories. Myriads of reviews and meta-analyses on studies using different assays for analysis of DNA fragmentation, different clinical Artificial Reproductive Treatments (ART), different definitions of successful ART outcome and small patient cohorts have been published. Although the area of DNA fragmentation in spermatozoa is highly relevant in the fertility clinics, the need for further studies focusing on standardization of the methods and clinical

  8. Effects of soil, altitude, rainfall, and distance on the floristic similarity of Atlantic Forest fragments in the east-Northeast

    Directory of Open Access Journals (Sweden)

    Flávia de Barros Prado Moura

    2013-09-01

    Full Text Available This paper presents the results of a floristic survey conducted on an Atlantic Forest fragment in the state of Alagoas, Brazil. Besides, the results of a similarity analysis between ten rainforest fragments from the Brazilian east-Northeast are presented. The floristic comparison was based on binary data with regard to the presence/ absence criterion for tree species identified in the ten fragments by means of Sørensen’s similarity index. A dendrogram was prepared using cluster analysis (Jaccard’s index and canonical correspondence analysis (CCA to test the abiotic factors, which can differently influence the similarity of fragments. The fragments showed low similarity indices. The variations were due to the fact that each fragment is a patch of what once was a continuous and heterogeneous region. However, the diversity loss, including the disappearance of more demanding species, can lead, in large-scale, to homogeneity and simplification of the northeastern Atlantic Forest.

  9. Intravascular foreign bodies: danger of unretrieved fragmented medical devices.

    Science.gov (United States)

    Tateishi, Minori; Tomizawa, Yasuko

    2009-01-01

    A warning on the danger of unretrieved device fragments and recommendations to mitigate the danger were issued by the Food and Drug Administration in January 2008. The causes of intravascular foreign bodies are classified into three main categories: improper manipulation and usage, device defects, and others, such as patient and anatomical factors. Device failure after long-term use is rarely predicted at the time of approval, since device abnormality is rarely experienced in animal studies and clinical trials conducted during development of the device. Stent fracture due to metal fatigue is one example. Complex complications could occur from simultaneous use of two or more devices with diverse characteristics. The success rate of percutaneous retrieval of intravascular foreign bodies has improved with the advances in commercially available devices. However, the procedure is not always successful and sometimes surgical removal becomes necessary. Appropriate device selection and acquisition of experience in using the device are important. When an intravascular foreign body cannot be retrieved, the risk of complication could be high. Magnetic resonance imaging examination sometimes causes adverse events, including burns due to the heat generated by metal movement. Such information should be correctly recorded. Furthermore, it is necessary to provide patients with adequate information about the characteristics of implanted devices and unretrieved fragments. We reviewed the literature on unretrieved medical device fragments and include articles that describe the Japanese experience.

  10. Neighborhood Economic Deprivation and Social Fragmentation: Associations With Children's Sleep.

    Science.gov (United States)

    Bagley, Erika J; Fuller-Rowell, Thomas E; Saini, Ekjyot K; Philbrook, Lauren E; El-Sheikh, Mona

    2016-12-09

    A growing body of work indicates that experiences of neighborhood disadvantage place children at risk for poor sleep. This study aimed to examine how both neighborhood economic deprivation (a measure of poverty) and social fragmentation (an index of instability) are associated with objective measures of the length and quality of children's sleep. Participants were 210 children (54.3% boys) living predominantly in small towns and semirural communities in Alabama. On average children were 11.3 years old (SD = .63); 66.7% of the children were European American and 33.3% were African American. The sample was socioeconomically diverse with 67.9% of the participants living at or below the poverty line and 32.1% from lower-middle-class or middle-class families. Indicators of neighborhood characteristics were derived from the 2012 American Community Survey and composited to create two variables representing neighborhood economic deprivation and social fragmentation. Child sleep period, actual sleep minutes, and efficiency were examined using actigraphy. Higher levels of neighborhood economic deprivation were associated with fewer sleep minutes and poorer sleep efficiency. More neighborhood social fragmentation was also linked with poorer sleep efficiency. Analyses controlled for demographic characteristics, child health, and family socioeconomic status. Findings indicate that living in economically and socially disadvantaged neighborhoods predicts risk for shorter and lower-quality sleep in children. Examination of community context in addition to family and individual characteristics may provide a more comprehensive understanding of the factors shaping child sleep.

  11. Investigating the structure and fragmentation of a highly filamentary IRDC

    CERN Document Server

    Henshaw, J D; Fontani, F; Jimenez-Serra, I; Tan, J C; Longmore, S N; Pineda, J E; Parker, R J; Barnes, A T

    2016-01-01

    We present 3.7 arcsec (~0.05 pc) resolution 3.2 mm dust continuum observations from the IRAM PdBI, with the aim of studying the structure and fragmentation of the filamentary Infrared Dark Cloud G035.39-00.33. The continuum emission is segmented into a series of 13 quasi-regularly spaced (~0.18pc) cores, following the major axis of the IRDC. We compare the spatial distribution of the cores with that predicted by theoretical work describing the fragmentation of hydrodynamic fluid cylinders, finding a significant (factor of ~8) discrepancy between the two. Our observations are consistent with the picture emerging from kinematic studies of molecular clouds suggesting that the cores are harboured within a complex network of independent sub-filaments. This result emphasises the importance of considering the underlying physical structure, and potentially, dynamically important magnetic fields, in any fragmentation analysis. The identified cores exhibit a range in (peak) beam-averaged column density ($3.6{\\rm x}10^{...

  12. Coordination of dibensothiophenes and corannulenes to organometallic ruthenium (II) fragments

    Energy Technology Data Exchange (ETDEWEB)

    Vecchi, Paul Anthony [Iowa State Univ., Ames, IA (United States)

    2005-01-01

    This dissertation contains five papers in the format required for journal publication which describe (in part) my research accomplishments as a graduate student at Iowa State University. This work can be broadly categorized as the binding of weakly-coordinating ligands to cationic organometallic ruthenium fragments, and consists of two main areas of study. Chapters 2-4 are investigations into factors that influence the binding of dibenzothiophenes to [Cp'Ru(CO)2(+ fragments, where Cp' = η5-C5H5 (Cp) and η5-C5Me5 (Cp*). Chapters 5 and 6 present the synthesis and structural characterization of complexes containing corannulene buckybowls that are η6-coordinated to [Cp*Ru(+ fragments. The first chapter contains a brief description of the difficulty in lowering sulfur levels in diesel fuel along with a review of corannulene derivatives and their metal complexes. After the final paper is a short summary of the work herein (Chapter 7). Each chapter is independent, and all equations, schemes, figures, tables, references, and appendices in this dissertation pertain only to the chapter in which they appear.

  13. [Urinary albumin fragmentation and immunoreactivity].

    Science.gov (United States)

    Kurihara, Yuriko; Nishimaki, Junichi; Nakajima, Toshie; Ida, Takashi; Shiba, Kiyoko

    2009-02-01

    Urinary albumin (ALB) has been measured as a marker for the early detection of diabetic nephropathy. In 2004, Comper et al. developed a gel-filtration high-performance liquid chromatography (HPLC) procedure for the determination of urinary ALB. They demonstrated the presence in its albumin fraction of non immunoreactive ALB with the total molecular weight of a monomeric ALB that was non-reactive with the existing anti-ALB antibody, and reported that the level of urinary non-immunoreactive ALB was higher in diabetic patients than in normal subjects. In this study, we isolated urinary ALB from diabetic patients using an anti-ALB antibody-coupled affinity column to test its immunoreactivity. In some diabetic patients, the results of HPLC and turbidimetric immunoassay for urinary ALB were discrepant. Western blot analysis showed that ALB samples from such patients were contaminated with proteins other than ALB, and contained ALB, whose molecular weight became lower using a reductive procedure. In addition, the reactivity of ALB with anti-ALB antibody differed depending on whether it was in a reduced or non-reduced state. These results indicate that ALB in such patients is susceptible to structural changes due to disease-induced urinary factors and, thus, their urine contains ALB with an altered reactivity to antibody.

  14. Short read DNA fragment anchoring algorithm.

    Science.gov (United States)

    Wang, Wendi; Zhang, Peiheng; Liu, Xinchun

    2009-01-30

    The emerging next-generation sequencing method based on PCR technology boosts genome sequencing speed considerably, the expense is also get decreased. It has been utilized to address a broad range of bioinformatics problems. Limited by reliable output sequence length of next-generation sequencing technologies, we are confined to study gene fragments with 30 - 50 bps in general and it is relatively shorter than traditional gene fragment length. Anchoring gene fragments in long reference sequence is an essential and prerequisite step for further assembly and analysis works. Due to the sheer number of fragments produced by next-generation sequencing technologies and the huge size of reference sequences, anchoring would rapidly becoming a computational bottleneck. We compared algorithm efficiency on BLAT, SOAP and EMBF. The efficiency is defined as the count of total output results divided by time consumed to retrieve them. The data show that our algorithm EMBF have 3 - 4 times efficiency advantage over SOAP, and at least 150 times over BLAT. Moreover, when the reference sequence size is increased, the efficiency of SOAP will get degraded as far as 30%, while EMBF have preferable increasing tendency. In conclusion, we deem that EMBF is more suitable for short fragment anchoring problem where result completeness and accuracy is predominant and the reference sequences are relatively large.

  15. Formation of wide binaries by turbulent fragmentation

    Science.gov (United States)

    Lee, Jeong-Eun; Lee, Seokho; Dunham, Michael M.; Tatematsu, Ken'ichi; Choi, Minho; Bergin, Edwin A.; Evans, Neal J.

    2017-08-01

    Understanding the formation of wide-binary systems of very low-mass stars (M ≤ 0.1 solar masses, M⊙) is challenging 1,2,3 . The most obvious route is through widely separated low-mass collapsing fragments produced by turbulent fragmentation of a molecular core4,5. However, close binaries or multiples from disk fragmentation can also evolve to wide binaries over a few initial crossing times of the stellar cluster through tidal evolution6. Finding an isolated low-mass wide-binary system in the earliest stage of formation, before tidal evolution could occur, would prove that turbulent fragmentation is a viable mechanism for (very) low-mass wide binaries. Here we report high-resolution ALMA observations of a known wide-separation protostellar binary, showing that each component has a circumstellar disk. The system is too young7 to have evolved from a close binary, and the disk axes are misaligned, providing strong support for the turbulent fragmentation model. Masses of both stars are derived from the Keplerian rotation of the disks; both are very low-mass stars.

  16. Supramolecular gel electrophoresis of large DNA fragments.

    Science.gov (United States)

    Tazawa, Shohei; Kobayashi, Kazuhiro; Oyoshi, Takanori; Yamanaka, Masamichi

    2017-07-06

    Pulsed-field gel electrophoresis is a frequent technique used to separate exceptionally large DNA fragments. In a typical continuous field electrophoresis, it is challenging to separate DNA fragments larger than 20 kbp because they migrate at a comparable rate. To overcome this challenge, it is necessary to develop a novel matrix for the electrophoresis. Here, we describe the electrophoresis of large DNA fragments up to 166 kbp using a supramolecular gel matrix and a typical continuous field electrophoresis system. C3 -symmetric tris-urea self-assembled into a supramolecular hydrogel in tris-boric acid-EDTA buffer, a typical buffer for DNA electrophoresis, and the supramolecular hydrogel was used as a matrix for electrophoresis to separate large DNA fragments. Three types of DNA marker, the λ-Hind III digest (2 to 23 kbp), Lambda DNA-Mono Cut Mix (10 to 49 kbp), and Marker 7 GT (10 to 165 kbp), were analyzed in this study. Large DNA fragments of greater than 100 kbp showed distinct mobility using a typical continuous field electrophoresis system. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Simvastatin inhibits CD44 fragmentation in chondrocytes.

    Science.gov (United States)

    Terabe, Kenya; Takahashi, Nobunori; Takemoto, Toki; Knudson, Warren; Ishiguro, Naoki; Kojima, Toshihisa

    2016-08-15

    In human osteoarthritic chondrocytes, the hyaluronan receptor CD44 undergoes proteolytic cleavage at the cell surface. CD44 cleavage is thought to require transit of CD44 into cholesterol-rich lipid rafts. The purpose of this study was to investigate whether statins exert a protective effect on articular chondrocytes due to diminution of cholesterol. Three model systems of chondrocytes were examined including human HCS-2/8 chondrosarcoma cells, human osteoarthritic chondrocytes and normal bovine articular chondrocytes. Treatment with IL-1β + Oncostatin M resulted in a substantial increase in CD44 fragmentation in each of the three chondrocyte models. Pre-incubation with simvastatin prior to treatment with IL-1β + Oncostatin M decreased the level of CD44 fragmentation, decreased the proportion of CD44 that transits into the lipid raft fractions, decreased ADAM10 activity and diminished the interaction between CD44 and ADAM10. In HCS-2/8 cells and bovine articular chondrocytes, fragmentation of CD44 was blocked by the knockdown of ADAM10. Inhibition of CD44 fragmentation by simvastatin also resulted in improved retention of pericellular matrix. Addition of cholesterol and farnesyl-pyrophosphate reversed the protective effects of simvastatin. Thus, the addition of simvastatin exerts positive effects on chondrocytes including reduced CD44 fragmentation and enhanced the retention of pericellular matrix. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Global-Scale Patterns of Forest Fragmentation

    Directory of Open Access Journals (Sweden)

    Kurt Riitters

    2000-12-01

    Full Text Available We report an analysis of forest fragmentation based on 1-km resolution land-cover maps for the globe. Measurements in analysis windows from 81 km 2 (9 x 9 pixels, "small" scale to 59,049 km 2 (243 x 243 pixels, "large" scale were used to characterize the fragmentation around each forested pixel. We identified six categories of fragmentation (interior, perforated, edge, transitional, patch, and undetermined from the amount of forest and its occurrence as adjacent forest pixels. Interior forest exists only at relatively small scales; at larger scales, forests are dominated by edge and patch conditions. At the smallest scale, there were significant differences in fragmentation among continents; within continents, there were significant differences among individual forest types. Tropical rain forest fragmentation was most severe in North America and least severe in Europe-Asia. Forest types with a high percentage of perforated conditions were mainly in North America (five types and Europe-Asia (four types, in both temperate and subtropical regions. Transitional and patch conditions were most common in 11 forest types, of which only a few would be considered as "naturally patchy" (e.g., dry woodland. The five forest types with the highest percentage of interior conditions were in North America; in decreasing order, they were cool rain forest, coniferous, conifer boreal, cool mixed, and cool broadleaf.

