Sample records for glanzmann thrombasthenia gt

  1. Diagnosis of Glanzmann thrombasthenia by whole blood impedance analyzer (MEA) vs. light transmission aggregometry.

    PubMed

    Albanyan, A; Al-Musa, A; AlNounou, R; Al Zahrani, H; Nasr, R; AlJefri, A; Saleh, M; Malik, A; Masmali, H; Owaidah, T

    2015-08-01

    Glanzmann thrombasthenia (GT) is a rare inherited platelet disorder that is characterized by spontaneous or postprocedural bleeding. The diagnosis of GT depends on identifying the dysfunction of the platelets. The aim of this study was to compare a whole blood impedance Multiplate analyzer (MEA) with the standard method, light transmission aggregometry (LTA) in diagnosis of GT. Fifteen patients with GT were assessed on MEA and LTA using arachidonic acid (ASPI: 15 mm), (TRAP: 1 mm), collagen (100 μg/mL), ADP (0.2 mm), and ristocetin (Risto: 10 mg/mL). Whole blood samples were collected in sodium citrate and hirudin vacuum, blood collection tubes and tested within 4 h. Platelet-rich plasma was used for LTA using platelet agonists (ristocetin 1.5 mg/mL) (arachidonic acid 0.5 mg/mL) (ADP 2.5 mg/mL) and (collagen 1 mg/mL). The platelet count and PFA-100 results were (average and SD) 319 ± 93 × 10(9) L and 252 ± 34 s, respectively. Flow cytometry analysis showed that all samples are positive for CD42a and CD42b, whereas 9/15 samples were negative for CD61 and CD41. The other six patients had either partial or full expression of CD61/CD41. Aggregation analysis using both methods showed that all samples had no aggregation response to any of the agonists used apart from six samples which, using only the MEA, showed minimal aggregation in response to collagen (average = 14.3 ± 7 μg, which may suggest ability to detect qualitative abnormality of GPIIb/IIIa). These results suggest that the MEA is sensitive for the detection of Glanzmann thrombasthenia. Furthermore, MEA may also be able to differentiate between the subtypes of Glanzmann thrombasthenia. © 2014 John Wiley & Sons Ltd.

  2. A rare case of bleeding disorder: Glanzmann's thrombasthenia.

    PubMed

    Swathi, Jami; Gowrishankar, A; Jayakumar, S A; Jain, Karun

    2017-01-01

    Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. To highlight this rare but potentially life-threating disorder, GT. We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.

  3. A Rare Case of Bleeding Disorder: Glanzmann's Thrombasthenia

    PubMed Central

    Swathi, Jami; Gowrishankar, A.; Jayakumar, S. A.; Jain, Karun

    2017-01-01

    Background: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is characterized by a lack of platelet aggregation. It is characterized by qualitative or quantitative abnormalities of the platelet membrane glycoprotein IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive plasma proteins, and this facilitates attachment and aggregation of platelets to ensure thrombus formation at sites of vascular injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation may be clinically variable, ranging from easy bruising to severe and potentially life-threatening hemorrhages. Objective: To highlight this rare but potentially life-threating disorder, GT. Case Report: We report a case of GT that was first detected because of the multiple episodes of gum bleeding. The patient was an 18-year-old girl who presented with a history of repeated episodes of gum bleeding since childhood. Till the first visit to our hospital, she had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising, gum bleeding, and prolonged bleeding time after abrasions and insect stings. GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with adenosine di phosphate, epinephrine and collagen. Conclusion: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder. PMID:29063905

  4. Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard-Soulier's Syndrome.

    PubMed

    Poon, Man-Chiu; d'Oiron, Roseline

    2018-06-07

    Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Glanzmann Thrombasthenia: State of the Art and Future Directions

    PubMed Central

    Nurden, Alan T; Pillois, Xavier; Wilcox, David A.

    2014-01-01

    Glanzmann thrombasthenia (GT) is the principal inherited disease of platelets and the most commonly encountered disorder of an integrin. GT is characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma due to platelets that fail to aggregate when stimulated by physiologic agonists. GT is caused by quantitative or qualitative deficiencies of αIIbβ3, an integrin coded by the ITGA2B and ITGB3 genes and which by binding fibrinogen and other adhesive proteins joins platelets together in the aggregate. Widespread genotyping has revealed mutations spread across both genes, yet the reason for the extensive variation in both the severity and intensity of bleeding between affected individuals remains poorly understood. Furthermore, while genetic defects of ITGB3 affect other tissues with β3 present as αvβ3 (the vitronectin receptor), the bleeding phenotype continues to dominate. Here, we look in detail at mutations that affect (i) the β-propeller region of the αIIb head domain and (ii) the membrane proximal disulfide-rich EGF domains of β3 and which often result in spontaneous integrin activation. We also examine deep vein thrombosis as an unexpected complication of GT and look at curative procedures for the disease including allogeneic stem cell transfer and the potential for gene therapy. PMID:23929305

  6. The in vivo effect of fibrinogen and factor XIII on clot formation and fibrinolysis in Glanzmann's thrombasthenia.

    PubMed

    Shenkman, Boris; Livnat, Tami; Misgav, Mudi; Budnik, Ivan; Einav, Yulia; Martinowitz, Uriel

    2012-01-01

    Glanzmann's thrombasthenia (GT) is characterized by increased bleeding risk. The treatment options in GT are limited. The aim of this study was to test the effect of GT blood supplementation with fibrinogen and factor XIII on thrombin generation, blood clotting, and fibrinolysis. Whole blood samples of GT patients and normal donors treated with eptifibatide (GT model) were subjected to clotting by CaCl(2) and tissue factor. Thrombin generation was measured in platelet-rich plasma. Clot formation and tPA-induced fibrinolysis were evaluated in whole blood by rotation thromboelastometry (ROTEM). Blood was supplemented with fibrinogen (3 g/L) and/or FXIII (2 IU/mL). Thrombin generation analysis of blood derived from GT model and GT patients revealed decreased endogenous thrombin potential and peak height and extended lag time compared to control. However, this method was not sensitive to blood spiking with fibrinogen and FXIII. ROTEM revealed lower maximum clot firmness (MCF) and area under curve (AUC) in the blood of GT model and GT patients. In the absence of exogenous tPA, blood spiking with fibrinogen markedly enhanced clot quality while FXIII had no effect. Combination of fibrinogen and FXIII did not add to the effect of fibrinogen. In contrast, by the addition of tPA, both fibrinogen and FXIII separately and, to more extent, in combination enhanced clot quality as well as resistance against tPA-induced fibrinolysis (increasing MCF, AUC, and lysis onset time). In conclusion, fibrinogen and FXIII exerted stimulation of blood clotting and inhibition of fibrinolysis. Treating normal blood with eptifibatide mimics the changes of coagulopathy in GT blood.

  7. A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia.

    PubMed

    Siddiq, S; Clark, A; Mumford, A

    2011-09-01

    Glanzmann Thrombasthenia (GT) is a rare autosomal recessive disorder which usually manifests as severe mucocutaneous bleeding and is caused by deficiency of the platelet glycoprotein IIb-IIIa. Pregnancy in women with GT presents particular challenges as there is increased risk of both maternal and foetal bleeding. To improve understanding and clarify the optimum management of pregnancy in this disorder, we performed a systematic review of the world literature of pregnancy and GT. This identified three single-centre case series of patients with GT that included brief descriptions of women in pregnancy and 31 detailed case reports of 40 pregnancies in 35 women that resulted in 38 live births. Among the detailed case reports, ante-natal bleeding was described in 50% of pregnancies but was usually mild and occurred at mucocutaneous sites. Primary postpartum haemorrhage (PPH) was reported in 34% of pregnancies and secondary PPH in 24%. PPH was frequently severe and occurred up to 20 days after delivery. There was a wide variation in approach to prevention and treatment of PPH but most women received platelet transfusion, sometimes with additional recombinant FVIIa and anti-fibrinolytics. Maternal alloimmunization against platelet antigens was reported in 73% of pregnancies and was associated with four neonatal deaths. These data emphasize the need for multidisciplinary management of pregnancy in women with GT. Delivery plans should recognize the need for prevention and aggressive treatment of PPH and should minimize foetal bleeding risk in pregnancies complicated by alloimmunization. © 2011 Blackwell Publishing Ltd.

  8. Genetics Home Reference: Glanzmann thrombasthenia

    MedlinePlus

    ... Citation on PubMed Nurden AT, Pillois X, Wilcox DA. Glanzmann thrombasthenia: state of the art and future ... V, Halimeh S, Santoso S, Kurnik K, Fischer L, Tsakiris DA, Sigl-Kraetzig M, Brand B, Bührlen M, Kraetzer ...

  9. Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.

    PubMed

    Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Myasoedova, Veronika; Amato, Manuela; Ventre, Itala; Tremoli, Elena; Minno, Alessandro Di

    2017-01-01

    In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel

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

    Newman, P.J.; Seligsohn, U.; Lyman, S.

    1991-04-15

    Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by a decrease or absence of functional platelet glycoprotein (GP) IIb-IIIa ({alpha}{sub IIb}{beta}{sub 3}) integrin receptors. Although thrombasthenia is a rare disorder, its occurrence is increased in some regions of the world where intracommunity marriage and consanguinity are commonplace, resulting in increased expression of autosomal recessive traits. The authors have been studying two populations having an unusually high frequency of Glanzmann disease, Iraqi Jews and Arabs living in Israel, and were able to distinguish the populations on the basis of immunodetectable GPIIIa and populations on the basis of immunodetectable GPIIIa andmore » platelet surface vitronectin receptor ({alpha}{sub v}{beta}{sub 3}) expression. In this article, they describe molecular genetic studies based on use of the PCR that have allowed us to characterize platelet mRNA sequences encoding GPIIb and GPIIIa from patients in these populations. These studies demonstrate the heterogeneity of Glanzmann thrombasthenia in different populations, and its homogeneity within geographically restricted populations, and offer insight into the requirements for integrin surface expression.« less

  11. Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies.

    PubMed

    Martin, Isabelle; Kriaa, Fayçal; Proulle, Valérie; Guillet, Benoît; Kaplan, Cécile; D'Oiron, Roseline; Debré, Marianne; Fressinaud, Edith; Laurian, Yyes; Tchernia, Gil; Charpentier, Bernard; Lambert, Thierry; Dreyfus, Marie

    2002-12-01

    Type I Glanzmann's thrombasthenia is a rare congenital platelet function disorder, characterized by undetectable platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa). Severe bleeding is controlled by transfusion of normal platelets, leading in some cases to the occurrence of anti-GPIIb-IIIa isoantibodies, which induces a loss of transfused platelet efficacy. We used immunoadsorption on protein A Sepharose (IA-PA), which has been shown to be efficient in decreasing the titre of antibodies in several immune diseases, in three patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies on five different occasions. IA-PA was well tolerated with no deleterious side-effects reported. It induced a dramatic decrease of total immunoglobulin (Ig)G, including anti-GPIIb-IIIa isoantibody levels, as assessed by the monoclonal antibody-specific immobilization of platelet antigens test and the ex vivo inhibition of normal platelet aggregation induced by the patient's platelet-rich or platelet-poor plasma. Elimination of the antibody was associated with a correction of the bleeding time following platelet transfusion. IA-PA combined with platelet transfusion made it possible to control two life-threatening haemorrhages, and allowed two surgical procedures and one bone marrow transplantation to be performed safely. Our experience suggests that IA-PA, which restores the haemostatic efficacy of platelet transfusion, is a valuable therapeutic strategy in patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies.

  12. αIIbβ3 variants defined by next-generation sequencing: Predicting variants likely to cause Glanzmann thrombasthenia

    PubMed Central

    Buitrago, Lorena; Rendon, Augusto; Liang, Yupu; Simeoni, Ilenia; Negri, Ana; Filizola, Marta; Ouwehand, Willem H.; Coller, Barry S.; Alessi, Marie-Christine; Ballmaier, Matthias; Bariana, Tadbir; Bellissimo, Daniel; Bertoli, Marta; Bray, Paul; Bury, Loredana; Carrell, Robin; Cattaneo, Marco; Collins, Peter; French, Deborah; Favier, Remi; Freson, Kathleen; Furie, Bruce; Germeshausen, Manuela; Ghevaert, Cedric; Gomez, Keith; Goodeve, Anne; Gresele, Paolo; Guerrero, Jose; Hampshire, Dan J.; Hadinnapola, Charaka; Heemskerk, Johan; Henskens, Yvonne; Hill, Marian; Hogg, Nancy; Johnsen, Jill; Kahr, Walter; Kerr, Ron; Kunishima, Shinji; Laffan, Michael; Natwani, Amit; Neerman-Arbez, Marguerite; Nurden, Paquita; Nurden, Alan; Ormiston, Mark; Othman, Maha; Ouwehand, Willem; Perry, David; Vilk, Shoshana Ravel; Reitsma, Pieter; Rondina, Matthew; Simeoni, Ilenia; Smethurst, Peter; Stephens, Jonathan; Stevenson, William; Szkotak, Artur; Turro, Ernest; Van Geet, Christel; Vries, Minka; Ward, June; Waye, John; Westbury, Sarah; Whiteheart, Sidney; Wilcox, David; Zhang, Bi

    2015-01-01

    Next-generation sequencing is transforming our understanding of human genetic variation but assessing the functional impact of novel variants presents challenges. We analyzed missense variants in the integrin αIIbβ3 receptor subunit genes ITGA2B and ITGB3 identified by whole-exome or -genome sequencing in the ThromboGenomics project, comprising ∼32,000 alleles from 16,108 individuals. We analyzed the results in comparison with 111 missense variants in these genes previously reported as being associated with Glanzmann thrombasthenia (GT), 20 associated with alloimmune thrombocytopenia, and 5 associated with aniso/macrothrombocytopenia. We identified 114 novel missense variants in ITGA2B (affecting ∼11% of the amino acids) and 68 novel missense variants in ITGB3 (affecting ∼9% of the amino acids). Of the variants, 96% had minor allele frequencies (MAF) < 0.1%, indicating their rarity. Based on sequence conservation, MAF, and location on a complete model of αIIbβ3, we selected three novel variants that affect amino acids previously associated with GT for expression in HEK293 cells. αIIb P176H and β3 C547G severely reduced αIIbβ3 expression, whereas αIIb P943A partially reduced αIIbβ3 expression and had no effect on fibrinogen binding. We used receiver operating characteristic curves of combined annotation-dependent depletion, Polyphen 2-HDIV, and sorting intolerant from tolerant to estimate the percentage of novel variants likely to be deleterious. At optimal cut-off values, which had 69–98% sensitivity in detecting GT mutations, between 27% and 71% of the novel αIIb or β3 missense variants were predicted to be deleterious. Our data have implications for understanding the evolutionary pressure on αIIbβ3 and highlight the challenges in predicting the clinical significance of novel missense variants. PMID:25827233

  13. Functional Comparison of Induced Pluripotent Stem Cell- and Blood-Derived GPIIbIIIa Deficient Platelets

    PubMed Central

    Haas, Jessica; Sandrock-Lang, Kirstin; Gärtner, Florian; Jung, Christian Billy; Zieger, Barbara; Parrotta, Elvira; Kurnik, Karin; Sinnecker, Daniel; Wanner, Gerhard; Laugwitz, Karl-Ludwig; Massberg, Steffen; Moretti, Alessandra

    2015-01-01

    Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application. PMID:25607928

  14. Formation of obstructing blood clot in the ureter in a patient with Glanzmann's thrombasthenia.

    PubMed

    Kilincaslan, Huseyin; Leblebisatan, Goksel; Tepeler, Abdulkadir; Karakus, Suleyman C

    2011-12-01

    Glanzman thrombasthenia is a rare hematologic disorder characterized by qualitative thrombocyte abnormality. Patients present with episodic mucocutaneous bleeding. Thrombosis is a paradox phenomenon observed in patients with Glanzman thrombasthenia and generally considered as a treatment complication. We present a 16-year-old girl referred for severe flank pain beginning after treatment of hematuria due to Glanzman thrombasthenia. The patient underwent endoscopy for further diagnosis and treatment because of the failure of radiologic evaluation. Although the resolution of the large clots was obtained with streptokinase instillation via the ureteral catheter, clot was mobilized with gentle insertion of ureteral catheter in the present case.

  15. Congenital platelet function defects

    MedlinePlus

    Platelet storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... This disorder may also cause severe bleeding. Platelet storage pool disorder (also called platelet secretion disorder) occurs ...

  16. Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.

    PubMed

    Norris, J W; Pombo, M; Shirley, E; Blevins, G; Tablin, F

    2015-01-01

    Two congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation. Platelet dysfunction in horses with this second thrombasthenia results from a secretory defect. Two affected and 6 clinically normal horses. Ex vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1). Platelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation. Defects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia. Copyright © The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  17. Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies

    ClinicalTrials.gov

    2017-12-03

    Sickle Cell Disease; Transfusion Dependent Alpha- or Beta- Thalassemia; Diamond Blackfan Anemia; Paroxysmal Nocturnal Hemoglobinuria; Glanzmann Thrombasthenia; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Non-Malignant Hematologic Disorders

  18. Glanzmann Thrombasthenia

    MedlinePlus

    ... and Women with Hemophilia Inheritance of Hemophilia Definitions & Terminology Bleeding Symptoms Carrier Diagnosis When to Test for ... and Women with Hemophilia Inheritance of Hemophilia Definitions & Terminology Bleeding Symptoms Carrier Diagnosis When to Test for ...

  19. Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

    ClinicalTrials.gov

    2017-07-24

    Thalassemia; Sickle Cell Disease; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic-granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Schwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Fanconi Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia

  20. BMT Abatacept for Non-Malignant Diseases

    ClinicalTrials.gov

    2018-05-16

    Hurler Syndrome; Fanconi Anemia; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Shwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia; Thalassemia Major; Hemophagocytic Lymphohistiocytosis; Sickle Cell Disease

  1. The effect of platelets on fibrin gel structure formed in the presence of recombinant factor VIIa in hemophilia plasma and in plasma from a patient with Glanzmann thrombasthenia.

    PubMed

    He, S; Ekman, G Jacobsson; Hedner, U

    2005-02-01

    Fibrin gel structure has been shown to be dependent on the thrombin concentration as well as the rate of thrombin generation. Accordingly, factor VIII (FVIII)- and FIX-deficient plasma (hemophilia A and B) form loose fibrin clots with high permeability constants. By adding rFVIIa in vitro to FVIII-deficient plasma containing platelets (frozen and thawed), the fibrin gel permeability constant normalized, indicating that extra rFVIIa (1.2 microg mL(-1) or higher) induced a tight fibrin structure. Thrombin generation is highly dependent on the number of platelets, and in this study it was demonstrated that the addition of rFVIIa (5 microg mL(-1)) normalizes the fibrin gel permeability in samples containing platelets (frozen-thawed) in numbers of at least down to 20 x 10(6) mL(-1). The effect of rFVIIa was not observed when unfrozen platelets instead of frozen-thawed platelets were added. Neither was any effect on the fibrin permeability seen, in the presence of annexin V, known to block the effect of phospholipids on the platelet surface. This indicates an important role of platelet phospholipids for the effect of rFVIIa. A similar effect on the fibrin permeability of rFVIIa was observed when added to platelet-rich plasma from a patient with Glanzmann thrombasthenia. Recombinant FVIIa has been found to induce hemostasis in patients with hemophilia and inhibitors against FVIII/FIX as well as in patients with Glanzmann thrombasthenia, indicating the importance of the formation of a tight fibrin gel structure, more resistant against premature proteolysis, for maintaining hemostasis. In conclusion, the addition of rFVIIa (5 microg mL(-1)) also substantially decreased the permeability constant of fibrin gels formed in FVIII-deficient plasma in the presence of low numbers of frozen-thawed platelets (down to 20 x 10(6) mL(-1)). A similar pattern was obtained in plasma from a Glanzmann patient. No effect was found in the presence of unfrozen instead of frozen-thawed platelets. Annexin V blocked any effect of rFVIIa. A normalization of the overall fibrinolysis potential (OFP) during the same condition supports the effect of rFVIIa on the fibrin permeability in the presence of a limited number of platelets.

  2. Intracranial hemorrhage in congenital bleeding disorders.

    PubMed

    Tabibian, Shadi; Motlagh, Hoda; Naderi, Majid; Dorgalaleh, Akbar

    2018-01-01

    : Intracranial hemorrhage (ICH), as a life-threatening bleeding among all kinds of congenital bleeding disorders (CBDs), is a rare manifestation except in factor XIII (FXIII) deficiency, which is accompanied by ICH, early in life, in about one-third of patients. Most inherited platelet function disorders (IPFDs) are mild to moderate bleeding disorders that can never experience a severe bleeding as in ICH; however, Glanzmann's thrombasthenia, a common and severe inherited platelet function disorder, can lead to ICH and occasional death. This bleeding feature can also be observed in grey platelet syndrome, though less frequently than in Glanzmann's thrombasthenia. In hemophilia, intracerebral hemorrhage is affected by various risk factors one of which is the severity of the disease. The precise prevalence of ICH in these patients is not clear but an estimated incidence of 3.5-4% among newborns with hemophilia is largely ascertained. Although ICH is a rare phenomenon in CBDs, it can be experienced by every patient with severe hemophilia A and B, FXIII deficiency (FXIIID), FVIID, FXD, FVD, FIID, and afibrinogenemia. Upon observing the general signs and symptoms of ICH such as vomiting, seizure, unconsciousness, and headache, appropriate replacement therapies and cranial ultrasound scans must be done to decrease ICH-related morbidity and mortality.

  3. [Glanzmann's thrombasthenia: first case descriptions in sub-Saharan Africa].

    PubMed

    Dokekias, A Elira; Galiba, F O Atipo; Koko, I

    2008-08-01

    Constitutive hemorrhagic diseases that affect primary haemostasis are reportedly rare in sub-Saharan Africa. This study arrived to report within a Congolese family five cases of Glanzmann's thromboasthenia. 5 cases of the congenital form of Glanzmann's thromboasthenia were depicted in a Congolese family. The disease was first discovered with a young student who was transferred in France, who had shown a tendency to develop hemorrhages since childhood. This tendency was enhanced following abdominal surgery to treat peritonitis. Like the other 3 cases, she had a prolonged bleeding time, albeit with normal von Willebrand factor plasma values. A 7 year old girl died following appendectomy from post-surgery hemorrhages. In this young patient, platelet aggregation could be induced only by ristocetine, all other conventional agonists failed. Flow cytometric analysis showed the total absence of GPIIbIIIa. The hemorrhages in the girls could be managed by cyclic administration of oestrogens and iron supplementation. Serologic analysis showed this patient to be positive for hepatitis C virus antibodies. This first description of Glanzmann's thrombo-asthenia in Blacks in sub-Saharan Africa shows the necessity of establish inter-hospital cooperation for the improvement of the management of constitutive hemorrhagic diseases in the Hematology wards.

  4. Safety update on the use of recombinant activated factor VII in approved indications.

    PubMed

    Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

    2015-06-01

    This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Type I Glanzmann thrombasthenia caused by an apparently silent beta3 mutation that results in aberrant splicing and reduced beta3 mRNA.

    PubMed

    Xie, Jingli; Pabón, Dina; Jayo, Asier; Butta, Nora; González-Manchón, Consuelo

    2005-05-01

    We report a novel genetic defect in a patient with type I Glanzmann thrombasthenia. Flow cytometry analysis revealed undetectable levels of platelet glycoproteins alphaIIb and beta3, although residual amounts of both proteins were detectable in immunoblotting analysis. Sequence analysis of reversely transcribed platelet beta3 mRNA showed a 100-base pair deletion in the 3'-boundary of exon 11, that results in a frame shift and appearance of a premature STOP codon. Analysis of the corresponding genomic DNA fragment revealed the presence of a homozygous C1815T transition in exon 11. The mutation does not change the amino acid residue but it creates an ectopic consensus splice donor site that is used preferentially, causing splicing out of part of exon 11. The parents of the proband, heterozygous for this mutation, were asymptomatic and had reduced platelet content of alphaIIbbeta3. PCR-based relative quantification of beta3 mRNA failed to detect the mutant transcript in the parents and showed a marked reduction in the patient. The results suggest that the thrombasthenic phenotype is, mainly, the result of the reduced availability of beta3-mRNA, most probably due to activation of the nonsense-mediated mRNA decay mechanism. They also show the convenience of analyzing both genomic DNA and mRNA, in order to ascertain the functional consequences of single nucleotide substitutions.

  6. Recombinant factor VIIa (eptacog alfa): a review of its use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders.

    PubMed

    Croom, Katherine F; McCormack, Paul L

    2008-01-01

    Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury. It is approved in many countries for use as an intravenous hemostatic agent in patients with congenital hemophilia with inhibitors, and also for acquired hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some countries. Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery in patients with congenital hemophilia with inhibitors, acquired hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available data, its efficacy in terms of patient-assessed response may be similar to that of activated prothrombin complex concentrate (aPCC), but treatment with a single 270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in patients with hemophilia, does not produce an anamnestic response in hemophilia patients with inhibitors, and has very low thrombogenicity. It is recommended in guidelines as the treatment of choice for bleeds in patients with hemophilia B with high-responding inhibitors and for patients with factor VII deficiency, and is also a first-line therapeutic option for high-responder hemophilia A patients with inhibitors and those with acquired hemophilia. Cost data from pharmacoeconomic analyses support its use in hemophilia patients with inhibitors. Thus, recombinant factor VIIa is a valuable treatment option for patients with these rare, but potentially serious, bleeding disorders.

  7. [Construction of rAAV2-GPIIb/IIIa vector and test of its expression and function in vitro].

    PubMed

    Wang, Kai; Peng, Jian-Qiang; Chen, Fang-Ping; Wu, Xiao-Bin

    2006-04-01

    This study was aimed to explore the possibility of rAAV2 vector-mediating gene therapy for Glanzmann' s thrombasthenia. The rAAV2-GPIIb/IIIa vector was constructed. The GPIIb/IIIa gene expression in mammal cell were examined by different methods, such as: detection of mRNA expression in BHK-21 cells after 24 hours of infection (MOI = 1 x 10(5) v.g/cell) was performed by RT-PCR; the relation between MOI and quantity of GPII6/IIIa gene expression was detected by FACS after 48 hours of infection; GPIIb/IIIa protein expression in BHK-21 cells after 48 hours of infection (MOI = 10(5) v x g/cell) was assayed by Western blot, GPIIb/IIIa protein expression on cell surface was detected by immunofluorescence, and the biological function of expressing product was determined by PAC-1 conjunct experiments. The results showed that GPIIb/IIIa gene expression in mRNA level could be detected in BHK-21 cells after 24 hours of infection at MOI = 1 x 10(5) v x g/cell and the GPIIb/IIIa gene expression in protein level could be detected in BHK-21 cells after 48 hours of infection at MOI = 1 x 10(5) v x g/cell. In certain range, quantity of GPIIb/IIIa gene expression increased with MOI, but overdose of MOI decreased quantity of GPIIb/IIIa gene expression. Activated product of GPIIb/IIIa gene expression could combined with PAC-I, and possesed normal biological function. In conclusion, rAAV2 vactor can effectively mediate GPIIb and GPIIIa gene expressing in mammal cells, and the products of these genes exhibit biological function. This result may provide a basis for application of rAAV2 vector in Glanzmann's thrombasthenia gene therapy in furture.

  8. Platelet gene therapy improves hemostatic function for integrin αIIbβ3-deficient dogs

    PubMed Central

    Fang, Juan; Jensen, Eric S.; Boudreaux, Mary K.; Du, Lily M.; Hawkins, Troy B.; Koukouritaki, Sevasti B.; Cornetta, Kenneth; Wilcox, David A.

    2011-01-01

    Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3’s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects. PMID:21606353

  9. Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.

    PubMed

    Fang, Juan; Jensen, Eric S; Boudreaux, Mary K; Du, Lily M; Hawkins, Troy B; Koukouritaki, Sevasti B; Cornetta, Kenneth; Wilcox, David A

    2011-06-07

    Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3's major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.

  10. Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

    ClinicalTrials.gov

    2018-06-13

    Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

  11. Recombinant activated factor VII: 30 years of research and innovation.

    PubMed

    Hedner, Ulla

    2015-06-01

    Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital haemophilia and inhibitors. The story of its development began in the 1970s, when FVIIa was identified as one of the activated coagulation factors that has minimal potential for inducing thromboembolic side-effects. Extensive research over the last 30 years has greatly increased our knowledge of the characteristics of FVII, its activation, and the mechanisms by which rFVIIa restores haemostasis. In haemophilia, the haemostatic effect of rFVIIa is mediated via binding to thrombin-activated platelets at the site of injury, thereby enhancing thrombin generation also in the absence of factor (F) VIII or FIX. The mechanism of action of rFVIIa has also allowed its successful use in other clinical scenarios characterised by impaired thrombin generation, and its licensed uses have now been extended to acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    PubMed

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  13. Abnormal Whole Blood Thrombi in Humans with Inherited Platelet Receptor Defects

    PubMed Central

    Castellino, Francis J.; Liang, Zhong; Davis, Patrick K.; Balsara, Rashna D.; Musunuru, Harsha; Donahue, Deborah L.; Smith, Denise L.; Sandoval-Cooper, Mayra J.; Ploplis, Victoria A.; Walsh, Mark

    2012-01-01

    To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS) and Glanzmann’s Thrombasthenia (GT). We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes. PMID:23300803

  14. Integrin αIIbβ3

    PubMed Central

    Bledzka, Kamila; Smyth, Susan S.; Plow, Edward F.

    2013-01-01

    From the initial description of platelets in 1882, their propensity to aggregate and to contribute to thrombosis was apparent. Indeed, excessive platelet aggregation is associated with myocardial infarction and other thrombotic diseases whereas Glanzmann thrombasthenia, in which platelet aggregation is reduced, is a bleeding syndrome. Over the last half of the 20th century, many investigators have provided insights into the cellular and molecular basis for platelet aggregation. The major membrane protein on platelets, integrin αIIbβ3, mediates this response by rapidly transiting from its resting to an activated state in which it serves as a receptor for ligands that can bridge platelets together. Monoclonal antibodies, natural products, and small peptides were all shown to inhibit αIIbβ3 dependent platelet aggregation, and these inhibitors became the forerunners of antagonists that proceeded through preclinical testing and into large patient trials to treat acute coronary syndromes, particularly in the context of percutaneous coronary interventions. Three such αIIbβ3 antagonists, abciximab, eptifibatide, and tirofiban, received Food and Drug Administration approval. Over the past 15 years, millions of patients have been treated with these αIIbβ3 antagonists and many lives have been saved by their administration. With the side effect of increased bleeding and the development of new antithrombotic drugs, the use of αIIbβ3 antagonists is waning. Nevertheless, they are still widely used for the prevention of periprocedural thrombosis during percutaneous coronary interventions. This review focuses on the biology of αIIbβ3, the development of its antagonists, and some of the triumphs and shortcomings of αIIbβ3 antagonism. PMID:23580774

  15. Talin does not associate exclusively with alpha 2b beta 3 integrin in activated human platelets.

    PubMed

    Escolar, G; Diaz-Ricart, M; White, J G

    1995-05-01

    Talin is a high-molecular-weight protein that may stabilize connections between cytoplasmic actin and the submembrane portion of glycoprotein IIb-IIIa (GPIIb-IIIa) (alpha 2b beta 3 integrin) in thrombin-stimulated human platelets. Using morphologic and electrophoretic techniques, we have examined the association of talin with the cytoskeleton of platelets activated by thrombin in the presence of fibrinogen-coated gold particles (Fgn/Au). Ultrastructural studies confirmed the presence of Fgn/Au firmly bound to the outside membranes of detergent-extracted platelets. Immunoblots of protein bands showed GPIIIa, but not talin, associated with cytoskeletons of activated platelets. Immunogold cytochemical techniques were performed on ultrathin cryosections of whole platelets to localize talin at the ultrastructural level. Studies were performed on normal platelets and platelets defective in GPIIb-IIIa (Glanzmann's thrombasthenia) and GPIb (Bernard-Soulier syndrome). Talin was randomly distributed in the cytoplasm of resting platelets. Activation resulted in binding of Fgn/Au to the surface membrane and redistribution of talin to the submembrane region. However, no definitive colocalization between the two markers was noted. Activated thrombasthenic platelets failed to bind Fgn/Au, but talin was localized to the submembrane location. After activation, talin was confined to the submembrane zone of Bernard-Soulier syndrome platelets. No definitive colocalization was observed between large clusters of Fgn/Au-occupied receptors and talin distributed in the submembrane region. GPIb and GPIIb-IIIa are not necessary for talin to localize in the submembrane region of activated cells. Talin does not redistribute exclusively with GPIIb-IIIa, and it may stabilize connections with other glycoproteins.

  16. Procoagulant Platelets Form an α-Granule Protein-covered “Cap” on Their Surface That Promotes Their Attachment to Aggregates*

    PubMed Central

    Abaeva, Anastasia A.; Canault, Matthias; Kotova, Yana N.; Obydennyy, Sergey I.; Yakimenko, Alena O.; Podoplelova, Nadezhda A.; Kolyadko, Vladimir N.; Chambost, Herve; Mazurov, Aleksei V.; Ataullakhanov, Fazoil I.; Nurden, Alan T.; Alessi, Marie-Christine; Panteleev, Mikhail A.

    2013-01-01

    Strongly activated “coated” platelets are characterized by increased phosphatidylserine (PS) surface expression, α-granule protein retention, and lack of active integrin αIIbβ3. To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the α-granule protein “coat.” Confocal microscopy revealed that fibrin(ogen) and thrombospondin colocalized as “cap,” a single patch on the PS-positive platelet surface. In aggregates, the cap was located at the point of attachment of the PS-positive platelets. Without fibrin(ogen) retention, their ability to be incorporated in aggregates was drastically reduced. The surface fibrin(ogen) was strongly decreased in the presence of a fibrin polymerization inhibitor GPRP and also in platelets from a patient with dysfibrinogenemia and a fibrinogen polymerization defect. In contrast, a fibrinogen-clotting protease ancistron increased the amount of fibrin(ogen) and thrombospondin on the surface of the PS-positive platelets stimulated with collagen-related peptide. Transglutaminases are also involved in fibrin(ogen) retention. However, platelets from patients with factor XIII deficiency had normal retention, and a pan-transglutaminase inhibitor T101 had only a modest inhibitory effect. Fibrin(ogen) retention was normal in Bernard-Soulier syndrome and kindlin-3 deficiency, but not in Glanzmann thrombasthenia lacking the platelet pool of fibrinogen and αIIbβ3. These data show that the fibrin(ogen)-covered cap, predominantly formed as a result of fibrin polymerization, is a critical mechanism that allows coated (or rather “capped”) platelets to become incorporated into thrombi despite their lack of active integrins. PMID:23995838

  17. Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII

    PubMed Central

    Mattheij, Nadine J.A.; Swieringa, Frauke; Mastenbroek, Tom G.; Berny-Lang, Michelle A.; May, Frauke; Baaten, Constance C.F.M.J.; van der Meijden, Paola E.J.; Henskens, Yvonne M.C.; Beckers, Erik A.M.; Suylen, Dennis P.L.; Nolte, Marc W.; Hackeng, Tilman M.; McCarty, Owen J.T.; Heemskerk, Johan W.M.; Cosemans, Judith M.E.M.

    2016-01-01

    Coated platelets, formed by collagen and thrombin activation, have been characterized in different ways: i) by the formation of a protein coat of α-granular proteins; ii) by exposure of procoagulant phosphatidylserine; or iii) by high fibrinogen binding. Yet, their functional role has remained unclear. Here we used a novel transglutaminase probe, Rhod-A14, to identify a subpopulation of platelets with a cross-linked protein coat, and compared this with other platelet subpopulations using a panel of functional assays. Platelet stimulation with convulxin/thrombin resulted in initial integrin αIIbβ3 activation, the appearance of a platelet population with high fibrinogen binding, (independently of active integrins, but dependent on the presence of thrombin) followed by phosphatidylserine exposure and binding of coagulation factors Va and Xa. A subpopulation of phosphatidylserine-exposing platelets bound Rhod-A14 both in suspension and in thrombi generated on a collagen surface. In suspension, high fibrinogen and Rhod-A14 binding were antagonized by combined inhibition of transglutaminase activity and integrin αIIbβ3. Markedly, in thrombi from mice deficient in transglutaminase factor XIII, platelet-driven fibrin formation and Rhod-A14 binding were abolished by blockage of integrin αIIbβ3. Vice versa, star-like fibrin formation from platelets of a patient with deficiency in αIIbβ3 (Glanzmann thrombasthenia) was abolished upon blockage of transglutaminase activity. We conclude that coated platelets, with initial αIIbβ3 activation and high fibrinogen binding, form a subpopulation of phosphatidylserine-exposing platelets, and function in platelet-dependent star-like fibrin fiber formation via transglutaminase factor XIII and integrin αIIbβ3. PMID:26721892

  18. Thrombasthénie de Glanzmann: à propos de 11 cas

    PubMed Central

    Mukendi, Jean-Louis Ntumba; Benkirane, Souad; Masrar, Azlarab

    2015-01-01

    Introduction La thrombasthénie de Glanzmann est une pathologie hémorragique héréditaire rare due à une déficience ou un dysfonctionnement du complexe glycoprotéique IIb/IIIa de la membrane plaquettaire. Le but de notre étude est de décrire les caractéristiques démographiques, cliniques et biologiques d'une série de patients atteints de thrombasthénie de Glanzmann. Méthodes C'est une étude portant sur tous les patients atteints de thrombasthénie de Glanzmann diagnostiqués au Laboratoire Central d'Hématologie du Centre Hospitalier Ibn Sina de Rabat au Maroc pendant la période allant du 1er mars 2011 au 31 mars 2013, soit 25 mois. Après avoir recueilli les données épidémiologiques et cliniques de nos patients, nous avons réalisé une étude biologique comportant une numération plaquettaire et une agrégométrie. Résultats 11 patients ont présenté des profils agrégométriques compatibles à une TG. La majorité de ces malades étaient issus de mariages consanguins (54,5%) et originaires de régions situées dans le nord du Maroc. Le syndrome hémorragique s'est révélé principalement cutanéo-muqueux, avec une prédominance des gingivorragies (72,7%), des épistaxis (63,6%) et des ecchymoses (45,5%). Conclusion Nos résultats ont montré que la thrombasthénie de Glanzmann est une pathologie relativement fréquente au Maroc. PMID:26587119

  19. The level of laboratory testing required for diagnosis or exclusion of a platelet function disorder using platelet aggregation and secretion assays.

    PubMed

    Mezzano, Diego; Quiroga, Teresa; Pereira, Jaime

    2009-03-01

    The major advances from research on platelet molecular and cell biology, physiology, and pathophysiology over the past decades have not been adequately translated to clinical laboratory diagnosis. Hereditary platelet function disorders (PFDs) are at least as prevalent in the general population as von Willebrand disease (VWD) although PFDs tend not be as well recognized or evaluated. Clinical mucous and skin bleeding in patients with PFDs is prototypic of primary hemostasis disorders, and the bleeding pattern is not distinguishable from that of other primary hemostasis disorders such as VWD. However, different treatment needs, between these discrete disorders, make a precise diagnosis mandatory. Currently, clinicians receive reliable laboratory reports when testing patients with severe PFDs, such as Glanzmann thrombasthenia and Bernard-Soulier syndrome, due to the distinctive laboratory defects that these disorders present, together with the availability of differential diagnostic tests. This is not the case for the majority of PFDs generically classified as "platelet secretion disorders," which are a heterogeneous group of "mild bleeding disorders," for which there are not universally accepted diagnostic criteria. An important reason for robust diagnostic tests is the high proportion (more than 50% in some reports) of patients with unequivocal bleeding who have no precise diagnosis established after a complete laboratory workup. It is paradoxical that the current "gold standard" test for PFD diagnosis, light transmission aggregometry (LTA), has not been standardized after more than four decades of worldwide clinical use. This review describes current diagnostic assays for PFD in a clinical hemostasis laboratory, relating these with current knowledge on platelet function and pathophysiology. Special emphasis will be given to LTA and platelet secretion tests, as well as to the reasons why sensitive tests are needed to explore the lesser known participation of platelets in blood clotting and fibrinolytic processes.

  20. Glanzmann disease

    MedlinePlus

    ... platelet and vascular function. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

  1. Assessing efficacy and therapeutic claims in emerging indications for recombinant factor VIIa: regulatory perspectives.

    PubMed

    Farrugia, Albert

    2006-01-01

    When compared with the evidence-based, cost-effectiveness criteria underpinning most government reimbursement schemes in the social market economies, the three regulatory hurdles of safety, quality and efficacy are probably of modest impact in influencing increased usage of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Nevertheless, efficacy claims must be supported if regulatory approval is to be granted for the wider range of indications that have been proposed for rFVIIa. With the refinement of clinical trial designs over the past 40 years, the randomized controlled trial (RCT) has assumed the role of gold standard, providing the highest level of evidence for therapeutic efficacy. However, it is incorrect to assume that regulatory authorities give sole credence to RCTs in assessing claims. It is noteworthy that the indications already accepted for rFVIIa by international regulatory authorities--including the treatment of inhibitors to factor VIII and factor IX, substitution for FVII deficiency, and treatment of Glanzmann's thrombasthenia--were supported not by RCTs but by studies conventionally considered to provide modest evidence levels. Therefore, the use of studies other than RCTs for the more recently proposed indications for rFVIIa in a range of conditions requiring hemostatic correction is perfectly feasible. What regulators expect are well-conducted and well-described studies adhering to principles of good clinical practice, which can be scrutinized for evidence of clinical efficacy and which are based on the initially proven principle for the drug. This paper discusses the regulatory history of rFVIIa in the major regulatory authorities and assesses the route needed to support claims being made in the mainstream literature. Recent episodes where post-market events have forced regulators to be more than usually cautious will be used as examples to suggest possible pitfalls to the extension of approved claims for rFVIIa. The major paths for enhancing access for indications in small patient numbers, where RCTs are even more difficult to perform, will be described and their use for possible extension of rFVIIa indications will be discussed.

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

    DTIC Science & Technology

    2011-11-01

    thrombasthenia.12 In trauma, when a blood vessel is injured, tissue factor on subendothelial pericytes is exposed and binds to endogenous FVII ...a more complex effect on coagulation than simply dilution of any single coagulation factor like FVII or fibrinogen (Fig. 1). It is interesting to note...ORIGINAL ARTICLE Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro Daniel N. Darlington, PhD, Angel

  3. Investigating energy deposition within cell populations using Monte Carlo simulations.

    PubMed

    Oliver, Patricia A K; Thomson, Rowan M

    2018-06-27

    In this work, we develop multicellular models of healthy and cancerous human soft tissues, which are used to investigate energy deposition in subcellular targets, quantify the microdosimetric spread in a population of cells, and determine how these results depend on model details. Monte Carlo (MC) tissue models combining varying levels of detail on different length scales are developed: microscopically-detailed regions of interest (>1500 explicitly-modelled cells) are embedded in bulk tissue phantoms irradiated by photons (20 keV to 1.25 MeV). Specific energy (<i>z</i>; energy imparted per unit mass) is scored in nuclei and cytoplasm compartments using the EGSnrc user-code egs_chamber; specific energy mean, <<i>z</i>>, standard deviation, <i>σ</i><sub><i>z</i></sub>, and distribution, <i>f</i>(<i>z</i>,<i>D</i>), are calculated for a variety of macroscopic doses, <i>D</i>. MC-calculated <i>f</i>(<i>z</i>,<i>D</i>) are compared with normal distributions having the same mean and standard deviation. For mGy doses, there is considerable variation in energy deposition (microdosimetric spread) throughout a cell population: <i>e</i>.<i>g</i>., for 30 keV photons irradiating melanoma with 7.5 μm cell radius and 3 μm nuclear radius, <i>σ</i><sub><i>z</i></sub>/<<i>z</i>> for nuclear targets is 170%, and the fraction of nuclei receiving no energy deposition, <i>f</i><sub><i>z</i>=0</sub>, is 0.31 for a dose of 10 mGy. If cobalt-60 photons are considered instead, then <i>σ</i><sub><i>z</i></sub>/<<i>z</i>> decreases to 84%, and <i>f</i><sub><i>z</i>=0</sub> decreases to 0.036. These results correspond to randomly arranged cells with cell/nucleus sizes randomly sampled from a normal distribution with a standard deviation of 1 μm. If cells are arranged in a hexagonal lattice and cell/nucleus sizes are uniform throughout the population, then <i>σ</i><sub><i>z</i></sub>/<<i>z</i>> decreases to 106% and 68% for 30 keV and cobalt-60,respectively; <i>f</i><sub><i>z</i>=0</sub> decreases to 0.25 and 0.00094 for 30 keV and cobalt-60, respectively. Thus, specific energy distributions are sensitive to cell/nucleus sizes and their distributions: variations in specific energy deposited over a cell population are underestimated if targets are assumed to be uniform in size compared with more realistic variation in target size. Bulk tissue dose differs from <<i>z</i>> for nuclei (cytoplasms) by up to 21% (12%) across all cell/nucleus sizes, bulk tissues, and incident photon energies, considering a 50 mGy dose level. Overall, results demonstrate the importance of microdosimetric considerations at low doses, and indicate the sensitivity of energy deposition within subcellular targets to incident photon energy, dose level, elemental compositions, and microscopic tissue model. © 2018 Institute of Physics and Engineering in Medicine.

  4. Thermal annealing and pressure effects on BaFe2-xCoxAs2 single crystals.

    PubMed

    Shin, Dongwon; Jung, Soon-Gil; Prathiba, G; Seo, Soonbeom; Choi, Ki-Young; Kim, Kee Hoon; Park, Tuson

    2017-11-26

    We investigate the pressure and thermal annealing effects on BaFe<sub>2-<i>x</i></sub>Co<sub><i>x</i></sub>As<sub>2</sub> (Co-Ba122) single crystals with <i>x</i> = 0.1 and 0.17 via electrical transport measurements. The thermal annealing treatment not only enhances the superconducting transition temperature (<i>T</i><sub>c</sub>) from 9.6 to 12.7 K for <i>x</i> = 0.1 and from 18.1 to 21.0 K for <i>x</i> = 0.17, but also increases the antiferromagnetic transition temperature (<i>T</i><sub>N</sub>). Simultaneous enhancement of <i>T</i><sub>c</sub> and <i>T</i><sub>N</sub> by the thermal annealing treatment indicates that thermal annealing could substantially improve the quality of the Co-doped Ba122 samples. Interestingly, <i>T</i><sub>c</sub> of the Co-Ba122 compounds shows a scaling behavior with a linear dependence on the resistivity value at 290 K, irrespective of tuning parameters, such as chemical doping, pressure, and thermal annealing. These results not only provide an effective way to access the intrinsic properties of the BaFe<sub>2</sub>As<sub>2</sub> system, but also may shed a light on designing new materials with higher superconducting transition temperature. © 2017 IOP Publishing Ltd.

  5. Probing conformational changes in the I-like domain and the cysteine-rich repeat of human beta 3 integrins following disulfide bond disruption by cysteine mutations: identification of cysteine 598 involved in alphaIIbbeta3 activation.

    PubMed

    Chen, P; Melchior, C; Brons, N H; Schlegel, N; Caen, J; Kieffer, N

    2001-10-19

    We have investigated receptor function and epitope expression of recombinant alpha(IIb)beta(3) mutated at Cys(177) or Cys(273) in the I-like domain as well as Cys(598), located in the fourth repeat of the membrane-proximal cysteine-rich region and mutated in a Glanzmann's thrombasthenia type II patient. The beta(3) mutants beta(3)C177A, beta(3)C273A, and beta(3)C598Y exhibited a decreased electrophoretic mobility in SDS-polyacrylamide gel electrophoresis under nonreducing conditions, confirming the disruption of the respective disulfide loops. Despite reduced surface expression, the alpha(IIb)beta(3)C177A, alpha(IIb)beta(3)C273A, and alpha(IIb)beta(3)C598Y receptors mediated cell adhesion to immobilized fibrinogen and translocated into focal adhesion plaques. The beta(3)C598Y mutation, but not the beta(3)C177A or beta(3)C273A mutations, induced spontaneous binding of the ligand mimetic monoclonal antibody PAC-1, while the beta(3)C177A and beta(3)C273A mutants exhibited reduced complex stability in the absence of Ca(2+). Epitope mapping of function-blocking monoclonal antibodies (mAbs) allowed the identification of two distinct subgroups; mAbs A2A9, pl2-46, 10E5, and P256 did not interact with alpha(IIb)beta(3)C273A and bound only weakly to alpha(IIb)beta(3)C177A, while mAbs AP2, LM609 and 7E3 bound normally to mutant alpha(IIb)beta(3)C273A, but interacted only weakly with mutant alpha(IIb)beta(3)C177A. Furthermore, a cryptic epitope recognized by mAb 4D10G3 and not exposed on wild type alpha(IIb)beta(3) became accessible only on mutant alpha(IIb)beta(3)C177A and was mapped to the 60-kDa chymotrypsin fragment of beta(3). Finally, the ligand-induced binding site (LIBS) epitopes AP5, D3, LIBS1, and LIBS2 were spontaneously expressed on all three mutants independent of RGDS or dithiothreitol treatment. Our results provide evidence that disruption of a single cysteine disulfide bond in the cysteine-rich repeat domain, but not in the I-like domain, activates integrin alpha(IIb)beta(3). In contrast, disruption of each of the disulfide bonds in the two long insertions of the I-like domain predicted to be in close contact with the alpha subunit beta-propeller domain affect the stability of the alpha(IIb)beta(3) heterodimer and inhibit complex-specific mAb binding without affecting the RGD binding capacity of the metal ion-dependent adhesion site-like domain.

  6. Magnetic and electronic properties of the Cu-substituted Weyl semimetal candidate ZrCo2Sn.

    PubMed

    Kushwaha, S K; Wang, Zhijun; Kong, Tai; Cava, Robert

    2018-01-04

    We report that the partial substitution of Cu for Co has a significant impact on the magnetic properties of the Heusler-phase Weyl fermion candidate ZrCo<sub>2</sub>Sn. Polycrystalline samples of ZrCo<sub>2-<i>x</i></sub>Cu<sub><i>x</i></sub>Sn (<i>x</i> = 0.0 to 1.0) exhibited a linearly decreasing ferromagnetic transition temperature and similarly decreasing saturated magnetic moment on increasing Cu substitution x. Materials with Cu contents near <i>x</i> = 1 and several other quaternary materials synthesized at the same <i>x</i> (ZrCo<i>T</i>'Sn (<i>T</i>' = Rh, Pd, Ni)) display what appears to be non-ferromagnetic magnetization behavior with spin glass characteristics. Electronic structure calculations suggest that the half-metallic nature of unsubstituted ZrCo<sub>2</sub>Sn is disrupted significantly by the Cu substitutions, leading to the breakdown of the magnetization vs. electron count guidelines usually followed by Heusler phases, and a more typical metallic non-spin-polarized electronic structure at high <i>x</i>. © 2018 IOP Publishing Ltd.

  7. Magnetization, resistivity, specific heat and ab initio calculations of Gd5Sb3.

    PubMed

    Samatham, S Shanmukharao; Patel, Akhilesh Kumar; Lukoyanov, Alexey V; Suresh, K G

    2018-06-07

    We report on the combined results of structural, magnetic, transport and calorimetric properties of Mn<sub>5</sub>Si<sub>3</sub>-type hexagonal Gd<sub>5</sub>Sb<sub>3</sub>, together with <i>ab-initio</i> calculations. It exhibits a ferromagnetic (FM)-like transition at 265 K, antiferromagnetic (AFM) Néel transition at 95.5 K followed by a spin-orientation transition at 62 K. The system is found to be in AFM state down to 2 K in a field of 70 kOe. The FM-AFM phase coexistence is not noticeable despite large positive Curie-Weiss temperature (θ<sub>CW</sub> = 223.5 ± 0.2 K). Instead, low-temperature AFM and high-temperature FM-like phases are separated in large temperatures. Temperature-magnetic field (<i>H</i>-<i>T</i>) phase diagram reveals field-driven complex magnetic phases. Within the AFM phase, the system is observed to undergo field-driven spin-orientation transitions. Field-induced tricritical and quantum critical points appear to be absent due to strong AFM nature and by the intervention of FM-like state between paramagnetic and AFM states, respectively. The metallic behavior of the compound is inferred from resistivity along with large Sommerfeld parameter. However, no sign of strong electron-correlations is reasoned from the Kadowaki-Wood's ratio <i>A</i>/γ<sup>2</sup> ∼ 1.9×10<sup>-6</sup> μΩ.cm.(mol.K)<sup>2</sup>(mJ)<sup>-2</sup>, despite heavy γ. Essentially, <i>ab initio</i> calculations accounting for electronic correlations confirm AFM nature of low-temperature magnetic state in Gd<sub>5</sub>Sb<sub>3</sub> and attainable FM ordering in agreement with experimental data. © 2018 IOP Publishing Ltd.

  8. Effect of dysprosium and lutetium metal buffer layers on the resistive switching characteristics of Cu-Sn alloy-based conductive-bridge random access memory.

    PubMed

    Vishwanath, Sujaya Kumar; Woo, Hyunsuk; Jeon, Sanghun

    2018-06-18

    Conductive-bridge random access memory (CBRAM) has become one of the most suitable candidates for non-volatile memory in next-generation information and communication technology. The resistive switching mechanism of CBRAM depends on the formation/annihilation of the conductive filament (CF) between the active metal electrode and the inert electrode. However, excessive ion injection from the active electrode into the solid electrolyte is reduces the uniformity and reliability of the resistive switching devices. To solve this problem, we investigated the resistive switching characteristics of a modified active electrode with different compositions of Cu<sub>x</sub>-Sn<sub><sub>1-x </sub></sub>(0.13 < X < 0.55). The resistive switching characteristics were further improved by inserting a dysprosium (Dy) or lutetium (Lu) buffer layer at the interface of Cu<sub>x</sub>-Sn<sub>1-x</sub>/Al<sub>2</sub>O<sub>3</sub>. Electrical analysis of the optimal Cu<sub>0.27</sub>-Sn<sub>0.73</sub>/Lu-based CBRAM exhibited stable resistive switching behavior with low operation voltage (SET: 0.7 V and RESET: -0.3 V), a high on/off resistive ratio (10<sup>6</sup>), cyclic endurance (>10<sup>4</sup>), and long-term retention (85℃/10 years). To achieve these performance parameters, CFs were locally formed inside the electrolyte using a modified CuSn active electrode, and the amount of Cu-ion injection was reduced by inserting the Dy or Lu buffer layer between the CuSn active electrode and the electrolyte. In particular, conductive-atomic force microscopy results at the Dy/ or Lu/Al<sub>2</sub>O<sub>3</sub> interface directly showed and defined the diameter of the CF. © 2018 IOP Publishing Ltd.

  9. Verotoxin and neuraminidase induced platelet aggregating activity in plasma: their possible role in the pathogenesis of the haemolytic uraemic syndrome.

    PubMed Central

    Rose, P E; Armour, J A; Williams, C E; Hill, F G

    1985-01-01

    Certain strains of Escherichia coli producing verotoxin have been isolated in the stools of patients with the haemolytic uraemic syndrome. A platelet aggregating activity has been found in normal plasma after incubation with verotoxin at 37 degrees C for 24 h. This activity, unlike neuraminidase, has an effect that is independent of changing factor VIII related antigen, but requires the IIA and IIIB platelet surface glycoprotein (deficient in thrombasthenia) to mediate its effect. Prostacyclin totally inhibited this effect, but other antiplatelet drugs and heparin were without inhibitory effects. PMID:2859303

  10. Stable High-Performance Perovskite Solar Cells Based on Inorganic Electron Transporting Bi-layers.

    PubMed

    Gu, Hao; Zhao, Chen; Zhang, Yiqiang; Shao, Guosheng

    2018-06-27

    As one of the significant electron transporting materials (ETM) in efficient planar heterojunction perovskite solar cells (PSCs), SnO<sub>2</sub> can collect/transfer photo-generated carriers produced in perovskite active absorbers and suppress the carrier recombination at interfaces. In this study, we demonstrate that mild solution-processed SnO<sub>2</sub> compact layer can be an eminent ETM for planar heterojunction PSCs. Here, the device based on chemical-bath-deposited SnO<sub>2</sub> electron transporting layer (ETL) exhibits a power conversion efficiency (PCE) of 16.10% and with obvious hysteresis effect (hysteresis index=19.5%), owing to the accumulation and recombination of charge carriers at SnO<sub>2</sub>/perovskite interface. In order to improve the carrier dissociation and transport process, an ultrathin TiO<sub>2</sub> film was deposited on the top of SnO<sub>2</sub> ETL passivating nonradiative recombination center. The corresponding device based on TiO<sub>2</sub>@SnO<sub>2</sub> electron transporting bi-layer (ETBL) exhibited a high PCE (17.45%) and a negligible hysteresis effect (hysteresis index=1.5%). These findings indicate that this facile solution-processed TiO<sub>2</sub>@SnO<sub>2</sub> ETBL paves a scalable and inexpensive way for fabricating hysteresis-less and high-performance PSCs. © 2018 IOP Publishing Ltd.

  11. Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes.

    PubMed

    Kato, Masaki; Hamada-Tsutsumi, Susumu; Okuse, Chiaki; Sakai, Aiko; Matsumoto, Nobuyuki; Sato, Masaaki; Sato, Toshiyuki; Arito, Mitsumi; Omoteyama, Kazuki; Suematsu, Naoya; Okamoto, Kazuki; Kato, Takanobu; Itoh, Fumio; Sumazaki, Ryo; Tanaka, Yasuhito; Yotsuyanagi, Hiroshi; Kato, Tomohiro; Kurokawa, Manae Suzuki

    2017-09-01

    In universal hepatitis B (HB) vaccination, single vaccine-derived polyclonal anti-HBs antibodies (anti-HBs) need to inhibit infection of HB viruses (HBV) of non-vaccine genotypes. We experimentally addressed this issue. Anti-HBs-positive sera were obtained by vaccination with genotype A- or C-derived HBs antigen (HBsAg, gtA-sera or gtC-sera). Their reactivity to genotype A- and C-derived HBsAg (gtA-Ag and gtC-Ag) was measured by ELISA. The capacity of sera to neutralize HBV was evaluated using an in vitro infection model. Of 135 anti-gtA-Ag-reactive gtA-sera, 134 (99.3%) were anti-gtC-Ag-reactive. All (100%) 120 anti-gtC-Ag-reactive gtC-sera were anti-gtA-Ag-reactive. The reactivity to gtA-Ag was strongly correlated with that to gtC-Ag (gtA-sera, ρ = 0.989; gtC-sera, ρ = 0.953; p < 0.01). In gtA-sera (n = 10), anti-HBs to gtA-Ag were less completely absorbed with gtC-Ag (96.4%) than with gtA-Ag (100%, p < 0.05). Similarly, in gtC-sera (n = 10), anti-HBs to gtC-Ag were less completely absorbed with gtA-Ag (96.0%) than with gtC-Ag (100%, p < 0.01). Thus, 3.6 and 4.0% of anti-HBs in gtA-sera and gtC-sera were vaccine genotype HBsAg-specific, respectively. In the neutralization test, gtA-sera (n = 4) and gtC-sera (n = 3) with anti-HBs titers adjusted to 100 mIU/mL equally inhibited genotype C HBV infection (92.8 vs. 95.4%, p = 0.44). However, at 30 mIU/mL, the gtA-sera less effectively inhibited infection than the gtC-sera (60.2 vs. 90.2%, p < 0.05). Vaccination with genotype A- or C-derived HBsAg provided polyclonal anti-HBs that sufficiently bound to non-vaccine genotype HBsAg. However, a small portion of anti-HBs were specific to the vaccine genotype HBsAg. High anti-HBs titers would be required to prevent HBV infection of non-vaccine genotypes. UMIN/CTR UMIN000014363.

  12. Studies on the genetic linkage of bilirubin and androsterone UDP-glucuronyltransferases by cross-breeding of two mutant rat strains.

    PubMed Central

    Nagai, F; Homma, H; Tanase, H; Matsui, M

    1988-01-01

    Gunn rats, which have defects in bilirubin and 4-nitrophenol UDP-glucuronyltransferases (GT), were crossed with LA Wistar rats with a defect in androsterone GT. The F1 hybrids showed normal GT activities towards androsterone, bilirubin and 4-nitrophenol, demonstrating that Gunn and LA ('low activity') Wistar rats inherit a homozygous dominant trait for androsterone GT and bilirubin GT respectively. The F2 progeny showed four different combinations of bilirubin and androsterone GT activities: defects in both GT activities, a single defect in bilirubin GT activity, a single defect in androsterone GT activity and two normal GT activities. They were segregated in the approximate ratio of 1:3:3:9, which is compatible with Mendel's Principle of Independent Assortment. These results provide evidence that androsterone GT and bilirubin GT are located on different chromosomes. In the F2 generation, defective bilirubin and 4-nitrophenol GT activities were not segregated, indicating that these two mutant genes are closely linked on the same chromosome. PMID:3138978

  13. Popularity of Russian information sources of medical education.

    PubMed

    Vasilyeva, Irina V; Arseniev, Sergey B

    2014-01-01

    The aim of the present study is to analyze the popularity of information sources of medical educational sites <webmedinfo.ru>, medical information portal <meduniver.com>, medical portal for students <6years.net>, electronic library of medical literature <booksmed.com>, <medliter.ru> and <medbook.net.ru>. Three sites (<www.webmedinfo.ru>, <meduniver.com> and <6years.net>) provide sources of medical literature, educational videos, medical histories, medical papers and medical popular literature. And three other sites (<www.booksmed.com>, <www.medliter.ru> and <www.medbook.net.ru>) provide sources for electronic medical books on various subjects. Using on-line programs Alexa and Cy-pr we have analyzed the website's rating and identified the main data and time-varying data of the sites. Calculated Alexa Rank rating was determined for each site. Our study has shown that the most popular information sources of medical education among the six studied sites for Russian users is <meduniver.com>; the site <booksmed.com> is at the second place referring to the Alexa Rank rating and the site <webmedinfo.ru> is at the second place referring to the citation index in Yandex. The most popular medical site of electronic medical books is <booksmed.com>.

  14. State-to-state rotationally inelastic scattering of ND[sub 3] on a graphite (0001) surface

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

    LaVilla, M.E.; Ionova, I.V.; Ionov, S.I.

    1992-12-15

    State-selected molecular beams of deuterated ammonia, [vert bar][ital JKM][epsilon][gt][vert bar]inversion[gt]=[vert bar]1111[gt][vert bar][minus][gt] or [vert bar]222[minus]1[gt][vert bar][minus][gt] and [vert bar]3331[gt][vert bar][minus][gt] states in the proportion 2.3:1, are produced via hexapole electrostatic focusing and then scattered at near-normal incidence on a graphite (0001) surface at [ital T][sub [ital s

  15. Pressure-induced structural change in liquid GeI4.

    PubMed

    Fuchizaki, Kazuhiro; Nishimura, Hironori; Hase, Takaki; Saitoh, Hiroyuki

    2017-12-13

    The similarity in the shape of the melting curve of GeI<sub>4</sub> to that of SnI<sub>4</sub> suggests that a liquid-liquid transition as observed in liquid SnI<sub>4</sub> is also expected to occur in liquid GeI<sub>4</sub>. Because the slope of the melting curve of GeI<sub>4</sub> abruptly changes at around 3 GPa, in situ synchrotron diffraction measurements were conducted to examine closely the structural changes upon compression at around 3 GPa. The reduced radial distribution functions of the high- and low-pressure liquid states of GeI<sub>4</sub> share the same feature inherent in the high-pressure (high-density) and low-pressure (low-density) radial distribution functions of liquid SnI<sub>4</sub>. This feature allows us to introduce local order parameters that we may use to observe the transition. Unlike the transition in liquid SnI<sub>4</sub>, the transition from the low-pressure to the high-pressure structure seems sluggish. We speculate that the liquid-liquid critical point of GeI<sub>4</sub> is no longer a thermodynamically stable state and is slightly located below the melting curve. As a result, the structural change is said to be a crossover rather than a transition. The behavior of the local-order parameters implies a metastable extension of the liquid-liquid phase boundary with a negative slope. . © 2017 IOP Publishing Ltd.

  16. Magnetotransport study of topological superconductor Cu0.10Bi2Se3 single crystal.

    PubMed

    Li, Mingtao; Fang, Yifei; Zhang, Jincang; Yi, Hemian; Zhou, Xingjiang; Lin, Chengtian

    2018-02-02

    We report a magnetotransport study of vortex-pinning in Cu<sub>0.10</sub>Bi<sub>2</sub>Se<sub>3</sub> single crystal. The sample is demonstrated to be in clean limit and absent of Pauli spin-limiting effect. Interestingly, the resistivity versus magnetic field shows an anomalously pronounced increase when approaching the superconducting-normal state boundary for both B∥ab and B∥c configurations. We have investigated the flux-flowing behavior under various magnetic field and temperatures, enabling us to establish its anisotropic vortex phase diagram. Our results suggest the Cu<sub>0.10</sub>Bi<sub>2</sub>Se<sub>3</sub> can be served as one unique material for exploring exotic surface vortex states in topological superconductors. © 2018 IOP Publishing Ltd.

  17. A Novel Glucosylation Reaction on Anthocyanins Catalyzed by Acyl-Glucose–Dependent Glucosyltransferase in the Petals of Carnation and Delphinium[C][W

    PubMed Central

    Matsuba, Yuki; Sasaki, Nobuhiro; Tera, Masayuki; Okamura, Masachika; Abe, Yutaka; Okamoto, Emi; Nakamura, Haruka; Funabashi, Hisakage; Takatsu, Makoto; Saito, Mikako; Matsuoka, Hideaki; Nagasawa, Kazuo; Ozeki, Yoshihiro

    2010-01-01

    Glucosylation of anthocyanin in carnations (Dianthus caryophyllus) and delphiniums (Delphinium grandiflorum) involves novel sugar donors, aromatic acyl-glucoses, in a reaction catalyzed by the enzymes acyl-glucose–dependent anthocyanin 5(7)-O-glucosyltransferase (AA5GT and AA7GT). The AA5GT enzyme was purified from carnation petals, and cDNAs encoding carnation Dc AA5GT and the delphinium homolog Dg AA7GT were isolated. Recombinant Dc AA5GT and Dg AA7GT proteins showed AA5GT and AA7GT activities in vitro. Although expression of Dc AA5GT in developing carnation petals was highest at early stages, AA5GT activity and anthocyanin accumulation continued to increase during later stages. Neither Dc AA5GT expression nor AA5GT activity was observed in the petals of mutant carnations; these petals accumulated anthocyanin lacking the glucosyl moiety at the 5 position. Transient expression of Dc AA5GT in petal cells of mutant carnations is expected to result in the transfer of a glucose moiety to the 5 position of anthocyanin. The amino acid sequences of Dc AA5GT and Dg AA7GT showed high similarity to glycoside hydrolase family 1 proteins, which typically act as β-glycosidases. A phylogenetic analysis of the amino acid sequences suggested that other plant species are likely to have similar acyl-glucose–dependent glucosyltransferases. PMID:20971893

  18. Effect of training data size and noise level on support vector machines virtual screening of genotoxic compounds from large compound libraries.

    PubMed

    Kumar, Pankaj; Ma, Xiaohua; Liu, Xianghui; Jia, Jia; Bucong, Han; Xue, Ying; Li, Ze Rong; Yang, Sheng Yong; Wei, Yu Quan; Chen, Yu Zong

    2011-05-01

    Various in vitro and in-silico methods have been used for drug genotoxicity tests, which show limited genotoxicity (GT+) and non-genotoxicity (GT-) identification rates. New methods and combinatorial approaches have been explored for enhanced collective identification capability. The rates of in-silco methods may be further improved by significantly diversified training data enriched by the large number of recently reported GT+ and GT- compounds, but a major concern is the increased noise levels arising from high false-positive rates of in vitro data. In this work, we evaluated the effect of training data size and noise level on the performance of support vector machines (SVM) method known to tolerate high noise levels in training data. Two SVMs of different diversity/noise levels were developed and tested. H-SVM trained by higher diversity higher noise data (GT+ in any in vivo or in vitro test) outperforms L-SVM trained by lower noise lower diversity data (GT+ in in vivo or Ames test only). H-SVM trained by 4,763 GT+ compounds reported before 2008 and 8,232 GT- compounds excluding clinical trial drugs correctly identified 81.6% of the 38 GT+ compounds reported since 2008, predicted 83.1% of the 2,008 clinical trial drugs as GT-, and 23.96% of 168 K MDDR and 27.23% of 17.86M PubChem compounds as GT+. These are comparable to the 43.1-51.9% GT+ and 75-93% GT- rates of existing in-silico methods, 58.8% GT+ and 79% GT- rates of Ames method, and the estimated percentages of 23% in vivo and 31-33% in vitro GT+ compounds in the "universe of chemicals". There is a substantial level of agreement between H-SVM and L-SVM predicted GT+ and GT- MDDR compounds and the prediction from TOPKAT. SVM showed good potential in identifying GT+ compounds from large compound libraries based on higher diversity and higher noise training data.

  19. Room temperature synthesis of ReS2 through aqueous perrhenate sulfidation.

    PubMed

    Borowiec, Joanna; Gillin, William P; Willis, Maureen; Boi, Filippo; He, Yi; Wen, Jiqiu; Wang, Shanling; Schulz, Leander

    2017-12-29

    In this study, a direct sulfidation reaction of ammonium perrhenate (NH<sub>4</sub>ReO<sub>4</sub>) leading to a synthesis of rhenium disulfide (ReS<sub>2</sub>) is demonstrated. These finding reveal the first example of a simplistic bottom-up approach to the chemical synthesis of crystalline ReS<sub>2</sub>. The reaction presented here takes place at room temperature, in an ambient and solvent-free environment and without the necessity of a catalyst. The atomic composition and structure of the as-synthesized product were characterized using several analysis techniques including energy dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetric analysis (TGA) and differential scannig calorimetry (DSC). The results indicated the formation of a lower symmetry (1T<sub>d</sub>) ReS<sub>2</sub> with a low degree of layer stacking. © 2017 IOP Publishing Ltd.

  20. Characterization of Samples Identified as Hepatitis C Virus Genotype 1 without Subtype by Abbott RealTime HCV Genotype II Assay Using the New Abbott HCV Genotype Plus RUO Test.

    PubMed

    Mokhtari, Camelia; Ebel, Anne; Reinhardt, Birgit; Merlin, Sandra; Proust, Stéphanie; Roque-Afonso, Anne-Marie

    2016-02-01

    Hepatitis C virus (HCV) genotyping continues to be relevant for therapeutic strategies. Some samples are reported as genotype 1 (gt 1) without subtype by the Abbott RealTime HCV Genotype II (GT II) test. To characterize such samples further, the Abbott HCV Genotype Plus RUO (Plus) assay, which targets the core region for gt 1a, gt 1b, and gt 6 detection, was evaluated as a reflex test in reference to NS5B or 5'-untranslated region (UTR)/core region sequencing. Of 3,626 routine samples, results of gt 1 without subtype were received for 171 samples (4.7%), accounting for 11.5% of gt 1 specimens. The Plus assay and sequencing were applied to 98 of those samples. NS5B or 5'-UTR/core region sequencing was successful for 91/98 specimens (92.9%). Plus assay and sequencing results were concordant for 87.9% of specimens (80/91 samples). Sequencing confirmed Plus assay results for 82.6%, 85.7%, 100%, and 89.3% of gt 1a, gt 1b, gt 6, and non-gt 1a/1b/6 results, respectively. Notably, 12 gt 6 samples that had been identified previously as gt 1 without subtype were assigned correctly here; for 25/28 samples reported as "not detected" by the Plus assay, sequencing identified the samples as gt 1 with subtypes other than 1a/1b. The genetic variability of HCV continues to present challenges for the current genotyping platforms regardless of the applied methodology. Samples identified by the GT II assay as gt 1 without subtype can be further resolved and reliably characterized by the new Plus assay. Copyright © 2016 Mokhtari et al.

  1. Evidence for the Confinement of Magnetic Monopoles in Quantum Spin Ice.

    PubMed

    Sarte, Paul Maximo; Aczel, Adam; Ehlers, Georg; Stock, Christopher; Gaulin, Bruce D; Mauws, Cole; Stone, Matthew B; Calder, Stuart; Nagler, Stephen; Hollett, Joshua; Zhou, Haidong; Gardner, Jason S; Attfield, J Paul; Wiebe, Christopher R

    2017-09-25

    Magnetic monopoles are hypothesised elementary particles connected by Dirac strings that behave like infinitely thin solenoids [Dirac 1931 Proc. Roy. Soc. A 133 60]. Despite decades of searches, free magnetic monopoles and their Dirac strings have eluded experimental detection, although there is substantial evidence for deconfined magnetic monopole quasiparticles in spin ice materials [Castelnovo, Moessner & Sondhi 2008 Nature 326 411]. Here we report the detection of a hierarchy of unequally-spaced magnetic excitations via high resolution inelastic neutron spectroscopic measurements on the quantum spin ice candidate Pr<sub>2</sub>Sn<sub>2</sub>O<sub>7</sub>. These excitations are well-described by a simple model of monopole pairs bound by a linear potential [Coldea et al. Science 327 177] with an effective tension of 0.7(1) K/Angstrom. The success of the linear potential model suggests that these low energy magnetic excitations are direct spectroscopic evidence for the confinement of magnetic monopole quasiparticles in the quantum spin ice candidate Pr<sub>2</sub>Sn<sub>2</sub>O<sub>7</sub>. © 2017 IOP Publishing Ltd.

  2. Landau theory for magnetic and structural transitions in CeCo0.85Fe0.15Si.

    PubMed

    Carreras, William Gabriel; Correa, Víctor Félix; Sereni, Julian G; García, Daniel J; Cornaglia, Pablo S

    2018-06-05

    We present a phenomenological analysis of the magnetoelastic properties of CeCo<sub>0.85</sub>Fe<sub>0.15</sub>Si at temperatures close to the Néel transition temperature T<sub>N</sub>. Using a Landau functional we provide a qualitative description of the thermal expansion, magnetostriction, magnetization and specific heat data. We show that the available experimental results [Journal of Physics: Condensed Matter <b>28</b> 346003 (2016)] are consistent with the presence of a structural transition at T<sub>s</sub>≧ T<sub>N</sub> and a strong magnetoelastic coupling. The magnetoelastic coupling presents a Janus-faced effect: while the structural transition is shifted to higher temperatures as the magnetic field is increased, the resulting striction at low temperatures decreases. The strong magnetoelastic coupling and the proximity of the structural transition to the onset temperature for magnetic fluctuations, suggest that the transition could be an analogue of the tetragonal to orthorhombic observed in Fe-based pcnictides. . © 2018 IOP Publishing Ltd.

  3. Using Grounded Theory Method to Capture and Analyze Health Care Experiences.

    PubMed

    Foley, Geraldine; Timonen, Virpi

    2015-08-01

    Grounded theory (GT) is an established qualitative research method, but few papers have encapsulated the benefits, limits, and basic tenets of doing GT research on user and provider experiences of health care services. GT can be used to guide the entire study method, or it can be applied at the data analysis stage only. We summarize key components of GT and common GT procedures used by qualitative researchers in health care research. We draw on our experience of conducting a GT study on amyotrophic lateral sclerosis patients' experiences of health care services. We discuss why some approaches in GT research may work better than others, particularly when the focus of study is hard-to-reach population groups. We highlight the flexibility of procedures in GT to build theory about how people engage with health care services. GT enables researchers to capture and understand health care experiences. GT methods are particularly valuable when the topic of interest has not previously been studied. GT can be applied to bring structure and rigor to the analysis of qualitative data. © Health Research and Educational Trust.

  4. Using Grounded Theory Method to Capture and Analyze Health Care Experiences

    PubMed Central

    Foley, Geraldine; Timonen, Virpi

    2015-01-01

    Objective Grounded theory (GT) is an established qualitative research method, but few papers have encapsulated the benefits, limits, and basic tenets of doing GT research on user and provider experiences of health care services. GT can be used to guide the entire study method, or it can be applied at the data analysis stage only. Methods We summarize key components of GT and common GT procedures used by qualitative researchers in health care research. We draw on our experience of conducting a GT study on amyotrophic lateral sclerosis patients’ experiences of health care services. Findings We discuss why some approaches in GT research may work better than others, particularly when the focus of study is hard-to-reach population groups. We highlight the flexibility of procedures in GT to build theory about how people engage with health care services. Conclusion GT enables researchers to capture and understand health care experiences. GT methods are particularly valuable when the topic of interest has not previously been studied. GT can be applied to bring structure and rigor to the analysis of qualitative data. PMID:25523315

  5. The Poplar GT8E and GT8F Glycosyltransferases are Functional Orthologs of Arabidopsis PARVUS Involved in Gulcuronoxylan Biosynthesis

    EPA Science Inventory

    The poplar GT8E and GT8F glycosyltransferases have previously been shown to be associated with wood formation, but their roles in the biosynthesis of wood components are not known. Here, we show that PoGT8E and PoGT8F are expressed in vessels and fibers during wood formation and ...

  6. Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

    PubMed

    Pan, Calvin Q; Tiongson, Benjamin C; Hu, Ke-Qin; Han, Steven-Huy B; Tong, Myron; Chu, Danny; Park, James; Lee, Tai Ping; Bhamidimarri, Kalyan Ram; Ma, Xiaoli; Xiao, Pei Ying; Mohanty, Smruti R; Wang, Dan

    2018-06-16

    Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

  7. Immunological comparison of sulfite oxidase

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

    Pollock, V.; Barber, M.J.

    1991-03-11

    Polyclonal antibodies (rabbit), elicited against FPLC-purified chicken and rat liver sulfite oxidase (SO), have been examined for inhibition and binding to purified chicken (C), rat (R), bovine (B), alligator (A) and shark (S) liver enzymes. Anti-CSO IgG cross-reacted with all five enzymes, with varying affinities, in the order CSO=ASO{gt}RSO{gt}BSO{gt}SSO. Anti-ROS IgG also cross-reacted with all five enzymes in the order RSO{gt}CSO=ASO{gt}BSO{gt}SSO. Anti-CSO IgG inhibited sulfite:cyt. c reductase (S:CR), sulfite:ferricyanide reductase (S:FR) and sulfite:dichlorophenolindophenol reductase (S:DR) activities of CSO to different extents (S:CR{gt}S:FR=S:DR). Similar differential inhibition was found for anti-ROS IgG and RSO S:CR, S:FR and S:DR activities. Anti-CSO IgG inhibitedmore » S:CR activities in the order CSO=ASO{much gt}SSO{gt}BSO. RSO was uninhibited. For anti-RSO IgG the inhibition order was RSO{gt}SSO{gt}BSO{gt}ASO. CSO was uninhibited. Anti-CSO and RSO IgGs partially inhibited Chlorella nitrate reductase (NR). Minor cross-reactivity was found for xanthine oxidase. Common antigenic determinants for all five SO's and NR are indicated.« less

  8. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations in North Egyptian population: implications for the genetic diagnosis in Egypt.

    PubMed

    El-Seedy, A; Pasquet, M C; Shafiek, H; Morsi, T; Kitzis, A; Ladevèze, V

    2016-11-30

    Cystic fibrosis (CF) occurrence in Arab populations is not common and still remains underidentified. Furthermore, the lack of disease awareness and diagnosis facilities have mislead the identification of cystic fibrosis for decades. The knowledge about cystic fibrosis (CF) in Egypt is very limited, and a few reports have drawn attention to the existence of CF or CFTR-related disorders (CFTR-RDs) in the Egyptian population. Therefore a comprehensive genetic analysis of the CFTR gene was realized in patients of North Egypt. DNA samples of 56 Egyptian patients were screened for the CFTR gene mutations. The 27 exons and their flanking regions of the CFTR gene were amplified by PCR, using the published primer pairs, and were studied by automated direct DNA sequencing to detect disease-causing mutations. Moreover, large duplication/deletion was analysed by MLPA technique. CFTR screening revealed the identification of thirteen mutations including four novel ones: c.92G>A (p.Arg31His), c.2782G>C (p.Ala928Pro), c.3718-24G>A, c.4207A>G (p.Arg1403Gly) and nine previously reported mutations: c.454A>T (p.Met152Leu), c.902A>G (p.Tyr301Cys), c.1418delG, c.2620-15C>G, c.2997_3000delAATT, c.3154T>G (p.Phe1052Val), c.3872A>G (p.Gln1291Arg), c.3877G>A (p.Val1293Ile), c.4242+10T>C. Furthermore, eight polymorphisms were found: c.743+40A>G, c.869+11C>T, c.1408A>G, c.1584G>A, c.2562T>G, c.3870A>G, c.4272C>T, c.4389G>A. These mutations and polymorphisms were not previously described in the Egyptian population except for the c.1408A>G polymorphism. Here we demonstrate the importance of the newly discovered mutations in Egyptian patients and the presence of CF, whereas the p.Phe508del mutation is not detected. The identification of CFTR mutations will become increasingly important in undocumented populations. The current findings will help us expand the mutational spectrum of CF and establish the first panel of the CFTR gene mutations in the Egyptian population and design an appropriate strategy for future genetic diagnosis of CF.

  9. Presence of rare hepatitis C virus subtypes, 2j, 2k, and 2r in Mexico City as identified by sequencing.

    PubMed

    Uribe-Noguez, Luis Antonio; Ocaña-Mondragón, Alicia; Mata-Marín, José Antonio; Gómez-Torres, María Elena; Ribas-Aparicio, Rosa María; Martínez-Rodríguez, María de la Luz

    2018-03-06

    The HCV 5'UTR, Core/E1, and NS5B regions of samples from fifty patients infected with the hepatitis C virus (HCV) were analyzed. Seventeen patients were identified with genotype (GT) 1b, eleven with GT-1a, nine with GT-2b and four with GT-3a. Two rare subtypes were detected: GT-2j in two patients and GT-2r in one patient. Three patients had mixed infections: one with GT-2k + 2j and two with GT-1b + 2b. This work identifies HCV GTs, 2j, 2k, and 2r for the first time in Mexico. © 2018 Wiley Periodicals, Inc.

  10. Comparison of microdosimetry-based absorbed doses to control tumours and clinically obtained tumour absorbed doses in treatments with 223Ra.

    PubMed

    Minguez Gabina, Pablo; Roeske, John C; Mínguez, Ricardo; Gomez de Iturriaga, Alfonso; Rodeño, Emilia

    2018-06-20

    We performed Monte Carlo simulations in order to determine by means of microdosimetry calculations the average number of hits to the cell nucleus required to reach a tumour control probability (TCP) of 0.9, 〈n<sub>0.9</sub> 〉, for the source geometry of a nucleus embedded in a homogeneous distribution of <sup>223</sup>Ra atoms. From the results obtained and following the MIRD methodology, we determined the values of lesion absorbed doses needed to reach a TCP of 0.9, D<sub>0.9</sub>, for different values of mass density, cell radiosensitivity, nucleus radius and lesion volume. The greatest variation of those absorbed doses occurred with cell radiosensitivity and no dependence was found on mass density. The source geometry used was chosen because we aimed to compare the values of D<sub>0.9</sub> with the lesion absorbed doses obtained from image-based macrodosimetry in treatments of metastatic castration-resistant prostate cancer with <sup>223</sup>Ra which were obtained assuming a homogeneous distribution of <sup>223</sup>Ra atoms within the lesion. In a comparison with a study including 29 lesions, results showed that even for the case of the most radiosensitive cells simulated, 45% of the lesions treated following a schedule of two cycles of 110 kBq/kg body mass would receive absorbed doses below the values of D<sub>0.9</sub> determined in this study. © 2018 Institute of Physics and Engineering in Medicine.

  11. The effect of green tea and olive oil on the mutagenic activity of heterocyclic amines extracted from common food consumed in Saudi Arabia.

    PubMed

    Awney, Hala

    2011-05-01

    The effect of green tea (GT) and green tea with olive oil (GT+OL) as antioxidants on the formation and mutagenic activity of heterocyclic aromatic amines (HCAs) extracted from beef shawerma, grilled chicken and fried beef liver was examined. HCAs were extracted by blue rayon, analyzed as spiked and unspiked samples with high-performance liquid chromatography and its mutagenic response was assessed by Sallmonela typhimurium 100 in the Ames test. Surprisingly, GT and GT+OL augmented HCAs measured in beef shawerma and grilled chicken but total HCAs measured in GT+OL were less than GT treatment. Both treatments altered the HCA profile as imidazoquinoline type became the most abundant. In control and GT+OL fried beef liver no HCAs were detected, but Trp-P1 was detected in GT treatment. Generally, the mutagenic response of HCAs measured in GT+OL was less than GT in beef shawerma and grilled chicken. However, the mutagenic response of control and 2% GT+OL fried liver was negative. These data suggest that GT concentrations used in this study may induce free radical formation during the Millared reaction due to its pro-oxidative effect, which augmented the HCAs formed and its mutagenic response. In order to optimize both safety and quality of our diets, more need to be done to fully understand the risk of HCAs in food.

  12. Rhombohedral R3c to orthorhombic Pnma phase transition induced by Y-doping in BiFeO3.

    PubMed

    Graf, Monica Elisabet; Di Napoli, Solange; Barral, Maria Andrea Andrea; Saleh Medina, Leila; Negri, R Martín; Sepliarsky, Marcelo; Llois, Ana María

    2018-05-23

    In this work we study, by means of <i>ab initio</i> calculations, the structural, electronic and magnetic properties of Y-doped BiFeO<sub>3</sub> compounds. We determine that there is a morphotropic phase boundary at an yttrium concentration of (18 ± 2)%, where the structure changes from <i>R3c</i> to <i>Pnma</i>. This structural transition is driven by the chemical pressure induced by the dopant. By analyzing the evolution of the oxygen octahedral tilts we find an enhanced antiferrodistortive distortion when increasing the Y-doping, together with a reduction of the ferroelectric distorsion, that gives rise to a smaller value of the electric polarization. These cooperative effects should lead to a larger canting of the Fe magnetic moments and to a larger ferromagnetic response in the <i>R3c</i> phase, as it is observed in the experiments. . © 2018 IOP Publishing Ltd.

  13. The role of N1 domain on the activity, stability, substrate specificity and raw starch binding of amylopullulanase of the extreme thermophile Geobacillus thermoleovorans.

    PubMed

    Nisha, M; Satyanarayana, T

    2015-07-01

    In order to understand the role of N1 domain (1-257 aa) in the amylopullulanase (gt-apu) of the extremely thermophilic bacterium Geobacillus thermoleovorans NP33, N1 deletion construct (gt-apuΔN) has been generated and expressed in Escherichia coli. The truncated amylopullulanase (gt-apuΔN) exhibits similar pH and temperature optima like gt-apu, but enhanced thermostability. The gt-apuΔN has greater hydrolytic action and specific activity on pullulan than gt-apu. The k cat (starch and pullulan) and K m (starch) values of gt-apuΔN increased, while K m (pullulan) decreased. The enzyme upon N1 deletion hydrolyzed maltotetraose as the smallest substrate in contrast to maltopentaose of gt-apu. The role of N1 domain of gt-apu in raw starch binding has been confirmed, for the first time, based on deletion and Langmuir-Hinshelwood kinetics. Furthermore, N1 domain appears to exert a negative influence on the thermostability of gt-apu because N1 truncation significantly improves thermostability.

  14. [Cloning of Chinese Banna minipig inbred-line alpha1,3-galactosyltransferase gene and construction of its recombinant eukaryotic expression vector].

    PubMed

    Zhu, Shengming; Wang, Yanping; Zheng, Hong; Cheng, Jingqiu; Lu, Yanrong; Zeng, Yangzhi; Wang, Yu; Wang, Zhu

    2009-04-01

    This study sought to clone Chinese Banna minipig inbred-line (BMI) alpha1,3-galactosyltransferase (alpha1,3-GT) gene and construct its recombinant eukaryotic expression vector. Total RNA was isolated from BMI liver. Full length cDNA of alpha1,3-GT gene was amplified by RT-PCR and cloned into pMD18-T vector to sequence. Subsequently, alpha1,3-GT gene was inserted into pEGFP-N1 to construct eukaryotic expression vector pEGFP-N1-GT. Then the reconstructed plasmid pEGFP-N1-GT was transiently transfected into human lung cancer cell line A549. The expression of alpha1,3-GT mRNA in transfected cells was detected by RT-PCR. FITC-BS-IB4 lectin was used in the direct immunofluorescence method, which was performed to observe the alpha-Gal synthesis function of BMI alpha1,3-GT in transfected cells. The results showed that full length of BMI alpha1,3-GT cDNA was 1116 bp. BMI alpha1,3-GT cDNA sequence was highly homogenous with those of mouse and bovine, and was exactly the same as the complete sequence of those of swine, pEGFP-N1-GT was confirmed by enzyme digestion and PCR. The expression of alpha1,3-GT mRNA was detected in A549 cells transfected by pEGFP-N1-GT. The expression of alpha-Gal was observed on the membrane of A549 cells transfected by pEGFP-N1-GT. Successful cloning of BMI alpha1,3-GT cDNA and construction of its eukaryotic expression vector have established a foundation for further research and application of BMI alpha1,3-GT in the fields of xenotransplantation and immunological therapy of cancer.

  15. Numeric Design and Performance Analysis of Solid Oxide Fuel Cell -- Gas Turbine Hybrids on Aircraft

    NASA Astrophysics Data System (ADS)

    Hovakimyan, Gevorg

    The aircraft industry benefits greatly from small improvements in aircraft component design. One possible area of improvement is in the Auxiliary Power Unit (APU). Modern aircraft APUs are gas turbines located in the tail section of the aircraft that generate additional power when needed. Unfortunately the efficiency of modern aircraft APUs is low. Solid Oxide Fuel Cell/Gas Turbine (SOFC/GT) hybrids are one possible alternative for replacing modern gas turbine APUs. This thesis investigates the feasibility of replacing conventional gas turbine APUs with SOFC/GT APUs on aircraft. An SOFC/GT design algorithm was created in order to determine the specifications of an SOFC/GT APU. The design algorithm is comprised of several integrated modules which together model the characteristics of each component of the SOFC/GT system. Given certain overall inputs, through numerical analysis, the algorithm produces an SOFC/GT APU, optimized for specific power and efficiency, capable of performing to the required specifications. The SOFC/GT design is then input into a previously developed quasi-dynamic SOFC/GT model to determine its load following capabilities over an aircraft flight cycle. Finally an aircraft range study is conducted to determine the feasibility of the SOFC/GT APU as a replacement for the conventional gas turbine APU. The design results show that SOFC/GT APUs have lower specific power than GT systems, but have much higher efficiencies. Moreover, the dynamic simulation results show that SOFC/GT APUs are capable of following modern flight loads. Finally, the range study determined that SOFC/GT APUs are more attractive over conventional APUs for longer range aircraft.

  16. Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

    PubMed Central

    2011-01-01

    Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level. PMID:21810243

  17. Gastrostomy Tube Feeding in Children With Developmental or Acquired Disorders: A Longitudinal Comparison on Healthcare Provision and Eating Outcomes 4 Years After Gastrostomy.

    PubMed

    Backman, Ellen; Karlsson, Ann-Kristin; Sjögreen, Lotta

    2018-03-30

    Studies on long-term feeding and eating outcomes in children requiring gastrostomy tube feeding (GT) are scarce. The aim of this study was to describe children with developmental or acquired disorders receiving GT and to compare longitudinal eating and feeding outcomes. A secondary aim was to explore healthcare provision related to eating and feeding. This retrospective cohort study reviewed medical records of children in 1 administrative region of Sweden with GT placement between 2005 and 2012. Patient demographics, primary diagnoses, age at GT placement, and professional healthcare contacts prior to and after GT placement were recorded and compared. Feeding and eating outcomes were assessed 4 years after GT placement. The medical records of 51 children, 28 boys and 23 girls, were analyzed and grouped according to "acquired" (n = 13) or "developmental" (n = 38) primary diagnoses. At 4 years after GT placement, 67% were still using GT. Only 6 of 37 (16%) children with developmental disorders transferred to eating all orally, as opposed to 10 of 11 (91%) children with acquired disorders. Children with developmental disorders were younger at the time of GT placement and displayed a longer duration of GT activity when compared with children with acquired disorders. This study demonstrates a clear difference between children with developmental or acquired disorders in duration of GT activity and age at GT placement. The study further shows that healthcare provided to children with GT is in some cases multidisciplinary, but primarily focuses on feeding rather than eating. © 2018 American Society for Parenteral and Enteral Nutrition.

  18. Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus NS5A Inhibitor.

    PubMed

    Owens, Christopher M; Brasher, Bradley B; Polemeropoulos, Alex; Rhodin, Michael H J; McAllister, Nicole; Wong, Kelly A; Jones, Christopher T; Jiang, Lijuan; Lin, Kai; Or, Yat Sun

    2016-10-01

    EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated in vitro and in vivo This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments in vitro using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs were similarly identified in GT1b NS5A at amino acid positions 31 and 93. Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239 individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H. RAMs were identified in GT1 patients at baseline or after dosing with EDP-239 that were similar to those detected in vitro Baseline RAMs identified at NS5A position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced treatment response. RAMs at additional positions were also detected and may have contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58 (GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks 24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study has been registered at ClinicalTrials.gov under identifier NCT01856426.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies.

    PubMed

    Mizokami, M; Dvory-Sobol, H; Izumi, N; Nishiguchi, S; Doehle, B; Svarovskaia, E S; De-Oertel, S; Knox, S; Brainard, D M; Miller, M D; Mo, H; Sakamoto, N; Takehara, T; Omata, M

    2016-10-01

    High rates of sustained virologic response (SVR) has been achieved in Japanese patients with chronic hepatitis C virus (HCV) genotype (GT)1 and GT2 infection treated with ledipasvir/sofosbuvir (LDV/SOF) ±ribavirin (RBV) and SOF+RBV, respectively. We evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized variants at virologic failure. Baseline deep sequencing for NS5A and NS5B genes was performed for all GT1 patients. Deep sequencing of NS5A (GT1 only) and NS5B (GT1 and GT2) was performed for patients who failed treatment or discontinued early with detectable HCV RNA (i.e., >25 IU/mL). In patients with HCV GT1 infection, 22.3% (GT1a: 2/11; GT1b: 74/330) had ≥1 baseline NS5A RAV. The most frequent NS5A RAVs in GT1b were Y93H (17.9%, 59/330) and L31M (2.4%, 8/330). Despite the presence of NS5A RAVs at baseline, 100% and 97% of patients achieved SVR12, compared with 100% and 99% for those with no NS5A RAVs with LDV/SOF and LDV/SOF+RBV, respectively. All patients with NS5B RAVs at baseline achieved SVR12. Of the 153 patients with GT2 infection (GT2a 60.1%, GT2b 39.9%), 3.3% (5/153) experienced viral relapse. No S282T or other NS5B RAVs were detected at baseline or relapse; no change in susceptibility to SOF or RBV was observed at relapse. In conclusion, LDV/SOF and SOF+RBV demonstrate a high barrier to resistance in Japanese patients with HCV GT1 and GT2 infection. The presence of baseline NS5A RAVs did not impact treatment outcome in GT1 Japanese patients treated with LDV/SOF for 12 weeks. © 2016 John Wiley & Sons Ltd.

  20. Evaluation of Dynamic Changes in Rating of Russian Information Sources of Medical Education Sites.

    PubMed

    Vasilyeva, Irina V; Arseniev, Sergey B

    2016-01-01

    The aim of the present study is to analyze dynamic changes in the rating of information sources of medical literature in the sites of the following electronic libraries (<rsl.ru>, <rssi.ru>, <elibrary.ru>) and the rating of information sources for electronic medical books (<booksmed.com>, <medliter.ru> <medbook.net.ru>). While using the on-line programs Alexa and Cy-pr, we have analyzed their website's rating and identified basic data and time-varying site data obtained for fourteen months. Alexa Rank rating was calculated for each sitemonthly. Our study has shown that the most popular information sources of medical education among the six studied sites for Russian users is <elibrary.ru>; the site <rssi.ru> is at the second place.

  1. Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger.

    PubMed

    Manzanares-Miralles, Lara; Sarikaya-Bayram, Özlem; Smith, Elizabeth B; Dolan, Stephen K; Bayram, Özgür; Jones, Gary W; Doyle, Sean

    2016-01-10

    Gliotoxin (GT) is a redox-active metabolite, produced by Aspergillus fumigatus, which inhibits the growth of other fungi. Here we demonstrate how Aspergillus niger responds to GT exposure. Quantitative proteomics revealed that GT dysregulated the abundance of 378 proteins including those involved in methionine metabolism and induced de novo abundance of two S-adenosylmethionine (SAM)-dependent methyltransferases. Increased abundance of enzymes S-adenosylhomocysteinase (p=0.0018) required for homocysteine generation from S-adenosylhomocysteine (SAH), and spermidine synthase (p=0.0068), involved in the recycling of Met, was observed. Analysis of Met-related metabolites revealed significant increases in the levels of Met and adenosine, in correlation with proteomic data. Methyltransferase MT-II is responsible for bisthiobis(methylthio)gliotoxin (BmGT) formation, deletion of MT-II abolished BmGT formation and led to increased GT sensitivity in A. niger. Proteomic analysis also revealed that GT exposure also significantly (p<0.05) increased hydrolytic enzyme abundance, including glycoside hydrolases (n=22) and peptidases (n=16). We reveal that in an attempt to protect against the detrimental affects of GT, methyltransferase-mediated GT thiomethylation alters cellular pathways involving Met and SAM, with consequential dysregulation of hydrolytic enzyme abundance in A. niger. Thus, it provides new opportunities to exploit the response of GT-naïve fungi to GT. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Characterization of recombinant amylopullulanase (gt-apu) and truncated amylopullulanase (gt-apuT) of the extreme thermophile Geobacillus thermoleovorans NP33 and their action in starch saccharification.

    PubMed

    Nisha, M; Satyanarayana, T

    2013-07-01

    A gene encoding amylopullulanase (gt-apu) of the extremely thermophilic Geobacillus thermoleovorans NP33 was cloned and expressed in Escherichia coli. The gene has an open reading frame of 4,965 bp that encodes a protein of 1,655 amino acids with molecular mass of 182 kDa. The six conserved regions, characteristic of GH13 family, have been detected in gt-apu. The recombinant enzyme has only one active site for α-amylase and pullulanase activities based on the enzyme kinetic analyses in a system that contains starch as well as pullulan as competing substrates and response to inhibitors. The end-product analysis confirmed that this is an endoacting enzyme. The specific enzyme activities for α-amylase and pullulanase of the truncated amylopullulanase (gt-apuT) are higher than gt-apu. Both enzymes exhibited similar temperature (60 °C) and pH (7.0) optima, although gt-apuT possessed a higher thermostability than gt-apu. The overall catalytic efficiency (K(cat)/K(m)) of gt-apuT is greater than that of gt-apu, with almost similar substrate specificities. The C-terminal region of gt-apu appeared to be non-essential, and furthermore, it negatively affects the substrate binding and stability of the enzyme.

  3. Malignant pericytes expressing GT198 give rise to tumor cells through angiogenesis.

    PubMed

    Zhang, Liyong; Wang, Yan; Rashid, Mohammad H; Liu, Min; Angara, Kartik; Mivechi, Nahid F; Maihle, Nita J; Arbab, Ali S; Ko, Lan

    2017-08-01

    Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 ( PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198 + pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models. In human oral cancer, GT198 + pericytes proliferate into GT198 + tumor cells, which migrate into lymph nodes. Increased GT198 expression is associated with increased lymph node metastasis and decreased progression-free survival in oral cancer patients. In rat brain U-251 glioblastoma xenografts, GT198 + pericytes of human tumor origin encase endothelial cells of rat origin to form mosaic angiogenic blood vessels, and differentiate into pericyte-derived tumor cells. The net effect is continued production of glioblastoma tumor cells from malignant pericytes via angiogenesis. In addition, activation of GT198 induces the expression of VEGF and promotes tube formation in cultured U251 cells. Furthermore, vaccination using GT198 protein as an antigen in mouse xenograft of GL261 glioma delayed tumor growth and prolonged mouse survival. Together, these findings suggest that GT198-expressing malignant pericytes can give rise to tumor cells through angiogenesis, and serve as a potential source of cells for distant metastasis. Hence, the oncoprotein GT198 has the potential to be a new target in anti-angiogenic therapies in human cancer.

  4. Mass Balance of the West Antarctic Ice-Sheet from ICESat Measurements

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Li, Jun; Robins, John; Saba, Jack L.; Yi, Donghui

    2011-01-01

    Mass balance estimates for 2003-2008 are derived from ICESat laser altimetry and compared with estimates for 1992-2002 derived from ERS radar altimetry. The net mass balance of 3 drainage systems (Pine Island, Thwaites/Smith, and the coast of Marie Bryd) for 2003-2008 is a loss of 100 Gt/yr, which increased from a loss of 70 Gt/yr for the earlier period. The DS including the Bindschadler and MacAyeal ice streams draining into the Ross Ice Shelf has a mass gain of 11 Gt/yr for 2003-2008, compared to an earlier loss of 70 Gt/yr. The DS including the Whillans and Kamb ice streams has a mass gain of 12 Gt/yr, including a significant thickening on the upper part of the Kamb DS, compared to a earlier gain of 6 Gt/yr (includes interpolation for a large portion of the DS). The other two DS discharging into the Ronne Ice Shelf and the northern Ellsworth Coast have a mass gain of 39 Gt/yr, compared to a gain of 4 Gt/yr for the earlier period. Overall, the increased losses of 30 Gt/yr in the Pine Island, Thwaites/Smith, and the coast of Marie Bryd DSs are exceeded by increased gains of 59 Gt/yr in the other 4 DS. Overall, the mass loss from the West Antarctic ice sheet has decreased to 38 Gt/yr from the earlier loss of 67 Gt/yr, reducing the contribution to sea level rise to 0.11 mm/yr from 0.19 mm/yr

  5. Inferences on hydrogen bond networks in water from isopermitive frequency investigations.

    PubMed

    Geethu, P M; Ranganathan, Venketesh T; Satapathy, Dillip K Kumar

    2018-06-26

    Intermolecular hydrogen bonds play a crucial role in determining the unique characteristics of liquid water. We present low-frequency (1 Hz - 40 MHz) dielectric spectroscopic investigations on water in the presence and absence of added solutes at different temperatures from 10°C to 60°C. The intersection points of temperature dependent permittivity contours at the vicinity of isopermitive frequency (IPF) in water are recorded and its properties are presumed to be related to the extent of hydrogen bond networks in water. IPF is defined as the frequency at which the relative permittivity of water is almost independent of temperature. The set of intersection points of temperature dependent permittivity contours at the vicinity of IPF are characterized by the mean (M<sub>IPF</sub>) and root-mean-square deviation/standard deviation (σ<sub>IPF</sub> ) associated with IPF. The tunability of M<sub>IPF</sub> by the addition of NaCl salt emphasizes the strong correlation between the concentration of ions in water and the M<sub>IPF</sub> . The σ<sub>IPF</sub> is surmised to be related to the orientational correlations of water dipoles as well as to the intermolecular hydrogen bond networks in water. Further, alterations in σ<sub>IPF</sub> is observed with the addition of kosmotropic and chaotropic solutes into water and are thought to arise due to the restructuring of hydrogen bond networks in water in presence of added solutes. Notably, the solute induced reconfiguration of hydrogen bond networks in water or often-discussed structure making/breaking effects of the added solutes in water can be inferred, albeit qualitatively, by examining the M<sub>IPF</sub> and σ<sub>IPF</sub>. Further, the Gaussian deconvoluted OH-stretching modes present in the Raman Spectra of water and aqueous solutions of IPA and DMF strongly endorses the structural rearrangements occurring in water in presence of kosmotropes and chaotropes and are in-line with the results derived from the root-mean-square deviation in IPF. . © 2018 IOP Publishing Ltd.

  6. Characterization of acute undifferentiated leukemia by combined analysis of plasma membrane-associated gamma-glutamyltranspeptidase and soluble terminal transferase.

    PubMed

    Heumann, D; Losa, G; Barras, C; Morell, A; von Fliedner, V

    1985-08-01

    gamma-Glutamyltranspeptidase (gamma-GT) is a plasma membrane-associated enzyme present in blasts of certain acute leukemias. We analyzed 90 cases of undifferentiated and differentiated acute leukemias for gamma-GT, using a colorimetric assay. Blasts of all patients with common acute lymphoblastic leukemia (ALL) and T-ALL were negative for gamma-GT (less than 5 units). In contrast, gamma-GT was significantly elevated in acute myeloblastic or monoblastic leukemia blasts (P less than .001). In 16 cases of acute undifferentiated leukemia (AUL) studied, the levels of gamma-GT ranged from 0 to 93 units; in eight cases, gamma-GT was positive (greater than 5 units), and six of these had 2% to 5% Sudan black-positive leukemic cells in the blast-enriched suspension. Combined gamma-GT/TdT analysis revealed that both enzyme markers were mutually exclusive in 75% of AUL cases, suggesting that gamma-GT+/TdT-blasts are of nonlymphoid origin, and gamma-GT-/TdT+ blasts are of lymphoid origin. Two cases were devoid of both enzyme activities and could represent truly undifferentiated leukemia. Thus, combined gamma-GT/TdT analysis underlines the heterogeneity of AUL and appears to be useful in defining the lineage commitment of undifferentiated leukemic blasts.

  7. Characteristics of thermostable amylopullulanase of Geobacillus thermoleovorans and its truncated variants.

    PubMed

    Nisha, M; Satyanarayana, T

    2015-05-01

    The far-UV CD spectroscopic analysis of the secondary structure in the temperature range between 30 and 90°C revealed a compact and thermally stable structure of C-terminal truncated amylopullulanase of Geobacillus thermoleovorans NP33 (gt-apuΔC) with a higher melting temperature [58°C] than G. thermoleovorans NP33 amylopullulanase (gt-apu) [50°C] and the N-terminal truncated amylopullulanase from G. thermoleovorans NP33 (gt-apuΔN) [55°C]. A significant decline in random coils in gt-apuΔC and gt-apuΔN suggested an improvement in conformational stability, and thus, an enhancement in their thermal stability. The improvement in the thermostability of gt-apuΔC was corroborated by the thermodynamic parameters for enzyme inactivation. The Trp fluorescence emission (335 nm) and the acrylamide quenching constant (22.69 M(-1)) of gt-apuΔC indicated that the C-terminal truncation increases the conformational stability of the protein with the deeply buried tryptophan residues. The 8-Anilino Naphthalene Sulfonic acid (ANS) fluorescence experiments indicated the unfolding of gt-apu to expose its hydrophobic surface to a greater extent than the gt-apuΔC and gt-apuΔN. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Analysis of Gauntlet Test Performance and Injury Risk in Intercollegiate Division I Female Soccer (Football) Players: A Retrospective Study.

    PubMed

    Ness, Brandon M; Zimney, Kory; Schweinle, William E

    2017-11-01

    Injury risk factors and relevant assessments have been identified in women's soccer athletes. Other tests assess fitness (eg, the Gauntlet Test [GT]). However, little empirical support exists for the utility of the GT to predict time loss injury. To examine the GT as a predictor of injury in intercollegiate Division I female soccer athletes. Retrospective, nonexperimental descriptive cohort study. College athletic facilities. 71 female Division I soccer athletes (age 19.6 ± 1.24 y, BMI 23.0 ± 2.19). GT, demographic, and injury data were collected over 3 consecutive seasons. GT trials were administered by coaching staff each preseason. Participation in team-based activities (practices, matches) was restricted until a successful GT trial. Soccer-related injuries that resulted in time loss from participation were recorded. 71 subjects met the inclusion criteria, with 12 lower body time loss injuries sustained. Logistic regression models indicated that with each unsuccessful GT attempt, the odds of sustaining an injury increased by a factor of 3.5 (P < .02). The Youden index was 2 GT trials for success, at which sensitivity = .92 and specificity = .46. For successive GT trials before success (1, 2, or 3), the predicted probabilities for injury were .063, .194, and .463, respectively. The GT appears to be a convenient and predictive screen for potential lowerbody injuries among female soccer athletes in this cohort. Further investigation into the appropriate application of the GT for injury prediction is warranted given the scope of this study.

  9. Separation of nitrogen heterocyclic compounds from model coal tar fraction by solvent extraction

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

    Kim, S.J.; Chun, Y.J.

    2005-07-01

    The separation of four kinds of nitrogen heterocyclic compounds (NHCs) from a model mixture comprising NHCs (indole (In), quinoline (Q), iso-quinoline (iQ), quinaldine (Qu)), three kinds of bicyclic aromatic compounds (BACs; 1-methyl-naphthalene (IMN), 2-methyl naphthalene (2MN), dimethylnaphthalene (DMN)), biphenyl (Bp) and phenyl ether (Pe) was examined by a solvent extraction. The model mixture used as a raw material of this work was prepared according to the components and compositions contained in coal tar fraction (the temperature ranges of fraction: 240-265{sup o}C). An aqueous solution of methanol, ethanol, iso-propyl alcohol, N,N-dimethyl acetamide, DMF, formamide, N-methylformamide/methanol, and formamide/methanol were used as solvents.more » An aqueous solution of formamide was found suitable for separating NHCs contained in coal tar fraction based on distribution coefficient and selectivity. The effect of operation factors on separating NHCs was investigated by the distribution equilibrium using an aqueous solution of formamide. Increasing the operation temperature and the volume ratio of solvent to feed at initial (S/F)(o) resulted in improving the distribution coefficients of each NHC, but increasing the volume fraction of water in the solvent at initial (y(w,O)) resulted in deteriorating the distribution coefficients of each NHC. With increasing y(w,O) and (S/F)(o), the selectivities of each NHC in reference to DMN increased. Increase in operation temperature resulted in decrease in selectivities of each NHC in reference to DMN. At an experimental condition fixed, the sequence of the distribution coefficient and selectivity in reference to DMN for each NHC was In {gt} iQ {gt} Q {gt} Qu, and also the sequence of the distribution coefficient for each BAC was IMN {gt} 2MN {gt} DMN. The sequence of the distribution coefficient for entire compounds analyzed by this work was In {gt} iQ {gt} Q {gt} Qu {gt} BP {gt} 1MN {gt} 2MN {gt} Pe {gt} DMN.« less

  10. Formulation with ascorbic acid and sucrose modulates catechin bioavailability from green tea

    PubMed Central

    Peters, Catrina M.; Green, Rodney J.; Janle, Elsa M.; Ferruzzi, Mario G.

    2009-01-01

    In order to investigate the impact of common food ingredients on catechin absorption, green tea (GT) extract (50 mg) was formulated plain, with sucrose (GT+S), with ascorbic acid (GT+AA) and with sucrose and ascorbic acid (GT+S+AA). Bioavailability and bioaccessibility were assessed in Sprague Dawley rats and an in vitro digestion/Caco-2 cell model respectively. Absorption of epigallocatechin (EGC) and epigallocatechin gallate (EGCG) was significantly (P<0.05) enhanced in GT+S+AA formulations (AUC0-6h= 3237.0 and 181.8 pmol*h/L plasma respectively) relative to GT control (AUC0-6h = 1304.1 and 61.0 pmol*h/L plasma respectively). In vitro digestive recovery was higher for EGC and epicatechin (EC) (∼51-53%) relative to EGCG and epicatechin gallate (ECG) (< 20%) and was modestly enhanced in GT+S and GT+S+AA formulations. Accumulation of EGC, EGCG and ECG by Caco-2 cells was significantly (P<0.05) higher from GT+S+AA compared to other formulations while retention of catechins was enhanced in presence of ascorbic acid. These data suggest that formulation with sucrose and ascorbic acid may improve catechin bioavailability by enhancing bioaccessibility and intestinal uptake from tea. PMID:20161530

  11. THE RHODOPSIN-TRANSDUCIN COMPLEX HOUSES TWO DISTINCT RHODOPSIN MOLECULES

    PubMed Central

    Jastrzebska, Beata; Ringler, Philipe; Palczewski, Krzysztof; Engel, Andreas

    2013-01-01

    Upon illumination the visual receptor rhodopsin (Rho) transitions to the activated form Rho*, which binds the heterotrimeric G protein, transducin (Gt) causing GDP to GTP exchange and Gt dissociation. Using succinylated concanavalin A (sConA) as a probe, we visualized native Rho dimers solubilized in 1 mM n-dodecyl-β-D-maltoside (DDM) and Rho monomers 5 mM in DDM. By nucleotide depletion and affinity chromatography together with crosslinking and size exclusion chromatography, we trapped and purified nucleotide-free Rho*•Gt and sConA-Rho*•Gt complexes kept in solution by either DDM or lauryl-maltose-neopentyl-glycol (LMNG). The 3-D envelope calculated from projections of negatively stained Rho*•Gt-LMNG complexes accommodated two Rho molecules, one Gt heterotrimer and a detergent belt. Visualization of triple sConA-Rho*•Gt complexes unequivocally demonstrated a pentameric assembly of the Rho*•Gt complex in which the photoactivated Rho* dimer serves as a platform for binding the Gt heterotrimer. Importantly, individual monomers of the Rho* dimer in the heteropentameric complex exhibited different capabilities to be regenerated with either 11-cis or 9-cis-retinal. PMID:23458690

  12. Conformational analysis of GT1B ganglioside and its interaction with botulinum neurotoxin type B: a study by molecular modeling and molecular dynamics.

    PubMed

    Venkateshwari, Sureshkumar; Veluraja, Kasinadar

    2012-01-01

    The conformational property of oligosaccharide GT1B in aqueous environment was studied by molecular dynamics (MD) simulation using all-atom model. Based on the trajectory analysis, three prominent conformational models were proposed for GT1B. Direct and water-mediated hydrogen bonding interactions stabilize these structures. The molecular modeling and 15 ns MD simulation of the Botulinum Neuro Toxin/B (BoNT/B) - GT1B complex revealed that BoNT/B can accommodate the GT1B in the single binding mode. Least mobility was seen for oligo-GT1B in the binding pocket. The bound conformation of GT1B obtained from the MD simulation of the BoNT/B-GT1B complex bear a close conformational similarity with the crystal structure of BoNT/A-GT1B complex. The mobility noticed for Arg 1268 in the dynamics was accounted for its favorable interaction with terminal NeuNAc. The internal NeuNAc1 tends to form 10 hydrogen bonds with BoNT/B, hence specifying this particular site as a crucial space for the therapeutic design that can restrict the pathogenic activity of BoNT/B.

  13. A novel FKRP-related muscular dystrophy founder mutation in South African Afrikaner patients with a phenotype suggestive of a dystrophinopathy.

    PubMed

    Mudau, M M; Essop, F; Krause, A

    2016-12-21

    Fukutin-related protein (FKRP) muscular dystrophy is an autosomal recessive disorder caused by mutations in the FKRP gene. The condition is often misdiagnosed as a dystrophinopathy. A previously unreported mutation, c.1100T>C in exon 4 of FKRP, had been identified in homozygous form in two white South African (SA) Afrikaner patients clinically diagnosed with a dystrophinopathy. To investigate whether the c.1100T>C mutation and the common European FKRP mutation c.826C>A are present in other patients of Afrikaner origin with suspected dystrophinopathy, and whether a founder haplotype exists. The c.1100T>C mutation was initially tested for using an amplification refractory mutation system technique in 45 white SA Afrikaner patients who had tested negative using multiplex ligation probe amplification screening for exonic deletions/duplications in the dystrophin gene. Sequencing analysis was used to confirm the c.1100T>C mutation and screen for the c.826C>A mutation. Two cohorts (each numbering 100) of Afrikaans and other white controls were screened for the c.1100T>C and c.826C>A mutations, respectively. Of the 45 patients, 8 patients (17.8%) were homozygous for c.1100T>C, 2 (4.4%) were compound heterozygotes for c.1100T>C and c.826C>A, and 1 (2.2%) was heterozygous for c.1100T>C with a second unidentified mutation. The c.1100T>C mutation was found in 1/100 controls, but no heterozygotes for the c.826C>A mutation were identified. Linked marker analysis for c.1100T>C showed a common haplotype, suggesting a probable founder mutation in the SA Afrikaner population. FKRP mutations may be relatively common in Afrikaners, and screening should be considered in patients who have a suggestive phenotype and test negative for a dystrophinopathy. This test will be useful for offering diagnostic, carrier and prenatal testing for affected individuals and their families. As FKRP muscular dystrophy is autosomal recessive in inheritance, the implications of a positive diagnosis in a family differ significantly from those of an X-linked dystrophinopathy.

  14. Hydrothermal Alteration of the Lower Oceanic Crust: Insight from OmanDP Holes GT1A and GT2A.

    NASA Astrophysics Data System (ADS)

    Harris, M.; Zihlmann, B.; Mock, D.; Akitou, T.; Teagle, D. A. H.; Kondo, K.; Deans, J. R.; Crispini, L.; Takazawa, E.; Coggon, J. A.; Kelemen, P. B.

    2017-12-01

    Hydrothermal circulation is a fundamental Earth process that is responsible for the cooling of newly formed ocean crust at mid ocean ridges and imparts a chemical signature on both the crust and the oceans. Despite decades of study, the critical samples necessary to resolve the role of hydrothermal circulation during the formation of the lower ocean crust have remained poorly sampled in the ocean basins. The Oman Drilling Project successfully cored 3 boreholes into the lower crust of the Semail ophiolite (Holes GT1A layered gabbros, GT2A foliated gabbros and GT3A dike/gabbro transition). These boreholes have exceptionally high recovery ( 100%) compared to rotary coring in the oceans and provide an unrivalled opportunity to quantitatively characterise the hydrothermal system in the lower oceanic crust. Hydrothermal alteration in Holes GT1A and GT2A is ubiquitous and manifests as secondary minerals replacing primary igneous phases and secondary minerals precipitated in hydrothermal veins and hydrothermal fault zones. Hole GT1A is characterised by total alteration intensities between 10 -100%, with a mean alteration intensity of 60%, and shows no overall trend downhole. However, there are discrete depth intervals (on the scale of 30 -100 m) where the total alteration intensity increases with depth. Alteration assemblages are dominated by chlorite + albite + amphibole, with variable abundances of epidote, clinozoisite and quartz. Hole GT1A intersected several hydrothermal fault zones, these range from 2-3 cm up to >1m in size and are associated with more complex secondary mineral assemblages. Hydrothermal veins are abundant throughout Hole GT1A, with a mean density of 37 vein/m. Hole GT2A is characterised by total alteration intensities between 6-100%, with a mean alteration intensity of 45%, and is highly variable downhole. Alteration halos and patches are slightly more abundant than in Hole GT1A. The secondary mineral assemblage is similar to Hole GT1A, but Hole GT2A has higher abundances of epidote, clinozoisite, quartz, laumontite and iron-oxydroxides. Vein density in Hole GT2A is 61 veins/m. In both holes, cross cutting vein relationships indicate a relative timing from earliest to latest of: amphibole; epidote + zoisite + qtz; chlorite + prehnite + qtz, calcite-laumontite-anhydrite; gypsum.

  15. Monoterpenyl Glycosyltransferases Differentially Contribute to Production of Monoterpenyl Glycosides in Two Aromatic Vitis vinifera Varieties

    PubMed Central

    Li, Xiang-Yi; Wen, Ya-Qin; Meng, Nan; Qian, Xu; Pan, Qiu-Hong

    2017-01-01

    HIGHLIGHTS A similar trend on accumulation of glycosidically bound monoterpenes was observed in both varietiesTwo VvGT7 alleles mutations occurred at key sites in Muscat blanc à PetitVvGT14 exerted a major role in production of monoterpenyl glycosides in both varieties Terpenoids are the major aroma components and generally exist as both free and glycosidically-bound forms, of which nonvolatile glycosides account for a large fraction in grape berries. Our previous study has indicated that differential accumulation of monoterpenyl glycosides in Vitis vinifera “Muscat blanc à Petit” between two regions is closely correlated to monoterpenyl glucosyltransferase (VvGT14, XM_002285734.2) transcript abundance. However, it has not been determined yet whether this correlation also exists in other Vitis vinifera varieties. This study investigated the evolution of free and glycosidically bound monoterpenes in two Vitis vinifera variety “Muscat blanc à Petit” and “Gewurztraminer” under two vintages, and further assessed the relation between the accumulation of bound monoterpenes and two monoterpenyl glycosyltransferase transcript levels. Results showed that free monoterpenes exhibited three evolution patterns in both varieties during berry development of two vintages, whereas glycosidically bound monoterpenes showed a concentration elevation with berry maturation. The Cis-rose oxide and geraniol were major components contributing to the aroma odors of “Gewürztraminer” grapes while linalool was major aroma contributor to the “Muscat blanc à Petit grain” grapes. The accumulation of glycosidically bound monoterpenes in both varieties was accompanied with the high expression of VvGT7 (XM_002276510.2) and VvGT14. Only one allele of VvGT7 was found in the variety “Gewürztraminer” and no mutation was observed in its enzyme active sites. XB-VvGT7-4 and XB-VvGT7-5 were two alleles of VvGT7 detected in “Muscat blanc à Petit grain.” The mutation on its enzyme active site inhibited the activity of XB-VvGT7-4, whereas VvGT7-5 exhibited an alteration on enzyme activity due to the insertion mutation at the position 443. Only one VvGT14 allele was found in both varieties, and the VvGT14 allele in both varieties showed the similarity on amino acid sequence. No mutation occurred in active sites of VvGT14 allele. These indicated that VvGT7 and VvGT14 differentially contributed to the production of monoterpenyl glycosides in these Vitis Vinifera varieties. PMID:28751905

  16. Monoterpenyl Glycosyltransferases Differentially Contribute to Production of Monoterpenyl Glycosides in Two Aromatic Vitis vinifera Varieties.

    PubMed

    Li, Xiang-Yi; Wen, Ya-Qin; Meng, Nan; Qian, Xu; Pan, Qiu-Hong

    2017-01-01

    HIGHLIGHTS A similar trend on accumulation of glycosidically bound monoterpenes was observed in both varietiesTwo VvGT7 alleles mutations occurred at key sites in Muscat blanc à Petit VvGT14 exerted a major role in production of monoterpenyl glycosides in both varieties Terpenoids are the major aroma components and generally exist as both free and glycosidically-bound forms, of which nonvolatile glycosides account for a large fraction in grape berries. Our previous study has indicated that differential accumulation of monoterpenyl glycosides in Vitis vinifera "Muscat blanc à Petit" between two regions is closely correlated to monoterpenyl glucosyltransferase ( VvGT14 , XM_002285734.2) transcript abundance. However, it has not been determined yet whether this correlation also exists in other Vitis vinifera varieties. This study investigated the evolution of free and glycosidically bound monoterpenes in two Vitis vinifera variety "Muscat blanc à Petit" and "Gewurztraminer" under two vintages, and further assessed the relation between the accumulation of bound monoterpenes and two monoterpenyl glycosyltransferase transcript levels. Results showed that free monoterpenes exhibited three evolution patterns in both varieties during berry development of two vintages, whereas glycosidically bound monoterpenes showed a concentration elevation with berry maturation. The Cis -rose oxide and geraniol were major components contributing to the aroma odors of "Gewürztraminer" grapes while linalool was major aroma contributor to the "Muscat blanc à Petit grain" grapes. The accumulation of glycosidically bound monoterpenes in both varieties was accompanied with the high expression of VvGT7 (XM_002276510.2) and VvGT14 . Only one allele of VvGT7 was found in the variety "Gewürztraminer" and no mutation was observed in its enzyme active sites. XB-VvGT7-4 and XB-VvGT7-5 were two alleles of VvGT7 detected in "Muscat blanc à Petit grain." The mutation on its enzyme active site inhibited the activity of XB-VvGT7-4 , whereas VvGT7-5 exhibited an alteration on enzyme activity due to the insertion mutation at the position 443. Only one VvGT14 allele was found in both varieties, and the VvGT14 allele in both varieties showed the similarity on amino acid sequence. No mutation occurred in active sites of VvGT14 allele. These indicated that VvGT7 and VvGT14 differentially contributed to the production of monoterpenyl glycosides in these Vitis Vinifera varieties.

  17. Site occupancy, composition and magnetic structure dependencies of martensitic transformation in Mn2Ni1+xSn1-x.

    PubMed

    Kundu, Ashis; Ghosh, Subhradip

    2017-11-14

    A delicate balance between various factors such as site occupancy, composition and magnetic ordering seems to affect the stability of the martensitic phase in Mn<sub>2</sub>Ni<sub>1+x</sub>Sn<sub>1-x</sub>. Using first-principles DFT calculations, we explore the impacts of each one of these factors on the martensitic stability of this system. Our results on total energies, magnetic moments and electronic structures upon changes in the composition, the magnetic configurations and the site occupancies show that the occupancies at the 4d sites in the Inverse Heusler crystal structure play the most crucial role. The presence of Mn at the 4d sites originally occupied by Sn and its interaction with the Mn atoms at other sites decide the stability of the martensitic phases. This explains the discrepancy between the experiments and earlier DFT calculations regarding phase stability in Mn<sub>2</sub>NiSn. Our results qualitatively explain the trends observed experimentally with regard to martensitic phase stability and the magnetisations in Ni-excess, Sn-deficient Mn<sub>2</sub>NiSn system. © 2017 IOP Publishing Ltd.

  18. Update of green tea interactions with cardiovascular drugs and putative mechanisms.

    PubMed

    Werba, José Pablo; Misaka, Shingen; Giroli, Monica Gianna; Shimomura, Kenju; Amato, Manuela; Simonelli, Niccolò; Vigo, Lorenzo; Tremoli, Elena

    2018-04-01

    Many patients treated with cardiovascular (CV) drugs drink green tea (GT), either as a cultural tradition or persuaded of its putative beneficial effects for health. Yet, GT may affect the pharmacokinetics and pharmacodynamics of CV compounds. Novel GT-CV drug interactions were reported for rosuvastatin, sildenafil and tacrolimus. Putative mechanisms involve inhibitory effects of GT catechins at the intestinal level on influx transporters OATP1A2 or OATP2B1 for rosuvastatin, on CYP3A for sildenafil and on both CYP3A and the efflux transporter p-glycoprotein for tacrolimus. These interactions, which add to those previously described with simvastatin, nadolol and warfarin, might lead, in some cases, to reduced drug efficacy or risk of drug toxicity. Oddly, available data on GT interaction with CV compounds with a narrow therapeutic index, such as warfarin and tacrolimus, derive from single case reports. Conversely, GT interactions with simvastatin, rosuvastatin, nadolol and sildenafil were documented through pharmacokinetic studies. In these, the effect of GT or GT derivatives on drug exposure was mild to moderate, but a high inter-individual variability was observed. Further investigations, including studies on the effect of the dose and the time of GT intake are necessary to understand more in depth the clinical relevance of GT-CV drug interactions. Copyright © 2018. Published by Elsevier B.V.