  19. Correlation measurements of fission-fragment properties

    Directory of Open Access Journals (Sweden)

    Oberstedt A.

    2010-10-01

    Full Text Available For the development of future nuclear fission applications and for a responsible handling of nuclear waste the a-priori assessment of the fission-fragments’ heat production and toxicity is a fundamental necessity. The success of an indispensable modelling of the fission process strongly depends on a good understanding of the particular mechanism of scission, the mass fragmentation and partition of excitation energy. Experimental observables are fission-fragment properties like mass- and energy-distributions, and the prompt neutron as well as γ-ray multiplicities and emission spectra. The latter quantities should preferably be known as a function of fragment mass and excitation energy. Those data are highly demanded as published by the OECD-NEA in its high priority data request list. With the construction of the double (v, E spectrometer VERDI we aim at measuring pre- and post-neutron masses directly and simultaneously to avoid prompt neutron corrections. From the simultaneous measurement of pre- and post-neutron fission-fragment data the prompt neutron multiplicity may then be inferred fully correlated with fragment mass yield and total kinetic energy. Using an ultra-fast fission event trigger spectral prompt fission γ-ray measurements may be performed. For that purpose recently developed lanthanum-halide detectors, with excellent timing characteristics, were coupled to the VERDI spectrometer allowing for a very good discrimination of fission γ-rays and prompt neutrons due to their different time-of-flight.

  20. Stream hydrological fragmentation drives bacterioplankton community composition.

    Directory of Open Access Journals (Sweden)

    Stefano Fazi

    Full Text Available In Mediterranean intermittent streams, the hydrological fragmentation in summer and the successive water flow re-convergence in autumn allow exploring how local processes shape the microbial community within the same habitat. The objectives of this study were to determine how bacterial community composition responded to hydrological fragmentation in summer, and to evaluate whether the seasonal shifts in community composition predominate over the effects of episodic habitat fragmentation. The bacterial community was assessed along the intermittent stream Fuirosos (Spain, at different levels of phylogenetic resolution by in situ hybridization, fingerprinting, and 16S rRNA gene sequencing. The hydrological fragmentation of the stream network strongly altered the biogeochemical conditions with the depletion of oxidized solutes and caused changes in dissolved organic carbon characteristics. In the isolated ponds, beta-Proteobacteria and Actinobacteria increased their abundance with a gradual reduction of the alpha-diversity as pond isolation time increased. Moreover, fingerprinting analysis clearly showed a shift in community composition between summer and autumn. In the context of a seasonal shift, the temporary stream fragmentation simultaneously reduced the microbial dispersion and affected local environmental conditions (shift in redox regime and quality of the dissolved organic matter tightly shaping the bacterioplankton community composition.

  1. Grain shape of basaltic ash populations: implications for fragmentation

    Science.gov (United States)

    Schmith, Johanne; Höskuldsson, Ármann; Holm, Paul Martin

    2017-02-01

    Here, we introduce a new quantitative method to produce grain shape data of bulk samples of volcanic ash, and we correlate the bulk average grain shape with magma fragmentation mechanisms. The method is based on automatic shape analysis of 2D projection ash grains in the size range 125-63 μm. Loose bulk samples from the deposits of six different basaltic eruptions were analyzed, and 20,000 shape measurements for each were obtained within 45 min using the Particle Insight™ dynamic shape analyzer (PIdsa). We used principal component analysis on a reference grain dataset to show that circularity, rectangularity, form factor, and elongation best discriminate between the grain shapes when combined. The grain population data show that the studied eruptive environments produce nearly the same range of grain shapes, although to different extents. Our new shape index (the regularity index (RI)) places an eruption on a spectrum between phreatomagmatic and dry magmatic fragmentation. Almost vesicle-free Surtseyan ash has an RI of 0.207 ± 0.002 (2σ), whereas vesiculated Hawaiian ash has an RI of 0.134 ± 0.001 (2σ). These two samples define the end-member RI, while two subglacial, one lacustrine, and another submarine ash sample show intermediate RIs of 0.168 ± 0.002 (2σ), 0.175 ± 0.002 (2σ), 0.187 ± 0.002 (2σ), and 0.191 ± 0.002 (2σ), respectively. The systematic change in RI between wet and dry eruptions suggests that the RI can be used to assess the relative roles of magmatic vs. phreatomagmatic fragmentation. We infer that both magmatic and phreatomagmatic fragmentation processes played a role in the subglacial eruptions.

  2. Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

    Directory of Open Access Journals (Sweden)

    MW Laschke

    2014-10-01

    Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

  3. Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway

    Directory of Open Access Journals (Sweden)

    José Aguilera

    2012-06-01

    Full Text Available When Clostridium tetani was discovered and identified as a Gram-positive anaerobic bacterium of the genus Clostridium, the possibility of turning its toxin into a valuable biological carrier to ameliorate neurodegenerative processes was inconceivable. However, the non-toxic carboxy-terminal fragment of the tetanus toxin heavy chain (fragment C can be retrogradely transported to the central nervous system; therefore, fragment C has been used as a valuable biological carrier of neurotrophic factors to ameliorate neurodegenerative processes. More recently, the neuroprotective properties of fragment C have also been described in vitro and in vivo, involving the activation of Akt kinase and extracellular signal-regulated kinase (ERK signaling cascades through neurotrophin tyrosine kinase (Trk receptors. Although the precise mechanism of the molecular internalization of fragment C in neuronal cells remains unknown, fragment C could be internalized and translocated into the neuronal cytosol through a clathrin-mediated pathway dependent on proteins, such as dynamin and AP-2. In this review, the origins, molecular properties and possible signaling pathways of fragment C are reviewed to understand the biochemical characteristics of its intracellular and synaptic transport.

  4. Identification of IGFBP-3 fragments generated by KLK2 and prevention of fragmentation by KLK2-inhibiting peptides.

    Science.gov (United States)

    Hekim, Can; Riipi, Tero; Weisell, Janne; Närvänen, Ale; Koistinen, Riitta; Stenman, Ulf-Håkan; Koistinen, Hannu

    2010-04-01

    Kallikrein-related peptidase 2 (KLK2) degrades insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in vitro. IGFBP-3 forms complexes with IGFs, preventing them from binding to their receptors and stimulating cell proliferation and survival. IGF-independent actions have also been described for IGFBP-3. The degradation of IGFBP-3 by KLK2 or other proteases in the prostate may promote the growth of prostate cancer. We studied IGFBP-3 degradation by immunoblotting and two specific immunoassays, one recognizing only native non-fragmented IGFBP-3 and the other one recognizing both intact and proteolytically cleaved IGFBP-3. Peptides were used to inhibit the enzyme activity of KLK2 and cleavage sites in IGFBP-3 were identified by mass spectrometry. KLK2 proteolyzed IGFBP-3 into several small fragments, mostly after Arg residues, in keeping with the trypsin-like activity of KLK2. The fragmentation could be inhibited by KLK2-inhibiting peptides in a dose-dependent fashion. As degradation of IGFBP-3 could lead to a more aggressive cancer phenotype, inhibition of KLK2 activity might be useful for treatment of prostate cancer and other diseases associated with increased KLK2 activity.

  5. GENETIC DIVERSITY AND THE ORIGINS OF CULTURAL FRAGMENTATION

    Science.gov (United States)

    Ashraf, Quamrul; Galor, Oded

    2013-01-01

    Despite the importance attributed to the effects of diversity on the stability and prosperity of nations, the origins of the uneven distribution of ethnic and cultural fragmentation across countries have been underexplored. Building on the role of deeply-rooted biogeographical forces in comparative development, this research empirically demonstrates that genetic diversity, predominantly determined during the prehistoric “out of Africa” migration of humans, is an underlying cause of various existing manifestations of ethnolinguistic heterogeneity. Further exploration of this uncharted territory may revolutionize the understanding of the effects of deeply-rooted factors on economic development and the composition of human capital across the globe. PMID:25506084

  6. Ternary fission fragmentation of 252Cf for all possible third fragments

    Science.gov (United States)

    Manimaran, K.; Balasubramaniam, M.

    2010-09-01

    The ternary fragmentation of 252Cf for all possible third fragments has been investigated using the recently proposed three-cluster model within a spherical approximation and satisfying the condition A 1 ≥ A 2 ≥ A 3 . The most probable ternary configurations in the fission of 252Cf accompanied with all possible third fragment mass numbers from A 3 = 1 to 84 are predicted and their independent and overall relative yields are calculated. The calculations of the properly charge minimized potential energy surface (PES) and yield reveal that even-mass third fragments are more favored than odd ones. In the most probable configuration having the minimum in the potential energy and the maximum in yield, among the three fragments, at least one (or two) of the fragment(s) associates itself with the neutron (or proton) closed shell and in some cases even with the doubly closed shell. The calculated relative yields imply that next to 14C (the heaviest third fragment observed in the spontaneous ternary fission of 252Cf , 34, 36, 38Si , 46, 48Ar , and 48, 50Ca are presenting themselves as the most favoured cases to be observed as the third particle in the spontaneous ternary fission of 252Cf.

  7. Fragmentation of methane molecules by antiproton impact

    Science.gov (United States)

    Salehzadeh, Arash; Kirchner, Tom

    2016-09-01

    Extending previous work for proton impact, we have investigated the fragmentation of methane molecules due to collisions with antiprotons in the 25 keV to 5 MeV impact energy range. The multi-center nature of the problem is addressed by using a spectral representation of the molecular Hartree-Fock-level Hamiltonian and a single-center expansion of the initially populated molecular orbitals. The two-center basis generator method (TC-BGM) is used for orbital propagation. Electron-removal cross sections obtained from the TC-BGM solutions are complemented with a dynamical decay-route fragmentation model to calculate cross sections for the production of fragment ions. Good agreement with the available experimental data is observed for CH4+,CH3+,CH2+and CH+. Work supported by NSERC, Canada.

  8. New information on photon fragmentation functions

    Science.gov (United States)

    Klasen, Michael; König, Florian

    2014-08-01

    Thermal photons radiated in heavy-ion collisions represent an important signal for a recently discovered new state of matter, the deconfined quark-gluon plasma. However, a clean identification of this signal requires precise knowledge of the prompt photons produced simultaneously in hard collisions of quarks and gluons, mostly through their fragmentation. In this paper, we demonstrate that PHENIX data on photons produced in proton-proton collisions with low transverse momenta allow to extract new information on this fragmentation process. While existing data do not yet convincingly favor one parameterization (BFG II) over the two other frequently used photon fragmentation functions (BFG I and GRV NLO), the data sets recorded by PHENIX and STAR at BNL RHIC in 2013 with tenfold higher statistics should allow for such an analysis.

  9. New information on photon fragmentation functions

    Energy Technology Data Exchange (ETDEWEB)

    Klasen, Michael; Koenig, Florian [Westfaelische Wilhelms-Universitaet Muenster, Institut fuer Theoretische Physik, Muenster (Germany)

    2014-08-15

    Thermal photons radiated in heavy-ion collisions represent an important signal for a recently discovered new state of matter, the deconfined quark-gluon plasma. However, a clean identification of this signal requires precise knowledge of the prompt photons produced simultaneously in hard collisions of quarks and gluons, mostly through their fragmentation. In this paper, we demonstrate that PHENIX data on photons produced in proton-proton collisions with low transverse momenta allow one to extract new information on this fragmentation process. While existing data do not yet convincingly favor one parameterization (BFG II) over the two other frequently used photon fragmentation functions (BFG I and GRV NLO), the data sets recorded by PHENIX and STAR at BNL RHIC in 2013 with tenfold higher statistics should allow for such an analysis. (orig.)

  10. Fragmentation of colliding planetesimals with water content

    CERN Document Server

    Maindl, Thomas I; Schäfer, Christoph; Speith, Roland

    2014-01-01

    We investigate the outcome of collisions of Ceres-sized planetesimals composed of a rocky core and a shell of water ice. These collisions are not only relevant for explaining the formation of planetary embryos in early planetary systems, but also provide insight into the formation of asteroid families and possible water transport via colliding small bodies. Earlier studies show characteristic collision velocities exceeding the bodies' mutual escape velocity which - along with the distribution of the impact angles - cover the collision outcome regimes 'partial accretion', 'erosion', and 'hit-and-run' leading to different expected fragmentation scenarios. Existing collision simulations use bodies composed of strengthless material; we study the distribution of fragments and their water contents considering the full elasto-plastic continuum mechanics equations also including brittle failure and fragmentation.

  11. Flow angle from intermediate mass fragment measurements

    Energy Technology Data Exchange (ETDEWEB)

    Rami, F.; Crochet, P.; Dona, R.; De Schauenburg, B.; Wagner, P.; Alard, J.P.; Andronic, A.; Basrak, Z.; Bastid, N.; Belyaev, I.; Bendarag, A.; Berek, G.; Best, D.; Caplar, R.; Devismes, A.; Dupieux, P.; Dzelalija, M.; Eskef, M.; Fodor, Z.; Gobbi, A.; Grishkin, Y.; Herrmann, N.; Hildenbrand, K.D.; Hong, B.; Kecskemeti, J.; Kirejczyk, M.; Korolija, M.; Kotte, R.; Lebedev, A.; Leifels, Y.; Merlitz, H.; Mohren, S.; Moisa, D.; Neubert, W.; Pelte, D.; Petrovici, M.; Pinkenburg, C.; Plettner, C.; Reisdorf, W.; Schuell, D.; Seres, Z.; Sikora, B.; Simion, V.; Siwek-Wilczynska, K.; Stoicea, G.; Stockmeir, M.; Vasiliev, M.; Wisniewski, K.; Wohlfarth, D.; Yushmanov, I.; Zhilin, A

    1999-02-15

    Directed sideward flow of light charged particles and intermediate mass fragments was measured in different symmetric reactions at bombarding energies from 90 to 800 A MeV. The flow parameter is found to increase with the charge of the detected fragment up to Z = 3-4 and then turns into saturation for heavier fragments. Guided by simple simulations of an anisotropic expanding thermal source, we show that the value at saturation can provide a good estimate of the flow angle, {theta}{sub flow}, in the participant region. It is found that {theta}{sub flow} depends strongly on the impact parameter. The excitation function of {theta}{sub flow} reveals striking deviations from the ideal hydrodynamical scaling. The data exhibit a steep rise of {theta}{sub flow} to a maximum at around 250 - 400 A MeV, followed by a moderate decrease as the bombarding energy increases further.