  19. Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury

    PubMed Central

    Banerjee, Sudip; Shah, Sumit K.; Melnyk, Stepan B.; Hauer-Jensen, Martin

    2018-01-01

    Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)-induced injury. However, the molecular targets that underlie the protective functions of GT3 are not yet known. We have reported that mice lacking CCAAT enhancer binding protein delta (Cebpd−/−) display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that Cebpd protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether Cebpd mediates the radio protective functions of GT3. We found that GT3-treated Cebpd−/− mice showed partial recovery of white blood cells compared to GT3-treated Cebpd+/+ mice at 2 weeks post-IR. GT3-treated Cebpd−/− mice showed an increased loss of intestinal crypt colonies, which correlated with increased expression of inflammatory cytokines and chemokines, increased levels of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine (3-NT) after exposure to IR compared to GT3-treated Cebpd+/+ mice. Cebpd is induced by IR as well as a combination of IR and GT3 in the intestine. Studies have shown that granulocyte-colony stimulating factor (G-CSF), mediates the radioprotective functions of GT3. Interestingly, we found that IR alone as well as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in both Cebpd+/+ and Cebpd−/− mice. These results identify a novel role for Cebpd in GT3-mediated protection against IR-induced injury, in part via modulation of IR-induced inflammation and oxidative/nitrosative stress, which is independent of G-CSF. PMID:29642403

  20. cDNA cloning and characterization of UDP-glucose: anthocyanidin 3-O-glucosyltransferase in Freesia hybrida.

    PubMed

    Sui, Xin; Gao, Xiang; Ao, Man; Wang, Qinmei; Yang, Dan; Wang, Meng; Fu, Yang; Wang, Li

    2011-07-01

    The enzyme that catalyzes the formation of the first stable anthocyanin in the biosynthesis of natural compounds is UDP-glucose: anthocyanidin 3-O-glucosyltransferase (UF3GT). A cDNA clone (Fh3GT1) encoding UF3GT was isolated from Freesia hybrida. Phylogenetic tree analysis indicated that Fh3GT1 was a novel member of glycosyltransferase, which was classified into monocot subgroups. Semi-quantitative RT-PCR analysis detected transcripts of Fh3GT1 in different organs of F. hybrida and in petals of Freesia cultivars of different colors, and the expression level reached the maximum at the fully opened stage of petals. Characterization of the enzymatic assays indicated that Fh3GT1 had a role in anthocyanin glycoside biosyntheses in vitro. To elucidate the function of Fh3GT1, RNA interference vector (pART-Fh3GT1i) was constructed, and introduced into Petunia grandiflora by Agrobacterium-mediated transformation. Integration of the Fh3GT1 in petunia genome was confirmed by PCR and Southern blotting. SqRT-PCR revealed that the endogenous Ph3GT1 mRNA expression levels decreased in transgenic lines compared with the wild-type. The content of total anthocyanin pigments also decreased with the reduction of mRNA transcript levels, and the transgenic petunia plants had significant changes on their flower colors. In summary, this work identified a UF3GT gene from Freesia hybrida and demonstrated a method to modify plant flower color by redirecting the anthocyanin biosynthesis.

  1. Direct interaction between surface β1,4-galactosyltransferase 1 and epidermal growth factor receptor (EGFR) inhibits EGFR activation in hepatocellular carcinoma

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

    Tang, Wenqing; Weng, Shuqiang; Zhang, Si

    2013-05-10

    Highlights: •β1,4GT1 interacts with EGFR both in vitro and in vivo. •β1,4GT1 co-localizes with EGFR on the cell surface. •β1,4GT1 inhibits {sup 125}I-EGF binding to EGFR. •β1,4GT1 inhibits EGF induced EGFR dimerization and phosphorylation. -- Abstract: Our previous studies showed that cell surface β1,4-galactosyltransferase 1 (β1,4GT1) negatively regulated cell survival through inhibition and modulation of the epidermal growth factor receptor (EGFR) signaling pathway in human hepatocellular carcinoma (HCC) SMMC-7721 cells. However, the underlying mechanism remains unclear. Here we demonstrated that β1,4-galactosyltransferase 1 (β1,4GT1) interacted with EGFR in vitro by GST pull-down analysis. Furthermore, we demonstrated that β1,4GT1 bound to EGFRmore » in vivo by co-immunoprecipitation and determined the co-localization of β1,4GT1 and EGFR on the cell surface via confocal laser scanning microscopy analysis. Finally, using {sup 125}I-EGF binding experiments and Western blot analysis, we found that overexpression of β1,4GT1 inhibited {sup 125}I-EGF binding to EGFR, and consequently reduced the levels of EGFR dimerization and phosphorylation. In contrast, RNAi-mediated knockdown of β1,4GT1 increased the levels of EGFR dimerization and phosphorylation. These data suggest that cell surface β1,4GT1 interacts with EGFR and inhibits EGFR activation.« less

  2. Delineation of fractures, foliation, and groundwater of the bedrock at a geothermal feasibility site on Roosevelt Island, New York County, New York

    USGS Publications Warehouse

    Stumm, Frederick; Chu, Anthony; Como, Michael D.; Noll, Michael L.; Joesten, Peter K.

    2015-01-01

    Advanced borehole-geophysical methods were used to investigate the hydrogeology of the crystalline bedrock in three boreholes on Roosevelt Island, New York County, New York. Cornell University was evaluating the feasibility of using geothermal energy for a future campus at the site. The borehole-logging techniques were used to delineate bedrock fractures, foliation, and groundwater-flow zones of the Fordham Gneiss in test boreholes at the site. Three fracture populations dominated by small (0.04 in or less) fractures were delineated in the three boreholes. A sub-horizontal population with low to moderate dipping fractures, a northeast dipping population with moderate to high angle fractures, and a small northwest dipping high angle fracture population. One large southwest dipping transmissive fracture underlies the entire study area with a mean dip azimuth of 235º southwest and a dip angle of 31º (N325ºW 31ºSW). The mean foliation dip azimuth was 296º northwest with a mean dip angle of 73º (N26ºE 73ºNW). Groundwater appears to flow through a network of fractures dominated by a large fracture underlying the site that is affected by tidal variations from the nearby East River. The total number of fractures penetrated by each borehole was 95, 63, and 68, with fracture indices of 0.26, 0.20, and 0.20 in GT-1 (NY292), GT-2 (NY293), and GT-3 (NY294), respectively. Aquifer test data indicate the specific capacity of boreholes GT-1 (NY292), GT-2 (NY293), and GT-3 (NY294) was 1.9, 1.5, and 3.7 gal/min/ft, respectively. The large contribution of flow from the leaking casing in borehole GT-3 (NY294) caused the doubling in specific capacity compared to boreholes GT-1 (NY292) and GT-2 (NY293). The transmissivities of the large fracture intersected by the three boreholes tested (GT-1, GT-2, and GT-3), calculated from aquifer-test analyses of time-drawdown data and flowmeter differencing, were 133, 124, and 65 feet squared per day (ft2/d), respectively. Gringarten analysis indicated the large fracture intersects a low transmissivity boundary or distant fracture network with an average transmissivity of 69 ft2/d, this distant hydraulic boundary averages about 200 ft away from boreholes GT-1 and GT-2. Field measurements of specific conductance of the three boreholes under ambient conditions at the site indicate an increase in conductivity toward the southwest part of the site. Specific conductance was 5, 6, and 23 millisiemens per centimeter (mS/cm) in boreholes GT-2, GT-3, and GT-1, respectively. Three borehole radar reflection logs collected at each of the boreholes indicated increased penetration with depth and the large fracture intersecting all three boreholes was imaged as far as 80 ft from the boreholes. A borehole radar attenuation tomogram from GT-1 to GT-2 indicated the large fracture intersected by the boreholes extends between the boreholes with a low angle southwest dip.

  3. Comparisons and Analyses of Gifted Students' Characteristics and Learning Methods

    ERIC Educational Resources Information Center

    Lu, Jiamei; Li, Daqi; Stevens, Carla; Ye, Renmin

    2017-01-01

    Using PISA 2009, an international education database, this study compares gifted and talented (GT) students in three groups with normal (non-GT) students by examining student characteristics, reading, schooling, learning methods, and use of strategies for understanding and memorizing. Results indicate that the GT and non-GT gender distributions…

  4. Potential Interference of Oil Vehicles on Genital Tubercle Development during the Fetal Period in ICR Mice.

    PubMed

    Nishioka, Yasushi; Tamai, Kazuki; Onda, Masanari; Hiromori, Youhei; Kimura, Tomoki; Hu, Jianying; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

    2018-01-01

    Corn oil, sesame oil, and 10% ethanol in corn oil are commonly used as dosing vehicles in toxicology studies. Since these vegetable oils contain bioactive compounds, it is important for toxicology studies to characterize the toxicities of the dosing vehicles themselves. It has been recently proposed that the width of the genital tubercle (GT), the dorsal-ventral length (D-V length) of the GT, and urethral tube closure in mouse fetuses can be used as novel markers for monitoring sexual development in mice. However, how these parameters are influenced by the dosing vehicles themselves remains unclear. Therefore, we evaluated the effects of corn oil, sesame oil, and 10% ethanol in corn oil on GT width, D-V length, and GT morphology in ICR mice. Our results showed that all three vehicles influenced GT width and D-V length, but not GT morphology, suggesting that the effects of dosing vehicles themselves might need to be considered when GT width or D-V length is used as a parameter to evaluate the effects of chemicals on GT development.

  5. The rhodopsin-transducin complex houses two distinct rhodopsin molecules.

    PubMed

    Jastrzebska, Beata; Ringler, Philippe; Palczewski, Krzysztof; Engel, Andreas

    2013-05-01

    Upon illumination the visual receptor rhodopsin (Rho) transitions to the activated form Rho(∗), which binds the heterotrimeric G protein, transducin (Gt) causing GDP to GTP exchange and Gt dissociation. Using succinylated concanavalin A (sConA) as a probe, we visualized native Rho dimers solubilized in 1mM n-dodecyl-β-d-maltoside (DDM) and Rho monomers in 5mM DDM. By nucleotide depletion and affinity chromatography together with crosslinking and size exclusion chromatography, we trapped and purified nucleotide-free Rho(∗)·Gt and sConA-Rho(∗)·Gt complexes kept in solution by either DDM or lauryl-maltose-neopentyl-glycol (LMNG). The 3 D envelope calculated from projections of negatively stained Rho(∗)·Gt-LMNG complexes accommodated two Rho molecules, one Gt heterotrimer and a detergent belt. Visualization of triple sConA-Rho(∗)·Gt complexes unequivocally demonstrated a pentameric assembly of the Rho(∗)·Gt complex in which the photoactivated Rho(∗) dimer serves as a platform for binding the Gt heterotrimer. Importantly, individual monomers of the Rho(∗) dimer in the heteropentameric complex exhibited different capabilities for regeneration with either 11-cis or 9-cis-retinal. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Correlation of gingival thickness with gingival width, probing depth, and papillary fill in maxillary anterior teeth in students of a dental college in Navi Mumbai.

    PubMed

    Singh, Jyotsna; Rathod, Varsha J; Rao, Prajakta R; Patil, Aardra A; Langade, Deepak G; Singh, Roshan K

    2016-01-01

    The gingival biotype is of utmost importance for esthetics and biologic function. Anatomical characteristic of periodontium such as gingival thickness (GT), width of keratinized gingiva, and alveolar bone morphology will determine the behavior of periodontium when subjected to physical, chemical, or bacterial insult or during therapeutic procedure. The aim of this study was to correlate the GT with gingival width (GW), probing depth (PD), and papillary fill (PF) in relation to maxillary anterior region. Undergraduate dental students and interns from a dental college in Navi Mumbai were enrolled in the study according to the inclusion criteria. Six teeth per subject were assessed; a total of 2178 maxillary anterior teeth were examined. Subjects were examined clinically for GT, width of keratinized gingiva, pocket depth, and interdental PF. The data obtained was tabulated and subjected to statistical analysis. Spearman's correlation analysis test was performed to find the correlation of GT with GW, PD, and PF. Positive correlation was found between GT and GW ( r = 0.241). No significant correlation could be found between GT and PD; and between GT and PF. The present study confirmed a positive correlation between GT and GW. A weak negative correlation was found between GT and PD.

  7. Prooxidant effects of the combination of green tea extract and sodium nitrite for accelerating lipolysis and lipid oxidation in pepperoni during storage.

    PubMed

    Lin, Yuhai; Huang, Ming; Zhou, Guanghong; Zou, Yufeng; Xu, Xinglian

    2011-01-01

    The individual and interactive effects of green tea (GT) extract and sodium nitrite (NT) on lipolysis and lipid oxidation were investigated in pepperoni during processing and storage (4 °C). Pepperoni was treated with GT at concentrations of 0.02%, 0.05%, 0.1%, 0.2%, 0.5%; and NT from 0.003% to 0.015% in increments of 0.003%; and a combination of 0.05% GT and 0.009% NT (GT/NT). The pH, color, residual nitrite, fatty acid (FA), and 2-thiobarbituric acid reactive substances (TBARS) values were measured. The results showed inhibitory effects on TBARS value were concentration dependent. The largest effect was at 0.05% for GT and 0.009% for NT. Adding 0.05% GT significantly decreased (P < 0.05) the TBARS values but did not affect color values during storage. NT (0.009%) was more effective than GT (0.05%) for maintaining lower TBARS values (P < 0.05). Total fatty acids were not affected by 0.05% GT and 0.009% NT treatments. However, adding GT/NT showed a significant prooxidant effect (P < 0.05) in pepperoni, which accelerated lipolysis and lipid oxidation significantly (P < 0.05) during storage, with depletion of nitrite. This suggests that adding GT and an appropriate amount of NT into pepperoni could promote lipolysis and lipid oxidation during storage, as compared to NT alone. When using GT extract as an antioxidant in industrial production of pepperoni, the interaction effect with NT should be considered, as it may lead to a prooxidant effect during refrigerated storage. © 2011 Institute of Food Technologists®

  8. Evidence for Conserved Function of γ–Glutamyltranspeptidase in Helicobacter Genus

    PubMed Central

    Revez, Joana; Javed, Sundus; El-Najjar, Nahed; Anderl, Florian; Hyytiäinen, Heidi; Vuorela, Pia; Gerhard, Markus; Hänninen, Marja-Liisa

    2012-01-01

    The confounding consequences of Helicobacter bilis infection in experimental mice populations are well recognized, but the role of this bacterium in human diseases is less known. Limited data are available on virulence determinants of this species. In Helicobacter pylori, γ-glutamyltranspeptidase (γGT) contributes to the colonization of the gastric mucosa and to the pathogenesis of peptic ulcer. The role of γGT in H. bilis infections remains unknown. The annotated genome sequence of H. bilis revealed two putative ggt genes and our aim was to characterize these H. bilis γGT paralogues. We performed a phylogenetic analysis to understand the evolution of Helicobacter γGTs and to predict functional activities of these two genes. In addition, both copies of H. bilis γGTs were expressed as recombinant proteins and their biochemical characteristics were analysed. Functional complementation of Esherichia coli deficient in γGT activity and deletion of γGT in H. bilis were performed. Finally, the inhibitory effect of T-cell and gastric cell proliferation by H. bilis γGT was assessed. Our results indicated that one gene is responsible for γGT activity, while the other showed no γGT activity due to lack of autoprocessing. Although both H. bilis and H. pylori γGTs exhibited a similar affinity to L-Glutamine and γ-Glutamyl-p-nitroanilide, the H. bilis γGT was significantly less active. Nevertheless, H. bilis γGT inhibited T-cell proliferation at a similar level to that observed for H. pylori. Finally, we showed a similar suppressive influence of both H. bilis and H. pylori γGTs on AGS cell proliferation mediated by an apoptosis-independent mechanism. Our data suggest a conserved function of γGT in the Helicobacter genus. Since γGT is present only in a few enterohepatic Helicobacter species, its expression appears not to be essential for colonization of the lower gastrointestinal tract, but it could provide metabolic advantages in colonization capability of different niches. PMID:22348013

  9. High-resolution study of Gamow-Teller excitations in the 42Ca(3He,t )42Sc reaction and the observation of a "low-energy super-Gamow-Teller state"

    NASA Astrophysics Data System (ADS)

    Fujita, Y.; Fujita, H.; Adachi, T.; Susoy, G.; Algora, A.; Bai, C. L.; Colò, G.; Csatlós, M.; Deaven, J. M.; Estevez-Aguado, E.; Guess, C. J.; Gulyás, J.; Hatanaka, K.; Hirota, K.; Honma, M.; Ishikawa, D.; Krasznahorkay, A.; Matsubara, H.; Meharchand, R.; Molina, F.; Nakada, H.; Okamura, H.; Ong, H. J.; Otsuka, T.; Perdikakis, G.; Rubio, B.; Sagawa, H.; Sarriguren, P.; Scholl, C.; Shimbara, Y.; Stephenson, E. J.; Suzuki, T.; Tamii, A.; Thies, J. H.; Yoshida, K.; Zegers, R. G. T.; Zenihiro, J.

    2015-06-01

    To study the Gamow-Teller (GT) transitions from the Tz=+1 nucleus 42Ca to the Tz=0 nucleus 42Sc, where Tz is the z component of isospin T , we performed a (p ,n )-type (3He,t ) charge-exchange reaction at 140 MeV/nucleon and scattering angles around 0∘. With an energy resolution of 29 keV, states excited by GT transitions (GT states) could be studied accurately. The reduced GT transition strengths B (GT) were derived up to the excitation energy of 13 MeV, assuming the proportionality between the cross sections at 0∘ and B (GT) values. The main part of the observed GT transition strength is concentrated in the lowest 0.611-MeV, Jπ=1+ GT state. All the other states at higher energies are weakly excited. Shell-model calculations could reproduce the gross feature of the experimental B (GT) distribution, and random-phase-approximation calculations including an attractive isoscalar interaction showed that the 0.611-MeV state has a collective nature. It was found that this state has all of the properties of a "low-energy super-Gamow-Teller state." It is expected that low-lying Jπ=1+ GT states have T =0 in the Tz=0 nucleus 42Sc. However, T =1 states are situated in a higher energy region. Assuming an isospin-analogous structure in A =42 isobars, analogous T =1 , 1+ states are also expected in 42Ca. Comparing the (3He 42,tCa) 42Sc and 42Ca(p ,p') spectra measured at 0∘, candidates for T =1 GT states could be found in the 10 -12 -MeV region of 42Sc. They were all weakly excited. The mass dependence of the GT strength distributions in Sc isotopes is also discussed.

  10. The characterisation of hepatic mitochondrial function in patients with non-alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test.

    PubMed

    Afolabi, Paul R; Scorletti, Eleonora; Smith, Debbie E; Almehmadi, Amal A; Calder, Philip C; Byrne, Christopher D

    2018-06-26

    Hepatic mitochondrial function (HMF) assessed by the <sup>13</sup>C-ketoisocaproate breath test (<sup>13</sup>C-KICA BT) has been previously shown to be significantly associated with the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However, it is uncertain whether any perturbation in HMF relates specifically to severity of liver disease or factors associated with metabolic syndrome within non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate whether there was any change in HMF assessed by <sup>13</sup>C-KICA BT in patients with NAFLD compared to control subjects, and to assess the factors that are independently associated with HMF. 77 patients with NAFLD and 11 healthy control subjects were studied. HMF was assessed using <sup>13</sup>C-KICA BT and expressed as cumulative % <sup>13</sup>C-dose recovered on breath over 1hr (cPDR over 1hr). Liver fat and fibrosis was assessed by transient elastography. Multi-variable linear regression modelling was undertaken to test the independence of associations with HMF. HMF (cPDR over 1hr) was lower in NAFLD compared to controls [13.4% (4.8) v. 21.0% (6.3); p< 0.0001)]. In NAFLD, HMF was lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p=0.003)]. Regression modelling showed age (β= -0.08; p=0.01), waist circumference (β= -0.08; p=0.01), hip circumference (β= -0.04; p=0.01), aspartate aminotransferase (AST) (β= -0.05; p=0.01) and diabetes status (β= -1.81; p=0.01) were independently associated with HMF (R<sup>2</sup>= 41.5%; p<0.0001). In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the <sup>13</sup>C-KICA BT. Furthermore, in patients with NAFLD, HMF is independent and inversely associated with age, waist and hip circumference, AST and diabetes status. © 2018 IOP Publishing Ltd.

  11. Initial report of the physical property measurement, ChikyuOman core description Phase I: sheeted dike and gabbro boundary from ICDP Holes GT1A, GT2A and GT3A

    NASA Astrophysics Data System (ADS)

    Abe, N.; Okazaki, K.; Hatakeyama, K.; Ildefonse, B.; Leong, J. A. M.; Tateishi, Y.; Teagle, D. A. H.; Takazawa, E.; Kelemen, P. B.; Michibayashi, K.; Coggon, J. A.; Harris, M.; de Obeso, J. C.

    2017-12-01

    We report results on the physical property measurements of the core samples from ICDP Holes GT1A, GT2A and GT3A drilled at Samail Ophiolite, Sultanate of Oman. Cores from Holes GT1A and GT2A in the lower crust section are mainly composed of gabbros (gabbro and olivine gabbro), and small amounts of ultramafic rocks (wehrlite and dunite), while cores from Hole GT3A at the boundary between sheeted dikes and gabbro are mainly composed of basalt and diabase, followed by gabbros (gabbro, olivine gabbro and oxide gabbro), and less common felsic dikes, trondhjemite and tonalite, intrude the mafic rocks. Measurements of physical properties were undertaken to characterize recovered core material. Onboard the Drilling Vessel Chikyu, whole-round measurements included X-ray CT image, natural gamma radiation, and magnetic susceptibility for Leg 1, and additional P-wave velocity, gamma ray attenuation density, and electrical resistivity during Leg 2. Split-core point magnetic susceptibility and color spectroscopy were measured for all core sections. P-wave velocity, bulk/grain density and porosity of more than 500 discrete cube samples, and thermal conductivity on more than 240 pieces from the working half of the split core sections were also measured. Physical Properties of gabbroic rocks from Holes GT1A and GT2A are similar to typical oceanic gabbros from ODP and IODP expeditions at Atlantis Bank, Southwestern Indian Ridge (ODP Legs 118, 176 and 179; IODP Exp 360) and at Hess Deep, Eastern Pacific (ODP Leg 147 and IODP Exp. 345). Average P-wave velocity, bulk density, grain density, porosity and thermal conductivity are 6.7 km/s, 2.92 g/cm^3, 2.93 g/cm^3, 0.98% and 2.46 W/m/K, respectively. P-wave velocity of samples from all three holes is inversely correlated with porosity. No clear correlation between the original lithology and physical properties is observed. GT3A cores show a wider range (e.g., Vp from 2.2 to 7.1 km/s) of values for the measured physical properties, compared to gabbros from Holes GT1A and GT2A.

  12. High-resolution study of Gamow-Teller transitions via the 54Fe(3He,t)54Co reaction

    NASA Astrophysics Data System (ADS)

    Adachi, T.; Fujita, Y.; Bacher, A. D.; Berg, G. P. A.; Black, T.; de Frenne, D.; Foster, C. C.; Fujita, H.; Fujita, K.; Hatanaka, K.; Honma, M.; Jacobs, E.; Jänecke, J.; Kanzaki, K.; Katori, K.; Nakanishi, K.; Negret, A.; Otsuka, T.; Popescu, L.; Roberts, D. A.; Sakemi, Y.; Shimbara, Y.; Shimizu, Y.; Stephenson, E. J.; Tameshige, Y.; Tamii, A.; Uchida, M.; Ueno, H.; Yamanaka, T.; Yosoi, M.; Zell, K. O.

    2012-02-01

    The Gamow-Teller transition strengths, B(GT), in pf-shell nuclei are of interest in nuclear physics as well as in nuclear astrophysics. A high-resolution (3He,t) charge-exchange (CE) reaction was performed on the Tz=+1 nucleus 54Fe at 0∘ and at an intermediate incident energy of 140 MeV/nucleon for the study of precise GT transition strengths to the final Tz=0 nucleus 54Co. By applying dispersion matching techniques for a high-quality 3He beam at RCNP, an energy resolution of 21 keV and an angular resolution of 5 mr were realized. The bumplike structure of the GT resonance observed in low-resolution CE reactions at around the excitation energy (Ex) of 10 MeV was resolved in individual L = 0, GT states. Excitation strengths were obtained for these GT states. If the R2 value that is defined by the ratio between GT and Fermi unit cross sections is known, the B(GT) values can be determined from the excitation strengths. For the derivation of the R2 value, the “merged analysis” combining the GT strength distribution from the 54Fe(3He,t)54Co study and the half-life from a 54Ni β decay was used, where T=1 isospin symmetry for A=54 isobars was assumed. The GT strengths were compared with a shell-model calculation using the GXPF1 interaction. The final GT states can have the isospin values T = 0, 1, and 2. The isospin T of each GT state observed in the 8.3≤Ex≤12.0 MeV region of the 54Fe(3He,t)54Co spectrum was identified by comparing the excitation strength with that of corresponding M1 state observed in a 54Fe(p,p')54Fe experiment. The B(GT) values of the states identified to have T=2, in particular, are of importance for the calculation of the electron capture rates at the core-collapse stage of presupernovae. The B(GT) strengths were further compared with B(M1) strengths measured in the 54Fe(e,e')54Fe reaction. In the M1 excitation using an electromagnetic probe, isoscalar (IS) and isovector (IV) orbital type operators are active in addition to the IV spin type operator that mediates the GT transitions. The contributions of the IS and IV orbital terms were studied by calculating the ratio of the strengths of analogous M1 and GT transitions.

  13. Differences in Reporting the Ragweed Pollen Season Using Google Trends across 15 Countries.

    PubMed

    Bousquet, Jean; Agache, Ioana; Berger, Uwe; Bergmann, Karl-Christian; Besancenot, Jean-Pierre; Bousquet, Philippe J; Casale, Tom; d'Amato, Gennaro; Kaidashev, Igor; Khaitov, Musa; Mösges, Ralph; Nekam, Kristof; Onorato, Gabrielle L; Plavec, Davor; Sheikh, Aziz; Thibaudon, Michel; Vautard, Robert; Zidarn, Mihaela

    2018-05-09

    Google Trends (GT) searches trends of specific queries in Google, which potentially reflect the real-life epidemiology of allergic rhinitis. We compared GT terms related to ragweed pollen allergy in American and European Union countries with a known ragweed pollen season. Our aim was to assess seasonality and the terms needed to perform the GT searches and to compare these during the spring and summer pollen seasons. We examined GT queries from January 1, 2011, to January 4, 2017. We included 15 countries with a known ragweed pollen season and used the standard 5-year GT graphs. We used the GT translation for all countries and the untranslated native terms for each country. The results of "pollen," "ragweed," and "allergy" searches differed between countries, but "ragweed" was clearly identified in 12 of the 15 countries. There was considerable heterogeneity of findings when the GT translation was used. For Croatia, Hungary, Romania, Serbia, and Slovenia, the GT translation was inappropriate. The country patterns of "pollen," "hay fever," and "allergy" differed in 8 of the 11 countries with identified "ragweed" queries during the spring and the summer, indicating that the perception of tree and grass pollen allergy differs from that of ragweed pollen. To investigate ragweed pollen allergy using GT, the term "ragweed" as a plant is required and the translation of "ragweed" in the native language needed. © 2018 S. Karger AG, Basel.

  14. Correlation of gingival thickness with gingival width, probing depth, and papillary fill in maxillary anterior teeth in students of a dental college in Navi Mumbai

    PubMed Central

    Singh, Jyotsna; Rathod, Varsha J.; Rao, Prajakta R.; Patil, Aardra A.; Langade, Deepak G.; Singh, Roshan K.

    2016-01-01

    Context: The gingival biotype is of utmost importance for esthetics and biologic function. Anatomical characteristic of periodontium such as gingival thickness (GT), width of keratinized gingiva, and alveolar bone morphology will determine the behavior of periodontium when subjected to physical, chemical, or bacterial insult or during therapeutic procedure. Aims: The aim of this study was to correlate the GT with gingival width (GW), probing depth (PD), and papillary fill (PF) in relation to maxillary anterior region. Settings and Design: Undergraduate dental students and interns from a dental college in Navi Mumbai were enrolled in the study according to the inclusion criteria. Six teeth per subject were assessed; a total of 2178 maxillary anterior teeth were examined. Subjects and Methods: Subjects were examined clinically for GT, width of keratinized gingiva, pocket depth, and interdental PF. The data obtained was tabulated and subjected to statistical analysis. Statistical Analysis Used: Spearman's correlation analysis test was performed to find the correlation of GT with GW, PD, and PF. Results: Positive correlation was found between GT and GW (r = 0.241). No significant correlation could be found between GT and PD; and between GT and PF. Conclusions: The present study confirmed a positive correlation between GT and GW. A weak negative correlation was found between GT and PD. PMID:27994424

  15. 78 FR 29810 - Receipt of Petition for Decision That Nonconforming 2003 BMW K 1200 GT Motorcycles Are Eligible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ...-0061; Notice 1] Receipt of Petition for Decision That Nonconforming 2003 BMW K 1200 GT Motorcycles Are... (NHTSA) of a petition for a decision that 2003 BMW K 1200 GT Motorcycles that were not originally...-005) has petitioned NHTSA to decide whether non-U.S. certified 2003 BMW K 1200 GT motorcycles are...

  16. Conformational dynamics of activation for the pentameric complex of dimeric G protein – coupled receptor and heterotrimeric G protein

    PubMed Central

    Orban, Tivadar; Jastrzebska, Beata; Gupta, Sayan; Wang, Benlian; Miyagi, Masaru; Chance, Mark R.; Palczewski, Krzysztof

    2012-01-01

    Summary Photoactivation of rhodopsin (Rho), a G protein-coupled receptor (GPCR), causes conformational changes that provide a specific binding site for the rod G protein, Gt. In this work we employed structural mass spectrometry (MS) techniques to elucidate the structural changes accompanying transition of ground state Rho to photoactivated Rho (Rho*) and in the pentameric complex between dimeric Rho* and heterotrimeric Gt. Observed differences in hydroxyl radical labeling and deuterium uptake between Rho* and the (Rho*)2-Gt complex suggest that photoactivation causes structural relaxation of Rho following its initial tightening upon Gt coupling. In contrast, nucleotide-free Gt in the complex is significantly more accessible to deuterium uptake allowing it to accept GTP and mediating complex dissociation. Thus, we provide direct evidence that in the critical step of signal amplification, Rho* and Gt exhibit dissimilar conformational changes when they are coupled in the (Rho*)2-Gt complex. PMID:22579250

  17. Association of monoamine oxidase A gene polymorphism with Alzheimer's disease and Lewy body variant.

    PubMed

    Takehashi, Masanori; Tanaka, Seigo; Masliah, Eliezer; Ueda, Kunihiro

    2002-07-19

    The association between (GT)n dinucleotide repeats in monoamine oxidase gene loci, monoamine oxidase A (MAOA) and B (MAOB), and Parkinson's disease (PD), Alzheimer's disease (AD), and Lewy body variant (LBV) of AD were determined. MAOA-GT polymorphisms were significantly associated with pure AD and LBV. MAOA-GT allele 113 was excessively represented in pure AD and LBV compared with controls. Furthermore, the frequency of females homozygous for MAOA-GT allele 113 was higher in pure AD and LBV than controls by 2.79- and 2.77-fold, respectively. In contrast, there was no association between MAOA-GT or MAOB-GT polymorphisms and PD. These results suggest that polymorphisms within the MAOA gene may have implication in AD pathology shared by pure AD and LBV.

  18. The Role of Catechol-O-Methyl Transferase Val(108/158)Met Polymorphism (rs4680) in the Effect of Green Tea on Resting Energy Expenditure and Fat Oxidation: A Pilot Study

    PubMed Central

    Hursel, Rick; Janssens, Pilou L. H. R.; Bouwman, Freek G.; Mariman, Edwin C.; Westerterp-Plantenga, Margriet S.

    2014-01-01

    Introduction Green tea(GT) is able to increase energy expenditure(EE) and fat oxidation(FATox) via inhibition of catechol-O-methyl transferase(COMT) by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMTH(Val/Val genotype), and low-activity COMTL(Met/Met genotype). Methods Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years) of whom 7 with the COMTH-genotype and 7 with the COMTL-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL) consumption. Results At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox) did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05). After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01), RQ(GT: 0.80 vs. PL: 0.83; p<0.01), FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001) and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001) were significantly different for subjects carrying the COMTH genotype, but not for subjects carrying the COMTL genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS), (RQ, GT: 0.81 vs. PL: 0.81; NS), (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS), (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS). Conclusion Subjects carrying the COMTH genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMTL genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for EE and FATox after GT treatment. Trial Registration Nederlands Trial register NTR1918 PMID:25238062

  19. Specific immune response genes of the guinea pig. II. Relationship between the poly-L-lysine gene and the genes controlling immune responsiveness to copolymers of L-glutamic acid and L-alanine and L-glutamic acid and L-tyrosine in random-bred Hartley guinea pigs.

    PubMed

    Bluestein, H G; Green, I; Benacerraf, B

    1971-08-01

    The ability of guinea pigs to make immune responses to GA, a linear random copolymer of L-glutamic acid and L-alanine, GT, a random linear copolymer of L-glutamic acid and L-tyrosine, and PLL, a linear homopolymer of L-lysine, is controlled by different autosomal dominant genes specific for each of those polymers. We have investigated the relationship between the PLL gene and the GA and GT immune response genes by simultaneously immunizing random-bred Hartley strain guinea pigs with GA and PLL, GT and PLL, or GA and GT. In most Hartley guinea pigs the ability to respond immunologically to GA and to PLL is inherited together; that is, most animals responding to GA respond to PLL and vice versa. However, a few animals respond to either GA or to PLL but not both, demonstrating that the GA and PLL immune response genes are not identical but linked in most Hartley animals. Conversely, when simultaneously immunized with GT and PLL, most Hartley guinea pigs respond to either PLL or GT but not both, indicating that GT and PLL responsiveness tends to segregate away from each other. Thus, the GT and PLL immune response genes also are not inherited independently but, rather, behave as alleles or pseudoalleles. Similar results are observed when Hartley guinea pigs are simultaneously immunized with GA and GT. The ability to respond to GA segregates away from the ability to respond to GT. Our studies demonstrated that the specific immune response genes thus far identified in guinea pigs controlling the ability to respond to GA, GT, and PLL, respectively, are found on the same chromosome. In most Hartley animals, the GA and PLL immune response genes are often linked, i.e. occur on the same chromosome strand, and tend to behave as alleles or pseudoalleles to the GT immune response gene.

  20. Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate Cancer Prior to Prostatectomy

    PubMed Central

    Henning, Susanne M.; Wang, Piwen; Said, Jonathan W.; Huang, Min; Grogan, Tristan; Elashoff, David; Carpenter, Catherine L.; Heber, David; Aronson, William J.

    2014-01-01

    Background Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. Methods In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation [nuclear and cytoplasmic nuclear factor kappa B (NFκB)] and oxidation [8-hydroxydeoxy- guanosine (8OHdG)]. Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. Results Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFkB was significantly decreased in RP tissue of men consuming GT (p=0.013) but not BT (p=0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (p=0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (p=0.04). Conclusion Given the GT-induced changes in NFkB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis. PMID:25545744

  1. Signaling States of Rhodopsin in Rod Disk Membranes Lacking Transducin βγ-Complex

    PubMed Central

    Lomonosova, Elena; Kolesnikov, Alexander V.; Kefalov, Vladimir J.

    2012-01-01

    Purpose. To characterize the possible role of transducin Gtβγ-complex in modulating the signaling properties of photoactivated rhodopsin and its lifetime in rod disc membranes and intact rods. Methods. Rhodopsin photolysis was studied using UV-visible spectroscopy and rapid scanning spectroscopy in the presence of hydroxylamine in highly purified wild-type and Gtγ-deficient mouse rod disc membranes. Complex formation between photoactivated rhodopsin and transducin was measured by extra-metarhodopsin (meta) II assay. Recovery of dark current and flash sensitivity in individual intact wild-type and Gtγ-deficient mouse rods was measured by single-cell suction recordings. Results. Photoconversion of rhodopsin to meta I/meta II equilibrium proceeds normally after elimination of the Gtβγ-complex. The meta I/meta II ratio, the rate of meta II decay, the reactivity of meta II toward hydroxylamine, and the rate of meta III formation in Gtγ-deficient rod disc membranes were identical with those observed in wild-type samples. Under low-intensity illumination, the amount of extra–meta II in Gtγ-deficient discs was significantly reduced. The initial rate of dark current recovery after 12% rhodopsin bleach was three times faster in Gtγ-deficient rods, whereas the rate of the late current recovery was largely unchanged. Mutant rods also exhibited faster postbleach recovery of flash sensitivity. Conclusions. Photoactivation and thermal decay of rhodopsin proceed similarly in wild-type and Gtγ-deficient mouse rods, but the complex formation between photoactivated rhodopsin and transducin is severely compromised in the absence of Gtβγ. The resultant lower transduction activation contributes to faster photoresponse recovery after a moderate pigment bleach in Gtγ-deficient rods. PMID:22266510

  2. Overview and Assessment of Antarctic Ice-Sheet Mass Balance Estimates: 1992-2009

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Giovinetto, Mario B.

    2011-01-01

    Mass balance estimates for the Antarctic Ice Sheet (AIS) in the 2007 report by the Intergovernmental Panel on Climate Change and in more recent reports lie between approximately ?50 to -250 Gt/year for 1992 to 2009. The 300 Gt/year range is approximately 15% of the annual mass input and 0.8 mm/year Sea Level Equivalent (SLE). Two estimates from radar altimeter measurements of elevation change by European Remote-sensing Satellites (ERS) (?28 and -31 Gt/year) lie in the upper part, whereas estimates from the Input-minus-Output Method (IOM) and the Gravity Recovery and Climate Experiment (GRACE) lie in the lower part (-40 to -246 Gt/year). We compare the various estimates, discuss the methodology used, and critically assess the results. We also modify the IOM estimate using (1) an alternate extrapolation to estimate the discharge from the non-observed 15% of the periphery, and (2) substitution of input from a field data compilation for input from an atmospheric model in 6% of area. The modified IOM estimate reduces the loss from 136 Gt/year to 13 Gt/year. Two ERS-based estimates, the modified IOM, and a GRACE-based estimate for observations within 1992 2005 lie in a narrowed range of ?27 to -40 Gt/year, which is about 3% of the annual mass input and only 0.2 mm/year SLE. Our preferred estimate for 1992 2001 is -47 Gt/year for West Antarctica, ?16 Gt/year for East Antarctica, and -31 Gt/year overall (?0.1 mm/year SLE), not including part of the Antarctic Peninsula (1.07% of the AIS area). Although recent reports of large and increasing rates of mass loss with time from GRACE-based studies cite agreement with IOM results, our evaluation does not support that conclusion

  3. High-resolution study of Gamow-Teller transitions in the 47Ti(3He,t)47V reaction

    NASA Astrophysics Data System (ADS)

    Ganioǧlu, E.; Fujita, H.; Fujita, Y.; Adachi, T.; Algora, A.; Csatlós, M.; Deaven, J. M.; Estevez-Aguado, E.; Guess, C. J.; Gulyás, J.; Hatanaka, K.; Hirota, K.; Honma, M.; Ishikawa, D.; Krasznahorkay, A.; Matsubara, H.; Meharchand, R.; Molina, F.; Okamura, H.; Ong, H. J.; Otsuka, T.; Perdikakis, G.; Rubio, B.; Scholl, C.; Shimbara, Y.; Susoy, G.; Suzuki, T.; Tamii, A.; Thies, J. H.; Zegers, R. G. T.; Zenihiro, J.

    2013-01-01

    Given the importance of Gamow-Teller (GT) transitions in nuclear structure and astrophysical nuclear processes, we have studied Tz=+3/2→+1/2, GT transitions starting from the 47Ti nucleus in the (3He,t) charge-exchange reaction at 0∘ and at an intermediate incident energy of 140 MeV/nucleon. The experiments were carried out at the Research Center for Nuclear Physics (RCNP), Osaka, using the high-resolution facility with a high-dispersion beam line and the Grand-Raiden spectrometer. With an energy resolution of 20 keV, individual GT transitions were observed and GT strength was derived for each state populated up to an excitation energy (Ex) of 12.5 MeV. The GT strength was widely distributed from low excitation energy up to 12.5 MeV, where we had to stop the analysis because of the high level density. The distribution of the GT strengths was compared with the results of shell model calculations using the GXPF1 interaction. The calculations could reproduce the experimental GT distributions well. The GT transitions from the ground state of 47Ti and the M1 transitions from the isobaric analog state in 47V to the same low-lying states in 47V are analogous. It was found that the ratios of GT transition strengths to the ground state, the 0.088-MeV state, and the 0.146-MeV state are similar to the ratios of the strengths of the analogous M1 transitions from the isobaric analog state (IAS) to these states. The measured distribution of the GT strengths was also compared with those starting from the Tz=+3/2 nucleus 41K to the Tz=+1/2 nucleus 41Ca.

  4. Multi-color lightcurve observation of the asteroid (163249) 2002 GT

    NASA Astrophysics Data System (ADS)

    Oshima, M.; Abe, S.

    2014-07-01

    NASA's Deep Impact/EPOXI spacecraft plans to encounter the asteroid (163249) 2002 GT, classified as a PHA (Potentially Hazardous Asteroid), on January 4, 2020. However, the taxonomic type and spin state of 2002 GT remain to be determined. We have carried out ground-based multi-color (B-V-R-I) lightcurve observations taking advantage of the 2002 GT Characterization Campaign by NASA. Multi-color lightcurve measurements allow us to estimate the rotation period and obtain strong constraints on the shape and pole orientation. Here we found that the rotation period of 2002 GT is estimated to be 3.7248 ± 0.1664 h. In mid-2013, 2002 GT passed at 0.015 au from the Earth, resulting an exceptional opportunity for ground-based characterization. Using the 0.81-m telescope of the Tenagra Observatory (110°52'44.8''W, +31°27'44.4''N, 1312 m) in Arizona, USA, and the Johnson-Cousins BVRI filters, we have found lightcurves of 2002 GT (Figure). The Tenagra II 0.81-m telescope is used for research of the Hayabusa2 target Asteroid (162173) 1999 JU_3. The lightcurves (relative magnitude) show that the rotation period of 2002 GT, the target of NASA's Deep Impact/EPOXI spacecraft, is estimated to be 3.7248 ± 0.1664 hr. On June 9, 2013, we had 7 hours of ground-based observations on 2002 GT from 4:00 to 11:00 UTC. The number of comparison stars for differential photometry was 34. Because of tracking the fast-moving asteroid, it was necessary to have the same comparison star among the fields of vision. We have also obtained absolute photometry of 2002 GT on June 13, 2013.

  5. The effects of optical sensor-tissue separation in endocavitary photoplethysmography.

    PubMed

    Patel, Zaibaa; Thaha, Mohamed A; Kyriacou, Panayiotis A

    2018-06-12

    <i>Objective:</i> Intestinal anastomotic failure that occurs mainly due to ischaemia is a serious risk in colorectal cancer patients undergoing surgery. Surgeons continue to rely on subjective methods such as visual inspection to assess intestinal viability during surgery and there are no clinical tools to directly monitor viability postoperatively. A dual wavelength, reflectance optical sensor has been developed for continuous and dynamic monitoring of intestinal viability via the intestinal lumen. Maintaining direct contact between the sensor and the inner intestinal wall can be difficult in an intraluminal design, therefore impacting on signal acquisition and quality. This paper investigates the effect of direct contact versus variable distances between the sensor and the tissue surface of the buccal mucosa as a surrogate. <i>Approach:</i> The <i>in-vivo</i> study involved 20 healthy volunteers to measure the effect of optical sensor-tissue distances on the ability to acquire photoplethysmography signals and their quality. Signals were acquired from the buccal mucosa at five optical sensor-tissue distances. <i>Main results:</i> Distances between 0 mm (contact) to 5 mm were the most optimal, producing signals of high quality and signal-to-noise ratio, resulting in reliable estimations of the blood oxygen saturation. Distances exceeding 5 mm compromised the acquired signals, and were of poor quality, thereby unreliably estimating the blood oxygen saturation. <i>Significance:</i> The developed optical sensor proved to be reliable for acquiring photoplethysmography signals for cases where distances between the optical sensor-tissue may arise during the assessment of intraluminal intestinal viability. © 2018 Institute of Physics and Engineering in Medicine.

  6. Large, Prospective Analysis of the Reasons Patients Do Not Pursue BRCA Genetic Testing Following Genetic Counseling.

    PubMed

    Hayden, Sommer; Mange, Sarah; Duquette, Debra; Petrucelli, Nancie; Raymond, Victoria M

    2017-08-01

    Genetic counseling (GC) and genetic testing (GT) identifies high-risk individuals who benefit from enhanced medical management. Not all individuals undergo GT following GC and understanding the reasons why can impact clinical efficiency, reduce GT costs through appropriate identification of high-risk individuals, and demonstrate the value of pre-GT GC. A collaborative project sponsored by the Michigan Department of Health and Human Services prospectively collects anonymous data on BRCA-related GC visits performed by providers in Michigan, including demographics, patient/family cancer history, GT results, and reasons for declining GT. From 2008 to 2012, 10,726 patients underwent GC; 3476 (32.4%) did not pursue GT. Primary reasons included: not the best test candidate (28.1%), not clinically indicated (23.3%), and insurance/out of pocket cost concerns (13.6%). Patient disinterest was the primary reason for declining in 17.1%. Insurance/out of pocket cost concerns were the primary reason for not testing in 13.4% of untested individuals with private insurance. Among untested individuals with breast and/or ovarian cancer, 22.5% reported insurance/out of pocket cost concerns as the primary reason for not testing and 6.6% failed to meet Medicare criteria. In a five-year time period, nearly one-third of patients who underwent BRCA GC did not pursue GT. GT was not indicated in almost half of patients. Insurance/out of pocket cost concerns continue to be barriers.

  7. Single polysaccharide assembly protein that integrates polymerization, termination, and chain-length quality control

    PubMed Central

    Williams, Danielle M.; Ovchinnikova, Olga G.; Koizumi, Akihiko; Mainprize, Iain L.; Kimber, Matthew S.; Lowary, Todd L.

    2017-01-01

    Lipopolysaccharides (LPS) are essential outer membrane glycolipids in most gram-negative bacteria. Biosynthesis of the O-antigenic polysaccharide (OPS) component of LPS follows one of three widely distributed strategies, and similar processes are used to assemble other bacterial surface glycoconjugates. This study focuses on the ATP-binding cassette (ABC) transporter-dependent pathway, where glycans are completed on undecaprenyl diphosphate carriers at the cytosol:membrane interface, before export by the ABC transporter. We describe Raoultella terrigena WbbB, a prototype for a family of proteins that, remarkably, integrates several key activities in polysaccharide biosynthesis into a single polypeptide. WbbB contains three glycosyltransferase (GT) modules. Each of the GT102 and GT103 modules characterized here represents a previously unrecognized GT family. They form a polymerase, generating a polysaccharide of [4)-α-Rhap-(1→3)-β-GlcpNAc-(1→] repeat units. The polymer chain is terminated by a β-linked Kdo (3-deoxy-d-manno-oct-2-ulosonic acid) residue added by a third GT module belonging to the recently discovered GT99 family. The polymerase GT modules are separated from the GT99 chain terminator by a coiled-coil structure that forms a molecular ruler to determine product length. Different GT modules in the polymerase domains of other family members produce diversified OPS structures. These findings offer insight into glycan assembly mechanisms and the generation of antigenic diversity as well as potential tools for glycoengineering. PMID:28137848

  8. Affective biasing of choices in gambling task decision making.

    PubMed

    Hinson, John M; Whitney, Paul; Holben, Heather; Wirick, Aaron K

    2006-09-01

    The proponents of the somatic marker hypothesis presume that rational decision making is guided by emotional reactions that are developed from prior experience. Supporting evidence for the hypothesis comes almost exclusively from the short-term affective reactions that are learned during the course of a hypothetical decision-making task--the gambling task (GT). We examined GT performance and affective reactions to choices when those choices were biased by words that had preexisting affective value. In one experiment, affectively valued words directly signaled good and bad choices. A congruent relation between affective value of word and choice outcome improved GT performance, whereas an incongruent relation greatly interfered with performance. In another experiment, affectively valued words were maintained as a working memory (WM) load between GT choices. A WM load with affectively positive words somewhat improved GT performance, whereas affectively negative words interfered with performance. Somatic markers-indicated by differential anticipatory skin conductance response (SCR) amplitude for good and bad choices-appeared at a point in the GT session when choice performance was superior. However, differential SCR developed during the session after good choice performance was already established. These results indicate that preexisting affective biases can influence GT decision making. In addition, the somatic markers that are regular accompaniments of GT decision making appeared to be temporally lagging indicators of choice performance.

  9. Mirror asymmetry for B(GT) of {sup 24}Si induced by Thomas-Ehrman shift

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

    Ichikawa, Y.; Kubo, T.; Aoi, N.

    We carried out the beta-decay spectroscopy on {sup 24}Si in order to investigate a change in configuration in the wave function induced by Thomas-Ehrman shift from a perspective of mirror asymmetry of B(GT). We observed two beta transitions to low-lying bound states in {sup 24}Al for the first time. In this proceeding, the B(GT) of {sup 24}Si is compared with that of the mirror nucleus {sup 24}Ne, and the mirror asymmetry of B(GT) is determined. Then the origin of the B(GT) asymmetry is discussed through the comparison with theoretical calculations.

  10. Terrestrial Carbon Sequestration with Biochar: A Preliminary Assessment of its Global Potential

    NASA Astrophysics Data System (ADS)

    Amonette, J.; Lehmann, J.; Joseph, S.

    2007-12-01

    Biochar technology involves the capture of CO2 from the atmosphere by photosynthesis and its ultimate conversion to biochar by pyrolysis. Energy is obtained during the pyrolysis process and the charcoal, or biochar, which is considerably more stable than biomass, may then be incorporated into agricultural lands where it serves to increase the nutrient- and water-holding capacity of soil. With an estimated half-life in soil on the order of centuries to millenia, biochar offers a way of safely storing C for long periods of time while enhancing the productivity of terrestrial ecosystems. Moreover, biochar technology, like other biomass conversion approaches that include C sequestration options, offers a way to decrease the levels of CO2 in the atmosphere. That is, biochar technology is one of the few inherently "carbon-negative" sources of energy. These positive attributes are of little consequence, however, if the total contribution to sequestration is small compared to the need. In this paper, we provide a preliminary assessment of the potential contribution of biochar technology to the mitigation of climate change, and identify some research needs. Currently, the atmospheric C levels are increasing by about 4.1 Gt/yr, with 7.2 Gt/yr being put into the atmosphere by fossil fuel combustion and cement production, and 3.1 Gt/yr being removed from the atmosphere by the ocean (2.2 Gt/yr) and terrestrial processes (0.9 Gt/yr). The uptake by terrestrial processes can be increased significantly by management of the 60.6 Gt/yr of biomass C that is fixed by photosynthesis (i.e., net primary productivity), of which 59 Gt/yr is decomposed and 1.6 Gt/yr combusted. Biomass pyrolysis converts about 50% of the biomass C to char. Of the other 50% that is converted to bio-oil and bio-gas, the net energy production is about 62% efficient. Thus, pyrolysis of 1 Gt of biomass C would provide energy equivalent to about 0.3 Gt of fossil C and could be used to offset that amount of fossil C, while sequestering 0.5 Gt as biochar. Of the 60.6 Gt/yr of biomass that is fixed in usable form, we estimate that perhaps 10% of it (6.1 Gt/yr) could become available in one form or another (crop and forestry residues, and animal waste) for pyrolysis. This level of pyrolysis would offset 1.8 Gt/yr of fossil C, and sequester 3.0 Gt/yr as biochar, enough to halt the increase and actually decrease the level of atmospheric C by 0.7 Gt/yr. Even at half this level (i.e., 5% of annually fixed biomass), pyrolysis would be sufficient to decrease the global C cycle imbalance by 2.4 Gt/yr and in combination with other sequestration options help to achieve the minimum goal of C neutrality. Clearly, the potential contribution of biochar technology is large, perhaps large enough to mitigate climate change alone. However, this preliminary assessment is tempered by several unknowns. Research is needed to further define the impacts of biochar amendments on soil biota, productivity, and greenhouse gas production. For example, there is some evidence that N2O and CH4 production is decreased by biochar amendments, but the mechanisms responsible are unknown. The impact of different types of biochar and pyrolysis conditions also needs to be determined. Lastly, total accounting for greenhouse gas emissions coupled with economic analyses to determine the economic potential of the technology under various scenarios is essential.

  11. Gyrator transform of generalized sine-Gaussian beams and conversion an edge-dislocation into a vortex

    NASA Astrophysics Data System (ADS)

    Zhu, Kaicheng; Tang, Huiqin; Tang, Ying; Xia, Hui

    2014-12-01

    We proposed a scheme that converts a sine-Gaussian beam with an edge dislocation into a dark hollow beam with a vortex. Based on the gyrator transform (GT) relation, the closed-form field distribution of generalized sine-Gaussian beams passing through a GT system is derived; the intensity distribution and the corresponding phase distribution associated with the transforming generalized sine-Gaussian beams are analyzed. According to the numerical method, the distributions are graphically demonstrated and found that, for appropriate beam parameters and the GT angle, dark hollow vortex beams with topological charge 1 can be achieved using sine-Gaussian beams carrying an edge dislocation. Moreover, the orbital angular momentum content of a GT sine-Gaussian beam is analyzed. It is proved that the GT retains the odd- or even-order spiral harmonics structures of generalized sine-Gaussian beams in the transform process. In particular, it is wholly possible to convert an edge dislocation embedded in sine-Gaussian beams into a vortex with GT. The study also reveals that to obtain a dark hollow beam making use of GT of cos-Gaussian beams is impossible.

  12. Production of alpha 1,3-galactosyltransferase gene-deficient pigs by somatic cell nuclear transfer: a novel selection method for gal alpha 1,3-Gal antigen-deficient cells.

    PubMed

    Fujimura, Tatsuya; Takahagi, Yoichi; Shigehisa, Tamotsu; Nagashima, Hiroshi; Miyagawa, Shuji; Shirakura, Ryota; Murakami, Hiroshi

    2008-09-01

    The objective of the present study was to isolate alpha 1,3-galactosyltransferase (GalGT)-gene double knockout (DKO) cells using a novel simple method of cell selection method. To obtain GalGT-DKO cells, GalGT-gene single knockout (SKO) fetal fibroblast cells were cultured for three to nine passages and GalGT-null cells were separated using a biotin-labeled IB4 lectin attached to streptavidin-coated magnetic beads. After 15-17 days of additional cultivation, seven GalGT-DKO cell colonies were obtained from a total of 2.5 x 10(7) GalGT-SKO cells. A total of 926 somatic nuclear transferred embryos reconstructed with the DKO cells were transferred into eight recipient pigs, producing four farrowed, three liveborns, and six stillborns. Absence of GalGT gene in the cloned pigs was confirmed by PCR and Southern blotting. Flow cytometric analysis revealed that alphaGal antigens were not present in the cells of the cloned DKO pigs.

  13. Studying Electron-Capture on ^64Zn in Supernovae with the (t,^3He) Charge-Exchange Reaction

    NASA Astrophysics Data System (ADS)

    Hitt, G. W.; Austin, Sam M.; Bazin, D.; Gade, A.; Guess, C. J.; Galaviz-Redondo, D.; Shimbara, Y.; Tur, C.; Zegers, R. G. T.; Horoi, M.; Howard, M. E.; Smith, E. E.

    2008-10-01

    A secondary, 115 MeV/u triton beam has been developed at NSCL for use in (t,^3He) charge-exchange(CE) reaction studies. This (n,p)-type CE reaction is useful for extracting the full Gamow-Teller (GT) response of the nucleus, overcoming Q-value restrictions present in conventional beta-decay studies. The strength (B(GT)) in ^64Cu has been determined from the absolute cross section measurement of ^64Zn(t,^3He) near zero-degrees, exploiting an empirical proportionality between cross section and B(GT). The detailed features of the B(GT) distribution in a nucleus has an important impact on electron-capture (EC) rates in Type Ia and Core-Collapse supernovae. The measured B(GT) in ^64Cu is directly compared with the results of modern shell model interactions which are used to calculate the GT contribution to EC on nuclei in supernova simulations.

  14. Baseline Polymorphisms and Emergence of Drug Resistance in the NS3/4A Protease of Hepatitis C Virus Genotype 1 following Treatment with Faldaprevir and Pegylated Interferon Alpha 2a/Ribavirin in Phase 2 and Phase 3 Studies.

    PubMed

    Berger, K L; Scherer, J; Ranga, M; Sha, N; Stern, J O; Quinson, A-M; Kukolj, G

    2015-10-01

    Analysis of data pooled from multiple phase 2 (SILEN-C1 to 3) and phase 3 studies (STARTVerso1 to 4) of the hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) protease inhibitor faldaprevir plus pegylated interferon alpha/ribavirin (PR) provides a comprehensive evaluation of baseline and treatment-emergent NS3/4A amino acid variants among HCV genotype-1 (GT-1)-infected patients. Pooled analyses of GT-1a and GT-1b NS3 population-based pretreatment sequences (n = 3,124) showed that faldaprevir resistance-associated variants (RAVs) at NS3 R155 and D168 were rare (<1%). No single, noncanonical NS3 protease or NS4A cofactor baseline polymorphism was associated with a reduced sustained virologic response (SVR) to faldaprevir plus PR, including Q80K. The GT-1b NS3 helicase polymorphism T344I was associated with reduced SVR to faldaprevir plus PR (P < 0.0001) but was not faldaprevir specific, as reduced SVR was also observed with placebo plus PR. Among patients who did not achieve SVR and had available NS3 population sequences (n = 507 GT-1a; n = 349 GT-1b), 94% of GT-1a and 83% of GT-1b encoded faldaprevir treatment-emergent RAVs. The predominant GT-1a RAV was R155K (88%), whereas GT-1b encoded D168 substitutions (78%) in which D168V was predominant (67%). The novel GT-1b NS3 S61L substitution emerged in 7% of virologic failures as a covariant with D168V, most often among the faldaprevir breakthroughs; S61L in combination with D168V had a minimal impact on faldaprevir susceptibility compared with that for D168V alone (1.5-fold difference in vitro). The median time to loss of D168 RAVs among GT-1b-infected patients who did not have a sustained virologic response at 12 weeks posttreatment (non-SVR12) after virologic failure was 5 months, which was shorter than the 14 months for R155 RAVs among GT-1a-infected non-SVR12 patients, suggesting that D168V is less fit than R155K in the absence of faldaprevir selective pressure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

    PubMed Central

    Jallet, Corinne; Jacob, Yves; Bahloul, Chokri; Drings, Astrid; Desmezieres, Emmanuel; Tordo, Noël; Perrin, Pierre

    1999-01-01

    The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH2 half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another GT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6). PMID:9847325

  16. The effect of developmental vitamin D deficiency in male and female Sprague-Dawley rats on decision-making using a rodent gambling task.

    PubMed

    Peak, J N; Turner, K M; Burne, T H J

    2015-01-01

    Developmental vitamin D (DVD) deficiency is a plausible risk factor for schizophrenia that has been associated with behavioural alterations including disruptions in latent inhibition and response inhibition. The rodent gambling task (rGT) assesses risk-based decision-making, which is a key cognitive deficit observed in schizophrenia patients. The primary aim of this study was to examine risk-based decision-making in DVD-deficient and control rats on the rGT. We also evaluated the performance of female Sprague-Dawley rats on the rGT for the first time. Adult male and female Sprague-Dawley rats from control and vitamin D deficient dams were trained to perform the rGT in standard operant chambers and their performance and choice-preferences were assessed. Female rats were significantly faster to reach rGT training criteria compared with male rats and DVD-deficient rats were faster to reach training criteria than control animals. After reaching stable performance on the rGT DVD-deficient and control rats showed a significant preference for the optimal choice-option in the rGT, but there were no significant effects of sex or diet on these responses. DVD deficiency did not alter the decision-making processes on the rGT because no significant changes in choice-preferences were evident. This is the first study to demonstrate that once established, the performance of females is comparable to male Sprague-Dawley rats on the rGT. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  17. The biomedical potential of genetically modified flax seeds overexpressing the glucosyltransferase gene

    PubMed Central

    2012-01-01

    Background Flax (Linum usitatissimum) is a potential source of many bioactive components that can be found in its oil and fibers, but also in the seedcake, which is rich in antioxidants. To increase the levels of medically beneficial compounds, a genetically modified flax type (named GT) with an elevated level of phenylopropanoids and their glycoside derivatives was generated. In this study, we investigated the influence of GT seedcake extract preparations on human fibroblast proliferation and migration, and looked at the effect on a human skin model. Moreover, we verified its activity against bacteria of clinical relevance. Methods The GT flax used in this study is characterized by overexpression of the glucosyltransferase gene derived from Solanum sogarandinum. Five GT seedcake preparations were generated. Their composition was assessed using ultra pressure liquid chromatography and confirmed using the UPLC-QTOF method. For the in vitro evaluation, the influence of the GT seedcake preparations on normal human dermal fibroblast proliferation was assessed using the MTT test and the wound scratch assay. A human skin model was used to evaluate the potential for skin irritation. To assess the antimicrobial properties of GT preparations, the percentage of inhibition of bacterial growth was calculated. Results The GT seedcake extract had elevated levels of phenylopropanoid compounds in comparison to the control, non-transformed plants. Significant increases in the content of ferulic acid, p-coumaric acid and caffeic acid, and their glucoside derivatives, kaempferol, quercitin and secoisolariciresinol diglucoside (SDG) were observed in the seeds of the modified plants. The GT seedcake preparations were shown to promote the proliferation of normal human dermal fibroblasts and the migration of fibroblasts in the wound scratch assay. The superior effect of GT seedcake extract on fibroblast migration was observed after a 24-hour treatment. The skin irritation test indicated that GT seedcake preparations have no harmful effect on human skin. Moreover, GT seedcake preparations exhibited inhibitory properties toward two bacterial strains: Staphylococcus aureus and Escherichia coli. Conclusions We suggest that preparations derived from the new GT flax are an effective source of phenylopropanoids and that their glycoside derivatives and might be promising natural products with both healing and bacteriostatic effects. This flax-derived product is a good candidate for application in the repair and regeneration of human skin and might also be an alternative to antibiotic therapy for infected wounds. PMID:23228136

  18. No evidence of a role for mitochondrial complex I in Helicobacter pylori pathogenesis.

    PubMed

    Ng, Garrett Z; Ke, Bi-Xia; Laskowski, Adrienne; Thorburn, David R; Sutton, Philip

    2017-06-01

    Complex I is the first enzyme complex in the mitochondrial respiratory chain, responsible for generating a large fraction of energy during oxidative phosphorylation. Recently, it has been identified that complex I deficiency can result in increased inflammation due to the generation of reactive oxygen species by innate immune cells. As a reduction in complex I activity has been demonstrated in human stomachs with atrophic gastritis, we investigated whether complex I deficiency could influence Helicobacter pylori pathogenesis. Ndufs6 gt/gt mice have a partial complex I deficiency. Complex I activity was quantified in the stomachs and immune cells of Ndufs6 gt/gt mice by spectrophotometric assays. Ndufs6 gt/gt mice were infected with H. pylori and bacterial colonization assessed by colony-forming assay, gastritis assessed histologically, and H. pylori -specific humoral response quantified by ELISA. The immune cells and stomachs of Ndufs6 gt/gt mice were found to have significantly decreased complex I activity, validating the model for assessing the effects of complex I deficiency in H. pylori infection. However, there was no observable effect of complex I deficiency on either H. pylori colonization, the resulting gastritis, or the humoral response. Although complex I activity is described to suppress innate immune responses and is decreased during atrophic gastritis in humans, our data suggest it does not affect H. pylori pathogenesis. © 2017 John Wiley & Sons Ltd.

  19. Formation of β-glucogallin, the precursor of ellagic acid in strawberry and raspberry

    PubMed Central

    Schulenburg, Katja; Feller, Antje; Hoffmann, Thomas; Schecker, Johannes H.; Martens, Stefan; Schwab, Wilfried

    2016-01-01

    Ellagic acid/ellagitannins are plant polyphenolic antioxidants that are synthesized from gallic acid and have been associated with a reduced risk of cancer and cardiovascular diseases. Here, we report the identification and characterization of five glycosyltransferases (GTs) from two genera of the Rosaceae family (Fragaria and Rubus; F.×ananassa FaGT2*, FaGT2, FaGT5, F. vesca FvGT2, and R. idaeus RiGT2) that catalyze the formation of 1-O-galloyl-β-d-glucopyranose (β-glucogallin) the precursor of ellagitannin biosynthesis. The enzymes showed substrate promiscuity as they formed glucose esters of a variety of (hydroxyl)benzoic and (hydroxyl)cinnamic acids. Determination of kinetic values and site-directed mutagenesis revealed amino acids that affected substrate preference and catalytic activity. Green immature strawberry fruits were identified as the main source of gallic acid, β-glucogallin, and ellagic acid in accordance with the highest GT2 gene expression levels. Injection of isotopically labeled gallic acid into green fruits of stable transgenic antisense FaGT2 strawberry plants clearly confirmed the in planta function. Our results indicate that GT2 enzymes might contribute to the production of ellagic acid/ellagitannins in strawberry and raspberry, and are useful to develop strawberry fruit with additional health benefits and for the biotechnological production of bioactive polyphenols. PMID:26884604

  20. The influence of atmosphere on performance of pure-phase WZ and ZB InAs nanowire transistors.

    PubMed

    Ullah, Abu Rifat; Joyce, Hannah J; Tan, Hoe; Jagadish, Chennupati; Micolich, Adam P

    2017-09-21

    We compare the characteristics of phase-pure MOCVD grown ZB and WZ InAs nanowire transistors in several atmospheres: air, dry pure N<sub>2</sub> and O<sub>2</sub>, and N<sub>2</sub> bubbled through liquid H<sub>2</sub>O and alcohols to identify whether phase-related structural/surface differences affect their response. Both WZ and ZB give poor gate characteristics in dry state. Adsorption of polar species reduces off-current by 2-3 orders of magnitude, increases on-off ratio and significantly reduces sub-threshold slope. The key difference is the greater sensitivity of WZ to low adsorbate level. We attribute this to facet structure and its influence on the separation between conduction electrons and surface adsorption sites. We highlight the important role adsorbed species play in nanowire device characterisation. WZ is commonly thought superior to ZB in InAs nanowire transistors. We show this is an artefact of the moderate humidity found in ambient laboratory conditions: WZ and ZB perform equally poorly in the dry gas limit yet equally well in the wet gas limit. We also highlight the vital role density-lowering disorder has in improving gate characteristics, be it stacking faults in mixed-phase WZ or surface adsorbates in pure-phase nanowires. © 2017 IOP Publishing Ltd.

  1. Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

    PubMed

    Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

    2017-05-01

    In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and that CHC patients with GT3 appear to have more severe liver disease. These findings highlight the importance of effective HCV treatment for all patients and support guidelines for treatment of high-risk patients, including those with GT3.

  2. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.

    PubMed

    Borad, Mitesh J; Reddy, Shantan G; Bahary, Nathan; Uronis, Hope E; Sigal, Darren; Cohn, Allen L; Schelman, William R; Stephenson, Joe; Chiorean, E Gabriela; Rosen, Peter J; Ulrich, Brian; Dragovich, Tomislav; Del Prete, Salvatore A; Rarick, Mark; Eng, Clarence; Kroll, Stew; Ryan, David P

    2015-05-01

    TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m(2)), gemcitabine plus TH-302 240 mg/m(2) (G+T240), or gemcitabine plus TH-302 340 mg/m(2) (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (-5,398 v -549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302-related AEs but were not associated with treatment discontinuation. PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979). © 2014 by American Society of Clinical Oncology.

  3. Mechanistic Characterization of GS-9190 (Tegobuvir), a Novel Nonnucleoside Inhibitor of Hepatitis C Virus NS5B Polymerase▿

    PubMed Central

    Shih, I-hung; Vliegen, Inge; Peng, Betty; Yang, Huiling; Hebner, Christy; Paeshuyse, Jan; Pürstinger, Gerhard; Fenaux, Martijn; Tian, Yang; Mabery, Eric; Qi, Xiaoping; Bahador, Gina; Paulson, Matthew; Lehman, Laura S.; Bondy, Steven; Tse, Winston; Reiser, Hans; Lee, William A.; Schmitz, Uli; Neyts, Johan; Zhong, Weidong

    2011-01-01

    GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain. PMID:21746939

  4. Biochemical and Molecular Characterization of a Flavonoid 3-O-glycosyltransferase Responsible for Anthocyanins and Flavonols Biosynthesis in Freesia hybrida

    PubMed Central

    Sun, Wei; Liang, Lingjie; Meng, Xiangyu; Li, Yueqing; Gao, Fengzhan; Liu, Xingxue; Wang, Shucai; Gao, Xiang; Wang, Li

    2016-01-01

    The glycosylation of flavonoids increases their solubility and stability in plants. Flowers accumulate anthocyanidin and flavonol glycosides which are synthesized by UDP-sugar flavonoid glycosyltransferases (UFGTs). In our previous study, a cDNA clone (Fh3GT1) encoding UFGT was isolated from Freesia hybrida, which was preliminarily proved to be invovled in cyanidin 3-O-glucoside biosynthesis. Here, a variety of anthocyanin and flavonol glycosides were detected in flowers and other tissues of F. hybrida, implying the versatile roles of Fh3GT1 in flavonoids biosynthesis. To further unravel its multi-functional roles, integrative analysis between gene expression and metabolites was investigated. The results showed expression of Fh3GT1 was positively related to the accumulation of anthocyanins and flavonol glycosides, suggesting its potential roles in the biosynthesis of both flavonoid glycosides. Subsequently, biochemical analysis results revealed that a broad range of flavonoid substrates including flavonoid not naturally occurred in F. hybrida could be recognized by the recombinant Fh3GT1. Both UDP-glucose and UDP-galactose could be used as sugar donors by recombinant Fh3GT1, although UDP-galactose was transferred with relatively low activity. Furthermore, regiospecificity analysis demonstrated that Fh3GT1 was able to glycosylate delphinidin at the 3-, 4-′, and 7- positions in a sugar-dependent manner. And the introduction of Fh3GT1 into Arabidopsis UGT78D2 mutant successfully restored the anthocyanins and flavonols phenotypes caused by lost-of-function of the 3GT, indicating that Fh3GT1 functions as a flavonoid 3-O-glucosyltransferase in vivo. In summary, these results demonstrate that Fh3GT1 is a flavonoid 3-O-glycosyltransferase using UDP-glucose as the preferred sugar donor and may involve in flavonoid glycosylation in F. hybrida. PMID:27064818

  5. Biochemical and Molecular Characterization of a Flavonoid 3-O-glycosyltransferase Responsible for Anthocyanins and Flavonols Biosynthesis in Freesia hybrida.

    PubMed

    Sun, Wei; Liang, Lingjie; Meng, Xiangyu; Li, Yueqing; Gao, Fengzhan; Liu, Xingxue; Wang, Shucai; Gao, Xiang; Wang, Li

    2016-01-01

    The glycosylation of flavonoids increases their solubility and stability in plants. Flowers accumulate anthocyanidin and flavonol glycosides which are synthesized by UDP-sugar flavonoid glycosyltransferases (UFGTs). In our previous study, a cDNA clone (Fh3GT1) encoding UFGT was isolated from Freesia hybrida, which was preliminarily proved to be invovled in cyanidin 3-O-glucoside biosynthesis. Here, a variety of anthocyanin and flavonol glycosides were detected in flowers and other tissues of F. hybrida, implying the versatile roles of Fh3GT1 in flavonoids biosynthesis. To further unravel its multi-functional roles, integrative analysis between gene expression and metabolites was investigated. The results showed expression of Fh3GT1 was positively related to the accumulation of anthocyanins and flavonol glycosides, suggesting its potential roles in the biosynthesis of both flavonoid glycosides. Subsequently, biochemical analysis results revealed that a broad range of flavonoid substrates including flavonoid not naturally occurred in F. hybrida could be recognized by the recombinant Fh3GT1. Both UDP-glucose and UDP-galactose could be used as sugar donors by recombinant Fh3GT1, although UDP-galactose was transferred with relatively low activity. Furthermore, regiospecificity analysis demonstrated that Fh3GT1 was able to glycosylate delphinidin at the 3-, 4-', and 7- positions in a sugar-dependent manner. And the introduction of Fh3GT1 into Arabidopsis UGT78D2 mutant successfully restored the anthocyanins and flavonols phenotypes caused by lost-of-function of the 3GT, indicating that Fh3GT1 functions as a flavonoid 3-O-glucosyltransferase in vivo. In summary, these results demonstrate that Fh3GT1 is a flavonoid 3-O-glycosyltransferase using UDP-glucose as the preferred sugar donor and may involve in flavonoid glycosylation in F. hybrida.

  6. The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

    NASA Astrophysics Data System (ADS)

    van Wessem, J. M.; Ligtenberg, S. R. M.; Reijmer, C. H.; van de Berg, W. J.; van den Broeke, M. R.; Barrand, N. E.; Thomas, E. R.; Turner, J.; Wuite, J.; Scambos, T. A.; van Meijgaard, E.

    2016-02-01

    This study presents a high-resolution (˜ 5.5 km) estimate of surface mass balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a firn densification model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in situ SMB observations and discharge rates from six glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes, complicating a full model evaluation. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr-1 in the western AP (WAP) and below 500 mm we yr-1 in the eastern AP (EAP), not resolved by coarser data sets such as ERA-Interim. The average AP ice-sheet-integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr-1 with an interannual variability of 58 Gt yr-1, which is dominated by precipitation (PR) (365 ± 57 Gt yr-1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr-1), where PR is large (276 ± 47 Gt yr-1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr-1) and PR (84 ± 11 Gt yr-1). Total sublimation is 11 ± 2 Gt yr-1 and meltwater runoff into the ocean is 4 ± 4 Gt yr-1. There are no significant trends in any of the modelled AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (-0.36 Gt yr-2).

  7. Chronic hepatitis C infection and liver disease in HIV co-infected patients in Asia

    PubMed Central

    Durier, Nicolas; Yunihastuti, Evy; Ruxrungtham, Kiat; Van Kinh, Nguyen; Kamarulzaman, Adeeba; Boettiger, David; Widhani, Alvina; Avihingsanon, Anchalee; Huy, Bui Vu; Omar, Sharifah Faridah binti Syed; Sanityoso, Andri; Chittmittrapap, Salyavit; Dung, Nguyen Thi Hoai; Pillai, Veena; Suwan-Ampai, Tuangporn; Law, Matthew; Sohn, Annette H.; Matthews, Gail

    2016-01-01

    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV co-infected patients in resource-limited settings are scarce. We assessed HCV-RNA, HCV genotype (GT), IL28B GT, and liver fibrosis (FibroScan®) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centers in South East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi, and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7–42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325–614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/ml. A total of 412 (85.8%) had detectable HCV-RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, 8 (2.1%) had GT4, 2 (0.5%) had GT2, and 7 (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan®, 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. A high proportion of HIV-HCV co-infected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (>=F2). PMID:27917597

  8. Chronic hepatitis C infection and liver disease in HIV-coinfected patients in Asia.

    PubMed

    Durier, N; Yunihastuti, E; Ruxrungtham, K; Kinh, N V; Kamarulzaman, A; Boettiger, D; Widhani, A; Avihingsanon, A; Huy, B V; Syed Omar, S F B; Sanityoso, A; Chittmittrapap, S; Dung, N T H; Pillai, V; Suwan-Ampai, T; Law, M; Sohn, A H; Matthews, G

    2017-03-01

    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan ® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm 3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log 10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan ® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan ® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2). © 2016 John Wiley & Sons Ltd.

  9. Assessment of Direct-to-Consumer Genetic Testing Policy in Korea Based on Consumer Preference.

    PubMed

    Jeong, Gicheol

    2017-01-01

    In June 2016, Korea permitted direct-to-consumer genetic testing (DTC-GT) on 42 genes. However, both the market and industry have not yet been fully activated. Considering the aforementioned context, this study provides important insights. The Korean DTC-GT policy assessment is based on consumer preference analysis using a discrete choice experiment. In August 2016, a web-based survey was conducted to collect data from 1,200 respondents. The estimation results show that consumers prefer a DTC-GT product that is cheap, tests various items or genes, offers accurate test results, and guarantees the confidentiality of all information. However, consumers are not entirely satisfied by current DTC-GT products due to the existence of insufficient and/or inadequate policies. First, the permitted testing of 42 genes is insufficient to satisfy consumers' curiosity regarding their genes. Second, the accuracy of the DTC-GT products has not been fully verified, assessed, and communicated to consumers. Finally, regulatory loopholes that allow information leaks in the DTC-GT process can occur. These findings imply that DTC-GT requires an improvement in government policy-making criteria and the implementation of practical measures to guarantee test accuracy and genetic information. © 2017 S. Karger AG, Basel.

  10. Health-Care Referrals from Direct-to-Consumer Genetic Testing

    PubMed Central

    Giovanni, Monica A.; Fickie, Matthew R.; Lehmann, Lisa S.; Green, Robert C.; Meckley, Lisa M.; Veenstra, David

    2010-01-01

    Background: Direct-to-consumer genetic testing (DTC-GT) provides personalized genetic risk information directly to consumers. Little is known about how and why consumers then communicate the results of this testing to health-care professionals. Aim: To query specialists in clinical genetics about their experience with individuals who consulted them after DTC-GT. Methods: Invitations to participate in a questionnaire were sent to three different groups of genetic professionals, totaling 4047 invitations, asking questions about individuals who consulted them after DTC-GT. For each case reported, respondents were asked to describe how the case was referred to them, the patient's rationale for DTC-GT, and the type of DTC-GT performed. Respondents were also queried about the consequences of the consultations in terms of additional testing ordered. The costs associated with each consultation were estimated. A clinical case series was compiled based upon clinician responses. Results: The invitation resulted in 133 responses describing 22 cases of clinical interactions following DTC-GT. Most consultations (59.1%) were self-referred to genetics professionals, but 31.8% were physician referred. Among respondents, 52.3% deemed the DTC-GT to be “clinically useful.” BRCA1/2 testing was considered clinically useful in 85.7% of cases; 35.7% of other tests were considered clinically useful. Subsequent referrals from genetics professionals to specialists and/or additional diagnostic testing were common, generating individual downstream costs estimated to range from $40 to $20,600. Conclusions: This clinical case series suggests that approximately half of clinical geneticists who saw patients after DTC-GT judged that testing was clinically useful, especially the BRCA1/2 testing. Further studies are needed in larger and more diverse populations to better understand the interactions between DTC-GT and the health-care system. PMID:20979566

  11. Health-care referrals from direct-to-consumer genetic testing.

    PubMed

    Giovanni, Monica A; Fickie, Matthew R; Lehmann, Lisa S; Green, Robert C; Meckley, Lisa M; Veenstra, David; Murray, Michael F

    2010-12-01

    direct-to-consumer genetic testing (DTC-GT) provides personalized genetic risk information directly to consumers. Little is known about how and why consumers then communicate the results of this testing to health-care professionals. to query specialists in clinical genetics about their experience with individuals who consulted them after DTC-GT. invitations to participate in a questionnaire were sent to three different groups of genetic professionals, totaling 4047 invitations, asking questions about individuals who consulted them after DTC-GT. For each case reported, respondents were asked to describe how the case was referred to them, the patient's rationale for DTC-GT, and the type of DTC-GT performed. Respondents were also queried about the consequences of the consultations in terms of additional testing ordered. The costs associated with each consultation were estimated. A clinical case series was compiled based upon clinician responses. the invitation resulted in 133 responses describing 22 cases of clinical interactions following DTC-GT. Most consultations (59.1%) were self-referred to genetics professionals, but 31.8% were physician referred. Among respondents, 52.3% deemed the DTC-GT to be "clinically useful." BRCA1/2 testing was considered clinically useful in 85.7% of cases; 35.7% of other tests were considered clinically useful. Subsequent referrals from genetics professionals to specialists and/or additional diagnostic testing were common, generating individual downstream costs estimated to range from $40 to $20,600. this clinical case series suggests that approximately half of clinical geneticists who saw patients after DTC-GT judged that testing was clinically useful, especially the BRCA1/2 testing. Further studies are needed in larger and more diverse populations to better understand the interactions between DTC-GT and the health-care system.

  12. Comparison of Gingival Biotype between different Genders based on Measurement of Dentopapillary Complex.

    PubMed

    Joshi, Aniruddha; Suragimath, Girish; Zope, Sameer Anil; Ashwinirani, S R; Varma, Siddhartha A

    2017-09-01

    Clinical and aesthetic outcomes after periodontal or implant surgical procedures are determined by anatomical and morphological characteristics of the gingiva like width of keratinized gingiva, thickness of gingiva and alveolar bone. Therefore, the knowledge of gingival biotype plays an important role in modifying the dental therapeutic procedures for the desired outcome and predictability. The aim of the present study was to assess and compare the gingival biotype among genders by clinical, photographic and radiographic parameters. A total of 800 subjects (400 males and 400 females) were considered for the study. Width of keratinized gingiva (GW), transparency of the periodontal probe through the sulcus (TRAN) were assessed clinically; Crown Width/Crown Length ratio (CW/CL) and Papillary Height (PH) were assessed photographically; Gingival Thickness (GT1, GT2, GT3) and Alveolar bone Thickness (AT1, AT2, AT3) were assessed radiographically. The obtained data was correlated to compare the gingival biotype between males and females. The collected data was statistically analysed using Pearson correlation coefficient (r) with the corresponding 95% confidence interval. The TRAN at GT1, GT2 and GT3 as well as at AT1, AT2 and AT3 showed a very strong positive correlation in males (r>0.8) as compared to females (r<0.8). A very strong positive correlation was observed between GT1, GT2, GT3 and AT1, AT2, AT3 in males (r>0.9) as compared to females (r<0.7). There are definite differences in the gingival biotype among different genders with predominance of a thin gingival biotype with reduced alveolar bone thickness in females as compared to males.

  13. Consensus-Degenerate Hybrid Oligonucleotide Primers for Amplification of Priming Glycosyltransferase Genes of the Exopolysaccharide Locus in Strains of the Lactobacillus casei Group

    PubMed Central

    Provencher, Cathy; LaPointe, Gisèle; Sirois, Stéphane; Van Calsteren, Marie-Rose; Roy, Denis

    2003-01-01

    A primer design strategy named CODEHOP (consensus-degenerate hybrid oligonucleotide primer) for amplification of distantly related sequences was used to detect the priming glycosyltransferase (GT) gene in strains of the Lactobacillus casei group. Each hybrid primer consisted of a short 3′ degenerate core based on four highly conserved amino acids and a longer 5′ consensus clamp region based on six sequences of the priming GT gene products from exopolysaccharide (EPS)-producing bacteria. The hybrid primers were used to detect the priming GT gene of 44 commercial isolates and reference strains of Lactobacillus rhamnosus, L. casei, Lactobacillus zeae, and Streptococcus thermophilus. The priming GT gene was detected in the genome of both non-EPS-producing (EPS−) and EPS-producing (EPS+) strains of L. rhamnosus. The sequences of the cloned PCR products were similar to those of the priming GT gene of various gram-negative and gram-positive EPS+ bacteria. Specific primers designed from the L. rhamnosus RW-9595M GT gene were used to sequence the end of the priming GT gene in selected EPS+ strains of L. rhamnosus. Phylogenetic analysis revealed that Lactobacillus spp. form a distinctive group apart from other lactic acid bacteria for which GT genes have been characterized to date. Moreover, the sequences show a divergence existing among strains of L. rhamnosus with respect to the terminal region of the priming GT gene. Thus, the PCR approach with consensus-degenerate hybrid primers designed with CODEHOP is a practical approach for the detection of similar genes containing conserved motifs in different bacterial genomes. PMID:12788729

  14. Thrombomodulin Contributes to Gamma Tocotrienol-Mediated Lethality Protection and Hematopoietic Cell Recovery in Irradiated Mice

    PubMed Central

    Pathak, Rupak; Shao, Lijian; Ghosh, Sanchita P.; Zhou, Daohong; Boerma, Marjan; Weiler, Hartmut; Hauer-Jensen, Martin

    2015-01-01

    Systemic administration of recombinant thrombomodulin (TM) confers radiation protection partly by accelerating hematopoietic recovery. The uniquely potent radioprotector gamma tocotrienol (GT3), in addition to being a strong antioxidant, inhibits the enzyme hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) and thereby likely modulates the expression of TM. We hypothesized that the mechanism underlying the exceptional radioprotective properties of GT3 partly depends on the presence of endothelial TM. In vitro studies confirmed that ionizing radiation suppresses endothelial TM (about 40% at 4 hr after 5 Gy γ-irradiation) and that GT3 induces TM expression (about 2 fold at the mRNA level after 5 μM GT3 treatment for 4 hr). In vivo survival studies showed that GT3 was significantly more effective as a radioprotector in TM wild type (TM+/+) mice than in mice with low TM function (TMPro/-). After exposure to 9 Gy TBI, GT3 pre-treatment conferred 85% survival in TM+/+ mice compared to only 50% in TMPro/-. Thus, GT3-mediated radiation lethality protection is partly dependent on endothelial TM. Significant post-TBI recovery of hematopoietic cells, particularly leukocytes, was observed in TM+/+ mice (p = 0.003), but not in TMPro/- mice, despite the fact that GT3 induced higher levels of granulocyte colony stimulating factor (G-CSF) in TMPro/- mice (p = 0.0001). These data demonstrate a critical, G-CSF-independent, role for endothelial TM in GT3-mediated lethality protection and hematopoietic recovery after exposure to TBI and may point to new strategies to enhance the efficacy of current medical countermeasures in radiological/nuclear emergencies. PMID:25860286

  15. Gum tragacanth/poly(l-lactic acid) nanofibrous scaffolds for application in regeneration of peripheral nerve damage.

    PubMed

    Ranjbar-Mohammadi, Marziyeh; Prabhakaran, Molamma P; Bahrami, S Hajir; Ramakrishna, Seeram

    2016-04-20

    Nanofibrous nerve guides have gained huge interest in supporting the peripheral nerve regeneration due to their abilities to simulate the topography, mechanical, biological and extracellular matrix morphology of native tissue. Gum tragacanth (GT) is a biocompatible mixture of polysaccharides that has been used in biomedical applications. During this study, we fabricated aligned and random nanofibers from poly(l-lactic acid) and gum tragacanth (PLLA/GT) in various ratios (100:0, 75:25, and 50:50) by electrospinning. Scanning electron microscope demonstrated smooth and uniform nanofibers with diameters in the range of 733±65nm and 226±73nm for align PLLA and random PLLA/GT 50:50 nanofibers, respectively. FTIR analysis, contact angle, in vitro biodegradation and tensile measurements were carried out to evaluate the chemical and mechanical properties of the different scaffolds. PLLA/GT 75:25 exhibited the most balanced properties compared to other scaffolds and was used for in vitro culture of nerve cells (PC12) to assess the potential of using these scaffolds as a substrate for nerve regeneration. The cells were found to attach and proliferate on aligned PLLA/GT 75:25 scaffolds, expressing bi-polar neurite extensions and the orientation of nerve cells was along the direction of the fiber alignment. Results of 8 days of in vitro culture of PC12 cells on aligned PLLA/GT 75:25 nanofibers, showed 20% increase in cell proliferation compared to PLLA/GT 75:25 random nanofibers. PLLA/GT 75:25 aligned nanofibers acted as a favorable cue to support neurite outgrowth and nerve cell elongation compared with PLLA nanofibers. Our results showed that aligned PLLA/GT 75:25 nanofibers are promising substrates for application as bioengineered grafts for nerve tissue regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Effect of green tea on resting energy expenditure and substrate oxidation during weight loss in overweight females.

    PubMed

    Diepvens, Kristel; Kovacs, Eva M R; Nijs, Ilse M T; Vogels, Neeltje; Westerterp-Plantenga, Margriet S

    2005-12-01

    We assessed the effect of ingestion of green tea (GT) extract along with a low-energy diet (LED) on resting energy expenditure (REE), substrate oxidation and body weight as GT has been shown to increase energy expenditure and fat oxidation in the short term in both animals and people. Forty-six overweight women (BMI 27.6 (sd 1.8) kg/m2) were fed in energy balance from day 1 to day 3, followed by a LED with GT (1125 mg tea catechins +225 mg caffeine/d) or placebo (PLAC) from day 4 to day 87. Caffeine intake was standardised to 300 mg/d. Energy expenditure was measured on days 4 and 32. Reductions in weight (4.19 (sd 2.0) kg PLAC, 4.21 (sd 2.7) kg GT), BMI, waist:hip ratio, fat mass and fat-free mass were not statistically different between treatments. REE as a function of fat-free mass and fat mass was significantly reduced over 32 d in the PLAC group (P<0.05) but not in the GT group. Dietary restraint increased over time (P<0.001) in both groups, whereas disinhibition and general hunger decreased (P<0.05). The GT group became more hungry over time and less thirsty, and showed increased prospective food consumption compared with PLAC (P<0.05). Taken together, the ingestion of GT along with a LED had no additional benefit for any measures of body weight or body composition. Although the decrease in REE as a function of fat-free mass and fat mass was not significant with GT treatment, whereas it was with PLAC treatment, no significant effect of treatment over time was seen, suggesting that a robust limitation of REE reduction during a LED was not achieved by GT.

  17. The role of garnet in (Y+REE) mobility during fluid-initiated, localized, solid state dehydration of an amphibole-bearing migmatised granitic gneiss to charnockite

    NASA Astrophysics Data System (ADS)

    Harlov, D. E.; Anczkiewicz, R.; Johansson, L.

    2013-12-01

    On either side of 1 m wide granitic pegmatoid dyke, Söndrum stone quarry, Halmstad, SW Sweden, extends a 2.5-3 m wide Opx-bearing dehydration zone (DZ) (650-700 °C; 800 MPa; Opx-Cpx-Bt-Amph-Gt-allanite), which overprints the gneissic banding of the surrounding migmatised granitic gneiss (MGG) (Amph-Bt-Gt-allanite) (Harlov et al., 2006, J Petrol 47, 3). Whole-rock chemistry indicates that dehydration of the MGG was predominantly isochemical. Exceptions include (Y+HREE), Ba, Sr, and F, which are markedly depleted throughout the DZ while LREE-bearing allanite remains unaltered. Systematic trends in the Gt, Bt, Amph, and FAp mineral chemistry across the DZ include depletion in Fe, (Y+HREE), Na, K, F, and Cl, and enrichment in Mg, Mn, Ca, and Ti. Fluid inclusion data suggest that the solid state dehydration event was due to advective transport of a CO2-rich fluid with a minor Cl and F component originating from a tectonic fracture represented today by the pegmatoid dyke. LA-ICPMS analysis of (Y+REE) in Gt (NIST 612 Glass standard; for operating conditions cf. Anczkiewicz et al. 2012 Chem Geol 318-319, 16) across the traverse indicates at least two distinct populations of Gt from the DZ variably depleted in (Y+HREE) and LREE (Fig. 1) by an order of magnitude compared to Gt in the MGG (Fig. 2). Depletion most likely is the result of (Y+HREE) and LREE partitioning from the Gt into the dehydrating fluid to complex with F and Cl. Variable depletion suggests preferred inter-granular pathways for fluid flow through the DZ during the dehydration event allowing some Gt grains greater exposure to the fluid than other Gt grains.

  18. Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats.

    PubMed

    Sung, Backil; Wang, Shuxing; Zhou, Bei; Lim, Grewo; Yang, Liling; Zeng, Qing; Lim, Jeong-Ae; Wang, Jing Dong; Kang, Jing X; Mao, Jianren

    2007-09-01

    Spinal glutamate transporters (GT) have been implicated in the mechanisms of neuropathic pain; however, how spinal GT uptake activity is regulated remains unclear. Here we show that alteration of spinal arachidonic acid (AA) turnover after peripheral nerve injury regulated regional GT uptake activity and glutamate homeostasis. Chronic constriction nerve injury (CCI) in rats significantly reduced spinal GT uptake activity ((3)H-glutamate uptake) with an associated increase in extracellular AA and glutamate concentration from spinal microdialysates on postoperative day 8. AACOCF3 (a cytosolic phospholipase A2 inhibitor, 30mug) given intrathecally twice a day for postoperative day 1-7 reversed this CCI-induced spinal AA production, prevented the reduced spinal GT uptake activity and increased extracellular glutamate concentration. Conversely, alteration of spinal AA metabolism by diclofenac (a cyclooxygenase 1/2 inhibitor, 200mug) further reduced spinal GT uptake activity and increased extracellular glutamate concentration in CCI rats. GT uptake activity was also attenuated when AA (10 or 100nM) was directly added into spinal samples of naïve rats in an in vitro(3)H-glutamate uptake assay, indicating a direct inhibitory effect of AA on GT uptake activity. Consistent with these findings, AACOCF3 reduced the development of both thermal hyperalgesia and mechanical allodynia, whereas diclofenac exacerbated thermal hyperalgesia, in CCI rats. Thus, spinal AA turnover may serve as a regulator in CCI-induced changes in regional GT uptake activity, glutamate homeostasis, and neuropathic pain behaviors. These data suggest that regulating spinal AA turnover may be a useful approach to improving the clinical management of neuropathic pain.

  19. A technique for measurement of earth station antenna G/T by radio stars and Applications Technology Satellites.

    NASA Technical Reports Server (NTRS)

    Kochevar, H. J.

    1972-01-01

    A new technique has been developed to accurately measure the G/T of a small aperture antenna using geostationary satellites and the well established radio star method. A large aperture antenna having the capability of accurately measuring its G/T by using a radio star of known power density is used to obtain an accurate G/T to use as a reference. The CNR of both the large and small aperture antennas are then measured using an Applications Technology Satellite (ATS). After normalizing the two C/N ratios to the large antenna system noise temperature the G/T or the gain G of the small aperture antenna can then be determined.

  20. The effect of gum tragacanth on the rheological properties of salep based ice cream mix.

    PubMed

    Kurt, Abdullah; Cengiz, Alime; Kahyaoglu, Talip

    2016-06-05

    The influence of concentration (0-0.5%, w/w) of gum tragacanth (GT) on thixotropy, dynamic, and creep-recovery rheological properties of ice cream mixes prepared with milk or water based were investigated. These properties were used to evaluate the viscoelastic behavior and internal structure of ice cream network. The textural properties of ice cream were also evaluated. Thixotropy values of samples were reduced by increasing GT concentration. The dynamic and creep-recovery analyses exhibited that GT addition increased both ice cream elastic and viscous behaviors. The increasing of Burger's model parameters with GT concentration indicated higher resistance network to the stress and more elastic behavior of samples. The applying of Cox-Merz rule is possible by using shift factor (α). GT also led to an increase in Young's modulus and the stickiness of ice creams. The obtained results highlighted the possible application of GT as a valuable member to promote structural properties of ice cream. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Gamow-Teller Strength in the Continuum Studied via the (p,n) Reaction

    NASA Astrophysics Data System (ADS)

    Wakasa, T.; Hatanaka, K.; Sakai, H.; Fujita, S.; Nonaka, T.; Ohnishi, T.; Yako, K.; Sekiguchi, K.; Okamura, H.; Otsu, H.; Ishida, S.; Sakamoto, N.; Uesaka, T.; Satou, Y.; Greenfield, M. B.

    2002-09-01

    The double differential cross sections for θ1ab between 0.0° and 14.7° and the polarization transfer coefficient DNN(0°) for the 27 Al(vec {p},vec {n}) reaction have been measured at a bombarding energy of 295 MeV. A multipole decomposition technique is applied for the cross section data to extract L = 0, 1, 2, and 3 contributions. The Gamow-Teller (GT) strength B(GT) deduced from the L = 0 contribution is compared with the B(GT) values calculated in a full sd shell-model space. The sum of B(GT) values up to 20 MeV excitation is Sβ- = 4.0 ± 0.1 ± 0.1. A fairly large L = 0 contribution is observed in the continuum region up to 50 MeV, which could be in part ascribed to the quenched GT strength. A limit on the effect that the Δ(1232)-isobar nucleon-hole admixture has upon the GT strength is estimated.

  2. Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs.

    PubMed

    Kong, Weili; Liu, Qinfang; Sun, Yipeng; Wang, Yu; Gao, Huijie; Liu, Lirong; Qin, Zhihua; He, Qiming; Sun, Honglei; Pu, Juan; Wang, Dayan; Guo, Xin; Yang, Hanchun; Chang, Kin-Chow; Shu, Yuelong; Liu, Jinhua

    2016-06-02

    Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models.

  3. Confirmation of gastric tube bedside placement with the sky blue method.

    PubMed

    Imamura, Takashi; Maeda, Hajime; Kinoshita, Hidetoshi; Shibukawa, Yasuko; Suda, Kiyomi; Fukuda, Yutaka; Goto, Aya; Nagasawa, Katsutoshi

    2014-02-01

    The purpose was to review our experiences and determine if applying the sky blue method is reliable in confirming gastric tube (GT) placement in neonates. The study population consisted of 44 infants (55 placements) who were admitted to the Takeda General Hospital between April 2012 and March 2013 and who required GT exchange. The sky blue method using indigo carmine (IC) was indicated for planned tube exchange only. Diluted IC was injected into the gastric space via the old GT just before the tube exchange. The tube was exchanged using a standard method. Then, we checked whether the diluted IC could be collected through the new GT or not. The reasons for GT placement were a gestational age of < 35 weeks in 31 (56.4%), poor sucking or swallowing disorders in 17 (30.4%), and respiratory disorders in 7 (12.7%) of the 55 placements. GT placement using the sky blue method was considered successful in 52 placements (94.4%), with the remaining 3 placements (5.6%) considered to be failures due to the inability to obtain IC from the gastric space. No adverse events were observed during the tube exchange period. Based on the results, the sky blue method can be considered to be reliable method for the confirmation of GT placement. These results also suggest that the number of radiologic evaluations performed to confirm correct replacement of the GT in infants can be reduced in the future.

  4. Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs

    PubMed Central

    Kong, Weili; Liu, Qinfang; Sun, Yipeng; Wang, Yu; Gao, Huijie; Liu, Lirong; Qin, Zhihua; He, Qiming; Sun, Honglei; Pu, Juan; Wang, Dayan; Guo, Xin; Yang, Hanchun; Chang, Kin-Chow; Shu, Yuelong; Liu, Jinhua

    2016-01-01

    Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models. PMID:27252023

  5. Purification and characterization of a novel phloretin-2'-O-glycosyltransferase favoring phloridzin biosynthesis.

    PubMed

    Zhang, Tingjing; Liang, Jianqiang; Wang, Panxue; Xu, Ying; Wang, Yutang; Wei, Xinyuan; Fan, Mingtao

    2016-10-12

    Phloretin-2'-O-glycosyltransferase (P2'GT) catalyzes the last glycosylation step in the biosynthesis of phloridzin that contributes to the flavor, color and health benefits of apples and processed apple products. In this work, a novel P2'GT of Malus x domestica (MdP2'GT) with a specific activity of 46.82 μkat/Kg protein toward phloretin and uridine diphosphate glucose (UDPG) at an optimal temperature of 30 °C and pH 8.0 was purified from the engineered Pichia pastoris broth to homogeneity by anion exchange chromatography, His-Trap affinity chromatography and gel filtration. The purified MdP2'GT was low N-glycosylated and secreted as a stable dimer with a molecular mass of 70.7 kDa in its native form. Importantly, MdP2'GT also exhibited activity towards quercetin and adenosine diphosphate glucose (ADPG), kaempferol and UDPG, quercetin and UDP-galactose, isoliquiritigenin and UDPG, and luteolin and UDPG, producing only one isoquercitrin, astragalin, hyperoside, isoliquiritin, or cynaroside, respectively. This broad spectrum of activities make MdP2'GT a promising biocatalyst for the industrial preparation of the corresponding polyphenol glycosides, preferably for their subsequent isolation and purification. Besides, MdP2'GT displayed the lowest K m and the highest k cat /K m for phloretin and UDPG compared to all previously reported P2'GTs, making MdP2'GT favor phloridzin synthesis the most.

  6. Purification and characterization of a novel phloretin-2′-O-glycosyltransferase favoring phloridzin biosynthesis

    PubMed Central

    Zhang, Tingjing; Liang, Jianqiang; Wang, Panxue; Xu, Ying; Wang, Yutang; Wei, Xinyuan; Fan, Mingtao

    2016-01-01

    Phloretin-2′-O-glycosyltransferase (P2′GT) catalyzes the last glycosylation step in the biosynthesis of phloridzin that contributes to the flavor, color and health benefits of apples and processed apple products. In this work, a novel P2′GT of Malus x domestica (MdP2′GT) with a specific activity of 46.82 μkat/Kg protein toward phloretin and uridine diphosphate glucose (UDPG) at an optimal temperature of 30 °C and pH 8.0 was purified from the engineered Pichia pastoris broth to homogeneity by anion exchange chromatography, His-Trap affinity chromatography and gel filtration. The purified MdP2′GT was low N-glycosylated and secreted as a stable dimer with a molecular mass of 70.7 kDa in its native form. Importantly, MdP2′GT also exhibited activity towards quercetin and adenosine diphosphate glucose (ADPG), kaempferol and UDPG, quercetin and UDP-galactose, isoliquiritigenin and UDPG, and luteolin and UDPG, producing only one isoquercitrin, astragalin, hyperoside, isoliquiritin, or cynaroside, respectively. This broad spectrum of activities make MdP2′GT a promising biocatalyst for the industrial preparation of the corresponding polyphenol glycosides, preferably for their subsequent isolation and purification. Besides, MdP2′GT displayed the lowest Km and the highest kcat/Km for phloretin and UDPG compared to all previously reported P2′GTs, making MdP2′GT favor phloridzin synthesis the most. PMID:27731384

  7. Self-propagating solar light reduction of graphite oxide in water

    NASA Astrophysics Data System (ADS)

    Todorova, N.; Giannakopoulou, T.; Boukos, N.; Vermisoglou, E.; Lekakou, C.; Trapalis, C.

    2017-01-01

    Graphite Oxide (GtO) is commonly used as an intermediate material for preparation of graphene in the form of reduced graphene oxide (rGO). Being a semiconductor with tunable band gap rGO is often coupled with various photocatalysts to enhance their visible light activity. The behavior of such rGO-based composites could be affected after prolonged exposure to solar light. In the present work, the alteration of the GtO properties under solar light irradiation is investigated. Water dispersions of GtO manufactured by oxidation of natural graphite via Hummers method were irradiated into solar light simulator for different periods of time without addition of catalysts or reductive agent. The FT-IR analysis of the treated dispersions revealed gradual reduction of the GtO with the increase of the irradiation time. The XRD, FT-IR and XPS analyses of the obtained solid materials confirmed the transition of GtO to rGO under solar light irradiation. The reduction of the GtO was also manifested by the CV measurements that revealed stepwise increase of the specific capacitance connected with the restoration of the sp2 domains. Photothermal self-propagating reduction of graphene oxide in aqueous media under solar light irradiation is suggested as a possible mechanism. The self-photoreduction of GtO utilizing solar light provides a green, sustainable route towards preparation of reduced graphene oxide. However, the instability of the GtO and partially reduced GO under irradiation should be considered when choosing the field of its application.

  8. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    PubMed

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology. © 2015 Wiley Periodicals, Inc.

  9. High dose of green tea infusion normalized spiral artery density in rats treated with the depot-medroxyprogesterone acetate.

    PubMed

    Emilda, A S; Veri, Nora; Alchalidi, Alchalidi

    2017-01-01

    The purpose of this study was to investigate the effects of green tea (GT) on the spiral artery density and endometrial thickness in female rats treated with the depot-medroxyprogesterone acetate (DMPA). A total of 24 female rats were randomly divided into four groups (n = 6 each): The control group (no treatment), the DMPA-treated group, treated with DMPA and GT doses of 165 mg/kg of body weight/day, and treated with DMPA and GT doses of 330 mg/kg of body weight/day. Spiral artery density and endometrial thickness were subjected to histopathological analysis. Spiral artery density decreased in the DMPA-treated group, despite the insignificant difference ( P > 0.05). With regard to the administration of GT at doses of 165 and 330 mg/g of body weight/day, only GT at the high dose was capable of significantly preventing a decrease in spiral artery density ( P < 0.05). At this dose, the spiral arteries achieved a density comparable to that of the control group ( P > 0.05). Meanwhile, the administration of DMPA and/or DMPA with GT did not cause significant changes in endometrial thickness relative to the control group ( P > 0.05). DMPA induced a decrease in spiral artery density, despite the insignificant differences, and these changes could be normalized by the administration of high doses of GT. Therefore, GT could be a candidate herb to prevent the adverse effects of the contraceptive DMPA.

  10. Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice

    PubMed Central

    Anderson, Sarah R.; Lee, Inyoul; Ebeling, Christine; Stephenson, Dennis A.; Schweitzer, Kelsey M.; Baxter, David; Moon, Tara M.; LaPierre, Sarah; Jaques, Benjamin; Silvius, Derek; Wegner, Michael; Hood, Leroy E.; Carlson, George; Gunn, Teresa M.

    2014-01-01

    Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype that includes pigmentation defects, megacolon, whole body tremors, sporadic seizures, hypo- and dysmyelination of the CNS and PNS, vacuolation of the CNS, and early death. Vacuolation similar to that caused by prions was originally reported to be transmissible, but subsequent studies showed the inherited disease was not infectious. The gt mutation mapped to distal mouse chromosome 15, to the same region as Sox10, which encodes a transcription factor with essential roles in neural crest survival and differentiation. As dominant mutations in mouse or human SOX10 cause white spotting and intestinal aganglionosis, we screened the Sox10 coding region for mutations in gt/gt DNA. An adenosine to guanine transversion was identified in exon 2 that changes a highly conserved glutamic acid residue in the SOX10 DNA binding domain to glycine. This mutant allele was not seen in wildtype mice, including the related GT/Le strain, and failed to complement a Sox10 null allele. Gene expression analysis revealed significant down-regulation of genes involved in myelin lipid biosynthesis pathways in gt/gt brains. Knockout mice for some of these genes develop CNS vacuolation and/or myelination defects, suggesting that their down-regulation may contribute to these phenotypes in gt mutants and could underlie the neurological phenotypes associated with Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung (PCWH) disease, caused by mutations in human SOX10. PMID:25399070

  11. Steroidogenesis in rainbow trout (Salmo gairdneri) at various preovulatory stages: changes in plasma hormone levels andin vivo andin vitro responses of the ovary to salmon gonadotropin.

    PubMed

    Fostier, A; Jalabert, B

    1986-10-01

    In order to specify the timing of some changes in ovarian steroid production during the transition from vitellogenesis to ovulation, plasma hormones levels andin vivo andin vitro responses of the ovary to salmon gonadotropin (s-GtH) or dibutyryl-cyclic adenosine mono-phosphate (db-cAMP) were recorded in relationship with the state of germinal vesicle migration in the oocyte.In vivo, a small, but significant, increase of plasma 17α-hydroxy-20β-dihydroprogesterone (17α, 20β-OH-P) level was detected earlier (at the "subperipheral germinal vesicle" stage) than the increase of GtH level (detectable at the "peripheral germinal vesicle" stage) and the decline of oestradiol-17β (E2-17β) (also detectable at the "peripheral germinal vesicle" stage). Negative correlations were established between E2-17β levels and GtH (ρ=-0.53) or 17α,20β-OH-P (ρ=-0,43) levels while a positive correlation occurred between 17α,20β-OH-P and GtH levels (ρ=+0,54).In vivo no action of GtH on the decline of E2-17β levels was detected GtH did not stimulate 17α,20β-OH-P production, within 72h, in females at the "end of vitellogenesis" stage. It had significant effect in females at other stages closer to ovulation, but the pattern of responses changed according to the stage.In vitro db-cAMP like GtH was able to stimulate 17α,20β-OH-P output from ovarian follicles. The greatest response was observed at the later stage. (GVBD). Testosterone output was also increased by GtH, but the lowest response was observed at the later stage (GVBD). Androstenedione output was lower than testosterone output.In vitro, a small but significant decline of E2-17β output was induced by GtH. We conclude that substantial changes occur during the very last stages prior to ovulation, both in the steroidogenic potential of the ovary and in the ovarian sensitivity to GtH. 20β-oxydoreductase is probably progressively induced during GV migration when GtH basal levels are increasing but still relatively low. Without minimizing the role of discrete pulses of GtH on this induction, we could expect synergic actions of other hormones. Thus a high testosterone/oestradiol ratio in the follicle environment favours 17α,20β-OH-P secretion.

  12. Registration of maize inbred line GT603

    USDA-ARS?s Scientific Manuscript database

    GT603 (Reg. No. xxxx, PI xxxxxx) is a yellow dent maize (Zea mays L.) inbred line developed and released by the USDA-ARS Crop Protection and Management Research Unit in cooperation with the University of Georgia Coastal Plain Experiment Station in 2010. GT603 was developed through seven generations ...

  13. 78 FR 27178 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-09

    ... Generation and Transmission cooperatives (G&T's) that generate or purchase power and transmit the power to the distribution systems. All RUS and G&T borrowers will enter into a Wholesale Power Contract with... the credit quality and credit worthiness of loans and loan guarantees to G&T borrowers. RUS works...

  14. 77 FR 6727 - Approval and Promulgation of Implementation Plans and Designation of Areas for Air Quality...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-09

    ... for Redesignation of Ozone and Carbon Monoxide Nonattainment Areas,'' Memorandum from G.T. Helms... Carbon Monoxide (CO) Redesignations,'' Memorandum from G.T. Helms, Chief, Ozone/Carbon Monoxide Programs...,'' Memorandum from G.T. Helms, Chief, Ozone/Carbon Monoxide Programs Branch, August 17, 1993; ``State...

  15. Evidence of β-antimonene at the Sb/Bi2Se3 interface.

    PubMed

    Flammini, Roberto; Colonna, Stefano; Hogan, Conor; Mahatha, Sanjoy; Papagno, Marco; Barla, Alessandro; Sheverdyaeva, Polina; Moras, Paolo; Aliev, Ziya; Babanly, M B; Chulkov, Evgueni V; Carbone, Carlo; Ronci, Fabio

    2017-12-19

    We report a study of the interface between antimony and the prototypical topological insulator Sb/Bi<sub>2</sub>Se<sub>3</sub>. Scanning tunnelling microscopy measurements show the presence of ordered domains displaying a perfect lattice match with bismuth selenide. Density functional theory calculations of the most stable atomic configurations demonstrate that the ordered domains can be attributed to stacks of β-antimonene. © 2017 IOP Publishing Ltd.

  16. United States Commercial Shipbuilding Productivity: An International View

    DTIC Science & Technology

    1990-12-01

    produced, U.S. shipbuilders would have ranked 36th. The U.S. output is just above Malaysia (2758 GT), Peru (3136 GT) and Chile (3372 GT), but below...2 6,172 0.05 35 GREECE 4 5,219 0.04 36 UNITED STATES 10 4,078 0.03 37 CHILE 8 3,372 0.03 38 PERU 7 3,136 0.02 39 MALAYSIA 2 2,758 0.02 40 THAILAND 2...Korean shipbuilders’ rank second behind Japan in total GT produced. Collectively, the three major yards, Hyundai Heavy Industries (HH I), Samsung , and

  17. Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain.

    PubMed

    Aoki, D; Lee, N; Yamaguchi, N; Dubois, C; Fukuda, M N

    1992-05-15

    Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4-galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30-Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi.

  18. Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain.

    PubMed Central

    Aoki, D; Lee, N; Yamaguchi, N; Dubois, C; Fukuda, M N

    1992-01-01

    Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4-galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30-Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi. Images PMID:1584766

  19. Cost-Utility of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1 Infection.

    PubMed

    Corman, Shelby; Elbasha, Elamin H; Michalopoulos, Steven N; Nwankwo, Chizoba

    2017-09-01

    To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA (< or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients. Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. The gap gene giant of Rhodnius prolixus is maternally expressed and required for proper head and abdomen formation.

    PubMed

    Lavore, Andrés; Pagola, Lucía; Esponda-Behrens, Natalia; Rivera-Pomar, Rolando

    2012-01-01

    The segmentation process in insects depends on a hierarchical cascade of gene activity. The first effectors downstream of the maternal activation are the gap genes, which divide the embryo in broad fields. We discovered a sequence corresponding to the leucine-zipper domain of the orthologue of the gene giant (Rp-gt) in traces from the genome of Rhodnius prolixus, a hemipteran with intermediate germ-band development. We cloned the Rp-gt gene from a normalized cDNA library and characterized its expression and function. Bioinformatic analysis of 12.5 kbp of genomic sequence containing the Rp-gt transcriptional unit shows a cluster of bona fide regulatory binding sites, which is similar in location and structure to the predicted posterior expression domain of the Drosophila orthologue. Rp-gt is expressed in ovaries and maternally supplied in the early embryo. The maternal contribution forms a gradient of scattered patches of mRNA in the preblastoderm embryo. Zygotic Rp-gt is expressed in two domains that after germ band extension are restricted to the head and the posterior growth zone. Parental RNAi shows that Rp-gt is required for proper head and abdomen formation. The head lacks mandibulary and maxillary appendages and shows reduced clypeus-labrum, while the abdomen lacks anterior segments. We conclude that Rp-gt is a gap gene on the head and abdomen and, in addition, has a function in patterning the anterior head capsule suggesting that the function of gt in hemipterans is more similar to dipterans than expected. Copyright © 2011. Published by Elsevier Inc.

  1. Evaluating the Role of Prophylactic Gastrostomy Tube Placement Prior to Definitive Chemoradiotherapy for Head and Neck Cancer

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

    Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.ed; Li Baoqing; Lau, Derick H.

    2010-11-15

    Purpose: To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. Methods and Materials: One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. Results: Prophylactic GT placement significantly reducedmore » weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001). Conclusions: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.« less

  2. The floor plate is sufficient for development of the sclerotome and spine without the notochord.

    PubMed

    Ando, Takashi; Semba, Kei; Suda, Hiroko; Sei, Akira; Mizuta, Hiroshi; Araki, Masatake; Abe, Kuniya; Imai, Kenji; Nakagata, Naomi; Araki, Kimi; Yamamura, Ken-ichi

    2011-01-01

    Danforth'sshort-tail (Sd) mouse is a semi-dominant mutation affecting the development of the vertebral column. Although the notochord degenerates completely by embryonic day 9.5, the vertebral column exists up to the lumber region, suggesting that the floor plate can substitute for notochord function. We previously established the mutant mouse line, Skt(Gt), through gene trap mutagenesis and identified the novel gene, Skt, which was mapped 0.95cM distal to the Sd locus. Taking advantage of the fact that monitoring notochordal development and genotyping of the Sd locus can be performed using the Skt(Gt) allele, we assessed the development of the vertebra, notochord, somite, floor plate and sclerotome in +-+/+-Skt(Gt), Sd-+/+-+, Sd-Skt(Gt)/+-+, Sd-Skt(Gt)/+-Skt(Gt), Sd-+/Sd-+ and Sd-Skt(Gt)/Sd-Skt(Gt) embryos. In Sd homozygous mutants with a C57BL/6 genetic background, the vertebral column was truncated in the 6th thoracic vertebra, which was more severe than previously reported. The floor plate and sclerotome developed to the level of somite before notochord degeneration and the number of remaining vertebrae corresponded well with the level of development of the floor plate and sclerotome. Defects to the sclerotome and subsequent vertebral development were not due to failure of somitogenesis. Taken together, these results suggest that the notochord induced floor plate development before degeneration, and that the remaining floor plate is sufficient for maintenance of differentiation of the somite into the sclerotome and vertebra in the absence of the notochord. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Surface plasmon resonance spectroscopy studies of membrane proteins: transducin binding and activation by rhodopsin monitored in thin membrane films.

    PubMed Central

    Salamon, Z; Wang, Y; Soulages, J L; Brown, M F; Tollin, G

    1996-01-01

    Surface plasmon resonance (SPR) spectroscopy can provide useful information regarding average structural properties of membrane films supported on planar solid substrates. Here we have used SPR spectroscopy for the first time to monitor the binding and activation of G-protein (transducin or Gt) by bovine rhodopsin incorporated into an egg phosphatidylcholine bilayer deposited on a silver film. Rhodopsin incorporation into the membrane, performed by dilution of a detergent solution of the protein, proceeds in a saturable manner. Before photolysis, the SPR data show that Gt binds tightly (Keq approximately equal to 60 nM) and with positive cooperativity to rhodopsin in the lipid layer to form a closely packed film. A simple multilayer model yields a calculated average thickness of about 57 A, in good agreement with the structure of Gt. The data also demonstrate that Gt binding saturates at a Gt/rhodopsin ratio of approximately 0.6. Moreover, upon visible light irradiation, characteristic changes occur in the SPR spectrum, which can be modeled by a 6 A increase in the average thickness of the lipid/protein film caused by formation of metarhodopsin II (MII). Upon subsequent addition of GTP, further SPR spectral changes are induced. These are interpreted as resulting from dissociation of the alpha-subunit of Gt, formation of new MII-Gt complexes, and possible conformational changes of Gt as a consequence of complex formation. The above results clearly demonstrate the ability of SPR spectroscopy to monitor interactions among the proteins associated with signal transduction in membrane-bound systems. Images FIGURE 1 PMID:8804611

  4. A Lytic Polysaccharide Monooxygenase with Broad Xyloglucan Specificity from the Brown-Rot Fungus Gloeophyllum trabeum and Its Action on Cellulose-Xyloglucan Complexes

    PubMed Central

    Kojima, Yuka; Várnai, Anikó; Ishida, Takuya; Sunagawa, Naoki; Petrovic, Dejan M.; Igarashi, Kiyohiko; Jellison, Jody; Goodell, Barry; Alfredsen, Gry; Westereng, Bjørge

    2016-01-01

    ABSTRACT Fungi secrete a set of glycoside hydrolases and lytic polysaccharide monooxygenases (LPMOs) to degrade plant polysaccharides. Brown-rot fungi, such as Gloeophyllum trabeum, tend to have few LPMOs, and information on these enzymes is scarce. The genome of G. trabeum encodes four auxiliary activity 9 (AA9) LPMOs (GtLPMO9s), whose coding sequences were amplified from cDNA. Due to alternative splicing, two variants of GtLPMO9A seem to be produced, a single-domain variant, GtLPMO9A-1, and a longer variant, GtLPMO9A-2, which contains a C-terminal domain comprising approximately 55 residues without a predicted function. We have overexpressed the phylogenetically distinct GtLPMO9A-2 in Pichia pastoris and investigated its properties. Standard analyses using high-performance anion-exchange chromatography–pulsed amperometric detection (HPAEC-PAD) and mass spectrometry (MS) showed that GtLPMO9A-2 is active on cellulose, carboxymethyl cellulose, and xyloglucan. Importantly, compared to other known xyloglucan-active LPMOs, GtLPMO9A-2 has broad specificity, cleaving at any position along the β-glucan backbone of xyloglucan, regardless of substitutions. Using dynamic viscosity measurements to compare the hemicellulolytic action of GtLPMO9A-2 to that of a well-characterized hemicellulolytic LPMO, NcLPMO9C from Neurospora crassa revealed that GtLPMO9A-2 is more efficient in depolymerizing xyloglucan. These measurements also revealed minor activity on glucomannan that could not be detected by the analysis of soluble products by HPAEC-PAD and MS and that was lower than the activity of NcLPMO9C. Experiments with copolymeric substrates showed an inhibitory effect of hemicellulose coating on cellulolytic LPMO activity and did not reveal additional activities of GtLPMO9A-2. These results provide insight into the LPMO potential of G. trabeum and provide a novel sensitive method, a measurement of dynamic viscosity, for monitoring LPMO activity. IMPORTANCE Currently, there are only a few methods available to analyze end products of lytic polysaccharide monooxygenase (LPMO) activity, the most common ones being liquid chromatography and mass spectrometry. Here, we present an alternative and sensitive method based on measurement of dynamic viscosity for real-time continuous monitoring of LPMO activity in the presence of water-soluble hemicelluloses, such as xyloglucan. We have used both these novel and existing analytical methods to characterize a xyloglucan-active LPMO from a brown-rot fungus. This enzyme, GtLPMO9A-2, differs from previously characterized LPMOs in having broad substrate specificity, enabling almost random cleavage of the xyloglucan backbone. GtLPMO9A-2 acts preferentially on free xyloglucan, suggesting a preference for xyloglucan chains that tether cellulose fibers together. The xyloglucan-degrading potential of GtLPMO9A-2 suggests a role in decreasing wood strength at the initial stage of brown rot through degradation of the primary cell wall. PMID:27590806

  5. Constraining East Antarctic mass trends using a Bayesian inference approach

    NASA Astrophysics Data System (ADS)

    Martin-Español, Alba; Bamber, Jonathan L.

    2016-04-01

    East Antarctica is an order of magnitude larger than its western neighbour and the Greenland ice sheet. It has the greatest potential to contribute to sea level rise of any source, including non-glacial contributors. It is, however, the most challenging ice mass to constrain because of a range of factors including the relative paucity of in-situ observations and the poor signal to noise ratio of Earth Observation data such as satellite altimetry and gravimetry. A recent study using satellite radar and laser altimetry (Zwally et al. 2015) concluded that the East Antarctic Ice Sheet (EAIS) had been accumulating mass at a rate of 136±28 Gt/yr for the period 2003-08. Here, we use a Bayesian hierarchical model, which has been tested on, and applied to, the whole of Antarctica, to investigate the impact of different assumptions regarding the origin of elevation changes of the EAIS. We combined GRACE, satellite laser and radar altimeter data and GPS measurements to solve simultaneously for surface processes (primarily surface mass balance, SMB), ice dynamics and glacio-isostatic adjustment over the period 2003-13. The hierarchical model partitions mass trends between SMB and ice dynamics based on physical principles and measures of statistical likelihood. Without imposing the division between these processes, the model apportions about a third of the mass trend to ice dynamics, +18 Gt/yr, and two thirds, +39 Gt/yr, to SMB. The total mass trend for that period for the EAIS was 57±20 Gt/yr. Over the period 2003-08, we obtain an ice dynamic trend of 12 Gt/yr and a SMB trend of 15 Gt/yr, with a total mass trend of 27 Gt/yr. We then imposed the condition that the surface mass balance is tightly constrained by the regional climate model RACMO2.3 and allowed height changes due to ice dynamics to occur in areas of low surface velocities (<10 m/yr) , such as those in the interior of East Antarctica (a similar condition as used in Zwally 2015). The model must find a solution that satisfies all the input data, given these constraints. By imposing these conditions, over the period 2003-13 we obtained a mass gain due to ice dynamics of 103±15 Gt/yr but this was offset by a negative trend in SMB of 47 Gt/yr, resulting in an overall positive trend of 56±15 Gt/yr. Over 2003-08, the ice dynamics trend is 96 Gt/yr, offset by a strong negative SMB trend of -81 Gt/yr, with a total mass trend of 15±13Gt/yr. Even after relaxing the ice dynamics constraint over East Antarctica, we are unable to reproduce the large positive trend obtained in Zwally2015. We conclude that this result is inconsistent with the combined observations, irrespective of any assumption made about the density of surface elevation changes.

  6. Variables Predicting Prospective Biology Teachers' Acceptance Perceptions Regarding Gene Technology

    ERIC Educational Resources Information Center

    Yilmaz, Mirac; Demirhan, Haydar

    2014-01-01

    The different opinions on products and applications of gene technology (GT) draw attention to the training and education activities related to GT. The purpose of this study is to review some variables predicting the acceptance perception regarding GT, and to investigate their changes at levels. The prospective teachers' subjective knowledge and…

  7. The National Research Center on the Gifted and Talented Newsletter, 2000.

    ERIC Educational Resources Information Center

    Gubbins, E. Jean; Siegle, Del, Ed.

    2000-01-01

    These two newsletters from the National Research Center on the Gifted and Talented (NRC/GT) contain the following articles: (1) "NRC/GT: Professional Development--Not an Event" (E. Jean Gubbins), discusses NRC/GT research-based principles related to professional development and the importance of ongoing professional development; (2)…

  8. What Does It Mean to Assess Gifted Students' Perceptions of Giftedness Labels?

    ERIC Educational Resources Information Center

    Meadows, Bryan; Neumann, Jacob W.

    2017-01-01

    Measuring gifted and talented ("GT") students' perceptions of their "GT" label might seem to be a relatively straightforward affair. Most of this research uses survey methods that ask "GT" students to complete Likert scale or open-ended response questionnaires about their perceptions of the label and then presents…

  9. NCEP Air Quality Forecast(AQF) Verification. NOAA/NWS/NCEP/EMC

    Science.gov Websites

    average Select forecast four: Day 1 AOD skill for all thresholds Day 1 Time series for AOD GT 0 Day 2 AOD skill for all thresholds Day 2 Time series for AOD GT 0 Diurnal plots for AOD GT 0 Select statistic type

  10. High-lying Gamow-Teller excited states in the deformed nuclei,76Ge,82Se and N = 20 nuclei in the island of inversion by the Deformed QRPA (DQRPA)

    NASA Astrophysics Data System (ADS)

    Cheoun, Myung-Ki; Ha, Eunja

    2013-07-01

    With the advent of high analysis technology in detecting the Gamow-Teller (GT) excited states beyond one nucleon emission threshold, the quenching of the GT strength to the Ikeda sum rule (ISR) seems to be recovered by the high-lying (HL) GT states. We address that these HL GT excited states result from the smearing of the Fermi surface by the increase of the chemical potential owing to the deformation within a framework of the deformed quasi-particle random phase approximation (DQRPA). Detailed mechanism leading to the smearing is discussed, and comparisons to the available experimental data on 76Ge,82Se and N = 20 nuclei are shown to explain the strong peaks on the HL GT excited states.