  12. Fragmentation of Kozai–Lidov Disks

    Science.gov (United States)

    Fu, Wen; Lubow, Stephen H.; Martin, Rebecca G.

    2017-02-01

    We analyze the gravitational instability (GI) of a locally isothermal inclined disk around one component of a binary system. Such a disk can undergo global Kozai–Lidov (KL) cycles if the initial disk tilt is above the critical KL angle (of about 40◦). During these cycles, an initially circular disk exchanges its inclination for eccentricity, and vice versa. Self-gravity may suppress the cycles under some circumstances. However, with hydrodynamic simulations that include self-gravity, we show that for a sufficiently high initial disk tilts and for certain disk masses, disks can undergo KL oscillations and fragment due to GI, even when the Toomre Q value for an equivalent undisturbed disk is well within the stable regime (Q> 2). We suggest that KL triggered disk fragmentation provides a mechanism for the efficient formation of giant planets in binary systems and may enhance the fragmentation of disks in massive black hole binaries.

  13. Antiproton Induced Fission and Fragmentation of Nuclei

    CERN Multimedia

    2002-01-01

    The annihilation of slow antiprotons with nuclei results in a large highly localized energy deposition primarily on the nuclear surface. \\\\ \\\\ The study of antiproton induced fission and fragmentation processes is expected to yield new information on special nuclear matter states, unexplored fission modes, multifragmentation of nuclei, and intranuclear cascades.\\\\ \\\\ In order to investigate the antiproton-nucleus interaction and the processes following the antiproton annihilation at the nucleus, we propose the following experiments: \\item A)~Measurement of several fragments from fission and from multifragmentation in coincidence with particle spectra, especially neutrons and kaons. \\item B)~Precise spectra of $\\pi$, K, n, p, d and t with time-of-flight techniques. \\item C)~Installation of the Berlin 4$\\pi$ neutron detector with a 4$\\pi$ Si detector placed inside for fragments and charged particles. This yields neutron multiplicity distributions and consequently distributions of thermal excitation energies and...

  14. Parton-to-Pion Fragmentation Reloaded

    CERN Document Server

    de Florian, D; Epele, M; Hernandez-Pinto, R J; Stratmann, M

    2014-01-01

    We present a new, comprehensive global analysis of parton-to-pion fragmentation functions at next-to-leading order accuracy in QCD. The obtained results are based on the latest experimental information on single-inclusive pion production in electron-positron annihilation, lepton-nucleon deep-inelastic scattering, and proton-proton collisions. An excellent description of all data sets is achieved, and the remaining uncertainties in parton-to-pion fragmentation functions are estimated based on the Hessian method. Extensive comparisons to the results from our previous global analysis are performed.

  15. Laser photoluminescence spectroscopy of photodissociation fragments

    Science.gov (United States)

    Jackson, W. M.; Cody, R. J.

    1974-01-01

    Laser induced photoluminescence spectroscopy has been used to study the energy partitioning among CN fragments produced by the photodissociation of C2N2. The CN radicals are produced in both the A 2Pi and the X 2Sigma+ states. The A state is formed primarily in the nu-prime = 0 level, and the X state is formed in the lower vibrational levels. Since the photodissociation process does not produce the maximum amount of vibrational excitation in the CN fragments, it is suggested that the excess energy goes into either translational and/or rotational excitation of the CN.

  16. Limit theorems for fragmentation processes with immigration

    CERN Document Server

    Knobloch, Robert

    2012-01-01

    In this paper we extend two limit theorems which were recently obtained for fragmentation processes to such processes with immigration. More precisely, in the setting with immigration we consider a limit theorem for the process counted with a random characteristic as well as the asymptotic behaviour of an empirical measure associated with the stopping line corresponding to the first blocks, in their respective line of descent, that are smaller than a given size. In addition, we determine the asymptotic decay rate of the size of the largest block in a homogeneous fragmentation process with immigration. The techniques used to proves these results are based on submartingale arguments.

  17. Radio Frequency Fragment Separator at NSCL

    Energy Technology Data Exchange (ETDEWEB)

    Bazin, D. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States)], E-mail: bazin@nscl.msu.edu; Andreev, V. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Becerril, A. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Joint Institute for Nuclear Astrophysics, Michigan State University, East Lansing, MI 48824 (United States); Doleans, M. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824 (United States); Mantica, P.F. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States); Ottarson, J. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Schatz, H. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Joint Institute for Nuclear Astrophysics, Michigan State University, East Lansing, MI 48824 (United States); Stoker, J.B. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States); Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States); Vincent, J. [National Superconducting Cyclotron Laboratory, Michigan State University, East Lansing, MI 48824-1321 (United States)

    2009-07-21

    A new device has been designed and built at NSCL which provides additional filtering of radioactive beams produced via projectile fragmentation. The Radio Frequency Fragment Separator (RFFS) uses the time micro structure of the beams accelerated by the cyclotrons to deflect particles according to their time-of-flight, in effect producing a phase filtering. The transverse RF (Radio Frequency) electric field of the RFFS has superior filtering performance compared to other electrostatic devices, such as Wien filters. Such filtering is critical for radioactive beams produced on the neutron-deficient side of the valley of stability, where strong contamination occurs at intermediate energies from 50 to 200 MeV/u.

  18. Parton Propagation and Fragmentation in QCD Matter

    Energy Technology Data Exchange (ETDEWEB)

    Alberto Accardi, Francois Arleo, William Brooks, David D' Enterria, Valeria Muccifora

    2009-12-01

    We review recent progress in the study of parton propagation, interaction and fragmentation in both cold and hot strongly interacting matter. Experimental highlights on high-energy hadron production in deep inelastic lepton-nucleus scattering, proton-nucleus and heavy-ion collisions, as well as Drell-Yan processes in hadron-nucleus collisions are presented. The existing theoretical frameworks for describing the in-medium interaction of energetic partons and the space-time evolution of their fragmentation into hadrons are discussed and confronted to experimental data. We conclude with a list of theoretical and experimental open issues, and a brief description of future relevant experiments and facilities.

  19. Radio Frequency Fragment Separator at NSCL

    Science.gov (United States)

    Bazin, D.; Andreev, V.; Becerril, A.; Doléans, M.; Mantica, P. F.; Ottarson, J.; Schatz, H.; Stoker, J. B.; Vincent, J.

    2009-07-01

    A new device has been designed and built at NSCL which provides additional filtering of radioactive beams produced via projectile fragmentation. The Radio Frequency Fragment Separator (RFFS) uses the time micro structure of the beams accelerated by the cyclotrons to deflect particles according to their time-of-flight, in effect producing a phase filtering. The transverse RF (Radio Frequency) electric field of the RFFS has superior filtering performance compared to other electrostatic devices, such as Wien filters. Such filtering is critical for radioactive beams produced on the neutron-deficient side of the valley of stability, where strong contamination occurs at intermediate energies from 50 to 200 MeV/u.

  20. Eigenmodes of decay and discrete fragmentation processes

    CERN Document Server

    Giraud, B G; Giraud, B G; Peschanski, R

    1994-01-01

    Linear rate equations are used to describe the cascading decay of an initial heavy cluster into fragments. This representation is based upon a triangular matrix of transition rates. We expand the state vector of mass multiplicities, which describes the process, into the biorthonormal basis of eigenmodes provided by the triangular matrix. When the transition rates have a scaling property in terms of mass ratios at binary fragmentation vertices, we obtain solvable models with explicit mathematical properties for the eigenmodes. A suitable continuous limit provides an interpolation between the solvable models. It gives a general relationship between the decay products and the elementary transition rates.

  1. Computer Model Of Fragmentation Of Atomic Nuclei

    Science.gov (United States)

    Wilson, John W.; Townsend, Lawrence W.; Tripathi, Ram K.; Norbury, John W.; KHAN FERDOUS; Badavi, Francis F.

    1995-01-01

    High Charge and Energy Semiempirical Nuclear Fragmentation Model (HZEFRG1) computer program developed to be computationally efficient, user-friendly, physics-based program for generating data bases on fragmentation of atomic nuclei. Data bases generated used in calculations pertaining to such radiation-transport applications as shielding against radiation in outer space, radiation dosimetry in outer space, cancer therapy in laboratories with beams of heavy ions, and simulation studies for designing detectors for experiments in nuclear physics. Provides cross sections for production of individual elements and isotopes in breakups of high-energy heavy ions by combined nuclear and Coulomb fields of interacting nuclei. Written in ANSI FORTRAN 77.

  2. Dissipative fragmentation in a phase space approach

    Energy Technology Data Exchange (ETDEWEB)

    Adorno, A.; Di Toro, M.; Bonasera, A.; Gregoire, C.; Gulminelli, F.

    Semi-classical approaches have evidenced the role of one and two-body dissipation in nucleus-nucleus collisions. On the other hand, a substantial energy dissipation and some angular momentum transfer have been observed at moderate energy where a fragmentation process is the dominant reaction mechanism. In order to analyse main features of these reactions, we developed a phenomenological model taking into account phase space constraints. The transition between deep inelastic collisions and abrasion-like fragmentation is described and a general agreement with available data is found.

  3. Association of pteridophyte species in two fragments of Atlantic Coastal Forest in the Brazilian Northeast

    Directory of Open Access Journals (Sweden)

    Iva Carneiro Leão Barros

    2006-09-01

    Full Text Available This study aims to investigate fern flora similarity and fern species relationships in the study areas, in terms of their substrates, habitat types, and life forms. The study was conducted in the Água Azul forest fragment, municipality of Timbaúba, Pernambuco, and the Maria Maior forest fragment, municipality of São José da Laje, Alagoas. The Jaccard similarity index was used for cluster analysis. The 112 species that occur in the two areas were used for numerical analysis. The floristic similarity was great (J=43.75%, principally due to similarities in the two areas vegetational types, as was expected due to their geographic proximity to one another and their similar climatic conditions. Five groups of associated species were determined for the Água Azul fragment and six groups for the Maria Maior fragment. In general, the ecological factors that determined fern species associations were habitat and type of substrate.

  4. Oral heparin results in the appearance of heparin fragments in the plasma of rats

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, A.K.; Lund, D.P.; Langer, R.; Folkman, J.

    1986-05-01

    We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of (/sup 35/S)heparin or (/sup 3/H)heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion.

  5. Responses of seed-dispersing birds to amount of rainforest in the landscape around fragments.

    Science.gov (United States)

    Moran, Cath; Catterall, Carla P

    2014-04-01

    Habitat loss and fragmentation alter the composition of bird assemblages in rainforest. Because birds are major seed dispersers in rainforests, fragmentation-induced changes to frugivorous bird assemblages are also likely to alter the ecological processes of seed dispersal and forest regeneration, but the specific nature of these changes is poorly understood. We assessed the influence of fragment size and landscape forest cover on the abundance, species composition, and functional properties of the avian seed disperser community in an extensively cleared, former rainforest landscape of subtropical Australia. Bird surveys of fixed time and area in 25 rainforest fragments (1-139 ha in size across a 1800 km(2) region) provided bird assemblage data which were coupled with prior knowledge of bird species' particular roles in seed dispersal to give measurements of seven different attributes of the seed disperser assemblage. We used multimodel regression to assess how patch size and surrounding forest cover (within 200 m, 1000 m, and 5000 m radii) influenced variation in the abundance of individual bird species and of functional groups based on bird species' responses to fragmentation and their roles in seed dispersal. Surrounding forest cover, specifically rainforest cover, generally had a greater effect on frugivorous bird assemblages than fragment size. Amount of rainforest cover within 200 m of fragments was the main factor positively associated with abundances of frugivorous birds that are both fragmentation sensitive and important seed dispersers. Our results suggest a high proportion of local rainforest cover is required for the persistence of seed-dispersing birds and the maintenance of seed dispersal processes. Thus, even small rainforest fragments can function as important parts of habitat networks for seed-dispersing birds, whether or not they are physically connected by vegetation. © 2014 Society for Conservation Biology.