  11. Investigation of Gamow Teller transition properties in 56-64Ni isotopes using QRPA methods

    NASA Astrophysics Data System (ADS)

    Cakmak, Sadiye; Nabi, Jameel-Un; Babacan, Tahsin

    2018-02-01

    Weak rates in nickel isotopes play an integral role in the dynamics of supernovae. Electron capture and β-decay of nickel isotopes, dictated by Gamow-Teller transitions, significantly alter the lepton fraction of the stellar matter. In this paper we calculate Gamow-Teller (GT) transitions for isotopes of nickel, Ni6456-, using QRPA methods. The GT strength distributions were calculated using four different QRPA models. Our results are also compared with previous theoretical calculations and measured strength distributions wherever available. Our investigation concluded that amongst all RPA models, the pn-QRPA(C) model best described the measured GT distributions (including total GT strength and centroid placement). It is hoped that the current investigation of GT properties would prove handy and may lead to a better understanding of the presupernova evolution of massive stars.

  12. GT-094, a NO-NSAID, inhibits colon cancer cell growth by activation of a reactive oxygen species-microRNA-27a: ZBTB10-specificity protein pathway.

    PubMed

    Pathi, Satya S; Jutooru, Indira; Chadalapaka, Gayathri; Sreevalsan, Sandeep; Anand, S; Thatcher, Gregory Rj; Safe, Stephen

    2011-02-01

    Ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094) is a novel nitric oxide (NO) chimera containing an nonsteroidal anti-inflammatory drug (NSAID) and NO moieties and also a disulfide pharmacophore that in itself exhibits cancer chemopreventive activity. In this study, the effects and mechanism of action of GT-094 were investigated in RKO and SW480 colon cancer cells. GT-094 inhibited cell proliferation and induced apoptosis in both cell lines and this was accompanied by decreased mitochondrial membrane potential (MMP) and induction of reactive oxygen species (ROS), and these responses were reversed after cotreatment with the antioxidant glutathione. GT-094 also downregulated genes associated with cell growth [cyclin D1, hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR)], survival (bcl-2, survivin), and angiogenesis [VEGF and its receptors (VEGFR1 and VEGFR2)]. Results of previous RNA interference studies in this laboratory has shown that these genes are regulated, in part, by specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 that are overexpressed in colon and other cancer cell lines and not surprisingly, GT-094 also decreased Sp1, Sp3, and Sp4 in colon cancer cells. GT-094-mediated repression of Sp and Sp-regulated gene products was due to downregulation of microRNA-27a (miR-27a) and induction of ZBTB10, an Sp repressor that is regulated by miR-27a in colon cancer cells. Moreover, the effects of GT-094 on Sp1, Sp3, Sp4, miR-27a, and ZBTB10 were also inhibited by glutathione suggesting that the anticancer activity of GT-094 in colon cancer cells is due, in part, to activation of an ROS-miR-27a:ZBTB10-Sp transcription factor pathway.

  13. Design and characterization of dexamethasone-loaded poly (glycerol sebacate)-poly caprolactone/gelatin scaffold by coaxial electro spinning for soft tissue engineering.

    PubMed

    Nadim, Afsaneh; Khorasani, Saied Nouri; Kharaziha, Mahshid; Davoodi, Seyyed Mohammadreza

    2017-09-01

    The aim of this research was to fabricate dexamethasone (Dex)-loaded poly (glycerol sebacate) (PGS)-poly (caprolactone) (PCL)/gelatin (Gt) (PGS-PCL/Gt-Dex) fibrous scaffolds in the form of core/shell structure which have potential application in soft tissues. In this regard, after synthesize and characterizations of PGS, PGS-PCL and gelatin fibrous scaffolds were separately developed in order to optimize the electrospinning parameters. In the next step, coaxial electrospun fibrous scaffold of PGS-PCL/Gt fibrous scaffold with PGS-PCL as core and Gt as shell was developed and its mechanical, physical and chemical properties were characterized. Moreover, degradability, hydrophilicity and biocompatibility of PGS-PCL/Gt fibrous scaffold were evaluated. In addition, Dex was encapsulated in PGS-PCL/Gt fibrous scaffold and drug release was assessed for tissue engineering application. Results demonstrated the formation of coaxial fibrous scaffold with average porosity of 79% and average fiber size of 294nm. Moreover, PGS-PCL/Gt fibrous scaffold revealed lower elastic modulus, ultimate tensile and ultimate elongation than those of PGS-PCL scaffold and more close to mechanical properties of natural tissue. Furthermore, lower contact angle of PGS-PCL/Gt than that of PGS-PCL demonstrated improved surface hydrophilicity of scaffold. DEX release was sustained over a period time of 30days from the scaffolds via three steps consisting of an initial burst release, secondary linear phase release pattern with slower rate over 20days followed by an apparent zero-order release phase. MTT observations demonstrated that there was no evidence of toxicity in the samples with and without Dex. Our findings indicated that core/shell PGS-PCL/Gt-Dex fibrous could be used as a carrier for the sustained release of drugs relevant for tissue engineering which makes it appropriate for soft tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The in vitro and in vivo biocompatibility evaluation of electrospun recombinant spider silk protein/PCL/gelatin for small caliber vascular tissue engineering scaffolds.

    PubMed

    Xiang, Ping; Wang, Shan-Shan; He, Meng; Han, Yong-He; Zhou, Zhi-Hua; Chen, Deng-Long; Li, Min; Ma, Lena Q

    2018-03-01

    Recombinant spider silk protein (pNSR32) and gelatin (Gt) were demonstrated to enhance cytocompatibility of electrospun pNSR32/PCL/Gt scaffold. However, its potential pro-inflammatory effects and interactions with tissue and blood are unknown. In this study, the physicochemical properties and in vitro and in vivo biocompatibility of such scaffolds were evaluated. The results showed that the pNSR32/PCL/Gt scaffold possessed larger average fiber diameters, wider fiber diameter distribution and faster degradation rate than that of pNSR32/PCL and PCL scaffolds. The addition of pNSR32 and Gt had little influence on the hemolysis and plasma re-calcification time, but prolonged kinetic clotting time and reduced the platelet adhesion. The Il-6 and Tnf-α mRNA expression levels were up-regulated in macrophages seeded on the PCL and pNSR32/PCL scaffolds. The lowest release of IL-6 and TNF-α appeared in the pNSR32/PCL/Gt scaffold. Histological results revealed that the PCL and pNSR32/PCL scaffolds elicited severe host tissue responses after implantation, while prominent ingrowth of host cells were observed in the pNSR32/PCL and pNSR32/PCL/Gt scaffolds. The comet assay and bone marrow micronucleus test demonstrated that the pNSR32/PCL/Gt scaffold did not increase the frequency of DNA damage or bone marrow micronucleus. In short, this study confirmed that the pNSR32/PCL/Gt scaffold exhibited better blood and tissue compatibility than pNSR32/PCL and PCL scaffolds. No induction of genotoxicity and inflammatory factor releases makes the pNSR32/PCL/Gt scaffold a good candidate for engineering small diameter vascular tissue. Copyright © 2017. Published by Elsevier B.V.

  15. Nebulization with Gamma-Tocopherol Ameliorates Acute Lung Injury after Burn and Smoke Inhalation in the Ovine Model

    PubMed Central

    Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sousse, Linda E.; Sakurai, Hiroyuki; Rehberg, Sebastian W.; Asmussen, Sven; Kraft, Edward R.; Wright, Charlotte L.; Bartha, Eva; Cox, Robert A.; Hawkins, Hal K.; Traber, Lillian D.; Traber, Maret G.; Szabo, Csaba; Herndon, David N.; Traber, Daniel L.

    2012-01-01

    We hypothesize that the nebulization of gamma-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome (ARDS) will effectively improve pulmonary function following burn and smoke inhalation after 96 hours. Adult ewes (n=14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 hours after the injury (g-T group, n=6), while the control group (n=5) was nebulized with only ethanol. Animals were weaned from the ventilator when possible. All animals were sacrificed after 96 hours, with the exception of one untreated animal that was euthanized after 64 hours. Lung g-T concentration significantly increased after g-T nebulization compared to the control group (38.5±16.8 nmol/g vs. 0.39±0.46, p<0.01). The PaO2/FiO2 ratio was significantly higher after treatment with g-T compared to the control group (310±152 vs 150±27.0, p<0.05). The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9±0.87 vs 4.6±1.4, p<0.05), and bronchiolar obstruction (2.0±1.1% vs 4.6±1.7%, p<0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn and smoke injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of ALI patients who have sustained oxidative damage to the airway. PMID:22266978

  16. Identification of Small Molecules against Botulinum Neurotoxin B Binding to Neuronal Cells at Ganglioside GT1b Binding Site with Low to Moderate Affinity

    DTIC Science & Technology

    2014-10-01

    BoNT serotype B (BoNT/B) for the trisaccharide GT1b were identified from the x-ray crystal structure of the BoNT/B/trisaccharide (GT1b) complex ( PDB ...trisaccharide and all the water from the structure and identified four potential binding pockets (Pocket-1, Pocket-2, and Pocket-4) as shown in...four potential binding sites or pockets on BoNT serotype B (BoNT/B) for the trisaccharide GT1b were identified from the x-ray crystal structure of the

  17. Relationship of Rice Grain Amylose, Gelatinization Temperature and Pasting Properties for Breeding Better Eating and Cooking Quality of Rice Varieties

    PubMed Central

    Wang, Xiaoqian; Franje, Neil Johann; Revilleza, Jastin Edrian; Xu, Jianlong; Li, Zhikang

    2016-01-01

    A total of 787 non-waxy rice lines– 116 hybrids and 671 inbreds–were used to study the apparent amylose content (AAC), gelatinization temperature (GT), and rapid visco analyzer (RVA) pasting viscosity properties of rice starch to understand their importance in breeding better rice varieties. The investigated traits showed a wide range of diversity for both hybrid (HG) and inbred (IG) groups. The combinations of the different categories of AAC and GT were random in HG but were non-random in IG. For inbred lines, the high level of AAC tended to combine with the low level of GT, the intermediate level of AAC tended to have high or intermediate GT, and the low level of AAC tended to have high or low GT. Some stable correlations of the AAC, GT, and RVA properties may be the results derived from the physicochemical relationships among these traits, which rice breeders could utilize for selection in advanced breeding generations. Through cluster analysis, IG and HG were divided into 52 and 31 sub-clusters, respectively. Identifying the cultivars having AAC, GT, and RVA properties similar to that of popular high-quality rice varieties seems to be an interesting strategy and could be directly used for adaptation trials to breed high-quality rice varieties in targeted areas in a more customized manner. PMID:27992591

  18. Selective propagation of mouse-passaged scrapie prions with long incubation period from a mixed prion population using GT1-7 cells

    PubMed Central

    Masujin, Kentaro; Okada, Hiroyuki; Ushiki-Kaku, Yuko; Matsuura, Yuichi; Yokoyama, Takashi

    2017-01-01

    In our previous study, we demonstrated the propagation of mouse-passaged scrapie isolates with long incubation periods (L-type) derived from natural Japanese sheep scrapie cases in murine hypothalamic GT1-7 cells, along with disease-associated prion protein (PrPSc) accumulation. We here analyzed the susceptibility of GT1-7 cells to scrapie prions by exposure to infected mouse brains at different passages, following interspecies transmission. Wild-type mice challenged with a natural sheep scrapie case (Kanagawa) exhibited heterogeneity of transmitted scrapie prions in early passages, and this mixed population converged upon one with a short incubation period (S-type) following subsequent passages. However, when GT1-7 cells were challenged with these heterologous samples, L-type prions became dominant. This study demonstrated that the susceptibility of GT1-7 cells to L-type prions was at least 105 times higher than that to S-type prions and that L-type prion-specific biological characteristics remained unchanged after serial passages in GT1-7 cells. This suggests that a GT1-7 cell culture model would be more useful for the economical and stable amplification of L-type prions at the laboratory level. Furthermore, this cell culture model might be used to selectively propagate L-type scrapie prions from a mixed prion population. PMID:28636656

  19. Effects of green tea and bisphosphonate association on dental socket repair of rats.

    PubMed

    Mada, Edson Yoshihiro; Santos, Alana Claro Cunha; Fonseca, Angelica Cristina; Biguetti, Claudia Cristina; Neves, Fernando Tozze Alves; Saraiva, Patrícia Pinto; Matsumoto, Mariza Akemi

    2017-03-01

    To evaluate the effects of green tea intake and zoledronic acid intravenous therapy on teeth socket repair. Sixty male albinus Wistar rats were divided into 4 groups: C-Control, intravenous (IV) 0.9% saline solution (SS), GT-1% green tea in drinking water and IV SS, BP-IV zoledronic acid (BP), and BP+GT-IV BP and 1% green tea. 0.035mg/kg of BP was administered every two weeks. After ten weeks, right upper molars were extracted and the green tea started to be offered for GT and BP+GT. After 7, 14, and 28days the animals were euthanized. Histopathology analysis revealed lack of socket repair in BP and BP+GT groups, which presented significant increased number of polimorphonuclear leukocytes at day 28, in comparison with C (p<0.05). No significant differences were detected between C and the experimental groups at the same period (p<0.05) when considering mononuclear leukocytes. Immunolabeling revealed that the association of BP and GT caused a slight disturbance in OPG/RANKL system and retarded Runx-2 labeling. Although strong TRAP labeling was observed, most of the positive cells in BP and BP+GT groups were not located on bone surface. Socket healing of rats treated with BP and regular drinking green tea presented no relevant differences in comparison to those treated with BP alone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Selective propagation of mouse-passaged scrapie prions with long incubation period from a mixed prion population using GT1-7 cells.

    PubMed

    Miyazawa, Kohtaro; Masujin, Kentaro; Okada, Hiroyuki; Ushiki-Kaku, Yuko; Matsuura, Yuichi; Yokoyama, Takashi

    2017-01-01

    In our previous study, we demonstrated the propagation of mouse-passaged scrapie isolates with long incubation periods (L-type) derived from natural Japanese sheep scrapie cases in murine hypothalamic GT1-7 cells, along with disease-associated prion protein (PrPSc) accumulation. We here analyzed the susceptibility of GT1-7 cells to scrapie prions by exposure to infected mouse brains at different passages, following interspecies transmission. Wild-type mice challenged with a natural sheep scrapie case (Kanagawa) exhibited heterogeneity of transmitted scrapie prions in early passages, and this mixed population converged upon one with a short incubation period (S-type) following subsequent passages. However, when GT1-7 cells were challenged with these heterologous samples, L-type prions became dominant. This study demonstrated that the susceptibility of GT1-7 cells to L-type prions was at least 105 times higher than that to S-type prions and that L-type prion-specific biological characteristics remained unchanged after serial passages in GT1-7 cells. This suggests that a GT1-7 cell culture model would be more useful for the economical and stable amplification of L-type prions at the laboratory level. Furthermore, this cell culture model might be used to selectively propagate L-type scrapie prions from a mixed prion population.

  1. Genetically Modified Flax Expressing NAP-SsGT1 Transgene: Examination of Anti-Inflammatory Action

    PubMed Central

    Matusiewicz, Magdalena; Kosieradzka, Iwona; Zuk, Magdalena; Szopa, Jan

    2014-01-01

    The aim of the work was to define the influence of dietary supplementation with GM (genetically modified) GT#4 flaxseed cake enriched in polyphenols on inflammation development in mice liver. Mice were given ad libitum isoprotein diets: (1) standard diet; (2) high-fat diet rich in lard, high-fat diet enriched with 30% of (3) isogenic flax Linola seed cake; and (4) GM GT#4 flaxseed cake; for 96 days. Administration of transgenic and isogenic seed cake lowered body weight gain, of transgenic to the standard diet level. Serum total antioxidant status was statistically significantly improved in GT#4 flaxseed cake group and did not differ from Linola. Serum thiobarbituric acid reactive substances, lipid profile and the liver concentration of pro-inflammatory cytokine tumor necrosis factor-α were ameliorated by GM and isogenic flaxseed cake consumption. The level of pro-inflammatory cytokine interferon-γ did not differ between mice obtaining GM GT#4 and non-GM flaxseed cakes. The C-reactive protein concentration was reduced in animals fed GT#4 flaxseed cake and did not differ from those fed non-GM flaxseed cake-based diet. Similarly, the liver structure of mice consuming diets enriched in flaxseed cake was improved. Dietetic enrichment with GM GT#4 and non-GM flaxseed cakes may be a promising solution for health problems resulting from improper diet. PMID:25247574

  2. The National Research Center on the Gifted and Talented (NRC/GT) Newsletter, June 1991-Winter 1997.

    ERIC Educational Resources Information Center

    Gubbins, E. Jean, Ed.; Siegle, Del L., Ed.

    1997-01-01

    These 15 newsletters from the National Research Center on the Gifted and Talented (NRC/GT) contain the following articles: (1) "National Research Needs Assessment Process" (Brian D. Reid); (2) "NRC/GT: Update of Year 2 Activities" (E. Jean Gubbins); (3) "Parents: Their Impact on Gifted Adolescents" (Julie L. Sherman);…

  3. The National Research Center on the Gifted and Talented (NRC/GT) Newsletter, 1998.

    ERIC Educational Resources Information Center

    Gubbins, E. Jean, Ed.; Siegle, Del, Ed.

    1998-01-01

    These two newsletters of The National Research Center on the Gifted and Talented (NRC/GT) present articles concerned with research on the education of gifted and talented students. The articles are: "NRC/GT's Suggestions: Evaluating Your Programs and Services" (E. Jean Gubbins); "Professional Development Practices in Gifted Education: Results of a…

  4. Global carbon budget 2013

    NASA Astrophysics Data System (ADS)

    Le Quéré, C.; Peters, G. P.; Andres, R. J.; Andrew, R. M.; Boden, T.; Ciais, P.; Friedlingstein, P.; Houghton, R. A.; Marland, G.; Moriarty, R.; Sitch, S.; Tans, P.; Arneth, A.; Arvanitis, A.; Bakker, D. C. E.; Bopp, L.; Canadell, J. G.; Chini, L. P.; Doney, S. C.; Harper, A.; Harris, I.; House, J. I.; Jain, A. K.; Jones, S. D.; Kato, E.; Keeling, R. F.; Klein Goldewijk, K.; Körtzinger, A.; Koven, C.; Lefèvre, N.; Omar, A.; Ono, T.; Park, G.-H.; Pfeil, B.; Poulter, B.; Raupach, M. R.; Regnier, P.; Rödenbeck, C.; Saito, S.; Schwinger, J.; Segschneider, J.; Stocker, B. D.; Tilbrook, B.; van Heuven, S.; Viovy, N.; Wanninkhof, R.; Wiltshire, A.; Zaehle, S.; Yue, C.

    2013-11-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe datasets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil-fuel combustion and cement production (EFF) are based on energy statistics, while emissions from Land-Use Change (ELUC), including deforestation, are based on combined evidence from land-cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated for the first time in this budget with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of Dynamic Global Vegetation Models. All uncertainties are reported as ± 1 sigma, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2003-2012), EFF was 8.6 ± 0.4 GtC yr-1, ELUC 0.8 ± 0.5 GtC yr-1, GATM 4.3 ± 0.1 GtC yr-1, SOCEAN 2.6 ± 0.5 GtC yr-1, and SLAND 2.6 ± 0.8 GtC yr-1. For year 2012 alone, EFF grew to 9.7 ± 0.5 GtC yr-1, 2.2% above 2011, reflecting a continued trend in these emissions; GATM was 5.2 ± 0.2 GtC yr-1, SOCEAN was 2.9 ± 0.5 GtC yr-1, and assuming and ELUC of 0.9 ± 0.5 GtC yr-1 (based on 2001-2010 average), SLAND was 2.5 ± 0.9 GtC yr-1. GATM was high in 2012 compared to the 2003-2012 average, almost entirely reflecting the high EFF. The global atmospheric CO2 concentration reached 392.52 ± 0.10 ppm on average over 2012. We estimate that EFF will increase by 2.1% (1.1-3.1%) to 9.9 ± 0.5 GtC in 2013, 61% above emissions in 1990, based on projections of World Gross Domestic Product and recent changes in the carbon intensity of the economy. With this projection, cumulative emissions of CO2 will reach about 550 ± 60 GtC for 1870-2013, 70% from EFF (390 ± 20 GtC) and 30% from ELUC (160 ± 55 GtC). This paper is intended to provide a baseline to keep track of annual carbon budgets in the future. All data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (10.3334/CDIAC/GCP_2013_v1.1).

  5. Gamma-glutamyltransferase and disability pension: a cohort study of construction workers in Germany.

    PubMed

    Claessen, Heiner; Brenner, Hermann; Drath, Christoph; Arndt, Volker

    2010-02-01

    Given the accumulating evidence that gamma-glutamyltransferase (gamma-GT) is not merely a sensitive marker for liver and bile disorders but also a risk marker for a multiplicity of other chronic diseases, gamma-GT may represent a promising risk indicator for occupational disability, which has emerged as an important public health problem. The association between gamma-GT and disability pension was examined in a cohort of 16,520 male construction workers in Württemberg, Germany, who participated in routine occupational health examinations from 1986 to 1992 and who were followed until 2005. Using the Cox proportional hazards model, hazard ratios were calculated with gamma-GT concentrations in the lowest quartile (1 to 24 U/L) as reference category after adjustment for age and further adjustment for potential confounding factors such as nationality, type of occupation, smoking, alcohol consumption, cholesterol, and body mass index (BMI). Overall, a monotonically increasing association of gamma-GT with all-cause disability pension (total number: n = 2,998 cases) was observed, with the steepest increase at lower levels of gamma-GT. Particularly strong associations were observed for participants in the highest quartile (>67 U/L) and disability pension due to musculoskeletal disorders, diseases of the digestive system, and cardiovascular as well as mental diseases (age-adjusted hazard ratios with 95% confidence intervals: 1.53, 1.27-1.85; 9.68, 3.10-30.21; 1.76, 1.28-2.42; and 1.83, 1.23-2.72, respectively). gamma-GT is a strong risk indicator of all-cause occupational disability even at levels of gamma-GT in the "normal range" and is in particular associated with disability pension due to diseases of the digestive system, musculoskeletal disorders, cardiovascular, and mental diseases.

  6. Parental Perceptions of Quality of Life in Children on Long-Term Ventilation at Home as Compared to Enterostomy Tubes.

    PubMed

    Redouane, Brahim; Cohen, Eyal; Stephens, Derek; Keilty, Krista; Mouzaki, Marialena; Narayanan, Unni; Moraes, Theo; Amin, Reshma

    2016-01-01

    Health related quality of life (HRQL) of children using medical technology at home is largely unknown. Our aim was to examine the HRQL in children on long-term ventilation at home (LTHV) in comparison to a cohort using an enterostomy tube. Participants were divided into three groups: 1) LTHV without an enterostomy tube (LTHV cohort); 2) Enterostomy tube (GT cohort); 3) LTHV with an enterostomy tube (LTHV+GT cohort). Caregivers of children ≥ 5 years and followed at SickKids, Toronto, Canada, completed three questionnaires: Health Utilities Index 2/3 (HUI2/3), Caregiver Priorities Caregiver Health Index (CPCHILD), and the Paediatric Quality of Life Inventory (PedsQL). The primary outcome was the difference in utility (HUI2/3) scores between the cohorts. One hundred and nineteen children were enrolled; 47 in the LTHV cohort, 44 in the GT cohort, and 28 in the LTHV+GT cohort. In univariate analysis, HUI2 mean (SE) scores were lowest for the GT cohort, 0.4 (0.04) followed by the LTHV+GT, 0.42 (0.05) and then the LTHV cohort, 0.7 (0.04), p = 0.001. A similar trend was seen for the HUI3 mean (SE) scores: GT cohort, 0.1 (0.06), followed by the LTHV +GT cohort, 0.2 (0.08) and then the LTHV cohort, 0.5 (0.06), p = 0.0001. Technology cohort, nursing hours and the severity of health care needs predicted HRQL as measured by the HUI2/3. The HRQL of these children is low. Children on LTHV had higher HRQL than children using enterostomy tubes. Further work is needed to identify modifiable factors that can improve HRQL.

  7. Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis.

    PubMed

    Kobayashi, Tetsuo; Ishida, Kohei; Yoshie, Hiromasa

    2016-09-01

    DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP). DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay. The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03). The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Replacement of Dislodged Gastrostomy Tubes After Stoma Dilation in the Pediatric Emergency Department.

    PubMed

    Bhambani, Shiloni; Phan, Tammy H; Brown, Lance; Thorp, Andrea W

    2017-06-01

    A dislodged gastrostomy tube (GT) is a common complaint that requires evaluation in the pediatric emergency department (ED) and, on occasion, will require stoma dilation to successfully replace the GT. The objective of this study was to describe the frequency that stoma dilation is required, the success rate of replacement, complications encountered, and the techniques used to confirm placement of the GT after dilation. We conducted a retrospective medical record review of children 0-18 years who presented to the pediatric ED from February 2013 through February 2015 with a dislodged GT that required stoma dilation by pediatric emergency physicians with serially increasing Foley catheter sizes prior to successful placement of the GT. We reviewed a total of 302 encounters in 215 patients, with 97 (32%) of the encounters requiring stoma dilation prior to replacing a GT. The median amount of dilation was 2 French between the initial Foley catheter size and the final GT size. There was a single complication of a mal-positioned balloon that was identified at the index visit. No delayed complications were encountered. We performed confirmation of placement in all patients. The two most common forms of confirmation were aspiration of gastric contents (56/97 [58%]) followed by contrast radiograph in 39 (40%). The practice of serial dilation of a gastrostomy stoma site to allow successful replacement of a gastrostomy tube in pediatric patients who present to the ED with a dislodged gastrostomy tube is generally successful and without increased complication. All patients received at least one form of confirmation for appropriate GT placement with the most common being aspiration of gastric contents.

  9. Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis

    PubMed Central

    Henning, Susanne M.; Wang, Piwen; Said, Jonathan; Magyar, Clara; Castor, Brandon; Doan, Ngan; Tosity, Carmen; Moro, Aune; Gao, Kun; Li, Luyi; Heber, David

    2011-01-01

    It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis, and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi (GSTp1) to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 (DNMT1) mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice. PMID:22405694

  10. A novel Tetra-primer ARMS-PCR based assay for genotyping SNP rs12303764(G/T) of human Unc-51 like kinase 1 gene.

    PubMed

    Randhawa, Rohit; Duseja, Ajay; Changotra, Harish

    2017-02-01

    Various case-control studies have shown association of single nucleotide polymorphism rs12303764(G/T) in ULK1 with crohn's disease. The techniques used in these studies were time consuming, complicated and require sophisticated/expensive instruments. Therefore, in order to overcome these problems, we have developed a new, rapid and cost effective Tetra-primer ARMS-PCR assay to genotype single nucleotide polymorphism rs12303764(G/T) of ULK1 gene. We manually designed allele specific primers. DNA fragment amplified using outer primers was sequenced to obtain samples with known genotypes (GG, GT and TT) for further use in the development of T-ARMS-PCR assay. Amplification conditions were optimized for parameters; annealing temperature, Taq DNA polymerase and primers. The developed T-ARMS-PCR assay was applied to genotype one hundred samples from healthy individuals. Genotyping results of 10 DNA samples from healthy individuals for rs12303764(G/T) by T-ARMS-PCR assay and sequencing were concordant. The newly developed assay was further applied to genotype samples from 100 healthy individuals of North Indian origin. Genotype frequencies were 9, 34 and 57 % for GG, GT and TT, respectively. Allele frequencies were 0.26 and 0.74 for G and T, respectively. The allele frequencies were in Hardy-Weinberg's equilibrium (p = 0.2443). T-ARMS-PCR assay developed in our laboratory for genotyping rs12303764 (G/T) of ULK1 gene is time saving and cost-effective as compared to the available methods. Furthermore, this is the first study reporting allelic and genotype frequencies of ULK1 rs12303764 (G/T) variants in North Indian population.

  11. Influence of adiponectin gene polymorphism SNP276 (G/T) on adiponectin in response to exercise training.

    PubMed

    Huang, Hu; Tada Iida, Kaoruko; Murakami, Haruka; Saito, Yoko; Otsuki, Takeshi; Iemitsu, Motoyuki; Maeda, Seiji; Sone, Hirohito; Kuno, Shinya; Ajisaka, Ryuichi

    2007-12-01

    Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P<0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P<0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p<0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.

  12. Comparative Analysis of the Wako β-Glucan Test and the Fungitell® Assay for the Diagnosis of Candidemia and Pneumocystis jirovecii Pneumonia.

    PubMed

    Friedrich, Ricarda; Rappold, Elfriede; Bogdan, Christian; Held, Jürgen

    2018-06-13

    Background (1→3)-β-D-glucan (BDG) is a biomarker for invasive fungal disease. Until now, all BDG-data in the western hemisphere were obtained using the Fungitell® assay (FA). How it compares to the Wako β-Glucan Test (GT), that was recently launched in Europe, is largely unknown. Methods We conducted a case-control study to compare both assays in serum samples of 120 candidemia and 63 Pneumocystis jirovecii pneumonia (PCP) patients. 200 patients with bacteremia or negative blood cultures served as candidemia control group. Results In patients with candidemia the median BDG values of the FA and the GT were 351 and 8.4 pg/ml, respectively. With both assays, the BDG levels in candidemia were significantly higher than those measured in the control group (p<0.001). The sensitivity, specificity, positive and negative predictive values for the diagnosis of candidemia were 86.7%, 85.0%, 6.0% and 99.8% for the FA and 42.5%, 98.0%, 19.0% and 99.4% for the GT, respectively.In PCP patients the median BDG values of the FA and the GT were 963 and 57.7 pg/ml, respectively. The sensitivity for PCP diagnosis was 100% for the FA and 88.9% for the GT. In practical terms, the GT proved to be robust and applicable for testing single samples, whereas for economic reasons the FA required the samples to be tested in batch. Conclusions The sensitivity of the FA is superior to that of the GT. However, the GT is a valuable alternative to the FA especially in patients with suspected PCP and in laboratories with low sample throughput. Copyright © 2018 American Society for Microbiology.

  13. Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

    PubMed

    Eltahla, A A; Rodrigo, C; Betz-Stablein, B; Grebely, J; Applegate, T; Luciani, F; Schinkel, J; Dore, G J; Page, K; Bruneau, J; Morris, M D; Cox, A L; Kim, A Y; Shoukry, N H; Lauer, G M; Maher, L; Hellard, M; Prins, M; Lloyd, A R; Bull, R A

    2017-01-01

    Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. © 2016 John Wiley & Sons Ltd.

  14. Methane hydrate - A major reservoir of carbon in the shallow geosphere?

    USGS Publications Warehouse

    Kvenvolden, K.A.

    1988-01-01

    Methane hydrates are solids composed of rigid cages of water molecules that enclose methane. Sediment containing methane hydrates is found within specific pressure-temperature conditions that occur in regions of permafrost and beneath the sea in outer continental margins. Because methane hydrates are globally widespread and concentrate methane within the gas-hydrate structure, the potential amount of methane present in the shallow geosphere at subsurface depths of < ???2000 m is very large. However, estimates of the amount are speculative and range over about three orders of magnitude, from 2 ?? 103 to 4 ?? 106 Gt (gigatons = 1015 g) of carbon, depending on the assumptions made. The estimate I favor is ??? 1 ?? 104 Gt of carbon. The estimated amount of organic carbon in the methane-hydrate reservoir greatly exceeds that in many other reservoirs of the global carbon cycle - for example, the atmosphere (3.6 Gt); terrestrial biota (830 Gt); terrestrial soil, detritus and peat (1960 Gt); marine biota (3 Gt); and marine dissolved materials (980 Gt). In fact, the amount of carbon may exceed that in all fossil fuel deposits (5 ?? 103 Gt). Because methane hydrates contain so much methane and occur in the shallow geosphere, they are of interest as a potential resource of natural gas and as a possible source of atmospheric methane released by global warming. As a potential resource, methane hydrates pose both engineering and production problems. As a contributor to a changing global climate, destabilized methane hydrates, particularly those in shallow, nearshore regions of the Arctic Ocean, may have some effect, but this effect will probably be minimal, at least during the next 100 years. ?? 1988.

  15. Heavy Metal Resistances and Chromium Removal of a Novel Cr(VI)-Reducing Pseudomonad Strain Isolated from Circulating Cooling Water of Iron and Steel Plant.

    PubMed

    Zhang, Jian-Kun; Wang, Zhen-Hua; Ye, Yun

    2016-12-01

    Three bacterial isolates, GT2, GT3, and GT7, were isolated from the sludge and water of a circulating cooling system of iron and steel plant by screening on Cr(VI)-containing plates. Three isolates were characterized as the members of the genus Pseudomonas on the basis of phenotypic characteristics and 16S rRNA sequence analysis. All isolates were capable of resisting multiple antibiotics and heavy metals. GT7 was most resistant to Cr(VI), with a minimum inhibitory concentration (MIC) of 6.5 mmol L -1 . GT7 displayed varied rates of Cr(VI) reduction in M2 broth, which was dependent on pH, initial Cr(VI) concentration, and inoculating dose. Total chromium analysis revealed that GT7 could remove a part of chromium from the media, and the maximum rate of chromium removal was up to 40.8 %. The Cr(VI) reductase activity of GT7 was mainly associated with the soluble fraction of cell-free extracts and reached optimum at pH 6.0∼8.0. The reductase activity was apparently enhanced by external electron donors and Cu(II), whereas it was seriously inhibited by Hg(II), Cd(II), and Zn(II). The reductase showed a K m of 74 μmol L -1 of Cr(VI) and a V max of 0.86 μmol of Cr(VI) min -1  mg -1 of protein. The results suggested that GT7 could be a promising candidate for in situ bioremediation of Cr(VI).

  16. Persistent Genital Tract HIV-1 RNA Shedding After Change in Treatment Regimens in Antiretroviral-Experienced Women with Detectable Plasma Viral Load

    PubMed Central

    DeLong, Allison K.; Kantor, Rami; Chapman, Stacey; Ingersoll, Jessica; Kurpewski, Jaclynn; De Pasquale, Maria Pia; D'Aquila, Richard; Caliendo, Angela M.; Cu-Uvin, Susan

    2013-01-01

    Abstract Objective To longitudinally assess the association between plasma viral load (PVL) and genital tract human immunodeficiency virus (GT HIV) RNA among HIV-1 infected women changing highly active antiretroviral therapy (HAART) because of detectable PVL on current treatment. Methods Women were eligible for the study if they had detectable PVL (defined as two consecutive samples with PVL>1000 copies/mL) and intended to change their current HAART regimen at the time of enrollment. Paired plasma and GT HIV-1 RNA were measured prospectively over 3 years. Longitudinal analyses examined rates of GT HIV-1 RNA shedding and the association with PVL. Results Sixteen women were followed for a median of 11 visits contributing a total of 205 study visits. At study enrollment, all had detectable PVL and 69% had detectable GT HIV-1 RNA. Half of the women changed to a new HAART regimen with ≥3 active antiretroviral drugs. The probability of having detectable PVL ≥30 days after changing HAART was 0.56 (95% CI: 0.37 to 0.74). Fourteen women (88%) had detectable PVL on a follow-up visit ≥30 or 60 days after changing HAART; and 12 women (75%) had detectable GT HIV-1 RNA on a follow-up visit ≥30 or 60 days after changing HAART. When PVL was undetectable, GT shedding occurred at 11% of visits, and when PVL was detectable, GT shedding occurred at 47% of visits. Conclusions Some treatment-experienced HIV-infected women continue to have detectable virus in both the plasma and GT following a change in HAART, highlighting the difficulty of viral suppression in this patient population. PMID:23531097

  17. Photoregeneration of bovine rhodopsin from its signaling state.

    PubMed

    Arnis, S; Hofmann, K P

    1995-07-25

    In rhodopsin, 11-cis-retinal is bound by a protonated Schiff base and acts as a strong antagonist, which holds the receptor in its inactive ground state conformation. Light induces cis-/trans-retinal isomerization and a sequence of thermal transitions through intermediates. The active conformation that catalyzes GDP/GTP exchange in the G-protein (Gt) is generated from the metarhodopsin II intermediate (MII) and mediated by Schiff base proton translocation and proton uptake from the aqueous phase. In the stable nucleotide-free MII-Gt complex, any thermal transition of MII into other forms of rhodopsin is blocked. We have now studied how Gt affects flash-induced photochemical conversions of MII. Difference spectra from measured absorption changes show that MII photolyzes through two parallel pathways, with fast (1 ms) and slow (50 ms) kinetics (12 degrees C, pH 6). The slow pathway regenerates rhodopsin (9- or 11-cis) via Schiff base reprotonation and proton release. We infer a cis-isomerized early photoproduct (reverted meta, RM) preceding these thermal transitions. When MII is photolyzed in the MII-Gt complex, the slow absorption change is abolished, indicating that Gt blocks the completion of the regeneration process. This is due to the formation of a stable RM-Gt complex, as shown by successive photolysis of MII, RM, and ground state rhodopsin, and the application of GTP gamma S at different stages. The complex dissociates with GTP gamma S, and rhodopsin relaxes to the ground state. The results indicate that cis-retinal and Gt can bind to the receptor at the same time. We discuss the result that the protonations in the meta II state uncouple retinal geometry from Gt interaction.

  18. A Lytic Polysaccharide Monooxygenase with Broad Xyloglucan Specificity from the Brown-Rot Fungus Gloeophyllum trabeum and Its Action on Cellulose-Xyloglucan Complexes.

    PubMed

    Kojima, Yuka; Várnai, Anikó; Ishida, Takuya; Sunagawa, Naoki; Petrovic, Dejan M; Igarashi, Kiyohiko; Jellison, Jody; Goodell, Barry; Alfredsen, Gry; Westereng, Bjørge; Eijsink, Vincent G H; Yoshida, Makoto

    2016-11-15

    Fungi secrete a set of glycoside hydrolases and lytic polysaccharide monooxygenases (LPMOs) to degrade plant polysaccharides. Brown-rot fungi, such as Gloeophyllum trabeum, tend to have few LPMOs, and information on these enzymes is scarce. The genome of G. trabeum encodes four auxiliary activity 9 (AA9) LPMOs (GtLPMO9s), whose coding sequences were amplified from cDNA. Due to alternative splicing, two variants of GtLPMO9A seem to be produced, a single-domain variant, GtLPMO9A-1, and a longer variant, GtLPMO9A-2, which contains a C-terminal domain comprising approximately 55 residues without a predicted function. We have overexpressed the phylogenetically distinct GtLPMO9A-2 in Pichia pastoris and investigated its properties. Standard analyses using high-performance anion-exchange chromatography-pulsed amperometric detection (HPAEC-PAD) and mass spectrometry (MS) showed that GtLPMO9A-2 is active on cellulose, carboxymethyl cellulose, and xyloglucan. Importantly, compared to other known xyloglucan-active LPMOs, GtLPMO9A-2 has broad specificity, cleaving at any position along the β-glucan backbone of xyloglucan, regardless of substitutions. Using dynamic viscosity measurements to compare the hemicellulolytic action of GtLPMO9A-2 to that of a well-characterized hemicellulolytic LPMO, NcLPMO9C from Neurospora crassa revealed that GtLPMO9A-2 is more efficient in depolymerizing xyloglucan. These measurements also revealed minor activity on glucomannan that could not be detected by the analysis of soluble products by HPAEC-PAD and MS and that was lower than the activity of NcLPMO9C. Experiments with copolymeric substrates showed an inhibitory effect of hemicellulose coating on cellulolytic LPMO activity and did not reveal additional activities of GtLPMO9A-2. These results provide insight into the LPMO potential of G. trabeum and provide a novel sensitive method, a measurement of dynamic viscosity, for monitoring LPMO activity. Currently, there are only a few methods available to analyze end products of lytic polysaccharide monooxygenase (LPMO) activity, the most common ones being liquid chromatography and mass spectrometry. Here, we present an alternative and sensitive method based on measurement of dynamic viscosity for real-time continuous monitoring of LPMO activity in the presence of water-soluble hemicelluloses, such as xyloglucan. We have used both these novel and existing analytical methods to characterize a xyloglucan-active LPMO from a brown-rot fungus. This enzyme, GtLPMO9A-2, differs from previously characterized LPMOs in having broad substrate specificity, enabling almost random cleavage of the xyloglucan backbone. GtLPMO9A-2 acts preferentially on free xyloglucan, suggesting a preference for xyloglucan chains that tether cellulose fibers together. The xyloglucan-degrading potential of GtLPMO9A-2 suggests a role in decreasing wood strength at the initial stage of brown rot through degradation of the primary cell wall. Copyright © 2016 Kojima et al.

  19. Staying theoretically sensitive when conducting grounded theory research.

    PubMed

    Reay, Gudrun; Bouchal, Shelley Raffin; A Rankin, James

    2016-09-01

    Background Grounded theory (GT) is founded on the premise that underlying social patterns can be discovered and conceptualised into theories. The method and need for theoretical sensitivity are best understood in the historical context in which GT was developed. Theoretical sensitivity entails entering the field with no preconceptions, so as to remain open to the data and the emerging theory. Investigators also read literature from other fields to understand various ways to construct theories. Aim To explore the concept of theoretical sensitivity from a classical GT perspective, and discuss the ontological and epistemological foundations of GT. Discussion Difficulties in remaining theoretically sensitive throughout research are discussed and illustrated with examples. Emergence - the idea that theory and substance will emerge from the process of comparing data - and staying open to the data are emphasised. Conclusion Understanding theoretical sensitivity as an underlying guiding principle of GT helps the researcher make sense of important concepts, such as delaying the literature review, emergence and the constant comparative method (simultaneous collection, coding and analysis of data). Implications for practice Theoretical sensitivity and adherence to the GT research method allow researchers to discover theories that can bridge the gap between theory and practice.

  20. Multi-level storage and ultra-high speed of superlattice-like Ge50Te50/Ge8Sb92 thin film for phase-change memory application.

    PubMed

    Wu, Weihua; Chen, Shiyu; Zhai, Jiwei; Liu, Xinyi; Lai, Tianshu; Song, Sannian; Song, Zhitang

    2017-10-06

    Superlattice-like Ge 50 Te 50 /Ge 8 Sb 92 (SLL GT/GS) thin film was systematically investigated for multi-level storage and ultra-fast switching phase-change memory application. In situ resistance measurement indicates that SLL GT/GS thin film exhibits two distinct resistance steps with elevated temperature. The thermal stability of the amorphous state and intermediate state were evaluated with the Kissinger and Arrhenius plots. The phase-structure evolution revealed that the amorphous SLL GT/GS thin film crystallized into rhombohedral Sb phase first, then the rhombohedral GeTe phase. The microstructure, layered structure, and interface stability of SLL GT/GS thin film was confirmed by using transmission electron microscopy. The transition speed of crystallization and amorphization was measured by the picosecond laser pump-probe system. The volume variation during the crystallization was obtained from x-ray reflectivity. Phase-change memory (PCM) cells based on SLL GT/GS thin film were fabricated to verify the multi-level switching under an electrical pulse as short as 30 ns. These results illustrate that the SLL GT/GS thin film has great potentiality in high-density and high-speed PCM applications.

  1. Enzymatic modification of corn starch with 4-α-glucanotransferase results in increasing slow digestible and resistant starch.

    PubMed

    Jiang, Huan; Miao, Ming; Ye, Fan; Jiang, Bo; Zhang, Tao

    2014-04-01

    In this study, partial 4-α-glucanotransferase (4αGT) treatment was used to modulate the fine structure responsible for the slow digestion and resistant property of starch. Normal corn starch modified using 4αGT for 4h showed an increase of slowly digestible starch from 9.40% to 20.92%, and resistant starch from 10.52 to 17.63%, respectively. The 4αGT treatment decreased the content of amylose from 32.6% to 26.8%. The molecular weight distribution and chain length distribution of 4αGT-treated starch showed a reduction of molecular weight and a great number of short (DP<13) and long (DP>30) chains through cleaving and reorganization of starch molecules. Both the short and long chain fractions of modified amylopectin were attributed to the low in vitro digestibility. The viscosity was inversely related to the digestibility of the 4αGT-treated starch. These results suggested that the 4αGT modified starch synthesized the novel amylopectin clusters with slow digestible and resistant character. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  2. Comparison of older adults' steps per day using NL-1000 pedometer and two GT3X+ accelerometer filters.

    PubMed

    Barreira, Tiago V; Brouillette, Robert M; Foil, Heather C; Keller, Jeffrey N; Tudor-Locke, Catrine

    2013-10-01

    The purpose of this study was to compare the steps/d derived from the ActiGraph GT3X+ using the manufacturer's default filter (DF) and low-frequency-extension filter (LFX) with those from the NL-1000 pedometer in an older adult sample. Fifteen older adults (61-82 yr) wore a GT3X+ (24 hr/day) and an NL-1000 (waking hours) for 7 d. Day was the unit of analysis (n = 86 valid days) comparing (a) GT3X+ DF and NL-1000 steps/d and (b) GT3X+ LFX and NL-1000 steps/d. DF was highly correlated with NL-1000 (r = .80), but there was a significant mean difference (-769 steps/d). LFX and NL-1000 were highly correlated (r = .90), but there also was a significant mean difference (8,140 steps/d). Percent difference and absolute percent difference between DF and NL-1000 were -7.4% and 16.0%, respectively, and for LFX and NL-1000 both were 121.9%. Regardless of filter used, GT3X+ did not provide comparable pedometer estimates of steps/d in this older adult sample.

  3. The modelled surface mass balance of the Antarctic Peninsula at 5.5 km horizontal resolution

    NASA Astrophysics Data System (ADS)

    van Wessem, J. M.; Ligtenberg, S. R. M.; Reijmer, C. H.; van de Berg, W. J.; van den Broeke, M. R.; Barrand, N. E.; Thomas, E. R.; Turner, J.; Wuite, J.; Scambos, T. A.; van Meijgaard, E.

    2015-09-01

    This study presents a high-resolution (~ 5.5 km) estimate of Surface Mass Balance (SMB) over the period 1979-2014 for the Antarctic Peninsula (AP), generated by the regional atmospheric climate model RACMO2.3 and a Firn Densification Model (FDM). RACMO2.3 is used to force the FDM, which calculates processes in the snowpack, such as meltwater percolation, refreezing and runoff. We evaluate model output with 132 in-situ SMB observations and discharge rates from 6 glacier drainage basins, and find that the model realistically simulates the strong spatial variability in precipitation, but that significant biases remain as a result of the highly complex topography of the AP. It is also clear that the observations significantly underrepresent the high-accumulation regimes. The SMB map reveals large accumulation gradients, with precipitation values above 3000 mm we yr-1 over the western AP (WAP) and below 500 mm we yr-1 on the eastern AP (EAP), not resolved by coarser data-sets such as ERA-Interim. The other SMB components are one order of magnitude smaller, with drifting snow sublimation the largest ablation term removing up to 100 mm we yr-1 of mass. Snowmelt is widespread over the AP, reaching 500 mm we yr-1 towards the northern ice shelves, but the meltwater mostly refreezes. As a result runoff fluxes are low, but still considerable (200 mm we yr-1) over the Larsen (B/C), Wilkins and George VI ice shelves. The average AP ice sheet integrated SMB, including ice shelves (an area of 4.1 × 105 km2), is estimated at 351 Gt yr-1 with an interannual variability of 58 Gt yr-1, which is dominated by precipitation (PR) (365 ± 57 Gt yr-1). The WAP (2.4 × 105 km2) SMB (276 ± 47 Gt yr-1), where PR is large (276 ± 47 Gt yr-1), dominates over the EAP (1.7 × 105 km2) SMB (75 ± 11 Gt yr-1) and PR (84 ± 11 Gt yr-1). Total sublimation is 11 ± 2 Gt yr-1 and meltwater runoff into the ocean is 4 ± 4 Gt yr-1. There are no significant trends in any of the AP SMB components, except for snowmelt that shows a significant decrease over the last 36 years (-0.36 Gt yr-2).

  4. Assessment of Antarctic Ice-Sheet Mass Balance Estimates: 1992 - 2009

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Giovinetto, Mario B.

    2011-01-01

    Published mass balance estimates for the Antarctic Ice Sheet (AIS) lie between approximately +50 to -250 Gt/year for 1992 to 2009, which span a range equivalent to 15% of the annual mass input and 0.8 mm/year Sea Level Equivalent (SLE). Two estimates from radar-altimeter measurements of elevation change by European Remote-sensing Satellites (ERS) (+28 and -31 Gt/year) lie in the upper part, whereas estimates from the Input-minus-Output Method (IOM) and the Gravity Recovery and Climate Experiment (GRACE) lie in the lower part (-40 to -246 Gt/year). We compare the various estimates, discuss the methodology used, and critically assess the results. Although recent reports of large and accelerating rates of mass loss from GRACE=based studies cite agreement with IOM results, our evaluation does not support that conclusion. We find that the extrapolation used in the published IOM estimates for the 15 % of the periphery for which discharge velocities are not observed gives twice the rate of discharge per unit of associated ice-sheet area than the 85% faster-moving parts. Our calculations show that the published extrapolation overestimates the ice discharge by 282 Gt/yr compared to our assumption that the slower moving areas have 70% as much discharge per area as the faster moving parts. Also, published data on the time-series of discharge velocities and accumulation/precipitation do not support mass output increases or input decreases with time, respectively. Our modified IOM estimate, using the 70% discharge assumption and substituting input from a field-data compilation for input from an atmospheric model over 6% of area, gives a loss of only 13 Gt/year (versus 136 Gt/year) for the period around 2000. Two ERS-based estimates, our modified IOM, and a GRACE-based estimate for observations within 1992 to 2005 lie in a narrowed range of +27 to - 40 Gt/year, which is about 3% of the annual mass input and only 0.2 mm/year SLE. Our preferred estimate for 1992-2001 is - 47 Gt/year for West Antarctica, + 16 Gt/year for East Antarctica, and -31 Gt/year overall (+0.1 mm/year SLE), not including part of the Antarctic Peninsula (1.07 % of the AIS area)

  5. Gait initiation and termination strategies in patients with Prader-Willi syndrome.

    PubMed

    Cimolin, Veronica; Cau, Nicola; Galli, Manuela; Santovito, Cristina; Grugni, Graziano; Capodaglio, Paolo

    2017-05-23

    Gait Initiation (GI) is a functional task representing one of the first voluntary destabilizing behaviours observed in the development of a locomotor pattern as the whole body centre of mass transitions from a large to a small base of support. Conversely, Gait Termination (GT) consists in the transition from walking to standing which, in everyday life, is a very common movement. Compared to normal walking, it requires higher control of postural stability. For a safe GT, the forward movement of the body has to be slowed down to achieve a stable upright position. Stability requirements have to be fulfilled for safe GT. In individuals with Prader-Willi syndrome (PWS), excessive body weight negatively affects the movement, such as walking and posture, but there are no experimental studies about GI and GT in these individuals. The aim of this study was to quantitatively characterise the strategy of patients with PWS during GI and GT using parameters obtained by the Center of Pressure (CoP) track. Twelve patients with PWS, 20 obese (OG) and 19 healthy individuals (HG) were tested using a force platform during the GI and GT tasks. CoP plots were divided into different phases, and duration, length and velocity of the CoP trace in these phases were calculated and compared for each task. As for GI, the results showed a significant reduction of the task duration and lower velocity and CoP length parameters in PWS, compared to OG and HG. In PWS, those parameters were reduced to a higher degree with respect to the OG. During GT, longer durations, similar to OG, were observed in PWS than HG. Velocity is reduced when compared to OG and HG, especially in medio-lateral direction and in the terminal part of GT. From these data, GI appears to be a demanding task in most of its sub-phases for PWS individuals, while GT seems to require caution only towards the end of the task. Breaking the cycle of gait into the phases of GI and GT and implementing specific exercises focusing on weight transfer and foot clearance during the transition phase from the steady condition to gait will possibly improve the effectiveness of rehabilitation and fall and injury prevention.

  6. Motion control in free-standing shape-memory actuators

    NASA Astrophysics Data System (ADS)

    Belmonte, Alberto; Lama, Giuseppe C.; Cerruti, Pierfrancesco; Ambrogi, Veronica; Fernández-Francos, Xavier; De la Flor, Silvia

    2018-07-01

    In this work, free-standing shape-memory thermally triggered actuators are developed by laminating ‘thiol-epoxy’-based glassy thermoset (GT) and stretched liquid-crystalline network (LCN) films. A sequential curing process was used to obtain GTs with tailored thermomechanical properties and network relaxation dynamics, and also to assemble the final actuator. The actuation extent, rate and time were studied by varying the GT and the heating rate in thermo-actuation with an experimental approach. The results demonstrate that it is possible to tailor the actuation rate and time by designing GT materials with a glass transition temperature close to that of the liquid-crystalline-to-isotropic phase transition of the LCN, thus making it possible to couple the two processes. Such coupling is also possible in rapid heating processes even when the glass transition temperature of the GT is clearly lower than the isotropization temperature of the LCN, depending on the network relaxation dynamics of the GT and the presence of thermal gradients within the actuators. Interestingly, varying the GT network relaxation dynamics does not affect the actuation extent. As predicted by the analytical model developed in our previous work, the modulus of the GT layer is mainly responsible for the actuation extent. Finally, to demonstrate the enhanced control of the actuation, specifically designed actuators were assembled in a three-dimensional actuating device able to make complex motions (including ‘S-type’ bending). This approach makes it possible to engineer advanced functional materials for application in self-adaptable structures and soft robotics.

  7. The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

    PubMed Central

    2017-01-01

    The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with S-substitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening. PMID:28910418

  8. Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients.

    PubMed

    Nelson, Mark; Rubio, Rafael; Lazzarin, Adriano; Romanova, Svetlana; Luetkemeyer, Annie; Conway, Brian; Molina, Jean-Michel; Xu, Dong; Srinivasan, Subasree; Portsmouth, Simon

    2017-03-01

    To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received response-guided therapy. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post-treatment week 12 (SVR12). In cohort A (n = 104), 84.6% achieved SVR12 (95.0% in GT-2; 83.1% in GT-3). In cohort B (n = 196), 76.0% achieved SVR12 (71.7% in GT-1a; 86.0% in GT-1b; 70.7% in GT-4). Rates of discontinuation due to adverse events (AEs) (3.8% and 6.1%) and serious AEs (5.8% and 6.1%) were low in cohorts A and B, respectively. In addition, treatment with Lambda/RBV/DCV had little impact on CD4 counts. SVR12 rates with Lambda/RBV/DCV in an HCV/HIV-coinfected population ranged from 71.7% to 95.0%. Treatment was generally well tolerated, with a low proportion of patients discontinuing due to AEs. Clinical trial registration NCT01866930.

  9. Analogous Gamow-Teller and M1 Transitions in Tz = ±½ Mirror Nuclei and in Tz = ±1, 0 Triplet Nuclei relevant to Low-energy Super GT state

    NASA Astrophysics Data System (ADS)

    Fujita, Yoshitaka; Fujita, Hirohiko; Tanumura, Yusuke

    2018-05-01

    Nuclei have spin- and isospin-degrees of freedom. Therefore, Gamow-Teller (GT) transitions caused by the στ operator (spin-isospin operator) are unique tools for the studies of nuclear structure as well as nuclear interactions. They can be studied in β decays as well as charge-exchange (CE) reactions. Similarly, M1 γ decays are mainly caused by the στ operator. Combined studies of these transitions caused by Weak, Strong, and Electro-Magnetic interactions provide us a deeper understanding of nuclear spin-isospin-type transitions. We first compare the strengths of analogous GT and M1 transitions in the A = 27, Tz = ±½ mirror nuclei 27Al and 27Si. The comparison is extended to the Tz = ±1, 0 nuclei. The strength of GT transition from the ground state (g.s.) of 42Ca to the 0.611 MeV first Jπ = 1+ state in 42Sc is compared with that of the analogous M1 transition from the 0.611 MeV state to the T = 1, 0+ g.s. (isobaric analog state: IAS) in 42Sc. The 0.611 MeV state has the property of Low-energy Super GT (LeSGT) state, because it carries the main part of the GT strength of all available transitions from the g.s. of 42Ca (and 42Ti) to the Jπ = 1+ GT states in 42Sc.

  10. A Guide for Starting and Improving Gifted and Talented High School Programs: Program Options, Teaching Strategies, Models, Forms and Examples.

    ERIC Educational Resources Information Center

    Idaho State Dept. of Education. Special Education Section.

    This manual is designed to help Idaho school districts establish or improve programs for gifted and talented (G/T) high school students. It describes specific program options and administrative issues relating to gifted education. Chapter 1, "Starting and Administering a G/T High School Program," answers common questions about G/T high…

  11. Reduction of Radiation-Induced Vascular Nitrosative Stress by the Vitamin E Analog {gamma}-Tocotrienol: Evidence of a Role for Tetrahydrobiopterin

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

    Berbee, Maaike; Fu Qiang; Boerma, Marjan

    2011-03-01

    Purpose: The vitamin E analog {gamma}-tocotrienol (GT3) is a powerful radioprotector. GT3 reduces postradiation vascular peroxynitrite production, an effect dependent on inhibition of hydroxy-methylglutaryl-coenzyme A reductase. Hydroxy-methylglutaryl-coenzyme A reductase inhibitors mediate their pleiotropic effects via endothelial nitric oxide synthase that requires the cofactor tetrahydrobiopterin (BH4). This study investigated the effects of radiation on BH4 bioavailability and of GT3 on BH4 metabolism. Methods and Materials: Mice were exposed to 8.5 Gy of total body irradiation (TBI). Lung BH4 and total biopterin concentrations were measured 0, 3.5, 7, 14, and 21 days after TBI by use of differential oxidation followed by high-performancemore » liquid chromatography. The effect of exogenous GT3 and BH4 treatment on postradiation vascular oxidative stress and bone marrow colony-forming units were assessed in vivo. The effect of GT3 on endothelial cell apoptosis and endothelial expression of guanosine triphosphate (GTP) cyclohydrolase 1 (GTPCH), GTPCH feedback regulatory protein (GFRP), GFRP transcription, GFRP protein levels, and GFRP-GTPCH protein binding was determined in vitro. Results: Compared with baseline levels, lung BH4 concentrations decreased by 24% at 3.5 days after TBI, an effect that was reversed by GT3. At 14 and 21 days after TBI, compensatory increases in BH4 (58% and 80%, respectively) were observed. Relative to vehicle-treated controls, both GT3 and BH4 supplementation reduced postirradiation vascular peroxynitrite production at 3.5 days (by 66% and 33%, respectively), and BH4 resulted in a 68% increase in bone marrow colony-forming units. GT3 ameliorated endothelial cell apoptosis and reduced endothelial GFRP protein levels and GFRP-GTPCH binding by decreasing transcription of the GFRP gene. Conclusions: BH4 bioavailability is reduced in the early postradiation phase. Exogenous administration of BH4 reduces postirradiation vascular oxidative stress. GT3 potently reduces the expression of GFRP, one of the key regulatory proteins in the BH4 pathway, and may thus exert some of its beneficial effects on postradiation free radical production partly by counteracting the decrease in BH4.« less

  12. GT-57633 catalogue of Martian impact craters developed for evaluation of crater detection algorithms

    NASA Astrophysics Data System (ADS)

    Salamunićcar, Goran; Lončarić, Sven

    2008-12-01

    Crater detection algorithms (CDAs) are an important subject of the recent scientific research. A ground truth (GT) catalogue, which contains the locations and sizes of known craters, is important for the evaluation of CDAs in a wide range of CDA applications. Unfortunately, previous catalogues of craters by other authors cannot be easily used as GT. In this paper, we propose a method for integration of several existing catalogues to obtain a new craters catalogue. The methods developed and used during this work on the GT catalogue are: (1) initial screening of used catalogues; (2) evaluation of self-consistency of used catalogues; (3) initial registration from three different catalogues; (4) cross-evaluation of used catalogues; (5) additional registrations and registrations from additional catalogues; and (6) fine-tuning and registration with additional data-sets. During this process, all craters from all major currently available manually assembled catalogues were processed, including catalogues by Barlow, Rodionova, Boyce, Kuzmin, and our previous work. Each crater from the GT catalogue contains references to crater(s) that are used for its registration. This provides direct access to all properties assigned to craters from the used catalogues, which can be of interest even to those scientists that are not directly interested in CDAs. Having all these craters in a single catalogue also provides a good starting point for searching for craters still not catalogued manually, which is also expected to be one of the challenges of CDAs. The resulting new GT catalogue contains 57,633 craters, significantly more than any previous catalogue. From this point of view, GT-57633 catalogue is currently the most complete catalogue of large Martian impact craters. Additionally, each crater from the resulting GT-57633 catalogue is aligned with MOLA topography and, during the final review phase, additionally registered/aligned with 1/256° THEMIS-DIR, 1/256° MDIM and 1/256° MOC data-sets. Accordingly, the resulting GT-57633 catalogue can successfully be used as a part of the framework for evaluation of CDAs.

  13. Paleomagnetism of the Oman Ophiolite: New Results from Oman Drilling Project Cores

    NASA Astrophysics Data System (ADS)

    Horst, A. J.; Till, J. L.; Koornneef, L.; Usui, Y.; Kim, H.; Morris, A.

    2017-12-01

    The Oman Drilling Project drilled holes at four sites in a transect through the southern massifs of the Samail ophiolite, and recovered 1500 m of igneous and metamorphic rocks. We focus on three sites from the oceanic crustal section including lower layered gabbros (GT1A), the mid-crustal layered to foliated gabbro transition (GT2A), and the shallower transition from sheeted dikes to varitextured gabbros (GT3A). Detailed core descriptions, analyses, and paleomagnetic measurements, were made on D/V Chikyu from July to September 2017 to utilize the core laboratory facilities similar to IODP expeditions. Shipboard measurements included anisotropy of magnetic susceptibility (AMS) and alternating field and thermal demagnetization of 597 discrete samples. Sample demagnetization behavior is varied from each of the cores, with some revealing multiple components of magnetization, and others yielding nearly univectorial data. The interpretation of results from the lower crustal cores is complicated by the pervasive presence of secondary magnetite. In almost all samples, a stable component was resolved (interpreted as a characteristic remanent magnetization) after removal of a lower-coercivity or lower unblocking-temperature component. The inclinations of the stable components in the core reference frame are very consistent in Hole GT1A. However, a transition from negative to positive inclinations in GT2A suggests some structural complexity, possibly as a result of intense late faulting activity. Both abrupt and gradual transitions between multiple zones of negative and positive inclinations occur in Hole GT3A. Interpretation and direct comparison of remanence between drill sites is difficult as recovered core pieces currently remain azimuthally unoriented, and GT2A was drilled at a plunge of 60°, whereas GT1A and GT3A were both drilled vertically. Work is ongoing to use borehole imagery to reorient the core pieces and paleomagnetic data into a geographic in situ reference frame. We will present an overview of preliminary AMS and remanence data that will be used in the future to 1) document deformational histories, 2) characterize magmatic flow directions at different structural levels, and 3) identify the magnetic mineralogy of remanence carriers throughout the oceanic crustal section.

  14. Low-Emission combustion of fuel in aeroderivative gas turbines

    NASA Astrophysics Data System (ADS)

    Bulysova, L. A.; Vasil'ev, V. D.; Berne, A. L.