  6. Grain fragmentation in ultrasonic-assisted TIG weld of pure aluminum.

    Science.gov (United States)

    Chen, Qihao; Lin, Sanbao; Yang, Chunli; Fan, Chenglei; Ge, Hongliang

    2017-11-01

    Under the action of acoustic waves during an ultrasonic-assisted tungsten inert gas (TIG) welding process, a grain of a TIG weld of aluminum alloy is refined by nucleation and grain fragmentation. Herein, effects of ultrasound on grain fragmentation in the TIG weld of aluminum alloy are investigated via systematic welding experiments of pure aluminum. First, experiments involving continuous and fixed-position welding are performed, which demonstrate that ultrasound can break the grain of the TIG weld of pure aluminum. The microstructural characteristics of an ultrasonic-assisted TIG weld fabricated by fixed-position welding are analyzed. The microstructure is found to transform from plane crystal, columnar crystal, and uniform equiaxed crystal into plane crystal, deformed columnar crystal, and nonuniform equiaxed crystal after application of ultrasound. Second, factors influencing ultrasonic grain fragmentation are investigated. The ultrasonic amplitude and welding current are found to have a considerable effect on grain fragmentation. The degree of fragmentation first increases and then decreases with an increase in ultrasonic amplitude, and it increases with an increase in welding current. Measurement results of the vibration of the weld pool show that the degree of grain fragmentation is related to the intensity of acoustic nonlinearity in the weld pool. The greater the intensity of acoustic nonlinearity, the greater is the degree of grain fragmentation. Finally, the mechanism of ultrasonic grain fragmentation in the TIG weld of pure aluminum is discussed. A finite element simulation is used to simulate the acoustic pressure and flow in the weld pool. The acoustic pressure in the weld pool exceeds the cavitation threshold, and cavitation bubbles are generated. The flow velocity in the weld pool does not change noticeably after application of ultrasound. It is concluded that the high-pressure conditions induced during the occurrence of cavitation, lead to grain

  7. Postoperative care fragmentation and thirty-day unplanned readmissions after head and neck cancer surgery.

    Science.gov (United States)

    Graboyes, Evan M; Kallogjeri, Dorina; Saeed, Mohammed J; Olsen, Margaret A; Nussenbaum, Brian

    2017-04-01

    Postdischarge care fragmentation, readmission to a hospital other than the one performing the surgery, has not been described in head and neck cancer patients. We sought to determine the frequency, risk factors, and outcomes for head and neck cancer patients experiencing postdischarge care fragmentation. Retrospective cohort study. We analyzed patients in the 2008 to 2010 California State Inpatient Database with a 30-day unplanned readmission following head and neck cancer surgery. The frequency of postdischarge care fragmentation, patient- and hospital-level risk factors for care fragmentation, readmission diagnosis, and readmission outcomes were determined. Of 561 patients with a 30-day unplanned readmission, 210 (37.4%) were readmitted to a hospital other than the one performing the surgery. Surgical hospitalization length of stay ≥15 days (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.13-3.10) and discharge to a care facility (OR: 2.85, 95% CI: 1.77-4.58) were associated with care fragmentation. Overall, 39.8% of unplanned 30-day readmissions (223/561) were treatment complications, and 30.9% of treatment complication readmissions (69/223) occurred at a nonindex hospital. Patients with postdischarge care fragmentation had a 2.1-fold increased risk of in-hospital mortality within 30 days of readmission compared to patients readmitted to the index hospital (95% CI: 1.04-4.26). Postdischarge care fragmentation following head an neck cancer surgery is common, as 37% of readmitted patients and 31% of patients readmitted with a treatment complication are readmitted to a hospital other than the surgical hospital. Head and neck cancer patients experiencing care fragmentation are at increased risk of in-hospital mortality within 30 days of readmission. 4. Laryngoscope, 127:868-874, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  8. The relationship between sperm viability and DNA fragmentation rates

    OpenAIRE

    Mary K. Samplaski; Dimitromanolakis, Apostolos; Lo, Kirk C; Grober, Ethan D.; Mullen, Brendan; Garbens, Alaina; Jarvi, Keith A

    2015-01-01

    Background In humans, sperm DNA fragmentation rates have been correlated with sperm viability rates. Reduced sperm viability is associated with high sperm DNA fragmentation, while conversely high sperm viability is associated with low rates of sperm DNA fragmentation. Both elevated DNA fragmentation rates and poor viability are correlated with impaired male fertility, with a DNA fragmentation rate of > 30% indicating subfertility. We postulated that in some men, the sperm viability assay coul...

  9. The study of cytokeratin 18 fragments and inflammation related factors in non -alcoholic fatty liver disease%角蛋白18片段与炎症相关因子在脂肪性肝病诊断中的作用

    Institute of Scientific and Technical Information of China (English)

    李良平; 钟黄

    2012-01-01

    Objective To explore the clinical significance of the blood cytokeratin -18(CK-18) fragments and inflammation related cyto-kines level in nonalcoholic fatty liver disease( NAFLD) with metabolism syndrome (MS) ,and provide the evidence for preventing severe liver disease in these patients from early stage. Methods A total of 85 cases of NAFLD patient were enrolled in the study and 20 normal were recruited as normal control. All the 85 patients were divided into two groups according to whether or not combined with the metabolic syndrome as (NAFLD + MS) group and NAFLD group and 20 normal cases designated as normal control groups (NC). Serum level of CK -18 fragment (M30 - antigen) and total CK - 18 ( M65 -antigen) and inflammation related cytokines (TNFα > IL -6) were determined by ELISA. Level of hs - CRP was tested by rate of scattering method. Results There was a statistical significance of CK - 18 fragment serum level in MS + NAFLD group[ (143 ±38.7)ng/L] compared to NAFLD group and NC group (F = 4.251 andP<0.05 respectively). Serum TNF -alpha level in MS + NAFLD and NALFD group were higher[ (316 74. 5)ng/L] than NC group( F = 6. 994, P <0. 05). Hs - CRP, IL -6 plasma, ALT and GGT level was higher in MS + NAFLD than in NALFD and NC group(P <0.05) . Conclusion CK - 18 fragment combing with inflammation related factors may play a role in monitoring and preventing before severe liver disease in NAFLD.%目的 探讨非酒精性脂肪性肝病(NAFLD)伴代谢综合征(MS)的患者细胞角蛋白18片段、炎症相关因子的表达水平,为临床早期预防NAFLD伴有MS的患者向严重肝病进展提供依据.方法 采用横断面调查研究,成组设计.入组85例脂肪肝患者及20例正常对照者.根据是否伴MS分为三组:NAFLD +MS组、NAFLD组、NC组.采用酶联免疫吸附法(ELISA)检测各组血清中细胞角蛋白18片段、炎症相关因子肿瘤坏死因子(TNF)α、白细胞介素6(IL-6)表达水平.通过速率散射比浊法检测

  10. Inclusion: The Unifying Thread for Fragmented Metaphors

    Science.gov (United States)

    Doyle, Lynn H.

    2004-01-01

    The fabric of educational leadership is changing. Murphy (2001) has suggested three new metaphors for educational leaders: moral stewards, builders of communities, and educators for school improvement. However, shifting priorities and contradictions between these metaphors could result in fragmentation within the field. This article discusses…

  11. Modelling of the PELE fragmentation dynamics

    NARCIS (Netherlands)

    Verreault, J.

    2014-01-01

    The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a la

  12. Metagenome Fragment Classification Using -Mer Frequency Profiles

    Directory of Open Access Journals (Sweden)

    Gail Rosen

    2008-01-01

    Full Text Available A vast amount of microbial sequencing data is being generated through large-scale projects in ecology, agriculture, and human health. Efficient high-throughput methods are needed to analyze the mass amounts of metagenomic data, all DNA present in an environmental sample. A major obstacle in metagenomics is the inability to obtain accuracy using technology that yields short reads. We construct the unique -mer frequency profiles of 635 microbial genomes publicly available as of February 2008. These profiles are used to train a naive Bayes classifier (NBC that can be used to identify the genome of any fragment. We show that our method is comparable to BLAST for small 25 bp fragments but does not have the ambiguity of BLAST's tied top scores. We demonstrate that this approach is scalable to identify any fragment from hundreds of genomes. It also performs quite well at the strain, species, and genera levels and achieves strain resolution despite classifying ubiquitous genomic fragments (gene and nongene regions. Cross-validation analysis demonstrates that species-accuracy achieves 90% for highly-represented species containing an average of 8 strains. We demonstrate that such a tool can be used on the Sargasso Sea dataset, and our analysis shows that NBC can be further enhanced.

  13. [Fragmented QRS. Relevance in clinical practice].

    Science.gov (United States)

    Steger, Alexander; Sinnecker, Daniel; Berkefeld, Anna; Müller, Alexander; Gebhardt, Josef; Dommasch, Michael; Huster, Katharina M; Barthel, Petra; Schmidt, Georg

    2015-09-01

    The QRS complex represents the electrical depolarization of ventricular myocardium. In the case of an undisturbed depolarization, the QRS complex has a normal configuration and duration, but abnormal electrical conduction leads to widening of the QRS complex. The block of one of the Tawara branches results in a typical bundle branch block pattern. A QRS complex that cannot be classified as bundle branch block due to an atypical configuration and contains notched R or S waves is called a fragmented QRS. The underlying pathophysiologies are manifold and include myocardial scars induced by ischemic heart disease, myocardial fibrosis due to other diseases, primary cardiac pathologies as well as systemic diseases with cardiac involvement. Pathologies on the cellular level, such as ion channel dysfunctions, also correlate with fragmented QRS. Besides the diagnostic relevance, fragmented QRS is known to have prognostic properties, for example in identifying high risk patients with coronary artery disease, cardiomyopathy, Brugada syndrome and acquired long QT syndrome; however, fragmented QRS may also be detected in ECGs of healthy individuals.

  14. Element Distribution and Multiplicity of Heavy Fragments

    CERN Multimedia

    2002-01-01

    This experiment will measure the energy and angular distribution of heavy fragments produced in the reactions of |1|2C on several targets between |2|7Al and |2|3|8U at 86~MeV/u. The systematic investigation of a highly excited interaction region (fireball) by means of a clean N and Z identification of heavy tar fragments, may result in a better understanding of temperature concept and of the degree of equilibration of the local interaction region with respect to the total system. For this investigation a large-area position sensitive ionization chamber of 50~msr solid angle in conjunction with a time-of-flight telescope consisting of parallel-plate detectors will be used. \\\\ \\\\ In order to get information on the transverse momentum transfer and the inelasticity of the collision, the energy of the PROJECTILE-FRAGMENTS will be measured at forward angles with a plastic scintillator hodoscope. In addition to this inclusive measurement correlations between heavy fragments will be investigated by means of three pos...

  15. Distribution and Causes of Global Forest Fragmentation

    Directory of Open Access Journals (Sweden)

    K. Bruce Jones

    2003-12-01

    Full Text Available Because human land uses tend to expand over time, forests that share a high proportion of their borders with anthropogenic uses are at higher risk of further degradation than forests that share a high proportion of their borders with non-forest, natural land cover (e.g., wetland. Using 1-km advanced very high resolution radiometer (AVHRR satellite-based land cover, we present a method to separate forest fragmentation into natural and anthropogenic components, and report results for all inhabited continents summarized by World Wildlife Fund biomes. Globally, over half of the temperate broadleaf and mixed forest biome and nearly one quarter of the tropical rainforest biome have been fragmented or removed by humans, as opposed to only 4% of the boreal forest. Overall, Europe had the most human-caused fragmentation and South America the least. This method may allow for improved risk assessments and better targeting for protection and remediation by identifying areas with high amounts of human-caused fragmentation.

  16. DFT STUDIES OF DP-3 AMYLOSE FRAGMENTS

    Science.gov (United States)

    This study extends our work on mono- and disaccharides to structures with three glucose residues by two alpha-[1-4] bridges, denoted herein as DP-3's. DFT optimization studies of DP-3 fragments have been carried out at the B3LYP/6-311++G** level of theory. Different hydroxymethyl conformations (gg...

  17. Conformational studies of cellulosic fragments by DFT

    Science.gov (United States)

    The study of cellulosic fragments by DFTr is a continuation of our efforts to produce quality structural data that will be valuable to those working in the field of cellulose structure and enzymatic degradation. Using a reduced basis set and density functional DFTr (B3LYP), optimization of cellulosi...

  18. Computations in Fragments of Intuitionistic Propositional Logic

    NARCIS (Netherlands)

    Jongh, Dick de; Hendriks, Lex; Renardel de Lavalette, Gerard R.

    1991-01-01

    This article is a report on research in progress into the structure of finite diagrams of intuitionistic propositional logic with the aid of automated reasoning systems for larger calculations. A fragment of a propositional logic is the set of formulae built up from a finite number of propositional

  19. Oscillating Filaments. I. Oscillation and Geometrical Fragmentation

    Science.gov (United States)

    Gritschneder, Matthias; Heigl, Stefan; Burkert, Andreas

    2017-01-01

    We study the stability of filaments in equilibrium between gravity and internal as well as external pressure using the grid-based AMR code RAMSES. A homogeneous, straight cylinder below a critical line mass is marginally stable. However, if the cylinder is bent, such as with a slight sinusoidal perturbation, an otherwise stable configuration starts to oscillate, is triggered into fragmentation, and collapses. This previously unstudied behavior allows a filament to fragment at any given scale, as long as it has slight bends. We call this process “geometrical fragmentation.” In our realization, the spacing between the cores matches the wavelength of the sinusoidal perturbation, whereas up to now, filaments were thought to be only fragmenting on the characteristic scale set by the mass-to-line ratio. Using first principles, we derive the oscillation period as well as the collapse timescale analytically. To enable a direct comparison with observations, we study the line-of-sight velocity for different inclinations. We show that the overall oscillation pattern can hide the infall signature of cores.

  20. Intraday Price Discovery in Fragmented Markets

    NARCIS (Netherlands)

    S.R. Ozturk (Sait); M. van der Wel (Michel); D.J.C. van Dijk (Dick)

    2014-01-01

    textabstractFor many assets, trading is fragmented across multiple exchanges. Price discovery measures summarize the informativeness of trading on each venue for discovering the asset’s true underlying value. We explore intraday variation in price discovery using a structural model with

  1. Modelling of the PELE fragmentation dynamics

    NARCIS (Netherlands)

    Verreault, J.

    2014-01-01

    The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a

  2. Modelling of the PELE fragmentation dynamics

    Science.gov (United States)

    Verreault, J.

    2014-05-01

    The Penetrator with Enhanced Lateral Effect (PELE) is a type of explosive-free projectile that undergoes radial fragmentation upon an impact with a target plate. This type of projectile is composed of a brittle cylindrical shell (the jacket) filled in its core with a material characterized with a large Poisson's ratio. Upon an impact with a target, the axial compression causes the filling to expand in the radial direction. However, due to the brittleness of the jacket material, very little radial deformation can occur which creates a radial stress between the two materials and a hoop stress in the jacket. Fragmentation of the jacket occurs if the hoop stress exceeds the material's ultimate stress. The PELE fragmentation dynamics is explored via Finite-Element Method (FEM) simulations using the Autodyn explicit dynamics hydrocode. The numerical results are compared with an analytical model based on wave interactions, as well as with the experimental investigation of Paulus and Schirm (1996). The comparison is based on the mechanical stress in the filling and the qualitative fragmentation of the jacket.

  3. Searching Fragment Spaces with feature trees.

    Science.gov (United States)

    Lessel, Uta; Wellenzohn, Bernd; Lilienthal, Markus; Claussen, Holger

    2009-02-01

    Virtual combinatorial chemistry easily produces billions of compounds, for which conventional virtual screening cannot be performed even with the fastest methods available. An efficient solution for such a scenario is the generation of Fragment Spaces, which encode huge numbers of virtual compounds by their fragments/reagents and rules of how to combine them. Similarity-based searches can be performed in such spaces without ever fully enumerating all virtual products. Here we describe the generation of a huge Fragment Space encoding about 5 * 10(11) compounds based on established in-house synthesis protocols for combinatorial libraries, i.e., we encode practically evaluated combinatorial chemistry protocols in a machine readable form, rendering them accessible to in silico search methods. We show how such searches in this Fragment Space can be integrated as a first step in an overall workflow. It reduces the extremely huge number of virtual products by several orders of magnitude so that the resulting list of molecules becomes more manageable for further more elaborated and time-consuming analysis steps. Results of a case study are presented and discussed, which lead to some general conclusions for an efficient expansion of the chemical space to be screened in pharmaceutical companies.