    2017-12-01

    The paper is the first of a planned set of papers devoted to the world experience in development of Low Emission combustors (LEC) for industrial Gas Turbines (GT). The purpose of the article is to summarize and analyze the most successful experience of introducing the principles of low-emission combustion of the so-called "poor" (low fuel concentration in air when the excess air ratio is about 1.9-2.1) well mixed fuelair mixtures in the LEC for GTs and ways to reduce the instability of combustion. The consideration examples are the most successful and widely used aero-derivative GT. The GT development meets problems related to the difference in requirements and operation conditions between the aero, industrial, and power production GT. One of the main problems to be solved is the LEC development to mitigate emissions of the harmful products first of all the Nitrogen oxides NOx. The ways to modify or convert the initial combustors to the LEC are shown. This development may follow location of multiburner mixers within the initial axial envelope dimensions or conversion of circular combustor to the can type one. The most interesting are Natural Gas firing GT without water injection into the operating process or Dry Low emission (DLE) combustors. The current GT efficiency requirement may be satisfied at compressor exit pressure above 3 MPa and Turbine Entry temperature (TET) above 1500°C. The paper describes LEC examples based on the concept of preliminary prepared air-fuel mixtures' combustion. Each combustor employs its own fuel supply control concept based on the fuel flow-power output relation. In the case of multiburner combustors, the burners are started subsequently under a specific scheme. The can type combustors have combustion zones gradually ignited following the GT power change. The combustion noise problem experienced in lean mixtures' combustion is also considered, and the problem solutions are described. The GT test results show wide ranges of stable operation at needed levels of NOx and CO emissions. The world experience analysis and generalization and investigation of the further development directions for the high performance GT will assist development of domestic LEC for prospective GTs.

  15. Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False Gliotransmitter Release

    PubMed Central

    Pirttimaki, Tiina M.; Sims, Robert E.; Saunders, Gregory; Antonio, Serena A.; Codadu, Neela Krushna

    2017-01-01

    Astrocytes spontaneously release glutamate (Glut) as a gliotransmitter (GT), resulting in the generation of extrasynaptic NMDAR-mediated slow inward currents (SICs) in neighboring neurons, which can increase local neuronal excitability. However, there is a deficit in our knowledge of the factors that control spontaneous astrocyte GT release and the extent of its influence. We found that, in rat brain slices, increasing the supply of the physiological transmitter Glut increased the frequency and signaling charge of SICs over an extended period. This phenomenon was replicated by exogenous preexposure to the amino acid D-aspartate (D-Asp). Using D-Asp as a “false” GT, we determined the extent of local neuron excitation by GT release in ventrobasal thalamus, CA1 hippocampus, and somatosensory cortex. By analyzing synchronized neuronal NMDAR-mediated excitation, we found that the properties of the excitation were conserved in different brain areas. In the three areas, astrocyte-derived GT release synchronized groups of neurons at distances of >;200 μm. Individual neurons participated in more than one synchronized population, indicating that individual neurons can be excited by more than one astrocyte and that individual astrocytes may determine a neuron's synchronized network. The results confirm that astrocytes can act as excitatory nodes that can influence neurons over a significant range in a number of brain regions. Our findings further suggest that chronic elevation of ambient Glut levels can lead to increased GT Glut release, which may be relevant in some pathological states. SIGNIFICANCE STATEMENT Astrocytes spontaneously release glutamate (Glut) and other gliotransmitters (GTs) that can modify neuronal activity. Exposing brain slices to Glut and D-aspartate (D-Asp) before recording resulted in an increase in frequency of GT-mediated astrocyte–neuron signaling. Using D-Asp, it was possible to investigate the effects of specific GT release at neuronal NMDARs. Calcium imaging showed synchronized activity in groups of neurons in cortex, hippocampus, and thalamus. The size of these populations was similar in all areas and some neurons were involved in more than one synchronous group. The findings show that GT release is supply dependent and that the properties of the signaling and activated networks are largely conserved between different brain areas. PMID:28899919

  16. Minor elements, HREE and d18O distribution in UHP garnets from the Dora-Maira massif (western Alps)

    NASA Astrophysics Data System (ADS)

    Brunet, F.; Chazot, G.; Vielzeuf, D.; Chopin, C.

    2003-04-01

    The spatial distribution of minor elements, HREE and δ18O in garnet can be used as a probe of the availability and mobility of those elements and isotopes at the time of crystal growth, provided that the initial record was not significantly modified by intracrystalline diffusion and that growth took place under nearly constant pressure and temperature conditions. Garnets from three different Dora-Maira rock-types have been studied, (1) nearly pure pyrope (GT1) from the magnesian coesite-bearing quartzites, (2) almandine/pyrope dominant garnets (GT2) from jadeite-quartzite veins which crosscut the Mg-quartzite body, (3) almandine/grossular dominant garnets (GT3) from the country-rock gneiss, sampled in the vicinity of the quartzites. In GT1, minor elements are mainly Fe, Na and P. Na and P are incorporated according to a Na^+ + P5+ = Me2+ + Si4+ substitution with P_2O_5 contents up to 2000 to 2500 ppm. HREE concentrations obtained by LA-ICP-MS, vary by 2 orders of magnitude from core to rim. The δ18O ratio (Cameca 1270, Nancy), around 5 ppm (SMOW), is constant within error throughout the analysed crystals. In GT2, the situation is different since HREE concentrations appear remarkably constant within a given crystal and from one crystal to the other. In contrast with GT1, Na in GT2 is partly charge-balanced by yttrium incorporation. The δ18O ratio in GT2 of around 7 ppm is close to that encountered in GT3 (gneiss) between 7 and 8 ppm. In GT3, phosphorus content is close to detection limit (P_2O_5 below 300 ppm). HREE concentrations are highly variable from one crystal to the other and unfortunately, the size of garnet crystals does not allow profiling. Although δ18O ratio in garnet is imposed by the bulk-rock isotopic composition, HREE distribution is dominated by element availability through the fluid composition and/or absence/presence of accessory phases. The decrease in HREE and P concentration from GT1 cores to rims suggest that these elements are preferentially incorporated into garnet. Garnet growth leads to progressive depletion of these elements in the matrix. There is no significant influx of HREE during UHP garnet growth. The homogeneity of the δ18O ratio within garnet crystals is also an indication of UHP growth in a close metamorphic system. Jadeite-quartzite veins have geochemical characteristics close to that of the country-rock gneiss from which they could originate. They would then represent an evidence of Mg-quartzite and country gneiss interaction at UHP.

  17. Simulation and analysis of OOK-to-BPSK format conversion based on gain-transparent SOA used as optical phase-modulator.

    PubMed

    Hong, Wei; Huang, Dexiu; Zhang, Xinliang; Zhu, Guangxi

    2007-12-24

    All-optical on-off keying (OOK) to binary phase-shift keying (BPSK) modulation format conversion based on gain-transparent semiconductor optical amplifier (GT-SOA) is simulated and analyzed, where GT-SOA is used as an all-optical phase-modulator (PM). Numerical simulation of the phase modulation effect of GT-SOA is performed using a wideband dynamic model of GT-SOA and the quality of the BPSK signal is evaluated using the differential-phase-Q factor. Performance improvement by holding light injection is analyzed and non-return-to-zero (NRZ) and return-to-zero (RZ) modulation formats of the OOK signal are considered.

  18. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    NASA Astrophysics Data System (ADS)

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-05-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  19. Direct-to-Consumer Genetic Testing and Personal Genomics Services: A Review of Recent Empirical Studies

    PubMed Central

    Ostergren, Jenny

    2013-01-01

    Direct-to-consumer genetic testing (DTC-GT) has sparked much controversy and undergone dramatic changes in its brief history. Debates over appropriate health policies regarding DTC-GT would benefit from empirical research on its benefits, harms, and limitations. We review the recent literature (2011-present) and summarize findings across (1) content analyses of DTC-GT websites, (2) studies of consumer perspectives and experiences, and (3) surveys of relevant health care providers. Findings suggest that neither the health benefits envisioned by DTC-GT proponents (e.g., significant improvements in positive health behaviors) nor the worst fears expressed by its critics (e.g., catastrophic psychological distress and misunderstanding of test results, undue burden on the health care system) have materialized to date. However, research in this area is in its early stages and possesses numerous key limitations. We note needs for future studies to illuminate the impact of DTC-GT and thereby guide practice and policy regarding this rapidly evolving approach to personal genomics. PMID:24058877

  20. ["Grounded theory" develops medicine. Popular research method for exploring human behavior can discover new connections].

    PubMed

    Thulesius, Hans; Barfod, Toke; Ekström, Helene; Håkansson, Anders

    2004-09-30

    Grounded theory (GT) is a popular research method for exploring human behavior. GT was developed by the medical sociologists Glaser and Strauss while they studied dying in hospitals in the 1960s resulting in the book "Awareness of dying". The goal of a GT is to generate conceptual theories by using all types of data but without applying existing theories and hypotheses. GT procedures are mostly inductive as opposed to deductive research where hypotheses are tested. A good GT has a core variable that is a central concept connected to many other concepts explaining the main action in the studied area. A core variable answers the question "What's going on?". Examples of core variables are: "Cutting back after a heart attack"--how people adapt to life after a serious illness; and "Balancing in palliative cancer care"--a process of weighing, shifting, compensating and compromising when treating people with a progressive and incurable illness trajectory.

  1. Comparison of GT3X accelerometer and Yamax pedometer steps/day in a free-living sample of overweight and obese adults

    USDA-ARS?s Scientific Manuscript database

    The purpose of this study was to compare steps/day detected by the YAMAX SW-200 pedometer versus the Actigraph GT3X accelerometer in free-living adults. Daily YAMAX and GT3X steps were collected from a sample of 23 overweight and obese participants (78% female; age = 52.6 +/- 8.4 yr.; BMI = 31.0 +/-...

  2. Humanized in vivo Model for Autoimmune Diabetes

    DTIC Science & Technology

    2009-02-01

    Manuscripts Gebe JA, Yue BB, Unrath KA, Falk BA, and Nepom GT. Restricted autoantigen recognition associated with deletional and adaptive regulatory...Unrath KA, Falk BA, Ito K, Wen L, Daniels TL, Lernmark A, Nepom GT. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid...Miyake T, Falk BA, Nepom GT. Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice. J

  3. Chloride conducting light activated channel GtACR2 can produce both cessation of firing and generation of action potentials in cortical neurons in response to light.

    PubMed

    Malyshev, A Y; Roshchin, M V; Smirnova, G R; Dolgikh, D A; Balaban, P M; Ostrovsky, M A

    2017-02-15

    Optogenetics is a powerful technique in neuroscience that provided a great success in studying the brain functions during the last decade. Progress of optogenetics crucially depends on development of new molecular tools. Light-activated cation-conducting channelrhodopsin2 was widely used for excitation of cells since the emergence of optogenetics. In 2015 a family of natural light activated chloride channels GtACR was identified which appeared to be a very promising tool for using in optogenetics experiments as a cell silencer. Here we examined properties of GtACR2 channel expressed in the rat layer 2/3 pyramidal neurons by means of in utero electroporation. We have found that despite strong inhibition the light stimulation of GtACR2-positive neurons can surprisingly lead to generation of action potentials, presumably initiated in the axonal terminals. Thus, when using the GtACR2 in optogenetics experiments, its ability to induce action potentials should be taken into account. Our results also open an interesting possibility of using the GtACR2 both as cell silencer and cell activator in the same experiment varying the pattern of light stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A UDP-Glucose:Monoterpenol Glucosyltransferase Adds to the Chemical Diversity of the Grapevine Metabolome1[W

    PubMed Central

    Bönisch, Friedericke; Frotscher, Johanna; Stanitzek, Sarah; Rühl, Ernst; Wüst, Matthias; Bitz, Oliver; Schwab, Wilfried

    2014-01-01

    Terpenoids represent one of the major classes of natural products and serve different biological functions. In grape (Vitis vinifera), a large fraction of these compounds is present as nonvolatile terpene glycosides. We have extracted putative glycosyltransferase (GT) sequences from the grape genome database that show similarity to Arabidopsis (Arabidopsis thaliana) GTs whose encoded proteins glucosylate a diversity of terpenes. Spatial and temporal expression levels of the potential VvGT genes were determined in five different grapevine varieties. Heterologous expression and biochemical assays of candidate genes led to the identification of a UDP-glucose:monoterpenol β-d-glucosyltransferase (VvGT7). The VvGT7 gene was expressed in various tissues in accordance with monoterpenyl glucoside accumulation in grape cultivars. Twelve allelic VvGT7 genes were isolated from five cultivars, and their encoded proteins were biochemically analyzed. They varied in substrate preference and catalytic activity. Three amino acids, which corresponded to none of the determinants previously identified for other plant GTs, were found to be important for enzymatic catalysis. Site-specific mutagenesis along with the analysis of allelic proteins also revealed amino acids that impact catalytic activity and substrate tolerance. These results demonstrate that VvGT7 may contribute to the production of geranyl and neryl glucoside during grape ripening. PMID:24784757

  5. Probing in-plane anisotropy in fewlayer ReS2 using low frequency noise measurement.

    PubMed

    Mitra, Richa; Jariwala, Bhakti; Bhattacharya, Arnab; Das, Anindya

    2018-01-31

    ReS<sub>2</sub>, a layered two-dimensional material popular for its in-plane anisotropic properties is emerging as one of the potential candidates for flexible electronics and ultrafast optical applications. It is an n-type semiconducting material having a layer independent bandgap of 1.55 eV. In this paper we have characterized the intrinsic electronic noise level of fewlayer ReS<sub>2</sub> for the first time. Fewlayer ReS<sub>2</sub> FET devices show 1/f nature of noise for frequency ranging over three orders of magnitude. We have also observed that not only the electrical response of the material is anisotropic; the noise level is also direction dependent. In fact the noise is found to be more sensitive towards the anisotropy. This fact has been explained by evoking the theory where the Hooge parameter is not a constant quantity, but has a distinct power law dependence on mobility along the two axes direction. The anisotropy in 1/f noise measurement will pave the way to quantify the anisotropic nature of two-dimensional (2D) materials, which will be helpful for the design of low noise transistor in future. © 2018 IOP Publishing Ltd.

  6. Aspergillosis, a Natural Infection in Poultry: Mycological and Molecular Characterization and Determination of Gliotoxin in Aspergillus fumigatus Isolates.

    PubMed

    de Oca, Verónica Montes; Valdés, Sara Esther; Segundo, Carolina; Gómez, Gabriela Guadalupe; Ramírez, José; Cervantes, Roberto Arnulfo

    2017-03-01

    Aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. The main etiologic agent is Aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (GT), which is an immunosuppressive epipolythiodioxopiperazine molecule. Necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible with aspergillosis. A mycological culture was performed on the injured lungs of diseased birds, as was chloroform extraction of the GT, a thin-layer chromatography analysis (TLC), and a histopathology analysis with hematoxylin-eosin and Grocott stainings. The A. fumigatus identification was confirmed by PCR, where the ITS 1 5.1-5.8S-ITS 2 fragment of the rDNA complex was amplified. The in vitro GT production was studied by TLC in the recovered isolates from A. fumigatus . Seven isolates of A. fumigatus were obtained and in six of them, GT-like compounds were detected. In a lung sample, a compound with the same retention time (RF) as the reference GT was detected; whereas RF compounds different from the GT standard were observed in three lung samples.

  7. In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability, and induce apoptosis in the GT1-1 neuronal cell line.

    PubMed

    Pal, Lubna; Chu, Hsiao-Pai; Shu, Jun; Topalli, Ilir; Santoro, Nanette; Karkanias, George

    2007-10-01

    To evaluate for direct toxic effects of high glucose concentrations on cellular physiology in GnRH secreting immortalized GT1-1 neurons. Prospective experimental design. In vitro experimental model using a cell culture system. GT1-1 cells were cultured in replicates in media with two different glucose concentrations (450 mg/dL and 100 mg/dL, respectively) for varying time intervals (24, 48, and 72 hours). Effects of glucose concentrations on GnRH secretion by the GT1-1 neurons were evaluated using a static culture model. Cell viability, cellular apoptosis, and cell cycle events in GT1-1 neurons maintained in two different glucose concentrations were assessed by flow cytometry (fluorescence-activated cell sorter) using Annexin V-PI staining. Adverse influences of high glucose concentrations on GnRH secretion and cell viability were noted in cultures maintained in high glucose concentration (450 mg/dL) culture medium for varying time intervals. A significantly higher percentage of cells maintained in high glucose concentration medium demonstrated evidence of apoptosis by a fluorescence-activated cell sorter. We provide in vitro evidence of glucose-induced cellular toxicity in GnRH secreting GT1-1 neurons. Significant alterations in GnRH secretion, reduced cell viability, and a higher percentage of apoptotic cells were observed in GT1-1 cells maintained in high (450 mg/dL) compared with low (100 mg/dL) glucose concentration culture medium.

  8. Itraconazole inhibits TNF-α-induced CXCL10 expression in oral fibroblasts.

    PubMed

    Ohta, K; Ishida, Y; Fukui, A; Nishi, H; Naruse, T; Takechi, M; Kamata, N

    2015-01-01

    Itraconazole (ICZ) has a broad spectrum of antifungal activity including a wide range of Candida spp. TNF-α, an inflammatory cytokine associated with Th1-mediated oral inflammatory disease, enhances inflammatory mediators, such as CXCR3-agonistic chemokines including CXCL10. We examined the anti-inflammatory potential of ICZ against TNF-α-induced chemokines in oral fibroblasts. We investigated the effects of ICZ on mRNA expressions of various TNF-α-induced chemokines in immortalized oral keratinocytes (RT7) and oral fibroblasts (GT1) using quantitative PCR analysis. Subsequently, the effects of ICZ and fluconazole (FLZ) on TNF-α-induced CXCL10 proteins in GT1 and primary fibroblasts were examined using enzyme-linked immunosorbent assays (ELISA). The effect of ICZ on signal transduction protein phosphorylation involved in CXCL10 production from TNF-α-stimulated GT1 was examined by western blotting. ICZ inhibited TNF-α-induced CXCL10 mRNA in GT1, but not RT7. Although ICZ did not affect TNF-α-induced IL-8 mRNA, the mRNAs of TNF-α-induced CXCR3-agonistic chemokines such as CXCL9 and CXCL11 were inhibited by ICZ in GT1. TNF-α-induced CXCL10 protein production in GT1 and primary fibroblasts was inhibited by ICZ, but not FLZ. Finally, ICZ inhibited TNF-α-induced phosphorylation of c-JUN, which is related to CXCL10 production by TNF-α-stimulated GT1. ICZ may be useful as therapy for Th1-mediated oral inflammatory disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Determination of ganglioside composition and structure in human brain hemangioma by chip-based nanoelectrospray ionization tandem mass spectrometry.

    PubMed

    Schiopu, Catalin; Flangea, Corina; Capitan, Florina; Serb, Alina; Vukelić, Zeljka; Kalanj-Bognar, Svjetlana; Sisu, Eugen; Przybylski, Michael; Zamfir, Alina D

    2009-12-01

    We report here on a preliminary investigation of ganglioside composition and structure in human hemangioma, a benign tumor in the frontal cortex (HFC) in comparison to normal frontal cortex (NFC) tissue using for the first time advanced mass spectrometric methods based on fully automated chip-nanoelectrospray (nanoESI) high-capacity ion trap (HCT) and collision-induced dissociation (CID). The high ionization efficiency, sensitivity and reproducibility provided by the chip-nanoESI approach allowed for a reliable MS-based ganglioside comparative assay. Unlike NFC, ganglioside mixture extracted from HFC was found dominated by species of short glycan chains exhibiting lower overall sialic acid content. In HFC, only GT1 (d18:1/20:0), and GT3 (d18:1/25:1) polysialylated species were detected. Interestingly, none of these trisialylated forms was detected in NFC, suggesting that such components might selectively be associated with HFC. Unlike the case of previously investigated high malignancy gliosarcoma, in HFC one modified O-Ac-GD2 and one modified O-Ac-GM4 gangliosides were observed. This aspect suggests that these O-acetylated structures could be associated with cerebral tumors having reduced malignancy grade. Fragmentation analysis by CID in MS(2) mode using as precursors the ions corresponding to GT1 (d18:1/20:0) and GD1 (d18:1/20:0) provided data corroborating for the first time the presence of the common GT1a and GT1b isomers and the incidence of unusual GT1c and GT1d glycoforms in brain hemangioma tumor.

  10. Cholinergic control over attention in rats prone to attribute incentive salience to reward cues

    PubMed Central

    Paolone, Giovanna; Angelakos, Christopher C.; Meyer, Paul J.; Robinson, Terry E.; Sarter, Martin

    2013-01-01

    Some rats (sign-trackers, ST) are especially prone to attribute incentive salience to reward cues, relative to others (goal-trackers, GT). Thus, reward cues are more likely to promote maladaptive reward-seeking behavior in ST than GT. Here, we asked whether ST and GT differ on another trait that can contribute to poor restraint over behavior evoked by reward cues. We report that, relative to GT, ST have poor control over attentional performance, due in part to insufficient cholinergic stimulation of cortical circuitry. We found that, relative to GT, ST showed poor performance on a sustained attention task (SAT). Furthermore, their performance fluctuated rapidly between periods of good to near-chance performance. This finding was reproduced using a separate cohort of rats. As demonstrated earlier, performance on the SAT was associated with increases in extracellular levels of cortical acetylcholine (ACh); however, SAT performance-associated increases in ACh levels were significantly attenuated in ST relative to GT. Consistent with the view that the modulatory effects of ACh involves stimulation of α4β2* nicotinic acetylcholine receptors (nAChRs), systemic administration of the partial nAChR agonist ABT-089 improved SAT performance in ST and abolished the difference between SAT-associated ACh levels in ST and GT. Neither the nonselective nAChR agonist nicotine nor the psychostimulant amphetamine improved SAT performance. These findings suggest that individuals who have a propensity to attribute high incentive salience to reward cues also exhibit relatively poor attentional control. A combination of these traits may render individuals especially vulnerable to disorders such as obesity and addiction. PMID:23658172

  11. Medicine, market and communication: ethical considerations in regard to persuasive communication in direct-to-consumer genetic testing services.

    PubMed

    Schaper, Manuel; Schicktanz, Silke

    2018-06-05

    Commercial genetic testing offered over the internet, known as direct-to-consumer genetic testing (DTC GT), currently is under ethical attack. A common critique aims at the limited validation of the tests as well as the risk of psycho-social stress or adaption of incorrect behavior by users triggered by misleading health information. Here, we examine in detail the specific role of advertising communication of DTC GT companies from a medical ethical perspective. Our argumentative analysis departs from the starting point that DTC GT operates at the intersection of two different contexts: medicine on the one hand and the market on the other. Both fields differ strongly with regard to their standards of communication practices and the underlying normative assumptions regarding autonomy and responsibility. Following a short review of the ethical contexts of medical and commercial communication, we provide case examples for persuasive messages of DTC GT websites and briefly analyze their design with a multi-modal approach to illustrate some of their problematic implications. We observe three main aspects in DTC GT advertising communication: (1) the use of material suggesting medical professional legitimacy as a trust-establishing tool, (2) the suggestion of empowerment as a benefit of using DTC GT services and (3) the narrative of responsibility as a persuasive appeal to a moral self-conception. While strengthening and respecting the autonomy of a patient is the focus in medical communication, specifically genetic counselling, persuasive communication is the normal mode in marketing of consumer goods, presuming an autonomous, rational, independent consumer. This creates tension in the context of DTC GT regarding the expectation and normative assessment of communication strategies. Our analysis can even the ground for a better understanding of ethical problems associated with intersections of medical and commercial communication and point to perspectives of analysis of DTC GT advertising.

  12. Removal of arsenopyrite from complex sulfide minerals by froth flotation

    NASA Astrophysics Data System (ADS)

    Choi, Jin-young; Kim, Yang-soo; Kim, Dong-gyu; Han, Oh-hyung; Park, Chul-hyun

    2016-04-01

    Arsenic (As) is one of hazardous materials and a penalty element in metal concentrates and so metal concentrates containing arsenic of over 0.5% has been currently restricted in import and export trade. It also corrodes a smelting furnace as well as shortens its life cycle. In korea, Janggun mine that produces galena (PbS) /sphalerite (ZnS) concentrate containing arsenic of 1.78% charges a penalty of US 2/ton to LS-Nikko smelter. Hence in this work, flotation tests for removal of arsenopyrite (FeAsS) from sulfide mineral concentrates were carried out using lab scale flotation cell, which maintain grade and recovery of PbS and ZnS in comparison to flotation plant. Particularly, this study was focused on investigating the combination of several chemical reagents (depressant, collector, activator and etc.) that affect flotation performance. In the straight differential flotation for PbS, a PbS grade of 75.80% and a recovery of 90.12% could be obtained with FeAsS removal of 84.1% (0.2% As) under the conditions of 20% feed solids concentration, pH 8.5, 50g/t frother (AF65), 40g/t collector (AP242) and 800g/t As depressant (NaHSO3) and 600g/t Zn depressant (ZnSO4). In the ZnS flotation, the maximum separation achievable for ZnS using froth flotation has been shown to be a grade of 72.57% and a recovery of 95.43%. At this time, FeAsS removal of 87.8% (0.16% As) could be successfully accomplished under pH 11, and 800g/t Zn activator (CuSO4), 75g/t frother (AF65), 60g/t collector (AP211) and 600g/t As depressant (NaHSO3). Acknowledgments This work was supported by the Energy and Resources Engineering Program Grant funded by the Ministry of Trade, Industry and Energy, Korea

  13. Costs and outcomes of treating chronic hepatitis C patients in routine care - results from a nationwide multicenter trial.

    PubMed

    Stahmeyer, J T; Krauth, C; Bert, F; Pfeiffer-Vornkahl, H; Alshuth, U; Hüppe, D; Mauss, S; Rossol, S

    2016-02-01

    Viral hepatitis is a major public health problem affecting millions of people worldwide. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The aim of the study was to assess outcomes and costs of treating patients with chronic hepatitis C in clinical practice in Germany. We carried out a prospective noninterventional study. Information on treatment outcomes, resource utilization and quality of life was provided by 281 physicians throughout Germany. Data of 3708 monoinfected HCV-patients treated between 2008 and 2011 were analysed. Therapy consisted of peginterferon/ribavirin. Mean age of patients was 43.7 years, 60.3% were male and estimated duration of infection was 13.6 years. Predominantly genotype 1 (61.3%) or 3 (28.5%) infections were observed. Sustained viral response (SVR)-rates in most frequently observed genotypes were 49.2% in GT-1 and 61.9% in GT-3 treatment-naive patients (Relapser: GT-1: 35.3% and GT-3: 57.3%; Nonresponder: GT-1: 25.0% and GT-3: 33.3%). Average treatment costs were lowest in treatment-naive patients (€18 965) and higher in patients who failed previous treatments (relapsers: €24 753; nonresponders: €19 511). Differences according to genotype were observed. Average costs per SVR in treatment-naive patients were €44 744 for GT-1 and €22 218 for GT-3. Treatment was associated with a decrease in quality of life; post-treatment quality of life was higher in patients achieving SVR. Our insight on real-life treatment outcomes and costs can serve as a reference for a comparison with other treatments. There is high need for short-term and long-term cost-effectiveness analysis in real-life settings as newly introduced treatment strategies with direct acting antivirals result in high SVR-rates but are more costly. © 2015 John Wiley & Sons Ltd.

  14. A reconstructed computerized tomographic comparison of Ni-Ti rotary GT files versus traditional instruments in canals shaped by novice operators.

    PubMed

    Gluskin, A H; Brown, D C; Buchanan, L S

    2001-09-01

    The aim of this study was to compare the effects of preparation with conventional stainless steel Flexofiles and Gates Glidden burs versus nickel-titanium GT rotary files in the shaping of mesial root canals of extracted mandibular molars. A total of 54 canals from 27 mesial roots of mandibular molar teeth were prepared using one of two methods by novice dental students. One canal in each root was prepared by a crown-down approach. utilizing stainless steel Flexofiles and Gates Glidden burs. The other canal was prepared using nickel-titanium GT rotary files in a crown-down fashion as recommended by the manufacturer. Preoperative CT scans of each root were recorded and 50 canal specimens were available for postoperative comparisons. Following canal shaping, postoperative scans were superimposed on the original images. Changes in canal area, canal transportation and thickness of remaining root structure at strategic levels of the root were analyzed. The time taken for each method was also noted. At the coronal and mid-root coronal one-third sections, the rotary GT files produced a significantly smaller postoperative canal area (P < 0.05). In the mid-root sections there was significantly less transportation of the root canal toward the furcation, and less thinning of the root structure with GT files compared to the stainless steel files (P < 0.05). Overall, there was greater conservation of structure coronally and more adequate shape in the mid-root level. The GT rotary technique was significantly faster than the stainless steel hand-held file technique (P < 0.0001). Two GT instruments fractured during the study. Under the conditions of this study, novice dental students were able to prepare curved root canals with Ni-Ti GT rotary files with less transportation and greater conservation of tooth structure, compared to canals prepared with hand instruments. The rotary technique was significantly faster.

  15. A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces

    PubMed Central

    Plummer, Amy; Halsey, Kirstie; Lovegrove, Alison; Hammond-Kosack, Kim

    2017-01-01

    Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast “yeast-like” growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices. PMID:29020037

  16. Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward?

    PubMed

    Bechara, Antoine; Dolan, Sara; Hindes, Andrea

    2002-01-01

    On a decision-making instrument known as the "gambling task" (GT), a subgroup of substance dependent individuals (SDI) opted for choices that yield high immediate gains in spite of higher future losses. This resembles the behavior of patients with ventromedial (VM) prefrontal cortex lesions. In this study, we addressed the possibility that hypersensitivity to reward may account for the "myopia" for the future in this subgroup of SDI. We used a variant version of the GT, in which the good decks yielded high immediate punishment but higher delayed reward. The bad decks yielded low immediate punishment and lower delayed reward. We measured the skin conductance response (SCR) of subjects after receiving reward (reward SCR) and during their pondering from which deck to choose (anticipatory SCR). A subgroup of SDI who was not impaired on the original GT performed normally on the variant GT. The subgroup of SDI who was impaired on the original GT showed two levels of performance on the variant GT. One subgroup (36% of the sample) performed poorly on the variant GT, and showed similar behavioral and physiological impairments to VM patients. The other subgroup of SDI (64% of the sample) performed normally on the variant task, but had abnormally large physiological responses to reward, i.e. large SCR after receiving reward (reward SCR) and large SCR in anticipation of outcomes that yield large reward. Thus, the combined cognitive and physiological approach of assessing decision-making characterizes three sub-populations of SDI. One sub-population is without impairments that can be detected by any measure of the GT paradigm. Another sub-population is similar to VM patients in that they are insensitive to the future, both positive and negative. A third sub-population is hypersensitive to reward, so that the presence or the prospect of receiving, reward dominates their behavior.

  17. Multi-substrate flavonol O-glucosyltransferases from strawberry (Fragaria×ananassa) achene and receptacle

    PubMed Central

    Griesser, Markus; Vitzthum, Florian; Fink, Barbara; Bellido, Mari Luz; Raasch, Constanze; Munoz-Blanco, Juan; Schwab, Wilfried

    2008-01-01

    In an effort to characterize fruit ripening-related genes functionally, two glucosyltransferases, FaGT6 and FaGT7, were cloned from a strawberry (Fragaria×ananassa) cDNA library and the full-length open reading frames were amplified by rapid amplification of cDNA ends. FaGT6 and FaGT7 were expressed heterologously as fusion proteins in Escherichia coli and target protein was purified using affinity chromatography. Both recombinant enzymes exhibited a broad substrate tolerance in vitro, accepting numerous flavonoids, hydroxycoumarins, and naphthols. FaGT6 formed 3-O-glucosides and minor amounts of 7-O-, 4′-O-, and 3′-O-monoglucosides and one diglucoside from flavonols such as quercetin. FaGT7 converted quercetin to the 3-O-glucoside and 4′-O-glucoside and minor levels of the 7- and 3′-isomers but formed no diglucoside. Gene expression studies showed that both genes are strongly expressed in achenes of small-sized green fruits, while the expression levels were generally lower in the receptacle. Significant levels of quercetin 3-O-, 7-O-, and 4′-O-glucosides, kaempferol 3-O- and 7-O-glucosides, as well as isorhamnetin 7-O-glucoside, were identified in achenes and the receptacle. In the receptacle, the expression of both genes is negatively controlled by auxin which correlates with the ripening-related gene expression in this tissue. Salicylic acid, a known signal molecule in plant defence, induces the expression of both genes. Thus, it appears that FaGT6 and FaGT7 are involved in the glucosylation of flavonols and may also participate in xenobiotic metabolism. The latter function is supported by the proven ability of strawberries to glucosylate selected unnatural substrates injected in ripe fruits. This report presents the first biochemical characterization of enzymes mainly expressed in strawberry achenes and provides the foundation of flavonoid metabolism in the seeds. PMID:18487633

  18. Closing the Gap: The Challenges of Treating Hepatitis C Virus Genotype 3 Infection.

    PubMed

    Martin, Michelle T; Deming, Paulina

    2017-06-01

    The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatment-experienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Because GT 3 presents more clinical challenges than other GTs, this review focuses on the evolution and efficacy of direct-acting antiviral (DAA) treatment options for HCV GT 3 infection after the historical standard of care with pegylated interferon and ribavirin. Our objective was to review the SVR rates with available and late-pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment. Authors performed a literature search of the PubMed/MEDLINE database (inception to March 27, 2017) and narrowed the field to clinical trials published in English. Trials that evaluated alternative treatments, non-DAA historical treatment, and DAAs not currently indicated for HCV were excluded. Trials only involving patients with human immunodeficiency virus/HCV coinfection were also excluded. Additional trials were identified from a review of the ClinicalTrials.gov database. Authors further identified references from a review of literature citations and reviewed annual meeting abstracts from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver for pipeline and real-world GT 3 data. Phase III trial data were not available to support all GT 3 treatment recommendations found in the guidelines. The SVR rates were lower in treatment-experienced and cirrhotic patients with GT 3 than other HCV populations. Treatment failure was associated with resistance to current treatment regimens. Clinical studies included patients with various levels of advanced liver disease, but few patients with decompensated cirrhosis were represented. Recent advances in pharmacologic treatment with DAAs have greatly increased SVR rates in patients with all HCV GTs, but SVR rates for treatment-experienced cirrhotic patients with GT 3 are lower than for other GTs. Given the limited data and observed SVR rates in this patient population, the optimal therapy for patients with decompensated cirrhotic GT 3 HCV infection is not yet established. Newer agents and recommendations regarding baseline resistance are likely to evolve treatment strategies in the near future. © 2017 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals, Inc. on behalf of Pharmacotherapy Publications, Inc.

  19. Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

    PubMed

    Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

    2017-07-01

    Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir. The activity profiles of grazoprevir and elbasvir supported the testing of the direct-acting antivirals in clinical studies. Copyright © 2017 American Society for Microbiology.

  20. Global Carbon Budget 2017

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

    Le Quere, Corinne; Andrew, Robbie M.; Friedlingstein, Pierre

    Here an accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the global carbon budget – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO 2 emissions from fossil fuels and industry ( E FF) are based on energy statistics and cement production data, respectively, while emissions from land-use change ( E LUC), mainly deforestation, aremore » based on land-cover change data and bookkeeping models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. The ocean CO 2 sink ( S OCEAN) and terrestrial CO 2 sink ( S LAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance ( B IM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1 σ. For the last decade available (2007–2016), E FF was 9.4 ± 0.5 GtC yr –1, E LUC 1.3 ± 0.7 GtC yr –1, G ATM 4.7 ± 0.1 GtC yr –1, S OCEAN 2.4 ± 0.5 GtC yr –1, and S LAND 3.0 ± 0.8 GtC yr –1, with a budget imbalance B IM of 0.6 GtC yr –1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in E FF was approximately zero and emissions remained at 9.9 ±\\ 0.5 GtC yr –1. Also for 2016, E LUC was 1.3 ± .7 GtC yr –1, G ATM was 6.1 ± 0.2 GtC yr –1, S OCEAN was 2.6 ± 0.5 GtC yr –1, and S LAND was 2.7 ± 1.0 GtC yr –1, with a small B IM of –0.3 GtC. G ATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small S LAND consistent with El Niño conditions. The global atmospheric CO 2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in E FF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set.« less

  1. Global Carbon Budget 2017

    DOE PAGES

    Le Quere, Corinne; Andrew, Robbie M.; Friedlingstein, Pierre; ...

    2018-03-12

    Here an accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the global carbon budget – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO 2 emissions from fossil fuels and industry ( E FF) are based on energy statistics and cement production data, respectively, while emissions from land-use change ( E LUC), mainly deforestation, aremore » based on land-cover change data and bookkeeping models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. The ocean CO 2 sink ( S OCEAN) and terrestrial CO 2 sink ( S LAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance ( B IM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1 σ. For the last decade available (2007–2016), E FF was 9.4 ± 0.5 GtC yr –1, E LUC 1.3 ± 0.7 GtC yr –1, G ATM 4.7 ± 0.1 GtC yr –1, S OCEAN 2.4 ± 0.5 GtC yr –1, and S LAND 3.0 ± 0.8 GtC yr –1, with a budget imbalance B IM of 0.6 GtC yr –1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in E FF was approximately zero and emissions remained at 9.9 ±\\ 0.5 GtC yr –1. Also for 2016, E LUC was 1.3 ± .7 GtC yr –1, G ATM was 6.1 ± 0.2 GtC yr –1, S OCEAN was 2.6 ± 0.5 GtC yr –1, and S LAND was 2.7 ± 1.0 GtC yr –1, with a small B IM of –0.3 GtC. G ATM continued to be higher in 2016 compared to the past decade (2007–2016), reflecting in part the high fossil emissions and the small S LAND consistent with El Niño conditions. The global atmospheric CO 2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6–9 months indicate a renewed growth in E FF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set.« less

  2. Global Carbon Budget 2017

    NASA Astrophysics Data System (ADS)

    Le Quéré, Corinne; Andrew, Robbie M.; Friedlingstein, Pierre; Sitch, Stephen; Pongratz, Julia; Manning, Andrew C.; Korsbakken, Jan Ivar; Peters, Glen P.; Canadell, Josep G.; Jackson, Robert B.; Boden, Thomas A.; Tans, Pieter P.; Andrews, Oliver D.; Arora, Vivek K.; Bakker, Dorothee C. E.; Barbero, Leticia; Becker, Meike; Betts, Richard A.; Bopp, Laurent; Chevallier, Frédéric; Chini, Louise P.; Ciais, Philippe; Cosca, Catherine E.; Cross, Jessica; Currie, Kim; Gasser, Thomas; Harris, Ian; Hauck, Judith; Haverd, Vanessa; Houghton, Richard A.; Hunt, Christopher W.; Hurtt, George; Ilyina, Tatiana; Jain, Atul K.; Kato, Etsushi; Kautz, Markus; Keeling, Ralph F.; Klein Goldewijk, Kees; Körtzinger, Arne; Landschützer, Peter; Lefèvre, Nathalie; Lenton, Andrew; Lienert, Sebastian; Lima, Ivan; Lombardozzi, Danica; Metzl, Nicolas; Millero, Frank; Monteiro, Pedro M. S.; Munro, David R.; Nabel, Julia E. M. S.; Nakaoka, Shin-ichiro; Nojiri, Yukihiro; Padin, X. Antonio; Peregon, Anna; Pfeil, Benjamin; Pierrot, Denis; Poulter, Benjamin; Rehder, Gregor; Reimer, Janet; Rödenbeck, Christian; Schwinger, Jörg; Séférian, Roland; Skjelvan, Ingunn; Stocker, Benjamin D.; Tian, Hanqin; Tilbrook, Bronte; Tubiello, Francesco N.; van der Laan-Luijkx, Ingrid T.; van der Werf, Guido R.; van Heuven, Steven; Viovy, Nicolas; Vuichard, Nicolas; Walker, Anthony P.; Watson, Andrew J.; Wiltshire, Andrew J.; Zaehle, Sönke; Zhu, Dan

    2018-03-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere - the global carbon budget - is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on land-cover change data and bookkeeping models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) and terrestrial CO2 sink (SLAND) are estimated with global process models constrained by observations. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the last decade available (2007-2016), EFF was 9.4 ± 0.5 GtC yr-1, ELUC 1.3 ± 0.7 GtC yr-1, GATM 4.7 ± 0.1 GtC yr-1, SOCEAN 2.4 ± 0.5 GtC yr-1, and SLAND 3.0 ± 0.8 GtC yr-1, with a budget imbalance BIM of 0.6 GtC yr-1 indicating overestimated emissions and/or underestimated sinks. For year 2016 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr-1. Also for 2016, ELUC was 1.3 ± 0.7 GtC yr-1, GATM was 6.1 ± 0.2 GtC yr-1, SOCEAN was 2.6 ± 0.5 GtC yr-1, and SLAND was 2.7 ± 1.0 GtC yr-1, with a small BIM of -0.3 GtC. GATM continued to be higher in 2016 compared to the past decade (2007-2016), reflecting in part the high fossil emissions and the small SLAND consistent with El Niño conditions. The global atmospheric CO2 concentration reached 402.8 ± 0.1 ppm averaged over 2016. For 2017, preliminary data for the first 6-9 months indicate a renewed growth in EFF of +2.0 % (range of 0.8 to 3.0 %) based on national emissions projections for China, USA, and India, and projections of gross domestic product (GDP) corrected for recent changes in the carbon intensity of the economy for the rest of the world. This living data update documents changes in the methods and data sets used in this new global carbon budget compared with previous publications of this data set (Le Quéré et al., 2016, 2015b, a, 2014, 2013). All results presented here can be downloaded from https://doi.org/10.18160/GCP-2017 (GCP, 2017).

  3. Global carbon budget 2013

    NASA Astrophysics Data System (ADS)

    Le Quéré, C.; Peters, G. P.; Andres, R. J.; Andrew, R. M.; Boden, T. A.; Ciais, P.; Friedlingstein, P.; Houghton, R. A.; Marland, G.; Moriarty, R.; Sitch, S.; Tans, P.; Arneth, A.; Arvanitis, A.; Bakker, D. C. E.; Bopp, L.; Canadell, J. G.; Chini, L. P.; Doney, S. C.; Harper, A.; Harris, I.; House, J. I.; Jain, A. K.; Jones, S. D.; Kato, E.; Keeling, R. F.; Klein Goldewijk, K.; Körtzinger, A.; Koven, C.; Lefèvre, N.; Maignan, F.; Omar, A.; Ono, T.; Park, G.-H.; Pfeil, B.; Poulter, B.; Raupach, M. R.; Regnier, P.; Rödenbeck, C.; Saito, S.; Schwinger, J.; Segschneider, J.; Stocker, B. D.; Takahashi, T.; Tilbrook, B.; van Heuven, S.; Viovy, N.; Wanninkhof, R.; Wiltshire, A.; Zaehle, S.

    2014-06-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil-fuel combustion and cement production (EFF) are based on energy statistics, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated for the first time in this budget with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2 and land cover change (some including nitrogen-carbon interactions). All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2003-2012), EFF was 8.6 ± 0.4 GtC yr-1, ELUC 0.9 ± 0.5 GtC yr-1, GATM 4.3 ± 0.1 GtC yr-1, SOCEAN 2.5 ± 0.5 GtC yr-1, and SLAND 2.8 ± 0.8 GtC yr-1. For year 2012 alone, EFF grew to 9.7 ± 0.5 GtC yr-1, 2.2% above 2011, reflecting a continued growing trend in these emissions, GATM was 5.1 ± 0.2 GtC yr-1, SOCEAN was 2.9 ± 0.5 GtC yr-1, and assuming an ELUC of 1.0 ± 0.5 GtC yr-1 (based on the 2001-2010 average), SLAND was 2.7 ± 0.9 GtC yr-1. GATM was high in 2012 compared to the 2003-2012 average, almost entirely reflecting the high EFF. The global atmospheric CO2 concentration reached 392.52 ± 0.10 ppm averaged over 2012. We estimate that EFF will increase by 2.1% (1.1-3.1%) to 9.9 ± 0.5 GtC in 2013, 61% above emissions in 1990, based on projections of world gross domestic product and recent changes in the carbon intensity of the economy. With this projection, cumulative emissions of CO2 will reach about 535 ± 55 GtC for 1870-2013, about 70% from EFF (390 ± 20 GtC) and 30% from ELUC (145 ± 50 GtC). This paper also documents any changes in the methods and data sets used in this new carbon budget from previous budgets (Le Quéré et al., 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2013_V2.3).

  4. Global carbon budget 2014

    NASA Astrophysics Data System (ADS)

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.; Peters, G. P.; Ciais, P.; Friedlingstein, P.; Jones, S. D.; Sitch, S.; Tans, P.; Arneth, A.; Boden, T. A.; Bopp, L.; Bozec, Y.; Canadell, J. G.; Chini, L. P.; Chevallier, F.; Cosca, C. E.; Harris, I.; Hoppema, M.; Houghton, R. A.; House, J. I.; Jain, A. K.; Johannessen, T.; Kato, E.; Keeling, R. F.; Kitidis, V.; Klein Goldewijk, K.; Koven, C.; Landa, C. S.; Landschützer, P.; Lenton, A.; Lima, I. D.; Marland, G.; Mathis, J. T.; Metzl, N.; Nojiri, Y.; Olsen, A.; Ono, T.; Peng, S.; Peters, W.; Pfeil, B.; Poulter, B.; Raupach, M. R.; Regnier, P.; Rödenbeck, C.; Saito, S.; Salisbury, J. E.; Schuster, U.; Schwinger, J.; Séférian, R.; Segschneider, J.; Steinhoff, T.; Stocker, B. D.; Sutton, A. J.; Takahashi, T.; Tilbrook, B.; van der Werf, G. R.; Viovy, N.; Wang, Y.-P.; Wanninkhof, R.; Wiltshire, A.; Zeng, N.

    2015-05-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuel combustion and cement production (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover-change (some including nitrogen-carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2004-2013), EFF was 8.9 ± 0.4 GtC yr-1, ELUC 0.9 ± 0.5 GtC yr-1, GATM 4.3 ± 0.1 GtC yr-1, SOCEAN 2.6 ± 0.5 GtC yr-1, and SLAND 2.9 ± 0.8 GtC yr-1. For year 2013 alone, EFF grew to 9.9 ± 0.5 GtC yr-1, 2.3% above 2012, continuing the growth trend in these emissions, ELUC was 0.9 ± 0.5 GtC yr-1, GATM was 5.4 ± 0.2 GtC yr-1, SOCEAN was 2.9 ± 0.5 GtC yr-1, and SLAND was 2.5 ± 0.9 GtC yr-1. GATM was high in 2013, reflecting a steady increase in EFF and smaller and opposite changes between SOCEAN and SLAND compared to the past decade (2004-2013). The global atmospheric CO2 concentration reached 395.31 ± 0.10 ppm averaged over 2013. We estimate that EFF will increase by 2.5% (1.3-3.5%) to 10.1 ± 0.6 GtC in 2014 (37.0 ± 2.2 GtCO2 yr-1), 65% above emissions in 1990, based on projections of world gross domestic product and recent changes in the carbon intensity of the global economy. From this projection of EFF and assumed constant ELUC for 2014, cumulative emissions of CO2 will reach about 545 ± 55 GtC (2000 ± 200 GtCO2) for 1870-2014, about 75% from EFF and 25% from ELUC. This paper documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this living data set (Le Quéré et al., 2013, 2014). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2014).

  5. Sequences with high propensity to form G-quartet structures in kinetoplast DNA from Phytomonas serpens.

    PubMed

    Sá-Carvalho, D; Traub-Cseko, Y M

    1995-06-01

    Naturally occurring sequences containing repetitive guanine motifs have the potential to form tetraplex DNA. Phytomonas serpens minicircle DNA shows some regions where one strand is composed mainly of G and T (GT regions). These regions contain several stretches of contiguous guanines. An oligonucleotide was constructed with the sequence corresponding to one of these regions (Phyto-GT). It was demonstrated by native gel electrophoresis and methylation protection that Phyto-GT forms tetramolecular (G4), bimolecular (G'2) and unimolecular (G4') structures stabilized through G-quartets. Tetraplex DNA formation by this sequence could have biological relevance as it can be formed in physiological conditions and GT regions comprise approximately one-third of P. serpens and Crithidia oncopelti minicircles.

  6. Internet-Based Direct-to-Consumer Genetic Testing: A Systematic Review.

    PubMed

    Covolo, Loredana; Rubinelli, Sara; Ceretti, Elisabetta; Gelatti, Umberto

    2015-12-14

    Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them. The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon. A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term "Direct-to-consumer genetic test." In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers' health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive power, and do not measure genetic risk appropriately. The impact of DTC-GT on consumers' health perceptions and behaviors is an emerging concern. However, negative effects on consumers or health benefits have yet to be observed. Nevertheless, since the online market of DTC-GT is expected to grow, it is important to remain aware of a possible impact.

  7. Modeling of gas turbine - solid oxide fuel cell systems for combined propulsion and power on aircraft

    NASA Astrophysics Data System (ADS)

    Waters, Daniel Francis

    This dissertation investigates the use of gas turbine (GT) engine integrated solid oxide fuel cells (SOFCs) to reduce fuel burn in aircraft with large electrical loads like sensor-laden unmanned air vehicles (UAVs). The concept offers a number of advantages: the GT absorbs many SOFC balance of plant functions (supplying fuel, air, and heat to the fuel cell) thereby reducing the number of components in the system; the GT supplies fuel and pressurized air that significantly increases SOFC performance; heat and unreacted fuel from the SOFC are recaptured by the GT cycle offsetting system-level losses; good transient response of the GT cycle compensates for poor transient response of the SOFC. The net result is a system that can supply more electrical power more efficiently than comparable engine-generator systems with only modest (<10%) decrease in power density. Thermodynamic models of SOFCs, catalytic partial oxidation (CPOx) reactors, and three GT engine types (turbojet, combined exhaust turbofan, separate exhaust turbofan) are developed that account for equilibrium gas phase and electrochemical reaction, pressure losses, and heat losses in ways that capture `down-the-channel' effects (a level of fidelity necessary for making meaningful performance, mass, and volume estimates). Models are created in a NASA-developed environment called Numerical Propulsion System Simulation (NPSS). A sensitivity analysis identifies important design parameters and translates uncertainties in model parameters into uncertainties in overall performance. GT-SOFC integrations reduce fuel burn 3-4% in 50 kW systems on 35 kN rated engines (all types) with overall uncertainty <1%. Reductions of 15-20% are possible at the 200 kW power level. GT-SOFCs are also able to provide more electric power (factors >3 in some cases) than generator-based systems before encountering turbine inlet temperature limits. Aerodynamic drag effects of engine-airframe integration are by far the most important limiter of the combined propulsion/electrical generation concept. However, up to 100-200 kW can be produced in a bypass ratio = 8, overall pressure ratio = 40 turbofan with little or no drag penalty. This study shows that it is possible to create cooperatively integrated GT-SOFC systems for combined propulsion and power with better overall performance than stand-alone components.

  8. Internet-Based Direct-to-Consumer Genetic Testing: A Systematic Review

    PubMed Central

    Rubinelli, Sara; Ceretti, Elisabetta; Gelatti, Umberto

    2015-01-01

    Background Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them. Objective The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon. Methods A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term “Direct-to-consumer genetic test.” Results In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers’ health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive power, and do not measure genetic risk appropriately. Conclusions The impact of DTC-GT on consumers’ health perceptions and behaviors is an emerging concern. However, negative effects on consumers or health benefits have yet to be observed. Nevertheless, since the online market of DTC-GT is expected to grow, it is important to remain aware of a possible impact. PMID:26677835

  9. "It's our DNA, we deserve the right to test!" A content analysis of a petition for the right to access direct-to-consumer genetic testing.

    PubMed

    Su, Yeyang; Borry, Pascal; Otte, Ina C; Howard, Heidi C

    2013-09-01

    Various companies are currently advertising or selling genetic tests over the internet using a model of provision referred to as 'direct-to-consumer' (DTC). This commercial offer of DTC genetic testing (GT) has fueled a number of scientific, ethical and policy debates. To date there have been few studies published regarding the users' perspective. This study aimed to obtain information regarding the issues raised by individuals who signed a petition in support of DTC GT and the 'unrestricted' access to their genetic information. We conducted qualitative content analysis of comments written by individuals who signed a public online petition initiated by DIYgenomics (CA, USA) to support "personal access to genetic information". Of the 523 individuals who signed the petition sponsored by DIYgenomics, 247 individuals also wrote individual comments. A content analysis of these comments reveals that petitioners raised six main issues in support of unrestricted access to DTC GT: that their ownership of their DNA should allow them to have unrestricted access to their genomic information; that they should have the right to their genomic information; that the government has no place in (further) regulating DTC GT; that healthcare professionals should not be placed as intermediaries when purchasing DTC GT services; that many petioners who had already obtained DTC GT had positive experiences with this model of provision; and that genealogy or ancestry DNA testing is one of the main activities petitioners wish to have 'unrestricted' or 'direct' access. These results give insight into why individuals may support unrestricted access to their genomic information and confirm some of the motivations of users for purchasing DTC GT. Our analysis also brings to the forefront themes that have been raised less often in empirical studies involving motivations to purchase DTC GT services; these include the strongly held beliefs of some petitioners that, since they own their DNA, they should have the right to access the information without (further) government control or physician involvement. Interestingly, the comments left by petitioners also reveal a certain distrust of governmental agencies and healthcare professionals. This urges us to further study the public's views of these services and the potential impact of these views in order to responsibly address the ongoing debate on DTC GT.

  10. Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False Gliotransmitter Release.

    PubMed

    Pirttimaki, Tiina M; Sims, Robert E; Saunders, Gregory; Antonio, Serena A; Codadu, Neela Krushna; Parri, H Rheinallt

    2017-10-11

    Astrocytes spontaneously release glutamate (Glut) as a gliotransmitter (GT), resulting in the generation of extrasynaptic NMDAR-mediated slow inward currents (SICs) in neighboring neurons, which can increase local neuronal excitability. However, there is a deficit in our knowledge of the factors that control spontaneous astrocyte GT release and the extent of its influence. We found that, in rat brain slices, increasing the supply of the physiological transmitter Glut increased the frequency and signaling charge of SICs over an extended period. This phenomenon was replicated by exogenous preexposure to the amino acid D-aspartate (D-Asp). Using D-Asp as a "false" GT, we determined the extent of local neuron excitation by GT release in ventrobasal thalamus, CA1 hippocampus, and somatosensory cortex. By analyzing synchronized neuronal NMDAR-mediated excitation, we found that the properties of the excitation were conserved in different brain areas. In the three areas, astrocyte-derived GT release synchronized groups of neurons at distances of >;200 μm. Individual neurons participated in more than one synchronized population, indicating that individual neurons can be excited by more than one astrocyte and that individual astrocytes may determine a neuron's synchronized network. The results confirm that astrocytes can act as excitatory nodes that can influence neurons over a significant range in a number of brain regions. Our findings further suggest that chronic elevation of ambient Glut levels can lead to increased GT Glut release, which may be relevant in some pathological states. SIGNIFICANCE STATEMENT Astrocytes spontaneously release glutamate (Glut) and other gliotransmitters (GTs) that can modify neuronal activity. Exposing brain slices to Glut and D-aspartate (D-Asp) before recording resulted in an increase in frequency of GT-mediated astrocyte-neuron signaling. Using D-Asp, it was possible to investigate the effects of specific GT release at neuronal NMDARs. Calcium imaging showed synchronized activity in groups of neurons in cortex, hippocampus, and thalamus. The size of these populations was similar in all areas and some neurons were involved in more than one synchronous group. The findings show that GT release is supply dependent and that the properties of the signaling and activated networks are largely conserved between different brain areas. Copyright © 2017 Pirttimaki, Sims et al.

  11. Preoperative graft thickness measurements do not influence final BSCVA or speed of vision recovery after descemet stripping automated endothelial keratoplasty.

    PubMed

    Phillips, Paul M; Phillips, Louis J; Maloney, Charlene M

    2013-11-01

    To evaluate the influence of preoperative graft thickness (GT) on final visual acuity and speed of vision recovery after Descemet stripping automated endothelial keratoplasty (DSAEK). The best spectacle-corrected acuity (BSCVA) was measured after DSAEK was performed at 1, 3, 6, 12, and 24 months. A regression analysis was performed to determine whether GT predicted the BSCVA across each time gate. The time to achieve the "1-year maximum BSCVA" was determined to assess the "speed" of recovery for all eyes that had data at 1, 3, 6, and 12 months. Additionally, the final BSCVA was compared between 2 distinct groups of "thin" (<125-μm) versus "thick" (>165-μm) tissue. There were 144 eyes evaluated. No significant correlations were found between the GT and the BSCVA at any of the time gates: 1, 3, 6, 12, or 24 months. Speed of vision recovery was not affected by the GT. The average GT values of the eyes that achieved BSCVA by 1, 3, 6 months and 1 year were not significantly different and were 154.7, 141.3, 149, and 150.1 μm, respectively. No difference was found between the BSCVA of "thick" versus "thin" tissues at any of the time gates: 1, 3, 6, or 12 months. Preoperative GT measurements were not correlated with the BSCVA after the DSAEK was performed at 1, 6, 12, or 24 months postoperatively and do not determine the speed of vision recovery. Additionally, no difference was found in postoperative vision outcomes when directly comparing tissues at either end of the GT spectrum of this study.

  12. Pathways limiting warming to 1.5°C: a tale of turning around in no time?

    NASA Astrophysics Data System (ADS)

    Kriegler, Elmar; Luderer, Gunnar; Bauer, Nico; Baumstark, Lavinia; Fujimori, Shinichiro; Popp, Alexander; Rogelj, Joeri; Strefler, Jessica; van Vuuren, Detlef P.

    2018-05-01

    We explore the feasibility of limiting global warming to 1.5°C without overshoot and without the deployment of carbon dioxide removal (CDR) technologies. For this purpose, we perform a sensitivity analysis of four generic emissions reduction measures to identify a lower bound on future CO2 emissions from fossil fuel combustion and industrial processes. Final energy demand reductions and electrification of energy end uses as well as decarbonization of electricity and non-electric energy supply are all considered. We find the lower bound of cumulative fossil fuel and industry CO2 emissions to be 570 GtCO2 for the period 2016-2100, around 250 GtCO2 lower than the lower end of available 1.5°C mitigation pathways generated with integrated assessment models. Estimates of 1.5°C-consistent CO2 budgets are highly uncertain and range between 100 and 900 GtCO2 from 2016 onwards. Based on our sensitivity analysis, limiting warming to 1.5°C will require CDR or terrestrial net carbon uptake if 1.5°C-consistent budgets are smaller than 650 GtCO2. The earlier CDR is deployed, the more it neutralizes post-2020 emissions rather than producing net negative emissions. Nevertheless, if the 1.5°C budget is smaller than 550 GtCO2, temporary overshoot of the 1.5°C limit becomes unavoidable if CDR cannot be ramped up faster than to 4 GtCO2 in 2040 and 10 GtCO2 in 2050. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

  13. Pathways limiting warming to 1.5°C: a tale of turning around in no time?

    PubMed

    Kriegler, Elmar; Luderer, Gunnar; Bauer, Nico; Baumstark, Lavinia; Fujimori, Shinichiro; Popp, Alexander; Rogelj, Joeri; Strefler, Jessica; van Vuuren, Detlef P

    2018-05-13

    We explore the feasibility of limiting global warming to 1.5°C without overshoot and without the deployment of carbon dioxide removal (CDR) technologies. For this purpose, we perform a sensitivity analysis of four generic emissions reduction measures to identify a lower bound on future CO 2 emissions from fossil fuel combustion and industrial processes. Final energy demand reductions and electrification of energy end uses as well as decarbonization of electricity and non-electric energy supply are all considered. We find the lower bound of cumulative fossil fuel and industry CO 2 emissions to be 570 GtCO 2 for the period 2016-2100, around 250 GtCO 2 lower than the lower end of available 1.5°C mitigation pathways generated with integrated assessment models. Estimates of 1.5°C-consistent CO 2 budgets are highly uncertain and range between 100 and 900 GtCO 2 from 2016 onwards. Based on our sensitivity analysis, limiting warming to 1.5°C will require CDR or terrestrial net carbon uptake if 1.5°C-consistent budgets are smaller than 650 GtCO 2 The earlier CDR is deployed, the more it neutralizes post-2020 emissions rather than producing net negative emissions. Nevertheless, if the 1.5°C budget is smaller than 550 GtCO 2 , temporary overshoot of the 1.5°C limit becomes unavoidable if CDR cannot be ramped up faster than to 4 GtCO 2 in 2040 and 10 GtCO 2 in 2050.This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. © 2018 The Author(s).

  14. Physiological responses and energy cost of walking on the Gait Trainer with and without body weight support in subacute stroke patients

    PubMed Central

    2014-01-01

    Background Robotic-assisted walking after stroke provides intensive task-oriented training. But, despite the growing diffusion of robotic devices little information is available about cardiorespiratory and metabolic responses during electromechanically-assisted repetitive walking exercise. Aim of the study was to determine whether use of an end-effector gait training (GT) machine with body weight support (BWS) would affect physiological responses and energy cost of walking (ECW) in subacute post-stroke hemiplegic patients. Methods Participants: six patients (patient group: PG) with hemiplegia due to stroke (age: 66 ± 15y; time since stroke: 8 ± 3 weeks; four men) and 6 healthy subjects as control group (CG: age, 76 ± 7y; six men). Interventions: overground walking test (OWT) and GT-assisted walking with 0%, 30% and 50% BWS (GT-BWS0%, 30% and 50%). Main Outcome Measures: heart rate (HR), pulmonary ventilation, oxygen consumption, respiratory exchange ratio (RER) and ECW. Results Intervention conditions significantly affected parameter values in steady state (HR: p = 0.005, V’E: p = 0.001, V'O2: p < 0.001) and the interaction condition per group affected ECW (p = 0.002). For PG, the most energy (V’O2 and ECW) demanding conditions were OWT and GT-BWS0%. On the contrary, for CG the least demanding condition was OWT. On the GT, increasing BWS produced a decrease in energy and cardiac demand in both groups. Conclusions In PG, GT-BWS walking resulted in less cardiometabolic demand than overground walking. This suggests that GT-BWS walking training might be safer than overground walking training in subacute stroke patients. PMID:24720844

  15. Physiological responses and energy cost of walking on the Gait Trainer with and without body weight support in subacute stroke patients.

    PubMed

    Delussu, Anna Sofia; Morone, Giovanni; Iosa, Marco; Bragoni, Maura; Traballesi, Marco; Paolucci, Stefano

    2014-04-10

    Robotic-assisted walking after stroke provides intensive task-oriented training. But, despite the growing diffusion of robotic devices little information is available about cardiorespiratory and metabolic responses during electromechanically-assisted repetitive walking exercise. Aim of the study was to determine whether use of an end-effector gait training (GT) machine with body weight support (BWS) would affect physiological responses and energy cost of walking (ECW) in subacute post-stroke hemiplegic patients. six patients (patient group: PG) with hemiplegia due to stroke (age: 66 ± 15y; time since stroke: 8 ± 3 weeks; four men) and 6 healthy subjects as control group (CG: age, 76 ± 7y; six men). overground walking test (OWT) and GT-assisted walking with 0%, 30% and 50% BWS (GT-BWS0%, 30% and 50%). heart rate (HR), pulmonary ventilation, oxygen consumption, respiratory exchange ratio (RER) and ECW. Intervention conditions significantly affected parameter values in steady state (HR: p = 0.005, V'E: p = 0.001, V'O2: p < 0.001) and the interaction condition per group affected ECW (p = 0.002). For PG, the most energy (V'O2 and ECW) demanding conditions were OWT and GT-BWS0%. On the contrary, for CG the least demanding condition was OWT. On the GT, increasing BWS produced a decrease in energy and cardiac demand in both groups. In PG, GT-BWS walking resulted in less cardiometabolic demand than overground walking. This suggests that GT-BWS walking training might be safer than overground walking training in subacute stroke patients.