  4. Fragmentation of forest, grassland, and shrubland

    Science.gov (United States)

    Kurt H. Riitters

    2013-01-01

    As humans introduce competing land uses into natural landscapes, the public concerns regarding landcover patterns are expressed through headline issues such as urban sprawl, forest fragmentation, water quality, and wilderness preservation. The spatial arrangement of an environment affects all human perceptions and ecological processes within that environment, but this...

  5. The paradox of forest fragmentation genetics

    Science.gov (United States)

    Andrea T. Kramer; Jennifer L. Ison; Mary V. Ashley; Henry F. Howe

    2008-01-01

    Theory predicts widespread loss of genetic diversity from drift and inbreeding in trees subjected to habitat fragmentation, yet empirical support of this theory is scarce. We argue that population genetics theory may be misapplied in light of ecological realities that, when recognized, require scrutiny of underlying evolutionary assumptions. One ecological reality is...

  6. Targeting incentives to reduce habitat fragmentation

    Science.gov (United States)

    David Lewis; Andrew Plantinga; Junjie Wu

    2009-01-01

    This article develops a theoretical model to analyze the spatial targeting of incentives for the restoration of forested landscapes when wildlife habitat can be enhanced by reducing fragmentation. The key theoretical result is that the marginal net benefits of increasing forest can be convex, in which case corner solutions--converting either none or all of the...

  7. Brownian shape motion: Fission fragment mass distributions

    Directory of Open Access Journals (Sweden)

    Sierk Arnold J.

    2012-02-01

    Full Text Available It was recently shown that remarkably accurate fission-fragment mass distributions can be obtained by treating the nuclear shape evolution as a Brownian walk on previously calculated five-dimensional potential-energy surfaces; the current status of this novel method is described here.

  8. Fragment size distribution statistics in dynamic fragmentation of laser shock-loaded tin

    Directory of Open Access Journals (Sweden)

    Weihua He

    2017-06-01

    Full Text Available This work investigates the geometric statistics method to characterize the size distribution of tin fragments produced in the laser shock-loaded dynamic fragmentation process. In the shock experiments, the ejection of the tin sample with etched V-shape groove in the free surface are collected by the soft recovery technique. Subsequently, the produced fragments are automatically detected with the fine post-shot analysis techniques including the X-ray micro-tomography and the improved watershed method. To characterize the size distributions of the fragments, a theoretical random geometric statistics model based on Poisson mixtures is derived for dynamic heterogeneous fragmentation problem, which reveals linear combinational exponential distribution. The experimental data related to fragment size distributions of the laser shock-loaded tin sample are examined with the proposed theoretical model, and its fitting performance is compared with that of other state-of-the-art fragment size distribution models. The comparison results prove that our proposed model can provide far more reasonable fitting result for the laser shock-loaded tin.

  9. Fragmentation characteristics analysis of sandstone fragments based on impact rockburst test

    Directory of Open Access Journals (Sweden)

    Dongqiao Liu

    2014-06-01

    Full Text Available Impact rockburst test on sandstone samples with a central hole is carried out under true triaxial static loads and vertical dynamic load conditions, and rock fragments after the test are collected. The fragments of sandstone generated from strain rockburst test and uniaxial compression test are also collected. The fragments are weighed and the length, width and thickness of each piece of fragments are measured respectively. The fragment quantities with coarse, medium, fine and micro grains in different size ranges, mass and particles distributions are also analyzed. Then, the fractal dimension of fragments is calculated by the methods of size-frequency, mass-frequency and length-to-thickness ratio-frequency. It is found that the crushing degree of impact rockburst fragments is higher, accompanied with blocky characteristics observably. The mass percentage of small grains, including fine and micro grains, in impact rockburst test is higher than those in strain rockburst test and uniaxial compression test. Energy dissipation from rockburst tests is more than that from uniaxial compression test, as the quantity of micro grains generated does.

  10. Fragmentation characteristics analysis of sandstone fragments based on impact rockburst test

    Institute of Scientific and Technical Information of China (English)

    Dongqiao Liu; Dejian Li; Fei Zhao; Chengchao Wang

    2014-01-01

    Impact rockburst test on sandstone samples with a central hole is carried out under true triaxial static loads and vertical dynamic load conditions, and rock fragments after the test are collected. The fragments of sandstone generated from strain rockburst test and uniaxial compression test are also collected. The fragments are weighed and the length, width and thickness of each piece of fragments are measured respectively. The fragment quantities with coarse, medium, fine and micro grains in different size ranges, mass and particles distributions are also analyzed. Then, the fractal dimension of fragments is calculated by the methods of size-frequency, mass-frequency and length-to-thickness ratio-frequency. It is found that the crushing degree of impact rockburst fragments is higher, accompanied with blocky character-istics observably. The mass percentage of small grains, including fine and micro grains, in impact rock-burst test is higher than those in strain rockburst test and uniaxial compression test. Energy dissipation from rockburst tests is more than that from uniaxial compression test, as the quantity of micro grains generated does.

  11. A decadal view of magma fragmentation

    Science.gov (United States)

    Cashman, K. V.; Rust, A.

    2010-12-01

    Although the past decade has seen fundamental advances in studies of explosive volcanism, the disruption to air traffic caused by the 2010 eruption of Eyjafjallajökull, Iceland, highlights the need for improved understanding of magmatic fragmentation in general, and of fine ash generation in particular. To develop a theoretical basis for predicting the fine ash content of eruptive plumes, we need to understand not only fragmentation mechanisms but also the dependence of those mechanisms on conditions of magma ascent and degassing. Experimental and analytical approaches to this problem include experimental studies of vesiculation and permeability development in silicic melts, quantitative textural studies of pyroclasts to constrain conditions that reduce fragmentation efficiency (that is, allow vesicular clasts to be preserved), direct experiments on fragmentation in both natural and analog materials, and determination of total grain size distributions (TGSDs) of pyroclastic deposits. Experiments on silicic melts have demonstrated that very high supersaturations (overpressures ΔP) may be achieved in silicic melts prior to homogeneous bubble nucleation, and that the high bubble number densities of silicic pumice require not only homogeneous nucleation but also nucleation of a mixed H2O-CO2 gas phase. In most pumice and scoria clasts, resulting vesicle populations form power law size distributions; power law exponents >3 in silicic tephras indicate that small vesicles comprise most of the vesicle volume (consistent with rapid late-stage vesiculation at high ΔP), while exponents 60-70%) and show no dependence on either melt composition or mass eruption rate; this suggests that melt porosity is more important than either decompression rate or magma rheology for clast preservation. These pyroclasts also have uniformly high permeabilities, high pore connectivity, and simple porous pathways, all of which suggest that ease of gas escape also contributed to clast

  12. The Spectrum of Satellite Breakup and Fragmentation

    Science.gov (United States)

    Finkleman, D.

    The objective of this paper is to expose the spectrum of satellite breakup physics and is implications for debris production and observables. Satellite response to the debris environment generally emphasizes small scale hypervelocity impact or the interaction of intense, coherent radiation with satellite surfaces or internals. There are empirical correlations of fragment size distributions based on arena tests and extremely rare observations of breakups in space. Klinkrad describes well research on material response to hypervelocity impact such as the ballistic limit for various materials and shielding walls. Smirnov, et. al., report well the phenomenology of breakups under the influence of nonuniform internal loading of monolithic bodies, such as pressurized tanks. They set forth the transformation of elastic energy into fragment kinetic energy. They establish a sound physical framework for bounding the number of fragments. We took advantage of these works in our previous papers. There is not much research into the response of nonuniform structures to hypervelocity collisions with similarly massive and complex objects. This work generally employs complex hydrodynamic and finite element computation that is not well suited to real time, operational assessment of the consequences of such encounters. We hope to diminish the void between the extremes of microscopic impact and complex hydrocodes. Our previous reports employed the framework established by Chobotov and Spencer, fundamentally equilibrium, Newtonian approach. We now explore the spectrum of interactions and debris evolutions possible with realistic combinations of these theories. The spectrum encompasses Newtonian, semi-elastic energy and momentum transfer through little or no momentum exchange and from virtually all of the mass of the colliders being involved through fractional mass involvement. We observe that the more Newtonian outcomes do not agree well with sparse observations of the few collisions that

  13. Analysis of Fragmentation and Resulting Shrapnel Penetration of Naturally Fragmenting Cylindrical Bombs

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S.E.

    2000-08-01

    Fragmentation of exploding cylinders and penetration mechanics of surrounding vessel walls were examined and a qualitative understanding was achieved. This understanding provided a basis for making simplifying approximations and assumptions that aided in creating a shrapnel penetration model. Several mathematical models were discussed, and results from 6 cylinder tests were analyzed in order to select a model that best represented the data. It was determined that the overall best mathematical model to predict shrapnel penetration uses the modified Gurney equation to calculate fragment velocity, the Mott equation to calculate largest fragment weight, and the Christman/Gehring equation to calculate penetration depth.

  14. Incorporating fragmentation and non-native species into distribution models to inform fluvial fish conservation.

    Science.gov (United States)

    Taylor, Andrew T; Papeş, Monica; Long, James M

    2017-09-06

    Fluvial fishes face increased imperilment from anthropogenic activities, but the specific factors contributing most to range declines are often poorly understood. For example, the shoal bass (Micropterus cataractae) is a fluvial-specialist species experiencing continual range loss, yet how perceived threats have contributed to range loss is largely unknown. We employed species distribution models (SDMs) to disentangle which factors are contributing most to shoal bass range loss by estimating a potential distribution based on natural abiotic factors and by estimating a series of current, occupied distributions that also incorporated variables characterizing land cover, non-native species, and fragmentation intensity (no fragmentation, dams only, and dams and large impoundments). Model construction allowed for interspecific relationships between non-native congeners and shoal bass to vary across fragmentation intensities. Results from the potential distribution model estimated shoal bass presence throughout much of their native basin, whereas models of current occupied distribution illustrated increased range loss as fragmentation intensified. Response curves from current occupied models indicated a potential interaction between fragmentation intensity and the relationship between shoal bass and non-native congeners, wherein non-natives may be favored at the highest fragmentation intensity. Response curves also suggested that free-flowing fragment lengths of > 100 km were necessary to support shoal bass presence. Model evaluation, including an independent validation, suggested models had favorable predictive and discriminative abilities. Similar approaches that use readily-available, diverse geospatial datasets may deliver insights into the biology and conservation needs of other fluvial species facing similar threats. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Kinematics of current region fragmentation in semi-inclusive deeply inelastic scattering

    Science.gov (United States)

    Boglione, M.; Collins, J.; Gamberg, L.; Gonzalez-Hernandez, J. O.; Rogers, T. C.; Sato, N.

    2017-03-01

    Different kinematical regions of semi-inclusive deeply inelastic scattering (SIDIS) processes correspond to different underlying partonic pictures, and it is important to understand the transition between them. We find criteria in semi-inclusive deeply inelastic scattering (SIDIS) for identifying the current fragmentation region - the kinematical region where a factorization picture with fragmentation functions is appropriate, especially for studies of transverse-momentum-dependent (TMD) functions. This region is distinguished from the central (soft) and target fragmentation regions. The basis of our argument is in the errors in approximations used in deriving factorization. As compared with previous work, we show that it is essential to take account of the transverse momentum of the detected hadron, and we find a much more restricted range for genuine current fragmentation. We show that it is important to develop an extended factorization formulation to treat hadronization in the central region, as well as the current and target fragmentation regions, and to obtain a unified formalism spanning all rapidities for the detected hadron.

  16. Assessment of missile hazards: identification of reference fragmentation patterns.

    Science.gov (United States)

    Gubinelli, Gianfilippo; Cozzani, Valerio

    2009-04-30

    Industrial accidents involving fragment projection were investigated. The analysis of fracture mechanics fundamentals allowed the exploration of the relations between the fracture characteristics and the final event leading to equipment collapse. Reference fragmentation patterns were defined on the basis of the geometrical characteristics of the categories of process vessels that are more frequently involved in fragmentation accidents. Primary scenarios leading to fragment projection were correlated to specific fragmentation patterns. A database reporting a detailed analysis of more than 140 vessel fragmentation events provided the data needed to support and validate the approach. The available data also allowed the calculation of the expected probability of fragment projection following vessel fragmentation, and the probability of the alternative fragmentation patterns with respect to the different accidental scenarios, based on the observed frequencies over the available data set.

  17. PREFIX-BASED LABELING ANNOTATION FOR EFFECTIVE XML FRAGMENTATION

    Directory of Open Access Journals (Sweden)

    Kok-Leong Koong

    2015-05-01

    Full Text Available XML is gradually employed as a standard of data exchange in web environment since its inception in the 90s until present. It serves as a data exchange between systems and other applications. Meanwhile the data volume has grown substantially in the web and thus effective methods of storing and retrieving these data is essential. One recommended way is physically or virtually fragments the large chunk of data and distributes the fragments into different nodes. Fragmentation design of XML document contains of two parts: fragmentation operation and fragmentation method. The three fragmentation operations are Horizontal, Vertical and Hybrid. It determines how the XML should be fragmented. This paper aims to give an overview on the fragmentation design consideration and subsequently, propose a fragmentation technique using number addressing.