  16. Expression profiles of gonadotropins and their receptors during 17α-methyltestosterone implantation-induced sex change in the orange-spotted grouper (Epinephelus coioides).

    PubMed

    Hu, Xuesong; Liu, Xiaochun; Zhang, Haifa; Zhang, Yong; Li, Shuisheng; Sang, Qing; Wang, Qian; Luo, Wenna; Liu, Qizhi; Lu, Danqi; Meng, Zining; Lin, Haoran

    2011-06-01

    It is known that the hypothalamic-pituitary-gonadal axis participates in the sex change of hermaphrodite teleosts, and gonadal steroid hormones mediate this physiological process. The secretion of gonadal steroids is directly regulated by signaling pathways involving gonadotropins (GtHs) and gonadotropin receptors (GtHRs) in teleosts. To gain insight into the involvement of GtH/GtHR systems in the sex change process, cDNAs encoding follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were firstly isolated from gonads of orange-spotted grouper (Epinephelus coioides), a protogynous hermaphrodite fish. Reverse transcription-PCR (RT-PCR) analysis demonstrated that the expression of the FSHR was confined to the brain, pituitary gland, ovary, and testis, while the LHR was expressed only in the brain, ovary, and testis. Furthermore, the expression profiles of GtH subunits (FSHβ and LHβ) and their receptors were analyzed in parallel with the serum levels of estradiol-17β (E(2) ), testosterone (T), and 11-ketotestosterone (11-KT) during 17α-methyltestosterone (MT)-induced sex change. Quantitative real-time PCR determined that the abundances of FSHβ and FSHR were significantly inhibited after MT treatment for 2 and 4 weeks, but subsequently returned to the control level after 6 weeks. In contrast, the mRNA levels of LHβ and LHR were significantly elevated throughout the sex change process. During MT-induced sex change, serum concentrations of E(2) remained constant while T and 11-KT levels were significantly increased. Taken together, our results suggest that GtH/GtHR systems are involved in MT-induced sex change, and two signaling pathways may have distinct roles in modulating the variations of the corresponding steroid hormones in the orange-spotted grouper. Copyright © 2011 Wiley-Liss, Inc.

  17. Gluteal tendinopathy and hip osteoarthritis: Different pathologies, different hip biomechanics.

    PubMed

    Allison, Kim; Hall, Michelle; Hodges, Paul W; Wrigley, Tim V; Vicenzino, Bill; Pua, Yong-Hao; Metcalf, Ben; Grimaldi, Alison; Bennell, Kim L

    2018-03-01

    Gluteal tendinopathy (GT) and hip osteoarthritis (OA) are the most common causes of hip pain and associated disability in older adults. Pain and altered walking biomechanics are common to both conditions. This study aimed to compare three-dimensional walking biomechanics between individuals with unilateral, symptomatic GT and HOA. Sixty individuals with symptomatic unilateral GT confirmed by magnetic-resonance-imaging and 73 individuals with symptomatic unilateral HOA (Kellgren-Lawrence Grade ≥ 2) underwent three-dimensional gait analysis. Maximum and minimum values of the external sagittal hip moment, the first peak, second peak and mid-stance minimum of the hip adduction moment (HAM), sagittal plane hip excursion and hip joint angles, pelvic obliquity and trunk lean, at the three HAM time points during stance phase of walking were compared between groups. Compared to individuals with HOA, those with GT exhibited a greater hip peak extension moment (P < 0.001) and greater HAM throughout the stance phase of walking (P = 0.01-P < 0.001), greater hip adduction (P < 0.001) and internal rotation (P < 0.01-P < 0.001) angles and lower hip flexion angles and excursion (P = 0.02 - P < 0.001). Individuals with HOA exhibited a greater forward trunk lean (P ≤ 0.001) throughout stance, and greater ipsilateral trunk lean in the frontal plane (P < 0.001) than those with GT. Despite presence of pain in both conditions, hip kinematics and kinetics differ between individuals with symptomatic unilateral GT and those with symptomatic unilateral HOA. These condition-specific impairments may be targets for optimization of management of HOA and GT. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status.

    PubMed

    Singh, Vijay K; Hauer-Jensen, Martin

    2016-05-03

    The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication.

  19. A universal genetic testing initiative for patients with high-grade, non-mucinous epithelial ovarian cancer and the implications for cancer treatment.

    PubMed

    Bednar, Erica M; Oakley, Holly D; Sun, Charlotte C; Burke, Catherine C; Munsell, Mark F; Westin, Shannon N; Lu, Karen H

    2017-08-01

    Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC). We describe a universal genetic testing initiative to increase the rates of recommendation and acceptance of GC and GT to >80% for patients with HGOC at our institution. Data from a consecutive cohort of patients seen in our gynecologic oncology clinics between 9/1/2012 and 8/31/2015 for evaluation of HGOC were retrospectively analyzed. Data were abstracted from the tumor registry, medical records, and research databases. Descriptive statistics were used to evaluate patient characteristics and GC, GT, and PARP inhibitor use. Various clinic interventions were developed, influenced by the Plan-Do-Study-Act cycle method, which included physician-coordinated GT, integrated GC, and assisted GC referrals. A cohort of 1636 patients presented to the gynecologic oncology clinics for evaluation of HGOC during our study period, and 1423 (87.0%) were recommended to have GC and GT. Of these, 1214 (85.3%) completed GT and 217 (17.9%) were found to have a BRCA1 or BRCA2 mutation. Among BRCA-positive patients, 167 had recurrent or progressive disease, and 56 of those received PARP inhibitor therapy. The rates of GC and GT recommendation and completion among patients with HGOC at our institution exceeded 80% following the implementation of a universal genetic testing initiative. Universal genetic testing of patients with HGOC is one strategy to identify those who may benefit from PARP inhibitor therapy. Copyright © 2017. Published by Elsevier Inc.

  20. Utility of the Abbott RealTime HCV Genotype Plus RUO assay used in combination with the Abbott RealTime HCV Genotype II assay.

    PubMed

    He, Chao; Germer, Jeffrey J; Ptacek, Elizabeth R; Bommersbach, Carl E; Mitchell, P Shawn; Yao, Joseph D C

    Hepatitis virus C (HCV) genotype (GT) determination and subtype (ST) differentiation (1a versus 1b) remain important for the selection of appropriate direct-acting antiviral (DAA) therapy. This study is a retrospective comparison of HCV GT and ST result distribution when using the Abbott RealTime HCV Genotype II assay (HCVGT II) alone and in combination with the Abbott RealTime HCV Genotype Plus RUO assay (HCVGT Plus) for routine testing of clinical serum specimens at a reference laboratory. HCVGT II results of specimens tested from June 2014 through January 2016 (period 1) were compared with combined results from HCVGT II and HCVGT Plus (HCVGT II/Plus) performed from January 2016 through January 2017 (period 2). A total of 44,127 and 25,361 specimens were tested during periods 1 and 2, respectively. Use of HCVGT II/Plus significantly reduced the frequency of GT 1 results without ST (0.4%) when compared to preliminary HCVGT II results during period 2 (5.3%; p < 0.01) and final HCVGT II results in period 1 (5.5%; p < 0.01). HCVGT II/Plus also resulted in GT 6 reactivity in 38 specimens with results of "HCV detected" (n = 17) or GT 1 (n = 21) following initial HCVGT II testing during period 2. When compared to the use of HCVGT II alone, HCVGT II/Plus significantly reduced the frequency of GT 1 without ST results observed in a large reference laboratory, while also enabling the identification of HCV GT 6. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Molecular biology based assessment of green tea effects on oxidative stress and cardiac remodelling in dialysis patients.

    PubMed

    Calo, Lorenzo A; Vertolli, Ugo; Davis, Paul A; Maso, Lucia Dal; Pagnin, Elisa; Ravarotto, Verdiana; Maiolino, Giuseppe; Lupia, Mario; Seccia, Teresa M; Rossi, Gian Paolo

    2014-06-01

    Cardiovascular disease, the most common cause for morbidity and mortality in end-stage renal disease (ESRD), has prompted the exploration of multiple approaches to improve outcomes. Cardiovascular risk factors such as oxidative stress (OxSt) and cardiac remodelling are common in ESRD and dialysis patients. Green tea (GT) is well recognized as reducing OxSt. This 6 months study evaluated in 20 ESRD patients under chronic dialysis, the effect of GT treatment (1 g/day as commercially available capsule) on cellular and plasma OxSt and proliferation related markers using a molecular biology approach. Mononuclear cell p22(phox), Haeme Oxygenase (HO)-1 protein expression, and phosphorylated ERK1/2 status were evaluated in dialysis patients at baseline, after 3 and 6 months of GT treatment by Western blot analysis and plasma oxLDL by ELISA. Cardiac remodelling was assessed by echocardiographic left ventricular (LV) mass determination at baseline and at the end of the study. GT treatment reduced p22(phox) and pERK1/2 from baseline while HO-1 increased. At baseline, LV mass correlated with both p22(phox) and oxLDL. GT treatment decreased LV mass from baseline, which correlated with oxLDL. 9 patients had LV hypertrophy at baseline, which, at 6 months, was normalized in 5 and reduced in 3, showing a parallel decrease of p22(phox), pERK1/2, oxLDL and increase of HO-1. Treatment with GT decreased the expression of OxSt-related proteins tightly associated with cardiovascular disease and decreased LV mass. It appears highly likely that the addition of GT can provide a benefit in terms of cardiovascular protection in dialysis patients. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. γ-Tocotrienol as a Promising Countermeasure for Acute Radiation Syndrome: Current Status

    PubMed Central

    Singh, Vijay K.; Hauer-Jensen, Martin

    2016-01-01

    The hazard of ionizing radiation exposure due to nuclear accidents or terrorist attacks is ever increasing. Despite decades of research, still, there is a shortage of non-toxic, safe and effective medical countermeasures for radiological and nuclear emergency. To date, the U.S. Food and Drug Administration (U.S. FDA) has approved only two growth factors, Neupogen (granulocyte colony-stimulating factor (G-CSF), filgrastim) and Neulasta (PEGylated G-CSF, pegfilgrastim) for the treatment of hematopoietic acute radiation syndrome (H-ARS) following the Animal Efficacy Rule. Promising radioprotective efficacy results of γ-tocotrienol (GT3; a member of the vitamin E family) in the mouse model encouraged its further evaluation in the nonhuman primate (NHP) model. These studies demonstrated that GT3 significantly aided the recovery of radiation-induced neutropenia and thrombocytopenia compared to the vehicle controls; these results particularly significant after exposure to 5.8 or 6.5 Gray (Gy) whole body γ-irradiation. The stimulatory effect of GT3 on neutrophils and thrombocytes (platelets) was directly and positively correlated with dose; a 75 mg/kg dose was more effective compared to 37.5 mg/kg. GT3 was also effective against 6.5 Gy whole body γ-irradiation for improving neutrophils and thrombocytes. Moreover, a single administration of GT3 without any supportive care was equivalent, in terms of improving hematopoietic recovery, to multiple doses of Neupogen and two doses of Neulasta with full supportive care (including blood products) in the NHP model. GT3 may serve as an ultimate radioprotector for use in humans, particularly for military personnel and first responders. In brief, GT3 is a promising radiation countermeasure that ought to be further developed for U.S. FDA approval for the ARS indication. PMID:27153057

  3. A quantitative validated model reveals two phases of transcriptional regulation for the gap gene giant in Drosophila.

    PubMed

    Hoermann, Astrid; Cicin-Sain, Damjan; Jaeger, Johannes

    2016-03-15

    Understanding eukaryotic transcriptional regulation and its role in development and pattern formation is one of the big challenges in biology today. Most attempts at tackling this problem either focus on the molecular details of transcription factor binding, or aim at genome-wide prediction of expression patterns from sequence through bioinformatics and mathematical modelling. Here we bridge the gap between these two complementary approaches by providing an integrative model of cis-regulatory elements governing the expression of the gap gene giant (gt) in the blastoderm embryo of Drosophila melanogaster. We use a reverse-engineering method, where mathematical models are fit to quantitative spatio-temporal reporter gene expression data to infer the regulatory mechanisms underlying gt expression in its anterior and posterior domains. These models are validated through prediction of gene expression in mutant backgrounds. A detailed analysis of our data and models reveals that gt is regulated by domain-specific CREs at early stages, while a late element drives expression in both the anterior and the posterior domains. Initial gt expression depends exclusively on inputs from maternal factors. Later, gap gene cross-repression and gt auto-activation become increasingly important. We show that auto-regulation creates a positive feedback, which mediates the transition from early to late stages of regulation. We confirm the existence and role of gt auto-activation through targeted mutagenesis of Gt transcription factor binding sites. In summary, our analysis provides a comprehensive picture of spatio-temporal gene regulation by different interacting enhancer elements for an important developmental regulator. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

    PubMed

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

    2011-12-01

    Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or L (≥ 27 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Removal of arsenic in flotation of galena and sphalerite

    NASA Astrophysics Data System (ADS)

    Yu, Dae-hwan; Kim, Min-kyu; Han, Oh-hyung; Park, Chul-hyun

    2017-04-01

    In Korea, Janggun mine that produces the concentrate of galena (PbS) /sphalerite (ZnS) containing arsenic of 1.3% charges a penalty of US 3/ton to LS-Nikko smelter. Hence in this work, flotation tests for removal of arsenopyrite (FeAsS) from sulfide minerals were carried out using lab scale flotation cell, which maintain grade and recovery of PbS and ZnS in comparison to flotation plant. Particularly, this study was focused on investigating the combination of several chemical reagents such as depressant, collector, activator and etc. that affect flotation performance. In the straight differential flotation for PbS, a PbS grade of 67.80% and a recovery of 80.2% could be obtained with FeAsS removal of 84.1% (0.2% As) under the conditions of 20% feed solids concentration, pH 8.5, 50g/t frother (AF65), 50g/t collector (AP242) and 600g/t As depressant (NaHSO3) and 600g/t Zn depressant (ZnSO4). In the ZnS flotation, the maximum separation achievable for ZnS has been shown to be a grade of 50.27% and a recovery of 88.7%. At this time, FeAsS removal of 87.8% (0.16% As) could be successfully accomplished under pH 11, and 1.2kg/t Zn activator (CuSO4), 100g/t frother (AF65), 100g/t collector (AP211) and 400g/t As depressant (NaHSO3). Acknowledgments This work was supported by the Energy and Resources Engineering Program Grant funded by the Ministry of Trade, Industry and Energy, Korea

  6. The K-PG boundary: how geological events lead to collapse of marine primary producers

    NASA Astrophysics Data System (ADS)

    Hir guillaume, Le; frederic, Fluteau; yves, Goddéris

    2017-04-01

    The cause(s) of Cretaceous/Paleogene (K-Pg) mass extinction event is a matter of debate since three decades. A first scenario connects the K-Pg crisis with the Chicxulub impact while the second scenario evokes the emplacement of the Deccan traps in India as the cause for the K-Pg biodiversity collapse. Pierazzo et al. (1998) estimated that the extraterrestrial bolide lead to an instantaneously CO2 degassing ranging from 880 Gt to 2,960 Gt into the atmosphere, together with a massive release of SO2 ranging from 150 to 460 Gt.. Self et al. (2006, 2008) and Chenet et al. (2009) suggested that the emplacement of the Deccan traps released 15,000 Gt to 35,000 Gt of CO2 and 6,800 Gt to 17,000 Gt of SO2 over a 250 kyr-long period (Schoene et al., 2015). To decipher and quantify the long term environmental consequences of both events, we tested different scenarios: a pulse-like magmatic degassing, a bolide impact, and a combination of both. To understand the environmental changes and quantify biodiversity responses, we improve GEOCLIM, a coupled climate-carbon numerical model, by implementing a biodiversity model in which marine species are described by specific death/born rates, sensitivity to abiotic factors (temperature, pH, dissolved O2, calcite saturation state) and feeding relationships, each of these characteristics is assigned randomly. Preliminary simulations accounting for the eruption of the Deccan traps show that successive cooling events (S-aerosols effect) combined with a progressive acidification of surface water (caused by CO2 and SO2 injections) cause a major collapse of the marine biomass. Additional simulations in which Chicxulub impact, different community structures of primary producers will be discussed.

  7. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice

    PubMed Central

    Shin, Jihyun; Yang, Soo Jin

    2016-01-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1-α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1. PMID:28211759

  8. A Family-Based Association Analysis and Meta-Analysis of the Reading Disabilities Candidate Gene DYX1C1

    PubMed Central

    Tran, C.; Gagnon, F.; Wigg, K.G.; Feng, Y.; Gomez, L.; Cate-Carter, T.D.; Kerr, E.N.; Field, L.L.; Kaplan, B.J.; Lovett, M.W.; Barr, C.L.

    2017-01-01

    Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the −3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the −3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and −3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between −3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (−3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the −3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs −3G/A and 1249G/T and RD. PMID:23341075

  9. Correlation between the NPPB gene promoter c.-1298 G/T polymorphism site and pulse pressure in the Chinese Han population.

    PubMed

    Zeng, K; Wu, X D; Cai, H D; Gao, Y G; Li, G; Liu, Q C; Gao, F; Chen, J H; Lin, C Z

    2014-04-29

    The aim of this study was to investigate the correlation between the natriuretic peptide precursor B (NPPB) gene single nucleotide polymorphism (SNP) c.-1298 G/T and pulse pressure (PP) of the Chinese Han population and the association between genotype and clinical indicators of hypertension. Peripheral blood was collected from 180 unrelated patients with hypertension and 540 healthy volunteers (control group), and DNA was extracted to amplify the 5'-flanking region and 2 exons of the NPPB gene by polymerase chain reaction; the fragment was sequenced after purification. The clinical data of all subjects were recorded, the distribution of the NPPB gene c.-1298 G/T polymorphism was determined, and differences in clinical indicators between the two groups were evaluated. The mean arterial pressure PP, and creatinine levels were significantly higher in the hypertension group than in the control group (P<0.05), but no other clinical indicators differed between the groups. There were no significant differences in genotype frequency and distribution of the NPPB gene c.-1298 G/T polymorphism between the hypertension group and the control group (P>0.05); in the control group, the mean PP of individuals with the SNP c.-1298 GG genotype was greater than that of individuals with the GT+TT genotype (P<0.05). In conclusion, there was no significant correlation between the NPPB gene c.-1298 G/T polymorphism and the incidence of essential hypertension in the Han population; however, the PP of the SNP c.-1298 GG genotype was greater than that of the GT+TT genotype in the control group.

  10. Disruption of a Spermatogenic Cell-Specific Mouse Enolase 4 (Eno4) Gene Causes Sperm Structural Defects and Male Infertility1

    PubMed Central

    Nakamura, Noriko; Dai, Qunsheng; Williams, Jason; Goulding, Eugenia H.; Willis, William D.; Brown, Paula R.; Eddy, Edward M.

    2013-01-01

    ABSTRACT Sperm utilize glycolysis to generate ATP required for motility, and several spermatogenic cell-specific glycolytic isozymes are associated with the fibrous sheath (FS) in the principal piece of the sperm flagellum. We used proteomics and molecular biology approaches to confirm earlier reports that a novel enolase is present in mouse sperm. We then found that a pan-enolase antibody, but not antibodies to ENO2 and ENO3, recognized a protein in the principal piece of the mouse sperm flagellum. Database analyses identified two previously uncharacterized enolase family-like candidate genes, 64306537H0Rik and Gm5506. Northern analysis indicated that 64306537H0Rik (renamed Eno4) was transcribed in testes of mice by Postnatal Day 12. To determine the role of ENO4, we generated mice using embryonic stem cells in which an Eno4 allele was disrupted by a gene trap containing a beta galactosidase (beta-gal) reporter (Eno4+/Gt). Expression of beta-gal occurred in the testis, and male mice homozygous for the gene trap allele (Eno4Gt/Gt) were infertile. Epididymal sperm numbers were 2-fold lower and sperm motility was reduced substantially in Eno4Gt/Gt mice compared to wild-type mice. Sperm from Eno4Gt/Gt mice had a coiled flagellum and a disorganized FS. The Gm5506 gene encodes a protein identical to ENO1 and also is transcribed at a low level in testis. We conclude that ENO4 is required for normal assembly of the FS and provides most of the enolase activity in sperm and that Eno1 and/or Gm5506 may encode a minor portion of the enolase activity in sperm. PMID:23446454

  11. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus.

    PubMed

    Shin, Kwang-Soo; Kim, Young Hwan; Yu, Jae-Hyuk

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice.

    PubMed

    Shin, Jihyun; Yang, Soo Jin; Lim, Yunsook

    2017-03-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

  13. Cone-Beam Computed Tomography as a Diagnostic Method for Determination of Gingival Thickness and Distance between Gingival Margin and Bone Crest

    PubMed Central

    Borges, Germana Jayme; Ruiz, Luis Fernando Naldi; de Alencar, Ana Helena Gonçalves; Porto, Olavo César Lyra; Estrela, Carlos

    2015-01-01

    The objective of the present study was to assess cone-beam computed tomography (CBCT) as a diagnostic method for determination of gingival thickness (GT) and distance between gingival margin and vestibular (GMBC-V) and interproximal bone crests (GMBC-I). GT and GMBC-V were measured in 348 teeth and GMBC-I was measured in 377 tooth regions of 29 patients with gummy smile. GT was assessed using transgingival probing (TP), ultrasound (US), and CBCT, whereas GMBC-V and GMBC-I were assessed by transsurgical clinical evaluation (TCE) and CBCT. Statistical analyses used independent t-test, Pearson's correlation coefficient, and simple linear regression. Difference was observed for GT: between TP, CBCT, and US considering all teeth; between TP and CBCT and between TP and US in incisors and canines; between TP and US in premolars and first molars. TP presented the highest means for GT. Positive correlation and linear regression were observed between TP and CBCT, TP and US, and CBCT and US. Difference was observed for GMBC-V and GMBC-I using TCE and CBCT, considering all teeth. Correlation and linear regression results were significant for GMBC-V and GMBC-I in incisors, canines, and premolars. CBCT is an effective diagnostic method to visualize and measure GT, GMBC-V, and GMBC-I. PMID:25918737

  14. Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction.

    PubMed

    Stenmark, Pål; Dupuy, Jérôme; Imamura, Akihiro; Kiso, Makoto; Stevens, Raymond C

    2008-08-15

    Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

  15. Trps1 activates a network of secreted Wnt inhibitors and transcription factors crucial to vibrissa follicle morphogenesis

    PubMed Central

    Fantauzzo, Katherine A.; Christiano, Angela M.

    2012-01-01

    Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities. Trps1 is a vertebrate transcription factor that contains nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA. Mice in which the GATA domain of Trps1 has been deleted (Trps1Δgt/Δgt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally. To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis, comparing expression patterns in the whisker pads of wild-type versus Trps1Δgt/Δgt embryos. We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos and several extracellular matrix proteins that were upregulated in the mutant samples, and demonstrated that target gene expression levels were altered in vivo in Trps1Δgt/Δgt vibrissae. Unexpectedly, we discovered that Trps1 can directly bind the promoters of its target genes to activate transcription, expanding upon its established role as a transcriptional repressor. Our findings identify Trps1 as a novel regulator of the Wnt signaling pathway and of early hair follicle progenitors in the developing vibrissa follicle. PMID:22115758

  16. Ganglioside GT1b protects human spermatozoa from hydrogen peroxide-induced DNA and membrane damage.

    PubMed

    Gavella, Mirjana; Garaj-Vrhovac, Verica; Lipovac, Vaskresenija; Antica, Mariastefania; Gajski, Goran; Car, Nikica

    2010-06-01

    We have reported previously that various gangliosides, the sialic acid containing glycosphingolipids, provide protection against sperm injury caused by reactive oxygen species (ROS). In this study, we investigated the effect of treatment of human spermatozoa with ganglioside GT1b on hydrogen peroxide (H(2)O(2))-induced DNA fragmentation and plasma membrane damage. Single-cell gel electrophoresis (Comet assay) used in the assessment of sperm DNA integrity showed that in vitro supplemented GT1b (100 microm) significantly reduced DNA damage induced by H(2)O(2) (200 microm) (p < 0.05). Measurements of Annexin V binding in combination with the propidium iodide vital dye labelling demonstrated that the spermatozoa pre-treated with GT1b exhibited a significant increase (p < 0.05) in the percentage of live cells with intact membrane and decreased phosphatidylserine translocation after exposure to H(2)O(2). Flow cytometry using the intracellular ROS-sensitive fluorescence dichlorodihydrofluorescein diacetate dye employed to investigate the transport of the extracellularly supplied H(2)O(2) into the cell interior revealed that ganglioside GT1b completely inhibited the passage of H(2)O(2) through the sperm membrane. These results suggest that ganglioside GT1b may protect human spermatozoa from H(2)O(2)-induced damage by rendering sperm membrane more hydrophobic, thus inhibiting the diffusion of H(2)O(2) across the membrane.

  17. A chimeric α-amylase engineered from Bacillus acidicola and Geobacillus thermoleovorans with improved thermostability and catalytic efficiency.

    PubMed

    Parashar, Deepak; Satyanarayana, T

    2016-04-01

    The α-amylase (Ba-amy) of Bacillus acidicola was fused with DNA fragments encoding partial N- and C-terminal region of thermostable α-amylase gene of Geobacillus thermoleovorans (Gt-amy). The chimeric enzyme (Ba-Gt-amy) expressed in Escherichia coli displays marked increase in catalytic efficiency [K cat: 4 × 10(4) s(-1) and K cat/K m: 5 × 10(4) mL(-1) mg(-1) s(-1)] and higher thermostability than Ba-amy. The melting temperature (T m) of Ba-Gt-amy (73.8 °C) is also higher than Ba-amy (62 °C), and the CD spectrum analysis revealed the stability of the former, despite minor alteration in secondary structure. Langmuir-Hinshelwood kinetic analysis suggests that the adsorption of Ba-Gt-amy onto raw starch is more favourable than Ba-amy. Ba-Gt-amy is thus a suitable biocatalyst for raw starch saccharification at sub-gelatinization temperatures because of its acid stability, thermostability and Ca(2+) independence, and better than the other known bacterial acidic α-amylases.

  18. Analysis of frequency shifting in seismic signals using Gabor-Wigner transform

    NASA Astrophysics Data System (ADS)

    Kumar, Roshan; Sumathi, P.; Kumar, Ashok

    2015-12-01

    A hybrid time-frequency method known as Gabor-Wigner transform (GWT) is introduced in this paper for examining the time-frequency patterns of earthquake damaged buildings. GWT is developed by combining the Gabor transform (GT) and Wigner-Ville distribution (WVD). GT and WVD have been used separately on synthetic and recorded earthquake data to identify frequency shifting due to earthquake damages, but GT is prone to windowing effect and WVD involves ambiguity function. Hence to obtain better clarity and to remove the cross terms (frequency interference), GT and WVD are judiciously combined and the resultant GWT used to identify frequency shifting. Synthetic seismic response of an instrumented building and real-time earthquake data recorded on the building were investigated using GWT. It is found that GWT offers good accuracy for even slow variations in frequency, good time-frequency resolution, and localized response. Presented results confirm the efficacy of GWT when compared with GT and WVD used separately. Simulation results were quantified by the Renyi entropy measures and GWT shown to be an adequate technique in identifying localized response for structural damage detection.

  19. Glutathione S-conjugates as prodrugs to target drug-resistant tumors

    PubMed Central

    Ramsay, Emma E.; Dilda, Pierre J.

    2014-01-01

    Living organisms are continuously exposed to xenobiotics. The major phase of enzymatic detoxification in many species is the conjugation of activated xenobiotics to reduced glutathione (GSH) catalyzed by the glutathione-S-transferase (GST). It has been reported that some compounds, once transformed into glutathione S-conjugates, enter the mercapturic acid pathway whose end products are highly reactive and toxic for the cell responsible for their production. The cytotoxicity of these GSH conjugates depends essentially on GST and gamma-glutamyl transferases (γGT), the enzymes which initiate the mercapturic acid synthesis pathway. Numerous studies support the view that the expression of GST and γGT in cancer cells represents an important factor in the appearance of a more aggressive and resistant phenotype. High levels of tumor GST and γGT expression were employed to selectively target tumor with GST- or γGT-activated drugs. This strategy, explored over the last two decades, has recently been successful using GST-activated nitrogen mustard (TLK286) and γGT-activated arsenic-based (GSAO and Darinaparsin) prodrugs confirming the potential of GSH-conjugates as anticancer drugs. PMID:25157234

  20. A thermostable Gloeophyllum trabeum xylanase with potential for the brewing industry.

    PubMed

    Wang, Xiaoyu; Luo, Huiying; Yu, Wangning; Ma, Rui; You, Shuai; Liu, Weina; Hou, Lingyu; Zheng, Fei; Xie, Xiangming; Yao, Bin

    2016-05-15

    A xylanase gene of glycoside hydrolase family 10, GtXyn10, was cloned from Gloeophyllum trabeum CBS 900.73 and expressed in Pichia pastoris GS115. Purified recombinant GtXyn10 exhibited significant activities to xylan (100.0%), lichenan (11.2%), glucan (15.2%) and p-nitrophenol-β-cellobiose (18.6%), demonstrated the maximum xylanase and glucanase activities at pH 4.5-5.0 and 75°C, retained stability over the pH range of 2.0-7.5 and at 70°C, and was resistant to pepsin and trypsin, most metal ions and SDS. Multiple sequence alignment and modeled-structure analysis identified a unique Gly48 in GtXyn10, and site-directed mutagenesis of Gly48 to Lys improved the temperature optimum up to 80°C. Under simulated mashing conditions, GtXyn10 (80U) reduced the mash viscosity by 12.8% and improved the filtration rate by 31.3%. All these properties above make GtXyn10 attractive for potential applications in the feed and brewing industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Crossroads between Bacterial and Mammalian Glycosyltransferases

    PubMed Central

    Brockhausen, Inka

    2014-01-01

    Bacterial glycosyltransferases (GT) often synthesize the same glycan linkages as mammalian GT; yet, they usually have very little sequence identity. Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity. Thus, bacterial GT can be utilized for the enzymatic synthesis of both bacterial and mammalian types of complex glycan structures. A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria. These epitopes include Thomsen–Friedenreich (TF or T) antigen, blood group O, A, and B, type 1 and 2 chains, Lewis antigens, sialylated and fucosylated structures, and polysialic acids. Many different approaches can be taken to investigate the substrate binding and catalytic mechanisms of GT, including crystal structure analyses, mutations, comparison of amino acid sequences, NMR, and mass spectrometry. Knowledge of the protein structures and functions helps to design GT for specific glycan synthesis and to develop inhibitors. The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures. PMID:25368613

  2. Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort.

    PubMed

    Brandão, Ruben; Marcelino, Rute; Gonçalves, Fátima; Diogo, Isabel; Carvalho, Ana; Cabanas, Joaquim; Costa, Inês; Brogueira, Pedro; Ventura, Fernando; Miranda, Ana; Mansinho, Kamal; Gomes, Perpétua

    2018-04-26

    This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H ( p = 0.04).

  3. A new strategy for imaging biomolecular events through interactions between liquid crystals and oil-in-water emulsions.

    PubMed

    Hu, Qiong-Zheng; Jang, Chang-Hyun

    2012-11-21

    In this study, we demonstrate a new strategy to image biomolecular events through interactions between liquid crystals (LCs) and oil-in-water emulsions. The optical response had a dark appearance when a nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), is in contact with emulsion droplets of glyceryl trioleate (GT). In contrast, the optical response had a bright appearance when 5CB is in contact with GT emulsions decorated with surfactants such as sodium oleate. Since lipase can hydrolyze GT and produce oleic acid, the optical response also displays a bright appearance after 5CB has been in contact with a mixture of lipase and GT emulsions. These results indicate the feasibility of monitoring biomolecular events through interactions between LCs and oil-in-water emulsions.

  4. Current ethical and legal issues in health-related direct-to-consumer genetic testing.

    PubMed

    Niemiec, Emilia; Kalokairinou, Louiza; Howard, Heidi Carmen

    2017-09-01

    A variety of health-related genetic testing is currently advertized directly to consumers. This article provides a timely overview of direct-to-consumer genetic testing (DTC GT) and salient ethical issues, as well as an analysis of the impact of the recently adopted regulation on in vitro diagnostic medical devices on DTC GT. DTC GT companies currently employ new testing approaches, report on a wide spectrum of conditions and target new groups of consumers. Such activities raise ethical issues including the questionable analytic and clinical validity of tests, the adequacy of informed consent, potentially misleading advertizing, testing in children, research uses and commercialization of genomic data. The recently adopted regulation on in vitro diagnostic medical devices may limit the offers of predisposition DTC GT in the EU market.

  5. Quasiparticle Scattering in Type-II Weyl semimetal MoTe2.

    PubMed

    Lin, Chun-Liang; Arafune, Ryuichi; Minamitani, Emi; Kawai, Maki; Takagi, Noriaki

    2018-01-30

    The electronic structure of type-II Weyl semimetal molybdenum ditelluride (MoTe<sub>2</sub>) is studied by using scanning tunneling microscopy and density functional theory calculations. Through measuring energy-dependent quasiparticle interference (QPI) patterns with a cryogenic scanning tunneling microscope, several characteristic features are found in the QPI patterns. Two of them arise from the Weyl semimetal nature; one is the topological Fermi arc surface state and the other can be assigned to be a Weyl point. The remaining structures are derived from the scatterings relevant to the bulk electronic states. The findings lead to thorough understanding of the topological electronic structure of type-II Weyl semimetal MoTe<sub>2</sub>. © 2018 IOP Publishing Ltd.

  6. MA130301GT catalogue of Martian impact craters and advanced evaluation of crater detection algorithms using diverse topography and image datasets

    NASA Astrophysics Data System (ADS)

    Salamunićcar, Goran; Lončarić, Sven; Pina, Pedro; Bandeira, Lourenço; Saraiva, José

    2011-01-01

    Recently, all the craters from the major currently available manually assembled catalogues have been merged into the catalogue with 57 633 known Martian impact craters (MA57633GT). In addition, the work on crater detection algorithm (CDA), developed to search for still uncatalogued impact craters using 1/128° MOLA data, resulted in MA115225GT. In parallel with this work another CDA has been developed which resulted in the Stepinski catalogue containing 75 919 craters (MA75919T). The new MA130301GT catalogue presented in this paper is the result of: (1) overall merger of MA115225GT and MA75919T; (2) 2042 additional craters found using Shen-Castan based CDA from the previous work and 1/128° MOLA data; and (3) 3129 additional craters found using CDA for optical images from the previous work and selected regions of 1/256° MDIM, 1/256° THEMIS-DIR, and 1/256° MOC datasets. All craters from MA130301GT are manually aligned with all used datasets. For all the craters that originate from the used catalogues (Barlow, Rodionova, Boyce, Kuzmin, Stepinski) we integrated all the attributes available in these catalogues. With such an approach MA130301GT provides everything that was included in these catalogues, plus: (1) the correlation between various morphological descriptors from used catalogues; (2) the correlation between manually assigned attributes and automated depth/diameter measurements from MA75919T and our CDA; (3) surface dating which has been improved in resolution globally; (4) average errors and their standard deviations for manually and automatically assigned attributes such as position coordinates, diameter, depth/diameter ratio, etc.; and (5) positional accuracy of features in the used datasets according to the defined coordinate system referred to as MDIM 2.1, which incorporates 1232 globally distributed ground control points, while our catalogue contains 130 301 cross-references between each of the used datasets. Global completeness of MA130301GT is up to ˜ D≥2 km (it contains 85 783 such craters, while the smallest D is 0.924 km). This is a considerable improvement in comparison with the completeness of the Rodionova (˜10 km), Barlow (˜5 km) and Stepinski (˜3 km) catalogues. An accompanying result to the new catalogue is a contribution to the evaluation of CDAs - the following methods have been developed: (1) a new context-aware method for the advanced automated registration of craters with GT catalogues; (2) a new method for manual registration of newly found craters into GT catalogues; and (3) additional new accompanying methods for objective evaluation of CDAs using different datasets including optical images.

  7. Optimizing the G/T ratio of the DSS-13 34-meter beam-waveguide antenna

    NASA Technical Reports Server (NTRS)

    Esquivel, M. S.

    1992-01-01

    Calculations using Physical Optics computer software were done to optimize the gain-to-noise temperature (G/T) ratio of DSS-13, the DSN's 34-m beam-waveguide antenna, at X-band for operation with the ultra-low-noise amplifier maser system. A better G/T value was obtained by using a 24.2-dB far-field-gain smooth-wall dual-mode horn than by using the standard X-band 22.5-dB-gain corrugated horn.

  8. GT-WGS: an efficient and economic tool for large-scale WGS analyses based on the AWS cloud service.

    PubMed

    Wang, Yiqi; Li, Gen; Ma, Mark; He, Fazhong; Song, Zhuo; Zhang, Wei; Wu, Chengkun

    2018-01-19

    Whole-genome sequencing (WGS) plays an increasingly important role in clinical practice and public health. Due to the big data size, WGS data analysis is usually compute-intensive and IO-intensive. Currently it usually takes 30 to 40 h to finish a 50× WGS analysis task, which is far from the ideal speed required by the industry. Furthermore, the high-end infrastructure required by WGS computing is costly in terms of time and money. In this paper, we aim to improve the time efficiency of WGS analysis and minimize the cost by elastic cloud computing. We developed a distributed system, GT-WGS, for large-scale WGS analyses utilizing the Amazon Web Services (AWS). Our system won the first prize on the Wind and Cloud challenge held by Genomics and Cloud Technology Alliance conference (GCTA) committee. The system makes full use of the dynamic pricing mechanism of AWS. We evaluate the performance of GT-WGS with a 55× WGS dataset (400GB fastq) provided by the GCTA 2017 competition. In the best case, it only took 18.4 min to finish the analysis and the AWS cost of the whole process is only 16.5 US dollars. The accuracy of GT-WGS is 99.9% consistent with that of the Genome Analysis Toolkit (GATK) best practice. We also evaluated the performance of GT-WGS performance on a real-world dataset provided by the XiangYa hospital, which consists of 5× whole-genome dataset with 500 samples, and on average GT-WGS managed to finish one 5× WGS analysis task in 2.4 min at a cost of $3.6. WGS is already playing an important role in guiding therapeutic intervention. However, its application is limited by the time cost and computing cost. GT-WGS excelled as an efficient and affordable WGS analyses tool to address this problem. The demo video and supplementary materials of GT-WGS can be accessed at https://github.com/Genetalks/wgs_analysis_demo .

  9. Formulation of a dry green tea-apple product: study on antioxidant and color stability.

    PubMed

    Lavelli, Vera; Vantaggi, Claudia; Corey, Mark; Kerr, William

    2010-03-01

    A dry apple product enriched with green tea (GT) extract was designed as a novel food to deliver relevant amounts of catechins. The target water activity (a(w)) range between 0.11 and 0.32 was chosen for the GT-fortified apple, since it corresponds to low water mobility and, consequently, maximum stability of dehydrated apples. The GT-fortified product and a control dehydrated apple product were stored in air, at 30 degrees C, and evaluated for color, antioxidant contents (monomeric flavan 3-ols, total procyanidins, ascorbic acid, chlorogenic acid and dihydrochalcones), ferric reducing/antioxidant power (FRAP), and 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical (DPPH) scavenging capacity. After 1 mo of storage at the lowest a(w) level (0.11), the GT-fortified product retained 80 and 100% of the initial contents of the monomeric flavan 3-ols and total procyanidins, respectively. With increasing a(w) level to 0.32, the stability of antioxidants slowly decreased. The addition of GT to the apple product increased the FRAP value and the DPPH scavenging capacity by 3.6-fold and 4.6-fold respectively, which remained almost unchanged during storage. The GT-fortified product was similar in color to commercially available dehydrated apples. Results highlighted some advantages of using dehydrated apples as a target for green tea fortification, which deserve further trials to investigate potential applications for fortification of other dehydrated fruits.

  10. Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

    PubMed

    Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

    2008-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

  11. Activity-Based Profiling of a Physiologic Aglycone Library Reveals Sugar Acceptor Promiscuity of Family 1 UDP-Glucosyltransferases from Grape1[W

    PubMed Central

    Bönisch, Friedericke; Frotscher, Johanna; Stanitzek, Sarah; Rühl, Ernst; Wüst, Matthias; Bitz, Oliver; Schwab, Wilfried

    2014-01-01

    Monoterpenols serve various biological functions and accumulate in grape (Vitis vinifera), where a major fraction occurs as nonvolatile glycosides. We have screened the grape genome for sequences with similarity to terpene URIDINE DIPHOSPHATE GLYCOSYLTRANSFERASES (UGTs) from Arabidopsis (Arabidopsis thaliana). A ripening-related expression pattern was shown for three candidates by spatial and temporal expression analyses in five grape cultivars. Transcript accumulation correlated with the production of monoterpenyl β-d-glucosides in grape exocarp during ripening and was low in vegetative tissue. Targeted functional screening of the recombinant UGTs for their biological substrates was performed by activity-based metabolite profiling (ABMP) employing a physiologic library of aglycones built from glycosides isolated from grape. This approach led to the identification of two UDP-glucose:monoterpenol β-d-glucosyltransferases. Whereas VvGT14a glucosylated geraniol, R,S-citronellol, and nerol with similar efficiency, the three allelic forms VvGT15a, VvGT15b, and VvGT15c preferred geraniol over nerol. Kinetic resolution of R,S-citronellol and R,S-linalool was shown for VvGT15a and VvGT14a, respectively. ABMP revealed geraniol as the major biological substrate but also disclosed that these UGTs may add to the production of further glycoconjugates in planta. ABMP of aglycone libraries provides a versatile tool to uncover novel biologically relevant substrates of small-molecule glycosyltransferases that often show broad sugar acceptor promiscuity. PMID:25073706

  12. Crystal Structure of Botulinum Neurotoxin Type a in Complex With the Cell Surface Co-Receptor GT1b-Insight Into the Toxin-Neuron Interaction

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

    Stenmark, P.; Dupuy, J.; Inamura, A.

    2009-05-26

    Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in themore » toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.« less

  13. Direct-to-consumer genetic testing in Slovenia: availability, ethical dilemmas and legislation.

    PubMed

    Vrecar, Irena; Peterlin, Borut; Teran, Natasa; Lovrecic, Luca

    2015-01-01

    Over the last few years, many private companies are advertising direct-to-consumer genetic testing (DTC GT), mostly with no or only minor clinical utility and validity of tests and without genetic counselling. International professional community does not approve provision of DTC GT and situation in some EU countries has been analysed already. The aim of our study was to analyse current situation in the field of DTC GT in Slovenia and related legal and ethical issues. Information was retrieved through internet search, performed independently by two authors, structured according to individual private company and the types of offered genetic testing. Five private companies and three Health Insurance Companies offer DTC GT and it is provided without genetic counselling. Available tests include testing for breast cancer, tests with other health-related information (complex diseases, drug responses) and other tests (nutrigenetic, ancestry, paternity). National legislation is currently being developed and Council of Experts in Medical Genetics has issued an opinion about Genetic Testing and Commercialization of Genetic Tests in Slovenia. Despite the fact that Slovenia has signed the Additional protocol to the convention on human rights and biomedicine, concerning genetic testing for health purposes, DTC GT in Slovenia is present and against all international recommendations. There is lack of or no medical supervision, clinical validity and utility of tests and inappropriate genetic testing of minors is available. There is urgent need for regulation of ethical, legal, and social aspects. National legislation on DTC GT is being prepared.

  14. Whey protein concentrate and gum tragacanth as fat replacers in nonfat yogurt: chemical, physical, and microstructural properties.

    PubMed

    Aziznia, S; Khosrowshahi, A; Madadlou, A; Rahimi, J

    2008-07-01

    The effect of whey protein concentrate (WPC) and gum tragacanth (GT) as fat replacers on the chemical, physical, and microstructural properties of nonfat yogurt was investigated. The WPC (7.5, 15, and 20 g/L) and GT (0.25, 0.5, 0.75, and 1 g/L) were incorporated into the skim milk slowly at 40 to 45 degrees C with agitation. The yogurt mixes were pasteurized at 90 degrees C for 10 min, inoculated with 0.1% starter culture, and incubated at 42 degrees C to pH 4.6, then refrigerated overnight at 5 degrees C. A control nonfat yogurt and control full fat yogurt were prepared as described, but without addition of WPC and GT. Increasing amount of WPC led to the increase in total solids, total protein, acidity, and ash content, whereas GT did not affect chemical parameters. Increasing WPC caused a more compact structure consisting of robust casein particles and large aggregates. Firmness was increased and susceptibility to syneresis was decreased as WPC increased. No significant difference was observed for firmness and syneresis of yogurt fortified with GT up to 0.5 g/L compared with control nonfat yogurt. Increasing the amount of gum above 0.5 g/L produced softer gels with a greater tendency for syneresis than the ones prepared without it. Addition of GT led to the coarser and more open structure compared with control yogurt.

  15. Global carbon budget 2014

    NASA Astrophysics Data System (ADS)

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.; Peters, G. P.; Ciais, P.; Friedlingstein, P.; Jones, S. D.; Sitch, S.; Tans, P.; Arneth, A.; Boden, T. A.; Bopp, L.; Bozec, Y.; Canadell, J. G.; Chevallier, F.; Cosca, C. E.; Harris, I.; Hoppema, M.; Houghton, R. A.; House, J. I.; Jain, A.; Johannessen, T.; Kato, E.; Keeling, R. F.; Kitidis, V.; Klein Goldewijk, K.; Koven, C.; Landa, C. S.; Landschützer, P.; Lenton, A.; Lima, I. D.; Marland, G.; Mathis, J. T.; Metzl, N.; Nojiri, Y.; Olsen, A.; Ono, T.; Peters, W.; Pfeil, B.; Poulter, B.; Raupach, M. R.; Regnier, P.; Rödenbeck, C.; Saito, S.; Salisbury, J. E.; Schuster, U.; Schwinger, J.; Séférian, R.; Segschneider, J.; Steinhoff, T.; Stocker, B. D.; Sutton, A. J.; Takahashi, T.; Tilbrook, B.; van der Werf, G. R.; Viovy, N.; Wang, Y.-P.; Wanninkhof, R.; Wiltshire, A.; Zeng, N.

    2014-09-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe datasets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuel combustion and cement production (EFF) are based on energy statistics and cement production data, respectively, while emissions from Land-Use Change (ELUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent Dynamic Global Vegetation Models forced by observed climate, CO2 and land cover change (some including nitrogen-carbon interactions). We compare the variability and mean land and ocean fluxes to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2004-2013), EFF was 8.9 ± 0.4 GtC yr-1, ELUC 0.9 ± 0.5 GtC yr-1, GATM 4.3 ± 0.1 GtC yr-1, SOCEAN 2.6 ± 0.5 GtC yr-1, and SLAND 2.9 ± 0.8 GtC yr-1. For year 2013 alone, EFF grew to 9.9 ± 0.5 GtC yr-1, 2.3% above 2012, contining the growth trend in these emissions. ELUC was 0.9 ± 0.5 GtC yr-1, GATM was 5.4 ± 0.2 GtC yr-1, SOCEAN was 2.9 ± 0.5 GtC yr-1 and SLAND was 2.5 ± 0.9 GtC yr-1. GATM was high in 2013 reflecting a steady increase in EFF and smaller and opposite changes between SOCEAN and SLAND compared to the past decade (2004-2013). The global atmospheric CO2 concentration reached 395.31 ± 0.10 ppm averaged over 2013. We estimate that EFF will increase by 2.5% (1.3-3.5%) to 10.1 ± 0.6 GtC in 2014 (37.0 ± 2.2 GtCO2 yr-1), 65% above emissions in 1990, based on projections of World Gross Domestic Product and recent changes in the carbon intensity of the economy. From this projection of EFF and assumed constant ELUC for 2014, cumulative emissions of CO2 will reach about 545 ± 55 GtC (2000 ± 200 GtCO2) for 1870-2014, about 75% from EFF and 25% from ELUC. This paper documents changes in the methods and datasets used in this new carbon budget compared with previous publications of this living dataset (Le Quéré et al., 2013, 2014). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2014). Italic font highlights significant methodological changes and results compared to the Le Quéré et al. (2014) manuscript that accompanies the previous version of this living data.

  16. Global carbon budget 2014

    DOE PAGES

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.; ...

    2015-05-08

    Accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. COmore » 2 emissions from fossil fuel combustion and cement production ( E FF) are based on energy statistics and cement production data, respectively, while emissions from land-use change ( E LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. The mean ocean CO 2 sink ( S OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink ( S LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO 2, and land-cover-change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ;, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2004–2013), E FF was 8.9 ± 0.4 GtC yr⁻¹, E LUC 0.9 ± 0.5 GtC yr⁻¹, G ATM 4.3 ± 0.1 GtC yr⁻¹, S OCEAN 2.6 ± 0.5 GtC yr⁻¹, and S LAND 2.9 ± 0.8 GtC yr⁻¹. For year 2013 alone, E FF grew to 9.9 ± 0.5 GtC yr⁻¹, 2.3% above 2012, continuing the growth trend in these emissions, E LUC was 0.9 ± 0.5 GtC yr⁻¹, G ATM was 5.4 ± 0.2 GtC yr⁻¹, S OCEAN was 2.9 ± 0.5 GtC yr⁻¹, and S LAND was 2.5 ± 0.9 GtC yr⁻¹. G ATM was high in 2013, reflecting a steady increase in E FF and smaller and opposite changes between S OCEAN and S LAND compared to the past decade (2004–2013). The global atmospheric CO 2 concentration reached 395.31 ± 0.10 ppm averaged over 2013. We estimate that E FF will increase by 2.5% (1.3–3.5%) to 10.1 ± 0.6 GtC in 2014 (37.0 ± 2.2 GtCO 2 yr⁻¹), 65% above emissions in 1990, based on projections of world gross domestic product and recent changes in the carbon intensity of the global economy. From this projection of E FF and assumed constant E LUC for 2014, cumulative emissions of CO 2 will reach about 545 ± 55 GtC (2000 ± 200 GtCO 2) for 1870–2014, about 75% from E FF and 25% from E LUC. This paper documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this living data set (Le Quéré et al., 2013, 2014). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2014).« less

  17. Global carbon budget 2014

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

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.

    Accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. COmore » 2 emissions from fossil fuel combustion and cement production ( E FF) are based on energy statistics and cement production data, respectively, while emissions from land-use change ( E LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. The mean ocean CO 2 sink ( S OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink ( S LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO 2, and land-cover-change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ;, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2004–2013), E FF was 8.9 ± 0.4 GtC yr⁻¹, E LUC 0.9 ± 0.5 GtC yr⁻¹, G ATM 4.3 ± 0.1 GtC yr⁻¹, S OCEAN 2.6 ± 0.5 GtC yr⁻¹, and S LAND 2.9 ± 0.8 GtC yr⁻¹. For year 2013 alone, E FF grew to 9.9 ± 0.5 GtC yr⁻¹, 2.3% above 2012, continuing the growth trend in these emissions, E LUC was 0.9 ± 0.5 GtC yr⁻¹, G ATM was 5.4 ± 0.2 GtC yr⁻¹, S OCEAN was 2.9 ± 0.5 GtC yr⁻¹, and S LAND was 2.5 ± 0.9 GtC yr⁻¹. G ATM was high in 2013, reflecting a steady increase in E FF and smaller and opposite changes between S OCEAN and S LAND compared to the past decade (2004–2013). The global atmospheric CO 2 concentration reached 395.31 ± 0.10 ppm averaged over 2013. We estimate that E FF will increase by 2.5% (1.3–3.5%) to 10.1 ± 0.6 GtC in 2014 (37.0 ± 2.2 GtCO 2 yr⁻¹), 65% above emissions in 1990, based on projections of world gross domestic product and recent changes in the carbon intensity of the global economy. From this projection of E FF and assumed constant E LUC for 2014, cumulative emissions of CO 2 will reach about 545 ± 55 GtC (2000 ± 200 GtCO 2) for 1870–2014, about 75% from E FF and 25% from E LUC. This paper documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this living data set (Le Quéré et al., 2013, 2014). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2014).« less

  18. Isospin symmetry of Tz =±3/2→±1/2 Gamow-Teller transitions in A=41 nuclei

    NASA Astrophysics Data System (ADS)

    Fujita, Y.; Shimbara, Y.; Adachi, T.; Berg, G. P.; Brown, B. A.; Fujita, H.; Hatanaka, K.; Kamiya, J.; Nakanishi, K.; Sakemi, Y.; Sasaki, S.; Shimizu, Y.; Tameshige, Y.; Uchida, M.; Wakasa, T.; Yosoi, M.

    2004-11-01

    Under the assumption that isospin T is a good quantum number, isobaric analog states and various analogous transitions are expected in isobars with mass number A . The strengths of Tz =±3/2→±1/2 analogous Gamow-Teller (GT) transitions and analogous M1 transitions within the A=41 isobar quartet are compared in detail. The Tz =+3/2→+1/2 GT transitions from the Jπ = 3/2+ ground state of 41K leading to excited Jπ = 1/2+ , 3/2+ , and 5/2+ states in 41Ca were measured using the ( 3He ,t) charge-exchange reaction. With a high energy resolution of 35 keV , many fragmented states were observed, and the GT strength distribution was determined up to 10 MeV excitation energy ( Ex ) . The main part of the strength was concentrated in the Ex =4 6 MeV region. A shell-model calculation could reproduce the concentration, but not so well details of the strength distribution. The obtained distribution was further compared with two results of 41Ti β decay studying the analogous Tz =-3/2→-1/2 GT strengths. They reported contradicting distributions. One-to-one correspondences of analogous transitions and analog states were assigned up to Ex =6 MeV in the comparison with one of these 41Ti β -decay results. Combining the spectroscopic information of the analog states in 41Ca and 41Sc , the most probable Jπ values were deduced for each pair of analog states. It was found that 5/2+ states carry the main part of the observed GT strength, while much less GT strength was carried by 1/2+ and 3/2+ states. The gross features of the GT strength distributions for each J were similar for the isospin analogous Tz =±3/2→±1/2 transitions, but the details were somewhat different. From the difference of the distributions, isospin-asymmetry matrix elements of ≈8 keV were deduced. The Coulomb displacement energy, which is sensitive to the configuration of states, showed a sudden increase of about 50 keV at the excitation energy of 3.8 MeV . The strengths of several M1 transitions to the IAS in 41Ca were compared with the strengths of analogous GT transitions. It was found that ratios of the M1 and GT transition strengths were similar, suggesting that the contributions of the ℓτ term in M1 transitions are small.

  19. Computational Modeling and Simulation of Genital Tubercle Development

    EPA Pesticide Factsheets

    Hypospadias is a developmental defect of urethral tube closure that has a complex etiology involving genetic and environmental factors, including anti-androgenic and estrogenic disrupting chemicals; however, little is known about the morphoregulatory consequences of androgen/estrogen balance during genital tubercle (GT) development. Computer models that predictively model sexual dimorphism of the GT may provide a useful resource to translate chemical-target bipartite networks and their developmental consequences across the human-relevant chemical universe. Here, we describe a multicellular agent-based model of genital tubercle (GT) development that simulates urethrogenesis from the sexually-indifferent urethral plate stage to urethral tube closure. The prototype model, constructed in CompuCell3D, recapitulates key aspects of GT morphogenesis controlled by SHH, FGF10, and androgen pathways through modulation of stochastic cell behaviors, including differential adhesion, motility, proliferation, and apoptosis. Proper urethral tube closure in the model was shown to depend quantitatively on SHH- and FGF10-induced effects on mesenchymal proliferation and epithelial apoptosis??both ultimately linked to androgen signaling. In the absence of androgen, GT development was feminized and with partial androgen deficiency, the model resolved with incomplete urethral tube closure, thereby providing an in silico platform for probabilistic prediction of hypospadias risk across c

  20. Effects of Ex Vivo y-Tocopherol on Airway Macrophage ...

    EPA Pesticide Factsheets

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6)and mild house dust mite-sensitive allergic asthmatics (n =6) were treated ex vivo with GT (300 uM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206,CD36 and CD86 in allergic asthmatics but not in corntrols. Overall, GT caused down regulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor. Recent studies on the effects of the fat-soluble steriod hormone vitamins D and E suggest that dietary suplementation with these vitamins may be helpful for the prevention or in the treatment of inflammatory and immune-mediated diseases, including atopic asthma.

  1. Integration of Ganglioside GT1b Receptor into DPPE and DPPC Phospholipid Monolayers: An X-Ray Reflectivity and Grazing-Incidence Diffraction Study

    PubMed Central

    Miller, C. E.; Busath, D. D.; Strongin, B.; Majewski, J.

    2008-01-01

    Using synchrotron grazing-incidence x-ray diffraction (GIXD) and reflectivity, the in-plane and out-of-plane structures of mixed-ganglioside GT1b-phospholipid monolayers were investigated at the air-liquid interface and compared with monolayers of the pure components. The receptor GT1b is involved in the binding of lectins and toxins, including botulinum neurotoxin, to cell membranes. Monolayers composed of 20 mol % ganglioside GT1b, the phospholipid dipalmitoyl phosphatidylethanolamine (DPPE), and the phospholipid dipalmitoyl phosphatidylcholine (DPPC) were studied in the gel phase at 23°C and at surface pressures of 20 and 40 mN/m, and at pH 7.4 and 5. Under these conditions, the two components did not phase-separate, and no evidence of domain formation was observed. The x-ray scattering measurements revealed that GT1b was intercalated within the host DPPE/DPPC monolayers, and slightly expanded DPPE but condensed the DPPC matrix. The oligosaccharide headgroups extended normally from the monolayer surfaces into the subphase. This study demonstrated that these monolayers can serve as platforms for investigating toxin membrane binding and penetration. PMID:18599631

  2. Inverse Resistance Change Cr2Ge2Te6-Based PCRAM Enabling Ultralow-Energy Amorphization.

    PubMed

    Hatayama, Shogo; Sutou, Yuji; Shindo, Satoshi; Saito, Yuta; Song, Yun-Heub; Ando, Daisuke; Koike, Junichi

    2018-01-24

    Phase-change random access memory (PCRAM) has attracted much attention for next-generation nonvolatile memory that can replace flash memory and can be used for storage-class memory. Generally, PCRAM relies on the change in the electrical resistance of a phase-change material between high-resistance amorphous (reset) and low-resistance crystalline (set) states. Herein, we present an inverse resistance change PCRAM with Cr 2 Ge 2 Te 6 (CrGT) that shows a high-resistance crystalline reset state and a low-resistance amorphous set state. The inverse resistance change was found to be due to a drastic decrease in the carrier density upon crystallization, which causes a large increase in contact resistivity between CrGT and the electrode. The CrGT memory cell was demonstrated to show fast reversible resistance switching with a much lower operating energy for amorphization than a Ge 2 Sb 2 Te 5 memory cell. This low operating energy in CrGT should be due to a small programmed amorphous volume, which can be realized by a high-resistance crystalline matrix and a dominant contact resistance. Simultaneously, CrGT can break the trade-off relationship between the crystallization temperature and operating speed.

  3. Reliable high-power injection locked 6kHz 60W laser for ArF immersion lithography

    NASA Astrophysics Data System (ADS)

    Watanabe, Hidenori; Komae, Shigeo; Tanaka, Satoshi; Nohdomi, Ryoichi; Yamazaki, Taku; Nakarai, Hiroaki; Fujimoto, Junichi; Matsunaga, Takashi; Saito, Takashi; Kakizaki, Kouji; Mizoguchi, Hakaru

    2007-03-01

    Reliable high power 193nm ArF light source is desired for the successive growth of ArF-immersion technology for 45nm node generation. In 2006, Gigaphoton released GT60A, high power injection locked 6kHz/60W/0.5pm (E95) laser system, to meet the demands of semiconductor markets. In this paper, we report key technologies for reliable mass production GT laser systems and GT60A high durability performance test results up to 20 billion pulses.

  4. Optimizing the G/T ratio of the DSS-13 34-meter beam-waveguide antenna

    NASA Technical Reports Server (NTRS)

    Esquivel, M. S.

    1992-01-01

    Calculations using Physical Optics computer software were done to optimize the gain-to-noise-temperature (G/T) ratio of Deep Space Station (DSS)-13, the Deep Space Network's (DSN's) 34-m beam-waveguide antenna, at X-band for operation with the ultra-low-noise amplifier maser system. A better G/T value was obtained by using a 24.2-dB far-field-gain smooth-wall dual-mode horn than by using the standard X-band 22.5-dB-gain corrugated horn.

  5. Spontaneous mutations of the UDP-glucose:flavonoid 3-O-glucosyltransferase gene confers pale- and dull-colored flowers in the Japanese and common morning glories.

    PubMed

    Morita, Yasumasa; Ishiguro, Kanako; Tanaka, Yoshikazu; Iida, Shigeru; Hoshino, Atsushi

    2015-09-01

    UDP-glucose:flavonoid 3- O -glucosyltransferase is essential for maintaining proper production quantity, acylation, and glucosylation of anthocyanin, and defects cause pale and dull flower pigmentation in morning glories. The Japanese (Ipomoea nil) and the common (I. purpurea) morning glory display bright blue and dark purple flowers, respectively. These flowers contain acylated and glucosylated anthocyanin pigments, and a number of flower color mutants have been isolated in I. nil. Of these, the duskish mutants of I. nil produce pale- and dull-colored flowers. We found that the Duskish gene encodes UDP-glucose:flavonoid 3-O-glucosyltransferase (3GT). The duskish-1 mutation is a frameshift mutation caused by a 4-bp insertion, and duskish-2 is an insertion of a DNA transposon, Tpn10, at 1.3 kb upstream of the 3GT start codon. In the duskish-2 mutant, excision of Tpn10 is responsible for restoration of the expression of the 3GT gene. The recombinant 3GT protein displays expected 3GT enzymatic activities to catalyze 3-O-glucosylation of anthocyanidins in vitro. Anthocyanin analysis of a duskish-2 mutant and its germinal revertant showing pale and normal pigmented flowers, respectively, revealed that the mutation caused around 80 % reduction of anthocyanin accumulation. We further characterized two I. purpurea mutants showing pale brownish-red flowers, and found that they carry the same frameshift mutation in the 3GT gene. Most of the flower anthocyanins in the mutants were previously found to be anthocyanidin 3-O-glucosides lacking several caffeic acid and glucose moieties that are attached to the anthocyanins in the wild-type plants. These results indicated that 3GT is essential not only for production, but also for proper acylation and glucosylation, of anthocyanin in the morning glories.