  18. HIERARCHICAL FRAGMENTATION OF THE ORION MOLECULAR FILAMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Satoko; Ho, Paul T. P.; Su, Yu-Nung [Academia Sinica Institute of Astronomy and Astrophysics, P.O. Box 23-141, Taipei 10617, Taiwan (China); Teixeira, Paula S. [Institut fuer Astrophysik, Universitaet Wien, Tuerkenschanzstrasse 17, A-1180, Wien (Austria); Zapata, Luis A., E-mail: satoko_t@asiaa.sinica.edu.tw [Centro de Radioastronomia y Astrofisica, Universidad Nacional Autonoma de Mexico, Morelia, Michoacan 58090 (Mexico)

    2013-01-20

    We present a high angular resolution map of the 850 {mu}m continuum emission of the Orion Molecular Cloud-3 (OMC 3) obtained with the Submillimeter Array (SMA); the map is a mosaic of 85 pointings covering an approximate area of 6.'5 Multiplication-Sign 2.'0 (0.88 Multiplication-Sign 0.27 pc). We detect 12 spatially resolved continuum sources, each with an H{sub 2} mass between 0.3-5.7 M {sub Sun} and a projected source size between 1400-8200 AU. All the detected sources are on the filamentary main ridge (n{sub H{sub 2}}{>=}10{sup 6} cm{sup -3}), and analysis based on the Jeans theorem suggests that they are most likely gravitationally unstable. Comparison of multi-wavelength data sets indicates that of the continuum sources, 6/12 (50%) are associated with molecular outflows, 8/12 (67%) are associated with infrared sources, and 3/12 (25%) are associated with ionized jets. The evolutionary status of these sources ranges from prestellar cores to protostar phase, confirming that OMC-3 is an active region with ongoing embedded star formation. We detect quasi-periodical separations between the OMC-3 sources of Almost-Equal-To 17''/0.035 pc. This spatial distribution is part of a large hierarchical structure that also includes fragmentation scales of giant molecular cloud ( Almost-Equal-To 35 pc), large-scale clumps ( Almost-Equal-To 1.3 pc), and small-scale clumps ( Almost-Equal-To 0.3 pc), suggesting that hierarchical fragmentation operates within the Orion A molecular cloud. The fragmentation spacings are roughly consistent with the thermal fragmentation length in large-scale clumps, while for small-scale cores it is smaller than the local fragmentation length. These smaller spacings observed with the SMA can be explained by either a helical magnetic field, cloud rotation, or/and global filament collapse. Finally, possible evidence for sequential fragmentation is suggested in the northern part of the OMC-3 filament.

  19. The Fission-fragment Spectrometer VERDI

    Science.gov (United States)

    Frégeau, M. O.; Oberstedt, S.

    VERDI (VElocity foR Direct particle Identification) is a fission-fragment spectrometer presently under construction at the Joint Research Centre IRMM. It will allow measuring the kinetic energy and the velocity of both fission fragments simultaneously. The velocity information provide information about the pre-neutron mass of each fission fragment when isotropic prompt-neutron emission from the fragments is assumed. The kinetic energy, in complement of the velocity, will provide us with the post-neutron mass. From the difference between pre- and post-neutron masses the number of neutrons emitted by each fragment may be deter- mined. Knowledge of this quantity as a function of the total kinetic energy will contribute to the understanding of how the available excitation energy is shared between both fission fragments at scission. The contemplated pre-neutron mass resolving power, A/ΔA, of at least 126 requires a time-of-flight (TOF) resolution better than 200 ps (FWHM) and an energy resolution, ΔE/E of 0.3% for a post-neutron mass. The VERDI spectrometer provides the best compromise between geometrical efficiency and time of flight. It consists of an electron detector located very close to the fissionable target and a double array of silicon detectors located 50 cm away on both sides of the target. Each silicon detector has an area of 450 mm2 and is made from neutron transmutation-doped (NTD) silicon to reduce rise-time variation, to minimize pulse height defect and to reduce the plasma delay time. The intrinsic timing resolution of the electron detector was determined, using a 241Am alpha source (Eα = 5.49 MeV), against a previously characterized single-crystal diamond to σ = 140 ps. The timing resolution of the NTD silicon detectors was determined using the spontaneous fission of 252Cf in conjunction with Monte-Carlo simulations to σNTD = 150 ps. With the present timing resolution, σTOF VERDI is already close to the set goals. The excellent timing properties

  20. Within and Among Patch Variability in Patterns of Insect Herbivory Across a Fragmented Forest Landscape.

    Directory of Open Access Journals (Sweden)

    Dorothy Y Maguire

    Full Text Available Fragmentation changes the spatial patterns of landscapes in ways that can alter the flow of materials and species; however, our understanding of the consequences of this fragmentation and flow alteration for ecosystem processes and ecosystem services remains limited. As an ecological process that affects many ecosystem services and is sensitive to fragmentation, insect herbivory is a good model system for exploring the role of fragmentation, and the resulting spatial patterns of landscapes, in the provision of ecosystem services. To refine our knowledge of how changes in landscape pattern affect insect herbivory, we quantified the combined influence of among patch (patch area and patch connectivity and within patch (location within patch; canopy, edge, interior factors on amounts of insect herbivory in a fragmented forest landscape. We measured herbivory in 20 forest patches of differing size and connectivity in southern Quebec (Canada. Within each patch, herbivory was quantified at the interior, edge, and canopy of sugar maple trees during the spring and summer of 2011 and 2012. Results show that connectivity affects herbivory differently depending on the location within the patch (edge, interior, canopy, an effect that would have gone unnoticed if samples were pooled across locations. These results suggest considering structure at both the patch and within patch scales may help to elucidate patterns when studying the effects of fragmentation on ecosystem processes, with implications for the services they support.

  1. Fragmentation patterns of jets in pPb collisions in CMS

    Science.gov (United States)

    Baty, Austin

    2016-12-01

    The nuclear parton distribution function and flavor composition of hard scattering processes can be accurately studied using the jet fragmentation functions. Recent measurements of the pPb nuclear modification factor (RpPb), with diverging values for inclusive jets and charged hadrons, have raised question on jet fragmentation properties in pPb collisions. These spectra measurements are performed with pp reference at 5.02 TeV constructed by interpolation or extrapolation from different √{ s}, and on steeply falling power-law spectra. As the jet fragmentation function is only evolving logarithmically with √{ s}, this further underscores the importance of a direct measurement. Together with the CMS results in pPb inclusive jets and charged hadron RpPb, we introduce the new CMS measurement of fragmentation function in pPb collisions, where within our uncertainties, jets in pPb is found to have identical fragmentation property vs. pp jets. We will further discuss the consistency and tension among the results, and their possible origins. This measurement also gives important reference for the interpretation of the fragmentation function in PbPb collisions.

  2. Sperm DNA fragmentation abnormalities in men from couples with a history of recurrent miscarriage.

    Science.gov (United States)

    Leach, Mikaela; Aitken, Robert J; Sacks, Gavin

    2015-08-01

    Previous studies have described an association between sperm with DNA damage and a history of recurrent miscarriage (RM), although it is not clear whether there is benefit in screening for sperm DNA fragmentation and to what extent DNA fragmentation impacts upon RM. To identify what proportion of couples experiencing RM are affected by DNA fragmentation abnormalities. In this retrospective study, between 2008 and 2013, couples with a history of recurrent miscarriage (≥3 first trimester miscarriages) were investigated comprehensively for known causes (karyotype, uterine, antiphospholipid syndrome, thrombophilia) and also by semen analysis, including DNA fragmentation [sperm chromatin structure analysis (SCSA)]. Statistical analysis was performed on SPSS software with significance taken as P fragmentation index (DFI) of 9.50%. Normal levels were found in 70.5% of men (DFI 30%). Couples with otherwise unexplained recurrent miscarriage had significantly higher DFI than those with other causes identified on routine screening (P = 0.012). In couples experiencing RM, 30% (32/108) of men had sperm with high levels of DNA fragmentation (DFI > 15%). This may be a contributing factor to the clinical syndrome of RM, and future clinical trials of therapies for these couples are warranted. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  3. The causes and ecological correlates of head scale asymmetry and fragmentation in a tropical snake.

    Science.gov (United States)

    Brown, Gregory P; Madsen, Thomas; Dubey, Sylvain; Shine, Rick

    2017-09-12

    The challenge of identifying the proximate causes and ecological consequences of phenotypic variation can be facilitated by studying traits that are usually but not always bilaterally symmetrical; deviations from symmetry likely reflect disrupted embryogenesis. Based on a 19-year mark-recapture study of >1300 slatey-grey snakes (Stegonotus cucullatus) in tropical Australia, and incubation of >700 eggs, we document developmental and ecological correlates of two morphological traits: asymmetry and fragmentation of head scales. Asymmetry was directional (more scales on the left side) and was higher in individuals with lower heterozygosity, but was not heritable. In contrast, fragmentation was heritable and was higher in females than males. Both scale asymmetry and fragmentation were increased by rapid embryogenesis but were not affected by hydric conditions during incubation. Snakes with asymmetry and fragmentation exhibited slightly lower survival and increased (sex-specific) movements, and females with more scale fragmentation produced smaller eggs. Counterintuitively, snakes with more asymmetry had higher growth rates (possibly reflecting trade-offs with other traits), and snakes with more fragmentation had fewer parasites (possibly due to lower feeding rates). Our data paint an unusually detailed picture of the complex genetic and environmental factors that, by disrupting early embryonic development, generate variations in morphology that have detectable correlations with ecological performance.

  4. Fragmentation of massive dense cores down to ≲ 1000 AU: Relation between fragmentation and density structure

    Energy Technology Data Exchange (ETDEWEB)

    Palau, Aina; Girart, Josep M. [Institut de Ciències de l' Espai (CSIC-IEEC), Campus UAB-Facultat de Ciències, Torre C5-parell 2, E-08193 Bellaterra, Catalunya (Spain); Estalella, Robert [Departament d' Astronomia i Meteorologia (IEEC-UB), Institut de Ciències del Cosmos, Universitat de Barcelona, Martí i Franquès, 1, E-08028 Barcelona (Spain); Fuente, Asunción [Observatorio Astronómico Nacional, P.O. Box 112, E-28803 Alcalá de Henares, Madrid (Spain); Fontani, Francesco; Sánchez-Monge, Álvaro [Osservatorio Astrofisico di Arcetri, INAF, Lago E. Fermi 5, I-50125 Firenze (Italy); Commerçon, Benoit; Hennebelle, Patrick [Laboratoire de Radioastronomie, UMR CNRS 8112, École Normale Supérieure et Observatoire de Paris, 24 rue Lhomond, F-75231 Paris Cedex 05 (France); Busquet, Gemma [INAF-Istituto di Astrofisica e Planetologia Spaziali, Area di Recerca di Tor Vergata, Via Fosso Cavaliere 100, I-00133 Roma (Italy); Bontemps, Sylvain [Université de Bordeaux, LAB, UMR 5804, F-33270 Floirac (France); Zapata, Luis A. [Centro de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México, P.O. Box 3-72, 58090 Morelia, Michoacán (Mexico); Zhang, Qizhou [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Di Francesco, James, E-mail: palau@ieec.uab.es [Department of Physics and Astronomy, University of Victoria, P.O. Box 355, STN CSC, Victoria, BC, V8W 3P6 (Canada)

    2014-04-10

    In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 μm (or 1.2 mm in two cases) and the spectral energy distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. Even though the estimated fragmentation level is strictly speaking a lower limit, its relative value is significant and several trends could be explored with our data. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered the effects of rotational-to-gravitational energy ratio, non-thermal velocity dispersion, and turbulence mode on the density structure of the cores, and found that compressive turbulence seems to yield higher central densities. Finally, a possible explanation for the origin of cores with concentrated density profiles, which are the cores showing no fragmentation, could be related with a strong magnetic field, consistent with the outcome of radiation magnetohydrodynamic simulations.

  5. Assessment of Fragmentation Performance of Blast-enhanced Explosive Fragmentation Munitions

    Science.gov (United States)

    2010-10-01

    aluminized blast-enhanced PAX-Al composition. The experimental assessment of the fragmentation performance of tested charges was accomplished using...charges, rapid expansion of high pressure detonation products results in high-strain high-strain-rate dilation of the hardened steel shell, which...eventually ruptures generating a “spray” of high-velocity steel fragments. Defining the longitudinal axis of the munition as the polar axis z, the

  6. TNF-α is involved in activating DNA fragmentation in skeletal muscle

    Science.gov (United States)

    Carbó, N; Busquets, S; van Royen, M; Alvarez, B; López-Soriano, F J; Argilés, J M

    2002-01-01

    Intraperitoneal administration of 100 μg kg−1 (body weight) of tumour necrosis factor-α to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-α-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-α-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-α receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-α partly mediates DNA fragmentation during experimental cancer-associated cachexia. British Journal of Cancer (2002) 86, 1012–1016. DOI: 10.1038/sj/bjc/6600167 www.bjcancer.com © 2002 Cancer Research UK PMID:11953838

  7. Numerical Simulation of Rock Fragmentation under the Impact Load of Water Jet

    Directory of Open Access Journals (Sweden)

    Jiang Hongxiang

    2014-01-01

    Full Text Available To investigate the rock fragmentation and its influence factors under the impact load of water jet, a numerical method which coupled finite element method (FEM with smoothed particle hydrodynamics (SPH was adopted to simulate the rock fragmentation process by water jet. Linear and shock equations of state were applied to describe the dynamic characteristics of rock and water, respectively, while the maximum principal stress criterion was used for the rock failure detection. The dynamic stresses at the selected element containing points in rock are computed as a function of time under the impact load of water jet. The influences of the factors of boundary condition, impact velocity, confining pressure, and structure plane on rock dynamic fragmentation are discussed.

  8. Kinematics of Current Region Fragmentation in Semi-Inclusive Deeply Inelastic Scattering

    CERN Document Server

    Boglione, M; Gamberg, L; Gonzalez-Hernandez, J O; Rogers, T C; Sato, N

    2016-01-01

    Different kinematical regimes of semi-inclusive deeply inelastic scattering (SIDIS) processes correspond to different underlying partonic pictures, and it is important to understand the transition between them. This is particularly the case when there is sensitivity to intrinsic transverse momentum, in which case kinematical details can become especially important. We address the question of how to identify the current fragmentation region --- the kinematical regime where a factorization picture with fragmentation functions is appropriate. We distinguish this from soft and target fragmentation regimes. Our criteria are based on the kinematic regions used in derivations of factorization theorems. We argue that, when hard scales are of order a few GeVs, there is likely significant overlap between different rapidity regions that are normally understood to be distinct. We thus comment on the need to take this into account with more unified descriptions of SIDIS, which should span all rapidities for the produced h...

  9. Fragmentation of massive dense cores down to ~1000 AU: Relation between fragmentation and density structure

    CERN Document Server

    Palau, Aina; Girart, J M; Fuente, A; Fontani, F; Commercon, B; Busquet, G; Bontemps, S; Sanchez-Monge, A; Zapata, L A; Zhang, Q; Hennebelle, P; Di Francesco, J

    2014-01-01

    In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 micron (or 1.2 mm in two cases) and the Spectral Energy Distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered th...

  10. Characterization of Tumor-Avid Antibody Fragments Genetically Engineered for Mono-Specific Radionuclide Chelation

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, T.P.

    2003-12-31

    The successful clinical application of targeted-radiopharmaceuticals depends on the development of molecules that optimize tumor specific radionuclide deposition and minimize non-specific organ irradiation. To this end, this proposal outlines a research effort to identify and evaluate novel antibodies and antibody fragments that bind breast tumors. The tumor-avid antibodies will be investigated for as imaging and therapeutic agents and to gain a better understanding of the pharmacokinetics and metabolism of radiolabeled tumor-avid antibody fragments through the use of site-specifically labeled molecules. Antibodies or antibody fragments, that bind breast carcinoma carbohydrate antigens, will be obtained from hybridoma or bacteriophage library screening. More specifically, antibody fragments that bind the carcinoma-associated Thomsen-Friedenreich (T) antigen will be radiolabeled with {sup 99m}Tc and {sup 188}Re at a natural amino acid chelation site and will be investigated in vivo for their abilities to target human breast tumors. In addition, site-specific radiolabeled antibody fragments will be biosynthesized using misacylated suppressor tRNAs. Homogeneously radiolabeled populations of antibody fragments will be used to investigate the effects of radionuclide location and chelation chemistries on their biodistribution and metabolism. It is hypothesized that site-specifically radiolabeled antibody fragments will possess enhanced tumor imaging and therapeutic properties due to optimal label location and conjugation chemistries. New insights into the factors that govern antibody metabolism in vivo are also expected from this work. Results from these studies should enhance our ability to design and synthesize radiolabeled antibody fragments that have improved pharmacokinetic properties. The studies in this proposal involve basic research into the development of antibody-based radiopharmaceuticals, with the ultimate goal of application in humans. This type of basic

  11. Critical appraisal of the role of recombinant activated factor VII in the treatment of hemophilia patients with inhibitors

    Directory of Open Access Journals (Sweden)

    Ampaiwan Chuansumrit

    2010-03-01

    Full Text Available Ampaiwan Chuansumrit1, Pantep Angchaisuksiri2, Nongnuch Sirachainan11Departments of Pediatrics and 2Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University,  Bangkok, ThailandAbstract: Hemophilia patients with inhibitors faced the constraint of inadequate treatment for several years before the era of recombinant factor VIIa (rFVII. Initially, rFVIIa was used in the compassionate-use programs. After a worldwide license was issued, more than 1.5 million doses were administered. Bleeding of joints and muscles was controlled effectively by means of an early home treatment program, with either a standard dose of 90 μg/kg every 2 to 3 hours for a few doses or a single dose of 270 μg/kg. For more serious bleeding episodes or minor surgery, an initial dose of 90 μg/kg was given every 2 hours for 24 to 48 hours followed by increased intervals of 3 to 6 hours according to the severity of bleeding and efficacy of bleeding control. In cases of major surgery such as orthopedic procedures, the same regimen can be applied except for a higher initial dose of 120 to 180 μg/kg. However, increasing the dose should be considered if there are unexpected bleeding complications since the half-life and clearance of rFVIIa differ between individuals. In addition, prophylaxis is administered to a small number of patients. Finally, the reported thromboembolic events found in hemophilia patients with inhibitors receiving rFVIIa are extremely low, much less than 1%.Keywords: bleeding disorder, hemophilia, inhibitor, NovoSeven, recombinant factor VIIa

  12. The Coincident Fission Fragment Detector (CFFD)

    Science.gov (United States)

    Wakhle, A.; Hammerton, K.; Kohley, Z.; Yurkon, J.; Stiefel, K.

    2017-08-01

    A Parallel Plate Avalanche Counter (PPAC) based fission detector system, called the Coincident Fission Fragment Detector (CFFD), has been developed for the ReA3 re-accelerator facility of the National Superconducting Cyclotron Laboratory (NSCL). Binary reaction kinematics are reconstructed based on position and time-of-flight measurements of fission fragments. Large area PPACs provide 1 ns level time resolution and mm level position resolution. The detectors allow measurements of fission product angular and mass distributions of heavy-ion induced fusion reactions. The 30 cm by 40 cm active area of each PPAC provides large solid angle coverage well suited for measurements of low intensity rare-isotope beams (RIBs).

  13. Detecting Cortex Fragments During Bacterial Spore Germination.

    Science.gov (United States)

    Francis, Michael B; Sorg, Joseph A

    2016-06-25

    The process of endospore germination in Clostridium difficile, and other Clostridia, increasingly is being found to differ from the model spore-forming bacterium, Bacillus subtilis. Germination is triggered by small molecule germinants and occurs without the need for macromolecular synthesis. Though differences exist between the mechanisms of spore germination in species of Bacillus and Clostridium, a common requirement is the hydrolysis of the peptidoglycan-like cortex which allows the spore core to swell and rehydrate. After rehydration, metabolism can begin and this, eventually, leads to outgrowth of a vegetative cell. The detection of hydrolyzed cortex fragments during spore germination can be difficult and the modifications to the previously described assays can be confusing or difficult to reproduce. Thus, based on our recent report using this assay, we detail a step-by-step protocol for the colorimetric detection of cortex fragments during bacterial spore germination.

  14. Fragment formation in biased random walks

    Science.gov (United States)

    Ramola, Kabir

    2008-10-01

    We analyse a biased random walk on a 1D lattice with unequal step lengths. Such a walk was recently shown to undergo a phase transition from a state containing a single connected cluster of visited sites to one with several clusters of visited sites (fragments) separated by unvisited sites at a critical probability pc (Anteneodo and Morgado 2007 Phys. Rev. Lett. 99 180602). The behaviour of ρ(l), the probability of formation of fragments of length l, is analysed. An exact expression for the generating function of ρ(l) at the critical point is derived. We prove that the asymptotic behaviour is of the form \\rho (l) \\simeq 3/[l(\\log \\ l)^2] .

  15. HCH for Checking Containment of XPath Fragment

    Institute of Scientific and Technical Information of China (English)

    Jian-Hua Feng; Yu-Guo Liao; Yong Zhang

    2007-01-01

    XPath is ubiquitous in XML applications for navigating XML trees and selecting a set of element nodes. In XPath query processing, one of the most important issues is how to efficiently check containment relationship between two XPath expressions. To get out of the intricacy and complexity caused by numerous XPath features, we investigate this issue on a frequently used fragment of XPath expressions that consists of node tests, the child axis (/), the descendant axis (//), branches ([]) and label wildcards (*). Prior work has shown that homomorphism technology can be used for containment checking. However, homomorphism is the sufficient but not necessary condition for containment. For special classes of this fragment, the homomorphism algorithm returns false negatives. To address this problem, this paper proposes two containment techniques, conditioned homomorphism and hidden conditioned homomorphism, and then presents sound algorithms for checking containment. Experimental results confirm the practicability and efficiency of the proposed algorithms.

  16. Fission Fragment characterization with FALSTAFF at NFS

    Directory of Open Access Journals (Sweden)

    Pancin J.

    2013-03-01

    Full Text Available The Neutrons for Science (NFS facility will be one of the first installations of the SPIRAL2 facility. NFS will be composed of a time-of-flight baseline and irradiation stations and will allow studying neutron-induced reactions for energies going from some hundreds of keV up to 40 MeV. Continuous and quasi-monoenergetic energy neutron beams will be available. Taking advantage of this new installation, the development of an experimental setup for a full characterization of actinide fission fragments in this energy domain has been undertaken. To achieve this goal a new detection system called FALSTAFF (Four Arm cLover for the STudy of Actinide Fission Fragments in under development. In this paper, the characteristics of the NFS facility will be exposed and the motivations for the FALSTAFF experiment will be presented. The experimental setup will be described and the expected resolutions based on realistic GEANT4 simulations will be discussed.

  17. Spin dependence of heavy quark fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Cornet, Fernando [Departamento de Fisica Teorica y del Cosmos and Centro Anadaluz de Fisica de Particulas, Universidad de Granada, E-18071 Granada (Spain)], E-mail: cornet@ugr.es; Garcia Canal, Carlos A. [Departamento de Fisica, Universidad Nacional de La Plata, C.C. 67, La Plata (1900) (Argentina)

    2008-05-01

    We propose that the non-perturbative part of the fragmentation function describing the transition from a heavy quark to a heavy meson is proportional to the square of the produced meson wave function at the origin, taking into account hyperfine interactions. We analyze the effects of this proposal on the number of pseudoscalar mesons compared to the number of vector mesons produced and find a good agreement with experimental data. Finally, we discuss further experimental checks for our hypothesis.

  18. Size Effects in Heavy Ions Fragmentation

    CERN Document Server

    Barrañon, A; Dorso, C O

    2003-01-01

    Rise-Plateau Caloric curves for different Heavy Ion collisions have been obtained, in the range of experimental observations. Limit temperature decreases when the residual size is increased, in agreement with recent theoretical analysis of experimental results reported by other Collaborations. Besides, promptly emitted particles influence on temperature plateau is shown. LATINO binary interaction semiclassical model is used to reproduce the inter-nucleonic forces via Pandharipande Potential and fragments are detected with an Early Cluster Recognition Algorithm.

  19. A nuclear fragmentation energy deposition model

    Science.gov (United States)

    Ngo, D. M.; Wilson, J. W.; Fogarty, T. N.; Buck, W. W.; Townsend, L. W. (Principal Investigator)

    1991-01-01

    A formalism for target fragment transport is presented with application to energy loss spectra in thin silicon devices. A nuclear data base is recommended that agrees well with the measurements of McNulty et al. using surface barrier detectors. High-energy events observed by McNulty et al., which are not predicted by intranuclear cascade models, are well represented by the present work.

  20. New results on jet fragmentation at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Jindariani, Sergo; /Florida U.

    2006-12-01

    Presented are the latest results of jet fragmentation studies at the Tevatron using the CDF Run II detector. Studies include the distribution of transverse momenta (Kt) of particles jets, two-particle momentum correlations, and indirectly global event shapes in p{bar p} collisions. Results are discussed within the context of recent Next-to-Leading Log calculations as well as earlier experimental results from the Tevatron and e{sup +}e{sup -} colliders.

  1. Engineered single chain antibody fragments for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huhalov, A.; Chester, K. A. [Cancer Research UK Imaging and Targeting Group Royal Free, London (United Kingdom). Department of Oncology; University College Medical School Royal Free Campus, London (United Kingdom)

    2004-12-01

    An ideal molecule to deliver radioimmunotherapy (RIT) would be target specific and have prolonged residence time at high concentrations in the tumour with rapid clearance from normal tissues. It would also be non-immunogenic. These features can be rationally introduced into recombinant antibody-based proteins using antibody engineering techniques. This reviews focuses on the use of antibody engineering in the design and development of RIT molecules which have single chain Fv (scFv) antibody fragments as building blocks.

  2. Dendrite fragmentation by catastrophic elastic remelting

    OpenAIRE

    Ananiev, S.; Nikrityuk, P.; Eckert, K.

    2008-01-01

    The paper proposes a new fragmentation mechanism of dendrite arms. The theoretical basis of this mechanism is a shift in the thermodynamical equilibrium at the solid-liquid interface due to the presence of elastic energy. This effect is modelled by the generalized Gibbs-Thomson condition [1], where each term is calculated analytically using a simple Bernoulli-Euler beam model. The resulting nonlinear system of ordinary differential equations is integrated in time using a fully implicit scheme...

  3. Time invariant scaling in discrete fragmentation models

    CERN Document Server

    Giraud, B G; Giraud, B G; Peschanski, R

    1994-01-01

    Linear rate equations are used to describe the cascading decay of an initial heavy cluster into fragments. We consider moments of arbitrary orders of the mass multiplicity spectrum and derive scaling properties pertaining to their time evolution. We suggest that the mass weighted multiplicity is a suitable observable for the discovery of scaling. Numerical tests validate such properties, even for moderate values of the initial mass (nuclei, percolation clusters, jets of particles etc.). Finite size effects can be simply parametrized.

  4. Inhomogeneous Fragmentation of the Rolling Tachyon

    OpenAIRE

    Felder, Gary N; Kofman, Lev

    2004-01-01

    Dirac-Born-Infeld type effective actions reproduce many aspects of string theory classical tachyon dynamics of unstable Dp-branes. The inhomogeneous tachyon field rolling from the top of its potential forms topological defects of lower codimensions. In between them, as we show, the tachyon energy density fragments into a p-dimensional web-like high density network evolving with time. We present an analytic asymptotic series solution of the non-linear equations for the inhomogeneous tachyon an...

  5. Fragmentation and the Nuclear Equation of State

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Wolfgang [National Superconducting Cyclotron Laboratory and Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824-2320 (United States)]. E-mail: bauer@pa.msu.edu

    2007-05-01

    Progress on the determination of the order of the fragmentation phase transition, the location of its critical point in the nuclear matter phase diagram, the values of the critical exponents that determine the universality class of the transition, and finite size scaling effects is discussed. Evidence for the presence of Zipf-Mandelbrot-scaling in the relative size of the largest clusters is examined, and the connection to the value of the critical exponent {tau} is established.

  6. N/Z Dependence of Projectile Fragmentation

    CERN Document Server

    Trautmann, W; Aumann, T; Bacri, C O; Barczyk, T; Bassini, R; Bianchin, S; Boiano, C; Botvina, A S; Boudard, A; Brzychczyk, J; Chbihi, A; Cibor, J; Czech, B; De Napoli, M; Ducret, J -E; Emling, H; Frankland, J D; Hellström, M; Henzlova, D; Imme, G; Iori, I; Johansson, H; Kezzar, K; Lafriakh, A; Le Fèvre, A; Gentil, E Le; Leifels, Y; Lühning, J; Lukasik, J; Lynch, W G; Lynen, U; Majka, Z; Mocko, M; Müller, W F J; Mykulyak, A; Orth, H; Otte, A N; Palit, R; Pawlowski, P; Pullia, A; Raciti, G; Rapisarda, E; Sann, H; Schwarz, C; Sfienti, C; Simon, H; Sümmerer, K; Tsang, M B; Verde, G; Volant, C; Wallace, M; Weick, H; Wiechula, J; Wieloch, A; Zwieglinski, B

    2007-01-01

    The N/Z dependence of projectile fragmentation at relativistic energies has been studied in a recent experiment at the GSI laboratory with the ALADiN forward spectrometer coupled to the LAND neutron detector. Besides a primary beam of 124Sn, also secondary beams of 124La and 107Sn delivered by the FRS fragment separator have been used in order to extend the range of isotopic compositions of the produced spectator sources. With the achieved mass resolution of \\Delta A/A \\approx 1.5%, lighter isotopes with atomic numbers Z \\le 10 are individually resolved. The presently ongoing analyses of the measured isotope yields focus on isoscaling and its relation to the properties of hot fragments at freeze-out and on the derivation of chemical freeze-out temperatures which are found to be independent of the isotopic composition of the studied systems. The latter result is at variance with the predictions for limiting temperatures as obtained with finite-temperature Hartree-Fock calculations.

  7. Cationized Carbohydrate Gas-Phase Fragmentation Chemistry

    Science.gov (United States)

    Bythell, Benjamin J.; Abutokaikah, Maha T.; Wagoner, Ashley R.; Guan, Shanshan; Rabus, Jordan M.

    2016-11-01

    We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B n -Y m fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B n ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B n /Y m branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the 0,2 A 2 ion from the sodiated forms. Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies.

  8. Cationized Carbohydrate Gas-Phase Fragmentation Chemistry

    Science.gov (United States)

    Bythell, Benjamin J.; Abutokaikah, Maha T.; Wagoner, Ashley R.; Guan, Shanshan; Rabus, Jordan M.

    2017-04-01

    We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B n -Y m fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B n ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B n /Y m branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the 0,2 A 2 ion from the sodiated forms . Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies.

  9. Electroproduction in the Target Fragmentation Region

    Science.gov (United States)

    Avagyan, Harut

    2014-09-01

    The Semi-Inclusive DIS process in the Target Fragmentation Region (TFR), when the hadron is produced in the fragmentation process of the target remnants, can be described through the so-called Fracture Functions (FFs). They represent the joint probability of producing the final hadron from the target remnants, when a parton of the target nucleon is struck by the virtual photon in a hard scattering process. Like the ordinary parton distribution functions, the FFs are universal objects, thus they can be measured in one experiment at a given hard scale and then used to make predictions for other experiments, at another hard scale. Measurements of the Lambda multiplicities and polarization asymmetries in TFR, in particular, will provide information on corresponding Fracture Functions. The study of its Q2 dependence at JLab and EIC also will test the perturbative framework implied by Fracture Functions, simultaneously encoding the information on the interacting parton and on the fragmentation of the spectator system. We will present ongoing studies of electroproduction in TFR at Jefferson Lab, and proposed future measurement at upgraded JLab and Electron Ion Collider.

  10. Antibody Fragments as Probe in Biosensor Development

    Directory of Open Access Journals (Sweden)

    Serge Muyldermans

    2008-08-01

    Full Text Available Today’s proteomic analyses are generating increasing numbers of biomarkers, making it essential to possess highly specific probes able to recognize those targets. Antibodies are considered to be the first choice as molecular recognition units due to their target specificity and affinity, which make them excellent probes in biosensor development. However several problems such as difficult directional immobilization, unstable behavior, loss of specificity and steric hindrance, may arise from using these large molecules. Luckily, protein engineering techniques offer designed antibody formats suitable for biomarker analysis. Minimization strategies of antibodies into Fab fragments, scFv or even single-domain antibody fragments like VH, VL or VHHs are reviewed. Not only the size of the probe but also other issues like choice of immobilization tag, type of solid support and probe stability are of critical importance in assay development for biosensing. In this respect, multiple approaches to specifically orient and couple antibody fragments in a generic one-step procedure directly on a biosensor substrate are discussed.

  11. Detection of fission fragments by secondary emission; Detection des fragments de fission par emission secondaire

    Energy Technology Data Exchange (ETDEWEB)

    Audias, A. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1965-07-01

    This fission fragment detecting apparatus is based on the principle that fragments traversing a thin foil will cause emission of secondary electrons. These electrons are then accelerated (10 kV) and directly detected by means of a plastic scintillator and associated photomultiplier. Some of the advantages of such a detector are, its rapidity, its discriminating power between alpha particles and fission fragments, its small energy loss in detecting the fragments and the relatively great amount of fissionable material which it can contain. This paper is subdivided as follows: a) theoretical considerations b) constructional details of apparatus and some experimental details and c) a study of the secondary emission effect itself. (author) [French] Le detecteur de fragments de fission que nous avons realise est base sur le principe de l'emission secondaire produite par les fragments de fission traversant une feuille mince: les electrons secondaires emis sont acceleres a des tensions telles (de l'ordre de 10 kV), qu'ils soient directement detectables par un scintillateur plastique associe a un photomultiplicateur. L'interet d'un tel detecteur reside: dans sa rapidite, sa tres bonne discrimination alpha, fission, la possibilite de detecter les fragments de fission avec une perte d'energie pouvant rester relativement faible, et la possibilite d'introduire des quantites de matiere fissile plus importantes que dans les autres types de detecteurs. Ce travail comporte: -) un apercu bibliographique de la theorie du phenomene, -) realisation et mise au point du detecteur avec etude experimentale de quelques parametres intervenant dans l'emission secondaire, -) etude de l'emission secondaire (sur la face d'emergence des fragments de fission) en fonction de l'energie du fragment et en fonction de l'epaisseur de matiere traversee avant emission secondaire, et -) une etude comparative de l'emission secondaire sur la

  12. Fish responses to experimental fragmentation of seagrass habitat.

    Science.gov (United States)

    Macreadie, Peter I; Hindell, Jeremy S; Jenkins, Gregory P; Connolly, Rod M; Keough, Michael J

    2009-06-01

    Understanding the consequences of habitat fragmentation has come mostly from comparisons of patchy and continuous habitats. Because fragmentation is a process, it is most accurately studied by actively fragmenting large patches into multiple smaller patches. We fragmented artificial seagrass habitats and evaluated the impacts of fragmentation on fish abundance and species richness over time (1 day, 1 week, 1 month). Fish assemblages were compared among 4 treatments: control (single, continuous 9-m(2) patches); fragmented (single, continuous 9-m(2) patches fragmented to 4 discrete 1-m(2) patches); prefragmented/patchy (4 discrete 1-m(2) patches with the same arrangement as fragmented); and disturbance control (fragmented then immediately restored to continuous 9-m(2) patches). Patchy seagrass had lower species richness than actively fragmented seagrass (up to 39% fewer species after 1 week), but species richness in fragmented treatments was similar to controls. Total fish abundance did not vary among treatments and therefore was unaffected by fragmentation, patchiness, or disturbance caused during fragmentation. Patterns in species richness and abundance were consistent 1 day, 1 week, and 1 month after fragmentation. The expected decrease in fish abundance from reduced total seagrass area in fragmented and patchy seagrass appeared to be offset by greater fish density per unit area of seagrass. If fish prefer to live at edges, then the effects of seagrass habitat loss on fish abundance may have been offset by the increase (25%) in seagrass perimeter in fragmented and patchy treatments. Possibly there is some threshold of seagrass patch connectivity below which fish abundances cannot be maintained. The immediate responses of fish to experimental habitat fragmentation provided insights beyond those possible from comparisons of continuous and historically patchy habitat. ©2009 Society for Conservation Biology.

  13. Magnetic processes in a collapsing dense core. II. Fragmentation. Is there a fragmentation crisis?

    Science.gov (United States)

    Hennebelle, P.; Teyssier, R.

    2008-01-01

    Context: A large fraction of stars are found in binary systems. It is therefore important for our understanding of the star formation process, to investigate the fragmentation of dense molecular cores. Aims: We study the influence of the magnetic field, ideally coupled to the gas, on the fragmentation in multiple systems of collapsing cores. Methods: We present high resolution numerical simulations performed with the RAMSES MHD code starting with a uniform sphere in solid body rotation and a uniform magnetic field parallel to the rotation axis. We pay particular attention to the strength of the magnetic field and interpret the results using the analysis presented in a companion paper. Results: The results depend much on the amplitude, A, of the perturbations seeded initially. For a low amplitude, A=0.1, we find that for values of the mass-to-flux over critical mass-to-flux ratio, μ, as high as μ = 20, the centrifugally supported disk which fragments in the hydrodynamical case is stabilized and remains axisymmetric. Detailed investigations reveal that this is due to the rapid growth of the toroidal magnetic field induced by the differential motions within the disk. For values of μ smaller than ≃5, corresponding to higher magnetic intensities, there is no centrifugally supported disk because of magnetic braking. When the amplitude of the perturbation is equal to A=0.5, each initial peak develops independently and the core fragments for a large range of μ. Only for values of μ close to 1 is the magnetic field able to prevent the fragmentation. Conclusions: Since a large fraction of stars are binaries, the results of low magnetic intensities preventing the fragmentation in the case of weak perturbations is problematic. We discuss three possible mechanisms which could lead to the formation of binary systems, namely the presence of high amplitude fluctuations in the core initially, ambipolar diffusion and fragmentation during the second collapse.

  14. An evaluation of some innovative fragmentation systems for oil shale

    Energy Technology Data Exchange (ETDEWEB)

    Hieta, M.; Hustrulid, W.A. [Western Research Inst., Laramie, WY (United States)

    1991-06-01

    This report describes a large-scale underground mining method, large-hole stoping, using some innovative fragmentation systems (buffer blasting, continuous loading/hauling, and mechanical miners for development). This study includes a literature review and an experimental study of one of the key design factors--buffer blasting. The purpose of the buffer-blasting experiments is to examine the swell that is necessary to achieve satisfactory fragmentation results. The study also includes a technical and economic evaluation of the new mining method compared with conventional room and pillar mining. The purpose of this study is to examine innovative methods that exist today and may provide a more efficient mining system than that currently used. Note that this is a conceptual study, and that the mining for the two mine designs were compared using a daily production rate of 75,000 tones per day. This amount was chosen because it is the maximum amount possible for a rubber-tired room and pillar operation with only a one-shaft complex.

  15. Measurement of charm fragmentation fractions in photoproduction at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Abramowicz, H. [Tel Aviv Univ. (Israel). School of Physics; Max-Planck-Institute for Physics, Munich (Germany); Abt, I. [Max-Planck-Institute for Physics, Muinch (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Krakow (Poland). Faculty of Physics and Applied Computer Science] [and others; Collaboration: ZEUS Collaboration

    2013-06-15

    The production of D{sup 0}, D{sup *+}, D{sup +}, D{sub s}{sup +} and {Lambda}{sub c}{sup +} charm hadrons and their antiparticles in ep scattering at HERA has been studied with the ZEUS detector, using a total integrated luminosity of 372 pb{sup -1}. The fractions of charm quarks hadronising into a particular charm hadron were derived. In addition, the ratio of neutral to charged D-meson production rates, the fraction of charged D mesons produced in a vector state, and the strangeness-suppression factor have been determined. The measurements have been performed in the photoproduction regime. The charm hadrons were reconstructed in the range of transverse momentum p{sub T} > 3.8GeV and pseudorapidity vertical stroke {eta} vertical stroke <1.6. The charm fragmentation fractions are compared to previous results from HERA and from e{sup +}e{sup -} experiments. The data support the hypothesis that fragmentation is independent of the production process.

  16. Plant diversity in hedgerows amidst Atlantic Forest fragments

    Directory of Open Access Journals (Sweden)

    Carolina C. C. Oliveira

    2015-06-01

    Full Text Available Hedgerows are linear structures found in agricultural landscapes that may facilitate dispersal of plants and animals and also serve as habitat. The aim of this study was to investigate the relationships among diversity and ecological traits of woody plants, hedgerow characteristics (size, age, and origin, and the structure of the surrounding Atlantic Forest landscape. Field data were collected from 14 hedgerows, and landscape metrics from 1000-m buffers surrounding hedgerows were recorded from a thematic map. In all sampled hedgerows, arboreal species were predominantly zoochoric and early-succession species, and hedgerow width was an important factor explaining the richness and abundance of this group of species. Connection with forest vegetation did not explain richness and abundance of animal-dispersed species, but richness of non-zoochoric species increased in more connected hedgerows. These results suggest that hedgerows are probably colonized by species arriving from nearby early-succession sites, forest fragment edges, and isolated trees in the matrix. Nonetheless, hedgerows provide resources for frugivorous animals and influence landscape connectivity, highlighting the importance of these elements in the conservation of biodiversity in fragmented and rural landscapes.

  17. Within-patch habitat quality determines the resilience of specialist species in fragmented landscapes

    NARCIS (Netherlands)

    Ye, X.; Skidmore, A.K.; Wang, T.

    2013-01-01

    Patch geometry and habitat quality among patches are widely recognized as important factors affecting population dynamics in fragmented landscapes. Little is known, however, about the influence of within-patch habitat quality on population dynamics. In this paper, we investigate the relative importa

  18. Fragment Hazard Investigation Program: Natural Communication Detonation of 155-mm Projectiles

    Science.gov (United States)

    1981-07-01

    an accurate representa- S - tion of the percentage of hazardous fragments as a function of range. A good fit to thesO data Is provided by K k i;• vPH ...projected on a sphere equal to the radius of the recovery media, is divided into the total surface area of the polar zone. This ratio yields a zone factor

  19. Fragmentation Point Detection of JPEG Images at DHT Using Validator

    Science.gov (United States)

    Mohamad, Kamaruddin Malik; Deris, Mustafa Mat

    File carving is an important, practical technique for data recovery in digital forensics investigation and is particularly useful when filesystem metadata is unavailable or damaged. The research on reassembly of JPEG files with RST markers, fragmented within the scan area have been done before. However, fragmentation within Define Huffman Table (DHT) segment is yet to be resolved. This paper analyzes the fragmentation within the DHT area and list out all the fragmentation possibilities. Two main contributions are made in this paper. Firstly, three fragmentation points within DHT area are listed. Secondly, few novel validators are proposed to detect these fragmentations. The result obtained from tests done on manually fragmented JPEG files, showed that all three fragmentation points within DHT are successfully detected using validators.

  20. Colorado Plateau Rapid Ecoregion Assessment Indicators: Natural Vegetation Fragmentation

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — This dataset presents measures of landscape fragmentation calculated by FRAGSTATS at 4KM and HUC5 reporting unit levels. Fragmentation integrates the influence of...