  6. Tumor Necrosis Factor (TNF) –308G>A, Nitric Oxide Synthase 3 (NOS3) +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis

    PubMed Central

    Chen, Min; Tang, Wenjing; Hou, Lei; Liu, Ruozhuo; Dong, Zhao; Han, Xun; Zhang, Xiaofei; Wan, Dongjun; Yu, Shengyuan

    2015-01-01

    Background and Objective Conflicting data have been reported on the association between tumor necrosis factor (TNF) –308G>A and nitric oxide synthase 3 (NOS3) +894G>T polymorphisms and migraine. We performed a meta-analysis of case-control studies to evaluate whether the TNF –308G>A and NOS3 +894G>T polymorphisms confer genetic susceptibility to migraine. Method We performed an updated meta-analysis for TNF –308G>A and a meta-analysis for NOS3 +894G>T based on studies published up to July 2014. We calculated study specific odds ratios (OR) and 95% confidence intervals (95% CI) assuming allele contrast, dominant model, recessive model, and co-dominant model as pooled effect estimates. Results Eleven studies in 6682 migraineurs and 22591 controls for TNF –308G>A and six studies in 1055 migraineurs and 877 controls for NOS3 +894G>T were included in the analysis. Neither indicated overall associations between gene polymorphisms and migraine risk. Subgroup analyses suggested that the “A” allele of the TNF –308G>A variant increases the risk of migraine among non-Caucasians (dominant model: pooled OR = 1.82; 95% CI 1.15 – 2.87). The risk of migraine with aura (MA) was increased among both Caucasians and non-Caucasians. Subgroup analyses suggested that the “T” allele of the NOS3 +894G>T variant increases the risk of migraine among non-Caucasians (co-dominant model: pooled OR = 2.10; 95% CI 1.14 – 3.88). Conclusions Our findings appear to support the hypothesis that the TNF –308G>A polymorphism may act as a genetic susceptibility factor for migraine among non-Caucasians and that the NOS3 +894G>T polymorphism may modulate the risk of migraine among non-Caucasians. PMID:26098763

  7. Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection.

    PubMed

    Reau, Nancy; Kwo, Paul Y; Rhee, Susan; Brown, Robert S; Agarwal, Kosh; Angus, Peter; Gane, Edward; Kao, Jia-Horng; Mantry, Parvez S; Mutimer, David; Reddy, K Rajender; Tran, Tram T; Hu, Yiran B; Gulati, Abhishek; Krishnan, Preethi; Dumas, Emily O; Porcalla, Ariel; Shulman, Nancy S; Liu, Wei; Samanta, Suvajit; Trinh, Roger; Forns, Xavier

    2018-04-19

    Well-tolerated, ribavirin-free, pangenotypic hepatitis C virus (HCV) treatments for transplant recipients remain a high priority. Once-daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response for 12 weeks post-treatment (SVR12) across all major HCV genotypes (GT). This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1-6 infection who had received a liver or kidney transplant. MAGELLAN-2 was a phase 3, open-label trial conducted in patients who were ≥3 months post-transplant. Patients without cirrhosis who were HCV treatment-naïve (GT1-6) or treatment-experienced (GT1, 2, 4-6; with interferon-based therapy with or without sofosbuvir, or sofosbuvir plus ribavirin) received glecaprevir/pibrentasvir (300/120 mg) once daily for 12 weeks. The primary endpoint compared the percentage of patients receiving glecaprevir/pibrentasvir with SVR12 to a historic SVR12 rate based on the standard of care. Safety of glecaprevir/pibrentasvir was assessed. In total, 80 liver and 20 kidney transplant patients participated in the trial. Most patients had no or minimal fibrosis (80% had fibrosis scores F0-F1) and were infected with HCV GT1 (57%) or GT3 (24%). The overall SVR12 was 98% (n/N=98/100; 95% confidence interval, 95.3%-100%), which exceeded the pre-specified historic standard of care SVR12 threshold of 94%. One patient experienced virologic failure. One patient discontinued because of an adverse event considered to be unrelated to treatment; this patient achieved SVR12. Adverse events were mostly mild in severity and laboratory abnormalities were infrequent. Once-daily glecaprevir/pibrentasvir for 12 weeks is a well-tolerated and efficacious, ribavirin-free treatment for patients with chronic HCV GT1-6 infection who had received a liver or kidney transplant. ClinicalTrials.gov NCT02692703. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  8. Expression levels of the PiT-2 receptor explain, in part, the gestational age-dependent alterations in transduction efficiency after in utero retroviral-mediated gene transfer

    PubMed Central

    Ozturk, Ferhat; Park, Paul J.; Tellez, Joseph; Colletti, Evan; Eiden, Maribeth V.; Almeida-Porada, Graça; Porada, Christopher D.

    2014-01-01

    Background A fundamental obstacle to using retroviral-mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age-dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT-2 receptor. Methods Immunofluorescence was performed on tissues from sheep of varying developmental stages to assess the proliferative status of the predominant cells within each organ as a function of age. After developing an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcription chain reaction (qRT-PCR) assay, we then quantified PiT-2 expression at the protein and mRNA levels, respectively. Results The results obtained indicate that the proliferative status of organs at the time of fetal GT is not the major determinant governing transduction efficiency. By contrast, our ELISA and qRT-PCR analyses demonstrated that PiT-2 mRNA and protein levels vary with gestational age, correlating with the observed differences in transduction efficiency. Conclusions The findings of the present study explain the age-related differences that we previously observed in transduction efficiency after in utero GT. They also suggest it may be possible to achieve relatively selective GT to specific tissues by performing in utero GT when levels of PiT-2 are maximal in the desired target organ. PMID:22262359

  9. Effect of force tightening on cable tension and displacement in greater trochanter reattachment.

    PubMed

    Canet, Fanny; Duke, Kajsa; Bourgeois, Yan; Laflamme, G-Yves; Brailovski, Vladimir; Petit, Yvan

    2011-01-01

    The purpose of this study was to evaluate cable tension during installation, and during loading similar to walking in a cable grip type greater trochanter (GT), reattachment system. A 4th generation Sawbones composite femur with osteotomised GT was reattached with four Cable-Ready® systems (Zimmer, Warsaw, IN). Cables were tightened at 3 different target installation forces (178, 356 and 534 N) and retightened once as recommended by the manufacturer. Cables tension was continuously monitored using in-situ load cells. To simulate walking, a custom frame was used to apply quasi static load on the head of a femoral stem implant (2340 N) and abductor pull (667 N) on the GT. GT displacement (gap and sliding) relative to the femur was measured using a 3D camera system. During installation, a drop in cable tension was observed when tightening subsequent cables: an average 40+12.2% and 11 ± 5.9% tension loss was measured in the first and second cable. Therefore, retightening the cables, as recommended by the manufacturer, is important. During simulated walking, the second cable additionally lost up to 12.2+3.6% of tension. No difference was observed between the GT-femur gaps measured with cables tightened at different installation forces (p=0.32). The GT sliding however was significantly greater (0.9 ± 0.3 mm) when target installation force was set to only 178 N compared to 356 N (0.2 ± 0.1 mm); p<0.001. There were no significant changes when initial tightening force was increased to 534 N (0.3 ± 0.1 mm); p=0.11. In conclusion, the cable tightening force should be as close as possible to that recommended by the manufacturer, because reducing it compromises the stability of the GT fragment, whereas increasing it does not improve this stability, but could lead to cable breakage.

  10. Reduced MTHFD1 activity in male mice perturbs folate- and choline-dependent one-carbon metabolism as well as transsulfuration.

    PubMed

    Field, Martha S; Shields, Kelsey S; Abarinov, Elena V; Malysheva, Olga V; Allen, Robert H; Stabler, Sally P; Ash, Jessica A; Strupp, Barbara J; Stover, Patrick J; Caudill, Marie A

    2013-01-01

    Impaired utilization of folate is caused by insufficient dietary intake and/or genetic variation and has been shown to prompt changes in related pathways, including choline and methionine metabolism. These pathways have been shown to be sensitive to variation within the Mthfd1 gene, which codes for a folate-metabolizing enzyme responsible for generating 1-carbon (1-C)-substituted folate derivatives. The Mthfd1(gt/+) mouse serves as a potential model of human Mthfd1 loss-of-function genetic variants that impair MTHFD1 function. This study investigated the effects of the Mthfd1(gt/+) genotype and folate intake on markers of choline, folate, methionine, and transsulfuration metabolism. Male Mthfd1(gt/+) and Mthfd1(+/+) mice were randomly assigned at weaning (3 wk of age) to either a control (2 mg/kg folic acid) or folate-deficient (0 mg/kg folic acid) diet for 5 wk. Mice were killed at 8 wk of age following 12 h of food deprivation; blood and liver samples were analyzed for choline, methionine, and transsulfuration biomarkers. Independent of folate intake, mice with the Mthfd1(gt/+) genotype had higher hepatic concentrations of choline (P = 0.005), betaine (P = 0.013), and dimethylglycine (P = 0.004) and lower hepatic concentrations of glycerophosphocholine (P = 0.002) relative to Mthfd1(+/+) mice. Mthfd1(gt/+) mice also had higher plasma concentrations of homocysteine (P = 0.0016) and cysteine (P < 0.001) as well as lower plasma concentrations of methionine (P = 0.0003) and cystathionine (P = 0.011). The metabolic alterations observed in Mthfd1(gt/+) mice indicate perturbed choline and folate-dependent 1-C metabolism and support the future use of Mthfd1(gt/+) mice as a tool to investigate the impact of impaired 1-C metabolism on disease outcomes.

  11. Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion.

    PubMed

    Yang, Ying; Zhou, Li-bin; Liu, Shang-quan; Tang, Jing-feng; Li, Feng-yin; Li, Rong-ying; Song, Huai-dong; Chen, Ming-dao

    2005-08-01

    To investigate the expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in the control of GnRH secretion. Receptors of bombesin3, cholecystokinin (CCK)-A, CCK-B, glucagon-like peptide (GLP)1, melanin-concentrating hormone (MCH)1, orexin1, orexin2, neuromedin-B, neuropeptide Y (NPY)1 and NPY5, neurotensin (NT)1, NT2, NT3, and leptin receptor long form mRNA in GT1-7 cells were detected by reversed transcriptase-polymerase chain reaction. GT1-7 cells were treated with leptin, orexin A and orexin B at a cohort of concentrations for different lengths of time, and GnRH in medium was determined by radioimmunoassay (RIA). Receptors of bombesin 3, CCK-B, GLP1, MCH1, orexin1, neuromedin-B, NPY1, NPY5, NT1, NT3, and leptin receptor long form mRNA were expressed in GT1-7 cells, of which, receptors of GLP1, neuromedin-B, NPY1, and NT3 were highly expressed. No amplified fragments of orexin2, NT2, and CCK-A receptor cDNA were generated with GT1-7 RNA, indicating that the GT1-7 cells did not express mRNA of them. Leptin induced a significant stimulation of GnRH release, the results being most significant at 0.1 nmol/L for 15 min. In contrast to other studies in hypothalamic explants, neither orexin A nor orexin B affected basal GnRH secretion over a wide range of concentrations ranging from 1 nmol/L to 500 nmol/Lat 15, 30, and 60 min. Feeding and reproductive function are closely linked. Many orexigenic and anorexigenic signals may control feeding behavior as well as alter GnRH secretion through their receptors on GnRH neurons.

  12. The value of cure associated with treating treatment-naïve chronic hepatitis C genotype 1: Are the new all-oral regimens good value to society?

    PubMed

    Younossi, Zobair M; Park, Haesuk; Dieterich, Douglas; Saab, Sammy; Ahmed, Aijaz; Gordon, Stuart C

    2017-05-01

    All-oral regimens are associated with high cure rates in hepatitis C virus-genotype 1 (HCV-GT1) patients. Our aim was to assess the value of cure to the society for treating HCV infection. Markov model for HCV-GT1 projected long-term health outcomes, life years, and quality-adjusted life years (QALYs) gained. The model compared second-generation triple (sofosbuvir+pegylated interferon+ribavirin [PR] and simeprevir+PR) and all-oral (ledipasvir/sofosbuvir and ombitasvir+paritaprevir/ritonavir+dasabuvir±ribavirin) therapies with no treatment. Sustained virological response rates were based on Phase III RCTs. We assumed that 80% and 95% of HCV-GT1 patients were eligible for second-generation triple and all-oral regimens. Transition probabilities, utility and mortality were based on literature review. The value of cure was calculated by the difference in the savings from the economic gains associated with additional QALYs. Model estimated 1.52 million treatment-naïve HCV-GT1 patients in the US. Treating all eligible HCV-GT1 patients with second-generation triple and all-oral therapies resulted in 3.2 million and 4.8 million additional QALYs gained compared to no treatment respectively. Using $50,000 as value of QALY, these regimens lead to savings of $185 billion and $299 billion; costs of these regimens were $109 billion and $128 billion. The value of cure with second-generation triple and all-oral regimens was $55 billion and $111 billion, when we conservatively assumed only drug costs. Cost savings were greater for HCV-GT1 patient cured with cirrhosis compared to patients without cirrhosis. The recent evolution of regimens for HCV GT1 has increased efficacy and value of cure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Free-living cross-comparison of two wearable monitors for sleep and physical activity in healthy young adults.

    PubMed

    Cellini, Nicola; McDevitt, Elizabeth A; Mednick, Sara C; Buman, Matthew P

    2016-04-01

    There is a growing need for free-living monitoring of the full 24 h spectrum of behaviors with a single or integrated set of sensors. The validity of field standard wearable monitors in sleep and physical activity have yet to be assessed for the complementary behavior in the context of 24 h continuous monitoring. We conducted a free-living comparison study of the Actigraph GT3X+ (GT3X+) to assess sleep parameters as compared with the Actiwatch-64 (AW-64) and concurrently, the AW-64 to assess sedentary and physical activity behaviors as compared with the GT3X+. Thirty young adults (15 female, 19.2±0.86 years) wore both monitors for 3 consecutive days and 2 consecutive nights. Agreement of sleep, sedentary, and physical activity metrics were evaluated using analyses of variance, intraclass correlation coefficients, Bland-Altman plots with associated confidence limits, mean absolute percentage of errors and equivalence tests. For sleep, the GT3X+ showed high agreement for total sleep time and sleep efficiency, but underestimated wakefulness after sleep onset and sleep onset latency relative to the AW-64. For sedentary behavior and physical activity, the AW-64 showed a moderate agreement for activity energy expenditure, but not for sedentary, light or moderate-vigorous physical activities relative to the GT3X+. Overall our results showed good agreement of the GT3X+ with AW-64 for assessing sleep but a lack of agreement between AW-64 and GT3X+ for physical activity and sedentary behaviors. These results are likely due to the monitor placement (wrist vs hip), as well as the algorithm employed to score the data. Future validation work of existing and emerging technologies that may hold promise for 24 h continuous monitoring is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Comparison of 2 canal preparation techniques in the induction of microcracks: a pilot study with cadaver mandibles.

    PubMed

    Arias, Ana; Lee, Yoon H; Peters, Christine I; Gluskin, Alan H; Peters, Ove A

    2014-07-01

    The purpose of this pilot study in a cadaver model was to compare 2 different shaping techniques regarding the induction of dentinal microcracks. Three lower incisors from each of 6 adult human cadaver skulls were randomly distributed into 3 groups: the control group (CG, no instrumentation), the GT group (GT Profile hand files; Dentsply Tulsa Dental, Tulsa, OK), and the WO group (WaveOne; Dentsply Tulsa Dental). In the GT group, manual shaping in a crown-down sequence with GT Profile hand files was performed. In the WO group, Primary WaveOne files were used to the working length. Teeth were separated from the mandibles by careful removal of soft tissue and bone under magnification. Roots were sectioned horizontally at 3, 6, and 9 mm from the apex using a low-speed saw. Color photographs at 2 magnifications (25× and 40×) were obtained. Three blinded examiners registered the presence of microcracks (yes/no), extension (incomplete/complete), direction (buccolingual/mesiodistal), and location. Data were analyzed with chi-square tests at P < .05. Microcracks were found in 50% (CG and GT) and 66% (WO) of teeth at 3 mm, 16.6% (CG) and 33.3% (GT and WO) at 6 mm, and 16.6% in all 3 groups at 9 mm from the apex. There were no significant differences in the incidence of microcracks between all groups at 3 (P = .8), 6 (P = .8), or 9 mm (P = 1). All microcracks were incomplete, started at the pulpal wall, and had a buccolingual direction. Within the limitations of this pilot study, a relationship between the shaping techniques (GT hand and WaveOne) and the incidence of microcracks could not be shown compared with uninstrumented controls. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. 77 FR 64506 - Robert D. Willis Hydropower Rate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-22

    ... Brickfield Burchette Ritts and Stone, PC, on behalf of the Sam Rayburn G&T Electric Cooperative, Inc., which... comments, one on behalf of the Sam Rayburn G&T Electric Cooperative, Inc., the other on behalf of the...

  16. Effects of green tea on the shear bond strength of orthodontic brackets after in-office vital bleaching.

    PubMed

    Berger, Sandrine Bittencourt; Guiraldo, Ricardo Danil; Lopes, Murilo Baena; Oltramari-Navarro, Paula Vanessa; Fernandes, Thais Maria; Schwertner, Renata de Castro Alves; Ursi, Wagner José Silva

    2016-01-01

    The application of bleaching agents before placement of resin-bonded fixed appliances significantly, but temporarily, reduces bond strength to tooth structure. Antioxidants have been studied as a means to remove residual oxygen that compromises bonding to bleached enamel. This in vitro study evaluated whether green tea (GT) could restore the shear bond strength between bonded orthodontic brackets and bleached enamel. Six experimental groups were compared: group 1, no bleaching plus bracket bonding (positive control); group 2, bleaching with 35% hydrogen peroxide (HP) plus bracket bonding (negative control); group 3, 35% HP plus 10% sodium ascorbate (SA) plus bracket bonding; group 4, 35% HP plus 10% GT plus bracket bonding; group 5, no bleaching plus 10% SA plus bracket bonding; group 6, no bleaching plus 10% GT plus bracket bonding. Results suggested that GT, like SA, may be beneficial for bracket bonding immediately after bleaching.

  17. Gamow-Teller transitions in the 64Ni(3He, t)64Cu reaction

    NASA Astrophysics Data System (ADS)

    Popescu, L.; Adachi, T.; Berg, G. P. A.; von Brentano, P.; De Frenne, D.; Fujita, K.; Fujita, Y.; Hatanaka, K.; Jacobs, E.; Negret, A.; Nakanishi, K.; Sakemi, Y.; Shimbara, Y.; Shimizu, Y.; Tameshige, Y.; Tamii, A.; Uchida, M.; Yosoi, M.

    2005-10-01

    In order to study the Gamow-Teller (GT) transitions in the fp-shell nucleus 64Cu, the 64Ni(3He, t)64Cu charge-exchange reaction was investigated at E3He= 140 MeV/nucleon [1]. The outgoing tritons were momentum analysed by the Grand Raiden spectrometer at 0°. The very high energy resolution of 35 keV (FWHM) allowed the separation of individual levels in the excitation energy region from 0 to 3.5 MeV. An angular distribution analysis was performed for the observed transitions to these states. In addition to the ground state (g.s.), known to be a Jπ = 1+ GT state, several excited states showed L = 0 nature, making them candidates of GT states. At higher excitation energies, the level density becomes very high and a bump-like structure, the so-called GT Giant Resonance, dominates the spectrum.

  18. Regulating the advertising of genetic tests in Europe: a balancing act.

    PubMed

    Kalokairinou, Louiza; Borry, Pascal; Howard, Heidi Carmen

    2017-10-01

    Direct-to-consumer (DTC) genetic tests (GT) have provoked criticism over their potential adverse impact on public health. The European Parliament called for a ban on DTC advertising of GT during the debate for the adoption of a European Regulation on in vitro diagnostic medical devices. This proposal, however, was not ultimately retained in the final text. Instead, the regulation includes an article prohibiting misleading claims for this kind of advertising. These two different approaches raise questions about the optimal degree of regulation. Herein, we provide an overview of the ways GT have been advertised and related ethical issues. Subsequently, the laws regulating the advertising of GT at the European Union and national level are examined. Finally, recent regulatory developments are discussed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. GT-CATS: Tracking Operator Activities in Complex Systems

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.; Mitchell, Christine M.; Palmer, Everett A.

    1999-01-01

    Human operators of complex dynamic systems can experience difficulties supervising advanced control automation. One remedy is to develop intelligent aiding systems that can provide operators with context-sensitive advice and reminders. The research reported herein proposes, implements, and evaluates a methodology for activity tracking, a form of intent inferencing that can supply the knowledge required for an intelligent aid by constructing and maintaining a representation of operator activities in real time. The methodology was implemented in the Georgia Tech Crew Activity Tracking System (GT-CATS), which predicts and interprets the actions performed by Boeing 757/767 pilots navigating using autopilot flight modes. This report first describes research on intent inferencing and complex modes of automation. It then provides a detailed description of the GT-CATS methodology, knowledge structures, and processing scheme. The results of an experimental evaluation using airline pilots are given. The results show that GT-CATS was effective in predicting and interpreting pilot actions in real time.

  20. IMPACT OF NEW GAMOW–TELLER STRENGTHS ON EXPLOSIVE TYPE IA SUPERNOVA NUCLEOSYNTHESIS

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

    Mori, Kanji; Famiano, Michael A.; Kajino, Toshitaka

    2016-12-20

    Recent experimental results have confirmed a possible reduction in the Gamow–Teller (GT{sub +}) strengths of pf-shell nuclei. These proton-rich nuclei are of relevance in the deflagration and explosive burning phases of SNe Ia. While prior GT strengths result in nucleosynthesis predictions with a lower-than-expected electron fraction, a reduction in the GT{sub +} strength can result in a slightly increased electron fraction compared to previous shell model predictions, though the enhancement is not as large as previous enhancements in going from rates computed by Fuller, Fowler, and Newman based on an independent particle model. A shell model parametrization has been developed thatmore » more closely matches experimental GT strengths. The resultant electron-capture rates are used in nucleosynthesis calculations for carbon deflagration and explosion phases of SNe Ia, and the final mass fractions are compared to those obtained using more commonly used rates.« less

  1. Gamow-Teller Strength Distributions in {sup 48}Sc by the {sup 48}Ca(p,n) and {sup 48}Ti(n,p) Reactions and Two-Neutrino Double-beta Decay Nuclear Matrix Elements

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

    Yako, K.; Sasano, M.; Miki, K.

    2009-07-03

    The double-differential cross sections for the {sup 48}Ca(p,n) and {sup 48}Ti(n,p) reactions were measured at 300 MeV. A multipole decomposition technique was applied to the spectra to extract the Gamow-Teller (GT) components. The integrated GT strengths up to an excitation energy of 30 MeV in {sup 48}Sc are 15.3+-2.2 and 2.8+-0.3 in the (p,n) and (n,p) spectra, respectively. In the (n,p) spectra additional GT strengths were found above 8 MeV where shell models within the fp shell-model space predict almost no GT strengths, suggesting that the present shell-model description of the nuclear matrix element of the two-neutrino double-beta decay ismore » incomplete.« less

  2. Game Theory for Wireless Sensor Networks: A Survey

    PubMed Central

    Shi, Hai-Yan; Wang, Wan-Liang; Kwok, Ngai-Ming; Chen, Sheng-Yong

    2012-01-01

    Game theory (GT) is a mathematical method that describes the phenomenon of conflict and cooperation between intelligent rational decision-makers. In particular, the theory has been proven very useful in the design of wireless sensor networks (WSNs). This article surveys the recent developments and findings of GT, its applications in WSNs, and provides the community a general view of this vibrant research area. We first introduce the typical formulation of GT in the WSN application domain. The roles of GT are described that include routing protocol design, topology control, power control and energy saving, packet forwarding, data collection, spectrum allocation, bandwidth allocation, quality of service control, coverage optimization, WSN security, and other sensor management tasks. Then, three variations of game theory are described, namely, the cooperative, non-cooperative, and repeated schemes. Finally, existing problems and future trends are identified for researchers and engineers in the field. PMID:23012533

  3. Recruitment of intuitive versus analytic thinking strategies affects the role of working memory in a gambling task.

    PubMed

    Gozzi, Marta; Cherubini, Paolo; Papagno, Costanza; Bricolo, Emanuela

    2011-05-01

    Previous studies found mixed results concerning the role of working memory (WM) in the gambling task (GT). Here, we aimed at reconciling inconsistencies by showing that the standard version of the task can be solved using intuitive strategies operating automatically, while more complex versions require analytic strategies drawing on executive functions. In Study 1, where good performance on the GT could be achieved using intuitive strategies, participants performed well both with and without a concurrent WM load. In Study 2, where analytical strategies were required to solve a more complex version of the GT, participants without WM load performed well, while participants with WM load performed poorly. In Study 3, where the complexity of the GT was further increased, participants in both conditions performed poorly. In addition to the standard performance measure, we used participants' subjective expected utility, showing that it differs from the standard measure in some important aspects.

  4. Epigenetic effects of green tea polyphenols in cancer

    PubMed Central

    Henning, Susanne M; Wang, Piwen; Carpenter, Catherine L; Heber, David

    2014-01-01

    Epigenetics describes heritable alterations of gene expression and chromatin organization without changes in DNA sequence. Both hypermethylation and hypomethylation of DNA can affect gene expression and the multistep process of carcinogenesis. Epigenetic changes are reversible and may be targeted by dietary interventions. Bioactive compounds from green tea (GT) such as (–)-epigallocatechin gallate have been shown to alter DNA methyltransferase activity in studies of esophageal, oral, skin, Tregs, lung, breast and prostate cancer cells, which may contribute to the chemopreventive effect of GT. Three out of four mouse model studies have confirmed the inhibitory effect of (–)-epigallocatechin gallate on DNA methylation. A human study demonstrated that decreased methylation of CDX2 and BMP-2 in gastric carcinoma was associated with higher GT consumption. It is the goal of this review to summarize our current knowledge of the potential of GT to alter epigenetic processes, which may be useful in chemoprevention. PMID:24283885

  5. Historical warming reduced due to enhanced land carbon uptake.

    PubMed

    Shevliakova, Elena; Stouffer, Ronald J; Malyshev, Sergey; Krasting, John P; Hurtt, George C; Pacala, Stephen W

    2013-10-15

    Previous studies have demonstrated the importance of enhanced vegetation growth under future elevated atmospheric CO2 for 21st century climate warming. Surprisingly no study has completed an analogous assessment for the historical period, during which emissions of greenhouse gases increased rapidly and land-use changes (LUC) dramatically altered terrestrial carbon sources and sinks. Using the Geophysical Fluid Dynamics Laboratory comprehensive Earth System Model ESM2G and a reconstruction of the LUC, we estimate that enhanced vegetation growth has lowered the historical atmospheric CO2 concentration by 85 ppm, avoiding an additional 0.31 ± 0.06 °C warming. We demonstrate that without enhanced vegetation growth the total residual terrestrial carbon flux (i.e., the net land flux minus LUC flux) would be a source of 65-82 Gt of carbon (GtC) to atmosphere instead of the historical residual carbon sink of 186-192 GtC, a carbon saving of 251-274 GtC.

  6. Crystal structures of sialyltransferase from Photobacterium damselae

    DOE PAGES

    Huynh, Nhung; Li, Yanhong; Yu, Hai; ...

    2014-11-15

    Sialyltransferase structures fall into either GT-A or GT-B glycosyltransferase fold. Some sialyltransferases from the Photobacterium genus have been shown to contain an additional N-terminal immunoglobulin (Ig)-like domain. Photobacterium damselae α2–6-sialyltransferase has been used efficiently in enzymatic and chemoenzymatic synthesis of α2–6-linked sialosides. In this paper, we report three crystal structures of this enzyme. Two structures with and without a donor substrate analog CMP-3F(a)Neu5Ac contain an immunoglobulin (Ig)-like domain and adopt the GT-B sialyltransferase fold. The binary structure reveals a non-productive pre-Michaelis complex, which are caused by crystal lattice contacts that prevent the large conformational changes. The third structure lacks themore » Ig-domain. Finally, comparison of the three structures reveals small inherent flexibility between the two Rossmann-like domains of the GT-B fold.« less

  7. Impact of New Gamow-Teller Strengths on Explosive Type Ia Supernova Nucleosynthesis

    NASA Astrophysics Data System (ADS)

    Mori, Kanji; Famiano, Michael A.; Kajino, Toshitaka; Suzuki, Toshio; Hidaka, Jun; Honma, Michio; Iwamoto, Koichi; Nomoto, Ken'ichi; Otsuka, Takaharu

    2016-12-01

    Recent experimental results have confirmed a possible reduction in the Gamow-Teller (GT+) strengths of pf-shell nuclei. These proton-rich nuclei are of relevance in the deflagration and explosive burning phases of SNe Ia. While prior GT strengths result in nucleosynthesis predictions with a lower-than-expected electron fraction, a reduction in the GT+ strength can result in a slightly increased electron fraction compared to previous shell model predictions, though the enhancement is not as large as previous enhancements in going from rates computed by Fuller, Fowler, and Newman based on an independent particle model. A shell model parametrization has been developed that more closely matches experimental GT strengths. The resultant electron-capture rates are used in nucleosynthesis calculations for carbon deflagration and explosion phases of SNe Ia, and the final mass fractions are compared to those obtained using more commonly used rates.

  8. Ultrastructural evaluation of mesenchymal stem cells from inflamed periodontium in different in vitro conditions.

    PubMed

    Zaganescu, Raluca; Barbu Tudoran, Lucian; Pall, Emoke; Florea, Adrian; Roman, Alexandra; Soanca, Andrada; Mihaela Mihu, Carmen

    2015-09-01

    This research aimed to observe the behavior of mesenchymal stem cells (MSCs) isolated from periodontal granulation tissue (gt) when manipulated ex vivo to induce three-dimensional (3D) spheroid (aggregates) formation as well as when seeded on two bone scaffolds of animal origin. Periodontal gt was chosen as a MSC source because of its availability, considering that it is eliminated as a waste material during conventional surgical therapies. 3D aggregates of cells were generated; they were grown for 3 and 7 days, respectively, and then prepared for transmission electron microscopic analysis. The two biomaterials were seeded for 72 h with gtMSCs and prepared for scanning electronic microscopic observation. The ultrastructural analysis of 3D spheroids remarked some differences between the inner and the outer cell layers, with a certain commitment observed at the inner cells. Both scaffolds showed a relatively smooth surface at low magnification. Macro- and micropores having a scarce distribution were observed on both bone substitutes. gtMSCs grew with relative difficulty on the biomaterials. After 72 h of proliferation, gtMSCs scarcely covered the surface of bovine bone scaffolds, demonstrating fibroblast-like or star-like shapes with elongated filiform extensions. Our results add other data on the possible usefulness of gtMSC and could question the current paradigm regarding the complete removal of chronically inflamed gts from the defects during periodontal surgeries. Until optimal protocols for ex vivo manipulation of MSCs are available for clinical settings, it is advisable to use biocompatible bone substitutes that allow the development of progenitor cells. © 2015 Wiley Periodicals, Inc.

  9. Net mass balance calculations for the Shirase Drainage Basin, east Antarctica, using the mass budget method

    NASA Astrophysics Data System (ADS)

    Nakamura, Kazuki; Yamanokuchi, Tsutomu; Doi, Koichiro; Shibuya, Kazuo

    2016-06-01

    We quantify the mass budget of the Shirase drainage basin (SHI), Antarctica, by separately estimating snow accumulation (surface mass balance; SMB) and glacier ice mass discharge (IMD). We estimated the SMB in the SHI, using a regional atmospheric climate model (RACMO2.1). The SMB of the mainstream A flow region was 12.1 ± 1.5 Gt a-1 for an area of 1.985 × 105 km2. Obvious overestimation of the model round the coast, ∼0.5 Gt a-1, was corrected for. For calculating the IMD, we employed a 15-m resolution Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) with a digital elevation model (DEM) to determine the heights at the grounding line (GL), after comparison with the interpolated Bamber DEM grid heights; the results of this are referred to as the measured heights. Ice thickness data at the GL were inferred by using a free-board relationship between the measured height and the ice thickness, and considering the measured firn depth correction (4.2 m with the reference ice density of 910 kg m-3) for the nearby blue-ice area. The total IMD was estimated to be 14.0 ± 1.8 Gt a-1. Semi-empirical firn densification model gives the estimate within 0.1-0.2 Gt a-1 difference. The estimated net mass balance, -1.9 Gt a-1, has a two-σ uncertainty of ±3.3 Gt a-1, and probable melt water discharge strongly suggests negative NMB, although the associated uncertainty is large.

  10. Bayesian inference in an item response theory model with a generalized student t link function

    NASA Astrophysics Data System (ADS)

    Azevedo, Caio L. N.; Migon, Helio S.

    2012-10-01

    In this paper we introduce a new item response theory (IRT) model with a generalized Student t-link function with unknown degrees of freedom (df), named generalized t-link (GtL) IRT model. In this model we consider only the difficulty parameter in the item response function. GtL is an alternative to the two parameter logit and probit models, since the degrees of freedom (df) play a similar role to the discrimination parameter. However, the behavior of the curves of the GtL is different from those of the two parameter models and the usual Student t link, since in GtL the curve obtained from different df's can cross the probit curves in more than one latent trait level. The GtL model has similar proprieties to the generalized linear mixed models, such as the existence of sufficient statistics and easy parameter interpretation. Also, many techniques of parameter estimation, model fit assessment and residual analysis developed for that models can be used for the GtL model. We develop fully Bayesian estimation and model fit assessment tools through a Metropolis-Hastings step within Gibbs sampling algorithm. We consider a prior sensitivity choice concerning the degrees of freedom. The simulation study indicates that the algorithm recovers all parameters properly. In addition, some Bayesian model fit assessment tools are considered. Finally, a real data set is analyzed using our approach and other usual models. The results indicate that our model fits the data better than the two parameter models.

  11. A Metabolomic and Lipidomic Serum Signature from Nonhuman Primates Administered with a Promising Radiation Countermeasure, Gamma-Tocotrienol

    PubMed Central

    Cheema, Amrita K.; Mehta, Khyati Y.; Fatanmi, Oluseyi O.; Wise, Stephen Y.; Wolff, Josh

    2017-01-01

    The development of radiation countermeasures for acute radiation syndrome (ARS) has been underway for the past six decades, leading to the identification of multiple classes of radiation countermeasures. However, to date, only two growth factors (Neupogen and Neulasta) have been approved by the United States Food and Drug Administration (US FDA) for the mitigation of hematopoietic acute radiation syndrome (H-ARS). No radioprotector for ARS has been approved by the FDA yet. Gamma-tocotrienol (GT3) has been demonstrated to have radioprotective efficacy in murine as well as nonhuman primate (NHP) models. Currently, GT3 is under advanced development as a radioprotector that can be administered prior to radiation exposure. We are studying this agent for its safety profile and efficacy using the NHP model. In this study, we analyzed global metabolomic and lipidomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in serum samples of NHPs administered GT3. Our study, using 12 NHPs, demonstrates that alterations in metabolites manifest only 24 h after GT3 administration. Furthermore, metabolic changes are associated with transient increase in the bioavailability of antioxidants, including lactic acid and cholic acid and anti-inflammatory metabolites 3 deoxyvitamin D3, and docosahexaenoic acid. Taken together, our results show that the administration of GT3 to NHPs causes metabolic shifts that would provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3. PMID:29283379

  12. Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: results from the CLEAR HPV study.

    PubMed

    Castle, Phillip E; Cuzick, Jack; Stoler, Mark H; Wright, Thomas C; Reid, Jennifer L; Dockter, Janel; Giachetti, Cristina; Getman, Damon

    2015-02-01

    The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/ E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2 +) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2 + were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3 + were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis. Copyright© by the American Society for Clinical Pathology.

  13. Environmentally Responsive Systems for Drug Delivery.

    PubMed

    Bruschi, Marcos L; Borghi-Pangoni, Fernanda B; Junqueira, Mariana V; de Souza Ferreira, Sabrina B; da Silva, Jessica B

    2017-01-01

    In recent decades, the development of the environmentally responsive systems for drug delivery has been well regarded, with enormous potential in different applications. <P><P> Methods: These environmentally sensitive, smart, intelligent formulations have the ability to alter their physical properties in response to small changes in physical or chemical conditions, such as temperature, glucose, pH, ultrasound, light, electric field and redox potential with a huge potential in drug delivery systems. The use of formulations containing smart materials enables to carry the drug to the target tissue, cells and release in a triggered way. Consequently, they have demonstrated several advantages like decreased dose frequency, ease of preparation and administration, prolonged release with reduced side effects, as well as, reduced costs when compared to conventional processes for industrial applications. In this sense, many patents have deposited, displaying different pharmaceutical devices using responsive systems. <P><P> Results: There are more than twenty-five patents deposited about thermoresponsive systems. Furthermore, a few number of patents within glucose responsive, ultrasound responsive and light responsive deposited. There also are about eight patents that are pH-responsive, four as electric-field responsive. Most of them cover more than one type of stimuli. <P><P> Conclusion: Therefore, in this review, since 1975 to 2016, we have categorized, reviewed and discussed the patents, applications, pharmaceutical dosage forms, the importance and perspectives of this environmentally responsive approach as potentially useful therapeutic modality. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

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

    Choi, Solip; Nguyen, Van Thu; Tae, Nara

    Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE{sub 2}, butyl lucidenateD{sub 2} (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting themore » involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of these triterpenes. • The triterpenes induce heme oxygenase-1 expression via the AKT-Nrf2 pathway. • The mechanism explains the anti-inflammatory effect of triterpenes from G. lucidum.« less

  15. Comparison of the nutrient and chemical contents of traditional Korean Chungtaejeon and green teas.

    PubMed

    Park, Yong-Seo; Lee, Mi-Kyung; Heo, Buk-Gu; Ham, Kyung-Sik; Kang, Seong-Gook; Cho, Ja-Yong; Gorinstein, Shela

    2010-06-01

    This study was conducted in order to compare the nutrient and chemical contents of two Korean teas: traditional Chungtaejeon tea (CTJ) with that of green tea (GT). Main bioactive compounds and the antioxidant activities using four radical scavenging assays (ABTS, CUPRAC, FRAP and DPPH) in methanol and acetone extracts of both teas were determined. It was found that the contents of vitamin C, amino acids and total nitrogen in CTJ were lower than that of GT (p < 0.05). Caffeine, reducing sugar and chlorophyll contents in CTJ were similar to GT. Catechin (C), epicatechin (EC), and epigallocatechin (EGC) contents were lower in CTJ than in green tea (p < 0.05), but gallocatechin (GC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG) and catechin gallate (CG) showed no significant differences between CTJ and GT (p >/= 0.05). The contents of polyphenols, flavonoids, flavanols and tannins in CTJ methanol were 229.30 +/- 11.3 mg GAE/g dry weight (DW), 15.24 +/- 0.8 mg CE/g DW, 109.10 +/- 5.1 mg CE/g DW and 25.68 +/- 1.2 mg CE/g DW, respectively, and significantly higher than in acetone extracts (p < 0.05). Flavonoids (quercetin and kaempferol) were higher in GT than in CTJ and myricetin was higher in CTJ (p < 0.05). Threonine and aspartic acid was lower, and glutamic acid was higher in CTJ compared with GT (p < 0.05). Free amino acid content in CTJ and GT showed no significant difference. Potassium and magnesium in CTJ were lower compared to GT, but no significant difference was found for iron, manganese and calcium. Also, the level of the antioxidant activity by all four used assays was significantly higher in CTJ and in methanol was higher than in acetone extracts (p < 0.05). In conclusion, traditional fermented Korean tea Chungtaejeon contains high quantities of bioactive compounds and possesses high antioxidant activity. The contents of the bioactive compounds and the levels of antioxidant activities are significantly higher in methanol than in acetone extracts. 3-D fluorescence and FTIR- spectroscopy showed slight differences between the two investigated tea samples and can be used as additional tools for identification of polyphenols. Both studied teas can be recommended as a source of bioactive compounds.

  16. Photon energy readings in OSL dosimeter filters: an application to retrospective dose estimation for nuclear medicine workers.

    PubMed

    Villoing, Daphnée; Kitahara, Cari M; Passmore, Christopher; Simon, Steven L; Yoder, R Craig

    2018-06-19

    This work investigates the applicability of using data from personal monitoring dosimeters to assess photon energies to which medical workers were exposed. Such determinations would be important for retrospective assessments of organ doses to be used in occupational radiation epidemiology studies, particularly in the absence of work history or other information regarding the energy of the radiation source. Monthly personal dose equivalents and filter ratios under two different metallic filters contained in the Luxel+® dosimeter were collected from Landauer, Inc. from 19 nuclear medicine (NM) technologists employed by three medical institutions, the institution A only performing traditional NM imaging (primarily using <sup>99m</sup>Tc) and institutions B and C also performing positron emission tomography (PET, using <sup>18</sup>F). Calibration data of the Luxel+® dosimeter for various X-ray spectra were used to establish ranges of filter ratios from 1.1 to 1.6 for <sup>99m</sup>Tc and below 1.1 for <sup>18</sup>F. Median filter ratios were 1.33 (Interquartile range (IQR), 0.15) for institution A, 1.08 (IQR, 0.16) for institution B, and 1.08 (IQR, 0.14) for institution C. The distributions of these filter ratios were statistically-significantly different between the institution A only performing traditional NM imaging and institutions B and C also performing PET imaging. In this proof-of-concept study, filter ratios from personal dosimeters were used to assess differences in photon energies to which NM technologists were exposed. Dosimeters from technologists only performing traditional NM procedures mostly showed Al/Cu filter ratios above 1.2, those likely performing only PET in a particular month had filter ratios below 1.1, and those which showed filter ratios between 1.1 and 1.2 likely came from technologists rotating between traditional NM and PET imaging in the same month. These results suggest that it is possible to distinguish technologists who only worked with higher-energy procedures versus those who only worked with other types of NM procedures. © 2018 IOP Publishing Ltd.

  17. Global Carbon Budget 2016

    NASA Technical Reports Server (NTRS)

    Quéré, Corinne Le; Andrew, Robbie M.; Canadell, Josep G.; Sitch, Stephen; Korsbakken, Jan Ivar; Peters, Glen P.; Manning, Andrew C.; Boden, Thomas A.; Tans, Pieter P.; Houghton, Richard A.; hide

    2016-01-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere the global carbon budget is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates and consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models. We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as +/- 1(sigma), reflecting the current capacity to characterize the annual estimates of each component of the global carbon budget. For the last decade available (2006-2015), EFF was 9.3+/-0.5 GtC/yr, ELUC 1.0+/-0.5 GtC/yr,GATM 4.5+/-0.1 GtC/yr, SOCEAN 2.6+/-0.5 GtC/yr, and SLAND 3.1+/-0.9 GtC/yr. For year 2015 alone, the growth in EFF was approximately zero and emissions remained at 9.9+/-0.5 GtC/yr, showing a slowdown in growth of these emissions compared to the average growth of 1.8/yr that took place during 2006-2015.Also, for 2015, ELUC was 1.3+/-0.5 GtC/yr, GATM was 6.3+/-0.2 GtC/yr, SOCEAN was 3.0+/-0.5 GtC/yr, and SLAND was 1.9+/-0.9 GtC/yr. GATM was higher in 2015 compared to the past decade (2006-2015), reflecting a smaller SLAND for that year. The global atmospheric CO2 concentration reached 399.4+/-0.1 ppm averaged over 2015. For 2016, preliminary data indicate the continuation of low growth in EFF with +0.2% (range of -1.0 to +1.8% ) based on national emissions projections for China and USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. In spite of the low growth of EFF in 2016, the growth rate in atmospheric CO2 concentration is expected to be relatively high because of the persistence of the smaller residual terrestrial sink (SLAND) in response to El Nino conditions of 2015-2016. From this projection of EFF and assumed constant ELUC for 2016, cumulative emissions of CO2 will reach 565+/-55 GtC (2075+/-205 GtCO2) for 1870-2016, about 75% from EFF and 25% from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set.

  18. GEMINI-TITAN (GT)-4 - EARTH-SKY - OUTER SPACE

    NASA Image and Video Library

    1965-06-03

    S65-34776 (3-7 June 1965) --- This photograph shows the Nile Delta, Egypt, the Suez Canal, Israel, Jordan, Syria, Saudi Arabia, and Iraq as seen from the Gemini-Titan 4 (GT-4) spacecraft during its 12th revolution of Earth.

  19. Structural characterization of O- and C-glycosylating variants of the landomycin glycosyltransferase LanGT2.

    PubMed

    Tam, Heng Keat; Härle, Johannes; Gerhardt, Stefan; Rohr, Jürgen; Wang, Guojun; Thorson, Jon S; Bigot, Aurélien; Lutterbeck, Monika; Seiche, Wolfgang; Breit, Bernhard; Bechthold, Andreas; Einsle, Oliver

    2015-02-23

    The structures of the O-glycosyltransferase LanGT2 and the engineered, C-C bond-forming variant LanGT2S8Ac show how the replacement of a single loop can change the functionality of the enzyme. Crystal structures of the enzymes in complex with a nonhydrolyzable nucleotide-sugar analogue revealed that there is a conformational transition to create the binding sites for the aglycon substrate. This induced-fit transition was explored by molecular docking experiments with various aglycon substrates. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Driving electromechanically assisted Gait Trainer for people with stroke.

    PubMed

    Iosa, Marco; Morone, Giovanni; Bragoni, Maura; De Angelis, Domenico; Venturiero, Vincenzo; Coiro, Paola; Pratesi, Luca; Paolucci, Stefano

    2011-01-01

    Electromechanically assisted gait training is a promising task-oriented approach for gait restoration, especially for people with subacute stroke. However, few guidelines are available for selecting the parameter values of the electromechanical Gait Trainer (GT) (Reha-Stim; Berlin, Germany) and none is tailored to a patient's motor capacity. We assessed 342 GT sessions performed by 20 people with stroke who were stratified by Functional Ambulatory Category. In the first GT session of all patients, the body-weight support (BWS) required was higher than that reported in the literature. In further sessions, we noted a slow reduction of BWS and a fast increment of walking speed for the most-affected patients. Inverse trends were observed for the less-affected patients. In all the patients, the heart rate increment was about 20 beats per minute, even for sessions in which the number of strides performed was up to 500. In addition, the effective BWS measured during GT sessions was different from that initially selected by the physiotherapist. This difference depended mainly on the position of the GT platforms during selection. Finally, harness acceleration in the anteroposterior direction proved to be higher in patients with stroke than in nondisabled subjects. Our findings are an initial step toward scientifically selecting parameters in electromechanically assisted gait training.

  1. Structural Characterisation and Mechanical FE Analysis of Conventional and M-Wire Ni-Ti Alloys Used in Endodontic Rotary Instruments

    PubMed Central

    Montalvão, Diogo; Alçada, Francisca Sena; Braz Fernandes, Francisco Manuel; de Vilaverde-Correia, Sancho

    2014-01-01

    The purpose of this study is to understand how the M-Wire alloy conditions the mechanical flexibility of endodontic rotary files at body temperature.Two different rotary instruments, a Profile GT 20/.06 and a Profile GT Series X 20/.06, were selected due to their geometrical similarity and their different constituent alloy. GT series X files are made from M-Wire, a Ni-Ti alloy allegedly having higher flexibility at body temperature. Both files were analysed by X-Ray Diffraction and Differential Scanning Calorimetry to investigate phase transformations and the effects of working temperature on these different alloys. Mechanical behaviour was assessed by means of static bending and torsional Finite Element simulations, taking into account the nonlinear superelastic behaviour of Ni-Ti materials. It was found that GT files present austenitic phase at body temperature, whereas GT series X present R-phase at temperatures under 40°C with a potential for larger flexibility. For the same load conditions, simulations showed that the slight geometrical differences between the two files do not introduce great disagreement in the instruments' mechanical response. It was confirmed that M-Wire increases the instrument's flexibility, mainly due to the presence of R-phase at body temperature. PMID:24574937

  2. Structural characterisation and mechanical FE analysis of conventional and M-Wire Ni-Ti alloys used in endodontic rotary instruments.

    PubMed

    Montalvão, Diogo; Alçada, Francisca Sena; Braz Fernandes, Francisco Manuel; de Vilaverde-Correia, Sancho

    2014-01-01

    The purpose of this study is to understand how the M-Wire alloy conditions the mechanical flexibility of endodontic rotary files at body temperature.Two different rotary instruments, a Profile GT 20/.06 and a Profile GT Series X 20/.06, were selected due to their geometrical similarity and their different constituent alloy. GT series X files are made from M-Wire, a Ni-Ti alloy allegedly having higher flexibility at body temperature. Both files were analysed by X-Ray Diffraction and Differential Scanning Calorimetry to investigate phase transformations and the effects of working temperature on these different alloys. Mechanical behaviour was assessed by means of static bending and torsional Finite Element simulations, taking into account the nonlinear superelastic behaviour of Ni-Ti materials. It was found that GT files present austenitic phase at body temperature, whereas GT series X present R-phase at temperatures under 40 °C with a potential for larger flexibility. For the same load conditions, simulations showed that the slight geometrical differences between the two files do not introduce great disagreement in the instruments' mechanical response. It was confirmed that M-Wire increases the instrument's flexibility, mainly due to the presence of R-phase at body temperature.

  3. Growth rate of crystalline ice and the diffusivity of supercooled water from 126 to 262 K

    PubMed Central

    Xu, Yuntao; Smith, R. Scott; Kay, Bruce D.

    2016-01-01

    Understanding deeply supercooled water is key to unraveling many of water’s anomalous properties. However, developing this understanding has proven difficult due to rapid and uncontrolled crystallization. Using a pulsed-laser–heating technique, we measure the growth rate of crystalline ice, G(T), for 180 K < T < 262 K, that is, deep within water’s “no man’s land” in ultrahigh-vacuum conditions. Isothermal measurements of G(T) are also made for 126 K ≤ T ≤ 151 K. The self-diffusion of supercooled liquid water, D(T), is obtained from G(T) using the Wilson–Frenkel model of crystal growth. For T > 237 K and P ∼ 10−8 Pa, G(T) and D(T) have super-Arrhenius (“fragile”) temperature dependences, but both cross over to Arrhenius (“strong”) behavior with a large activation energy in no man’s land. The fact that G(T) and D(T) are smoothly varying rules out the hypothesis that liquid water’s properties have a singularity at or near 228 K at ambient pressures. However, the results are consistent with a previous prediction for D(T) that assumed no thermodynamic transitions occur in no man’s land. PMID:27956609

  4. The evaluation of MCI, MI, PMI and GT on both genders with different age and dental status.

    PubMed

    Bozdag, G; Sener, S

    2015-01-01

    The aim of this study was to measure the mandibular cortical index (MCI), mental index (MI), panoramic mandibular index (PMI) and cortical bone thickness in the zone of the gonial angle (GT) in panoramic radiographies from a large sample of males and females and to determine how they relate to patients' age, gender and dental status. 910 panoramic radiographs were obtained and grouped into age, dental status and gender. The MCI, MI, PMI and GT were analysed. Remarkable differences were observed for MCI and GT regarding gender, age groups and dental status on both sides (p < 0.05). While age and dental status had an effect on the MI and PMI in females, dental status had an effect on the MI and PMI in males (p < 0.05). Also, gender had an effect on the MI and PMI (p < 0.05). The effects of age and tooth loss are different in females and males. In females, the harmful effects of tooth loss and age are more prominent according to the PMI and MI measurements. The effects of age and tooth loss in the GT and MCI measurements are similar, and these indices can be accepted as more reliable in studies including both genders.

  5. The evaluation of MCI, MI, PMI and GT on both genders with different age and dental status

    PubMed Central

    Sener, S

    2015-01-01

    Objectives: The aim of this study was to measure the mandibular cortical index (MCI), mental index (MI), panoramic mandibular index (PMI) and cortical bone thickness in the zone of the gonial angle (GT) in panoramic radiographies from a large sample of males and females and to determine how they relate to patients' age, gender and dental status. Methods: 910 panoramic radiographs were obtained and grouped into age, dental status and gender. The MCI, MI, PMI and GT were analysed. Results: Remarkable differences were observed for MCI and GT regarding gender, age groups and dental status on both sides (p < 0.05). While age and dental status had an effect on the MI and PMI in females, dental status had an effect on the MI and PMI in males (p < 0.05). Also, gender had an effect on the MI and PMI (p < 0.05). Conclusions: The effects of age and tooth loss are different in females and males. In females, the harmful effects of tooth loss and age are more prominent according to the PMI and MI measurements. The effects of age and tooth loss in the GT and MCI measurements are similar, and these indices can be accepted as more reliable in studies including both genders. PMID:26133366

  6. Association of Colonization with Streptococcus mutans Genotypes from Mothers and Early Childhood Caries

    PubMed Central

    Childers, Noel K.; Momeni, Stephanie S.; Whiddon, Jennifer; Cheon, Kyounga; Cutter, Gary R.; Wiener, Howard W.; Ghazal, Tariq S.; Ruby, John D.; Moser, Stephen A.

    2016-01-01

    Purpose This study evaluated Streptococcus mutans (Sm) genotypes (GT) between mother and child (M-C) in a high caries risk cohort to explore the association with early childhood caries (ECC). Methods Sixty-nine infants (~1 year-old) had periodic oral examination (dmfs) and collection of microbial samples from dental plaque, saliva and oral other surfaces. Their mothers had an examination and plaque collected. Sm isolates were genotyped using repetitive extragenic palindromic-PCR (rep-PCR). Statistical analyses were conducted for associations of Sm in M-C dyads with caries outcomes. Results Twenty-seven Sm genotypes (GT) from 3,414 isolates were identified. M-C were categorized as GT Match (N=40) or no-Match (N=29). When modeling the severity of ECC at 36-months (~4 years old), the estimated dmfs in the Match group was 2.61 times that in the no-Match group (P=.014). Conclusions Colonization of children with Sm GT that matched with mothers was shown to be highly associated with ECC. Although the data suggest vertical transmission of Sm in 40 of 69 children that shared GT with their mother, it is possible that other individuals transmitted the Sm. Nonetheless, these findings support the importance of the mother's oral microbial status as a contributing influence to their children's oral health. PMID:28390463

  7. Feasibility study of solid oxide fuel cell engines integrated with sprinter gas turbines: Modeling, design and control

    NASA Astrophysics Data System (ADS)

    Jia, Zhenzhong; Sun, Jing; Dobbs, Herb; King, Joel

    2015-02-01

    Conventional recuperating solid oxide fuel cell (SOFC)/gas turbine (GT) system suffers from its poor dynamic capability and load following performance. To meet the fast, safe and efficient load following requirements for mobile applications, a sprinter SOFC/GT system concept is proposed in this paper. In the proposed system, an SOFC stack operating at fairly constant temperature provides the baseline power with high efficiency while the fast dynamic capability of the GT-generator is fully explored for fast dynamic load following. System design and control studies have been conducted by using an SOFC/GT system model consisting of experimentally-verified component models. In particular, through analysis of the steady-state simulation results, an SOFC operation strategy is proposed to maintain fairly constant SOFC power (less than 2% power variation) and temperature (less than 2 K temperature variation) over the entire load range. A system design procedure well-suited to the proposed system has also been developed to help determining component sizes and the reference steady-state operation line. In addition, control analysis has been studied for both steady-state and transient operations. Simulation results suggest that the proposed system holds the promise to achieve fast and safe transient operations by taking full advantage of the fast dynamics of the GT-generator.

  8. Productive infection of Epstein-Barr virus (EBV) in EBV-genome-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues.

    PubMed

    Takasaka, N; Tajima, M; Okinaga, K; Satoh, Y; Hoshikawa, Y; Katsumoto, T; Kurata, T; Sairenji, T

    1998-08-01

    We characterized the expression of Epstein-Barr virus (EBV) on two epithelial cell lines, GT38 and GT39, derived from human gastric tissues. The EBV nuclear antigen (EBNA) was detected in all cells of both cell lines. The EBV immediate-early BZLF 1 protein (ZEBRA), the early antigen diffuse component (EA-D), and one of the EBV envelope proteins (gp350/220) were expressed spontaneously in small proportions in the cells. EBNA 1, EBNA2, latent membrane protein 1, ZEBRA, and EA-D molecules were then observed by Western blotting in the cells. The lytic cycle was enhanced with treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate. The virus particles were observed in the TPA treated GT38 cells by electron microscopy. Infectious EBV was detected with the transformation of cord blood lymphocytes and also with the induction of early antigen to Raji cells by the supernatants of both cells lines. A major single and minor multiple fused terminal fragments and a ladder of smaller fragments of the EBV genome were detected with a Xhol probe in both cell lines. These epithelial cells lines and viruses will be useful in studying their association with EBV in gastric epithelial cells.

  9. [Hydrolyzable tannins; biochemistry, nutritional & analytical aspects and health effects].

    PubMed

    Olivas-Aguirre, Francisco Javier; Wall-Medrano, Abraham; González-Aguilar, Gustavo A; López-Díaz, Jose Alberto; Álvarez-Parrilla, Emilio; de la Rosa, Laura A; Ramos-Jimenez, Arnulfo

    2014-11-01

    Hydrolysable tannins (HT) have been of scientific interest because of their nutraceutical potential. Both gallotannins (GT) and ellagitannins (ET) show different biochemical properties that result in various health benefits (eg anti-diabetic, anti-mutagenic, anti-microbial) for consumers, all associated with their antioxidant capacity (AOXc). To analyze the most relevant aspects (biochemical, nutritional/analytical and health effects) of HT reported in the scientific literature. A systematic search was conducted in several databases (PubMed, Cochrane, ScienceDirect) and free-access repositories (Google Scholar) on HT, GT and ET. This information was further sub-classified into biochemical, nutritional and analytical aspects (narrative review) and health effects (systematic review). The high molecular complexity and amount of hydroxyl groups (-OH) in both ET and GT, are responsible not only for a plethora of methods for extraction and purification but also for the several pro-and anti-physiological effects of them such as enzyme inhibitions, protein excretion stimulation, AOXc and anti-proliferative effects. The association of ET/GT with several macromolecules present in foodstuffs and the digestive tract, counteract the AOXc of these compounds but conversely allow the differential distribution of GT and ET to different target organs in such way that their health effects seems to be different. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  10. Anterior maxillary and mandibular biotype: relationship between gingival thickness and width with respect to underlying bone thickness.

    PubMed

    La Rocca, Andres Pascual; Alemany, Antonio Santos; Levi, Paul; Juan, Monica Vicario; Molina, Jose Nart; Weisgold, Arnold S

    2012-12-01

    : Periodontal biotype is considered to be a significant factor related to successful dental treatments. The purpose of this study was to determine the relationship between gingival thickness (GT) and width with respect to the underlying bone thickness in the maxillary and mandibular anterior sextant. : Overall, 180 anterior teeth within healthy patients were assessed. GT and buccal bone thickness (BT) were measured at 3 locations: crestal/gingival margin, tooth apex, and a midpoint between the 2. In addition, the apicoincisal gingival width (GW) was recorded. Clinical and cone beam CT measurements were compared and correlated. : No statistically significant relations were observed between GT and BT measures at any of the 3 positions. The mean GT at crestal mid and apical position for the maxillary teeth was 1.01 (±0.58) mm, 1.06 (±0.48) mm, and 0.83 (±0.47) mm, respectively, and the corresponding mean BT was 1.24 (±0.90) mm, 0.81 (±0.33) mm, and 2.78 (±1.62) mm, respectively. The GW is directly related (R = 0.007; P < 0.05) to the crestal BT. : In this study, the GT is not linked to the BT. However, the GW seems to be associated with the crestal BT.

  11. Spatial and Temporal Antarctic Ice Sheet Mass Trends, Glacio-Isostatic Adjustment, and Surface Processes from a Joint Inversion of Satellite Altimeter, Gravity, and GPS Data

    NASA Technical Reports Server (NTRS)

    Martin-Espanol, Alba; Zammit-Mangion, Andrew; Clarke, Peter J.; Flament, Thomas; Helm, Veit; King, Matt A.; Luthcke, Scott B.; Petrie, Elizabeth; Remy, Frederique; Schon, Nana; hide

    2016-01-01

    We present spatiotemporal mass balance trends for the Antarctic Ice Sheet from a statistical inversion of satellite altimetry, gravimetry, and elastic-corrected GPS data for the period 2003-2013. Our method simultaneously determines annual trends in ice dynamics, surface mass balance anomalies, and a time-invariant solution for glacio-isostatic adjustment while remaining largely independent of forward models. We establish that over the period 2003-2013, Antarctica has been losing mass at a rateof -84 +/- 22 Gt per yr, with a sustained negative mean trend of dynamic imbalance of -111 +/- 13 Gt per yr. West Antarctica is the largest contributor with -112 +/- 10 Gt per yr, mainly triggered by high thinning rates of glaciers draining into the Amundsen Sea Embayment. The Antarctic Peninsula has experienced a dramatic increase in mass loss in the last decade, with a mean rate of -28 +/- 7 Gt per yr and significantly higher values for the most recent years following the destabilization of the Southern Antarctic Peninsula around 2010. The total mass loss is partly compensated by a significant mass gain of 56 +/- 18 Gt per yr in East Antarctica due to a positive trend of surface mass balance anomalies.

  12. Sedentary behaviours among adults across Canada.

    PubMed

    Herman, Katya M; Saunders, Travis J

    2016-12-27

     OBJECTIVES: While cross-Canada variations in physical activity and weight status have been illustrated, less is known about sedentary behaviour (SB). The aim of this study was to describe various SBs and their correlates among Canadian adults. METHODS: Cross-sectional data from the 2011-2012 Canadian Community Health Survey included 92,918 respondents aged 20-75+ years, representative of >22 million Canadian adults. TV/video viewing, computer, video game playing and reading time were self-reported. Associations with socio-demographic, health and health behaviour variables were examined. RESULTS: About 31% of adults reported >2 hours/day TV viewing, while 47% of men and 41% of women reported >5 hours/week computer use, 24% of men and 12% of women reported ≥1 hour/week video game playing, and 33% of men and 46% of women reported >5 hours/week reading; 28% of respondents reported ≥5 hours/day total SB time. Age was the strongest correlate: adults 75+ had 5 and 6 times greater odds respectively of reporting >2 hours/day TV viewing and >5 hours/week reading, but far lesser odds of reporting high computer or video game time, compared to adults 20-24. Other variables associated with specific SBs included gender, marital status, education, occupation, income and immigrant status, as well as BMI, weight perceptions, smoking, diet and physical activity. CONCLUSION: Common sedentary behaviours were associated with numerous socio-demographic, health and health behaviour characteristics in a large representative sample of Canadians. These correlates differed according to the type of SB. Public health interventions targeting SB should be behavior-specific and tailored to the population segment of interest.

  13. Sediment and Particular Organic Carbon (POC) fluxes changes over the past decades in the Yellow River system

    NASA Astrophysics Data System (ADS)

    Lu, Xixi; Ran, Lishan

    2015-04-01

    The Yellow River system used to have very high sediment export to ocean (around 1.5 Gt/yr in the 1950s) because of severe soil erosion on the Loess Plateau. However, its sediment export has declined to <0.25 Gt/yr in recent years (in the 2000s), mainly due to human activities like construction of reservoirs and check dams and other soil and water conservations such as construction of terraces and vegetation restoration. Such drastic reduction in soil erosion and sediment flux and subsequently in associated Particular Organic Carbon (POC) transport can potentially play a significant role in carbon cycling. Through the sediment flux budget we examined POC budget and carbon sequestration through vegetation restoration and various soil and water conservations including reservoirs construction over the past decades in the Yellow River system. Landsat imageries were used to delineate the reservoirs and check dams for estimating the sediment trapping. The reservoirs and check dams trapped a total amount of sediment 0.94 Gt/yr, equivalent to 6.5 Mt C. Soil erosion controls through vegetation restoration and terrace construction reduced soil erosion 1.82 Gt/yr, equivalent to 12 Mt C. The annual NPP increased from 0.150 Gt C in 2000 to 0.1889 Gt C in 2010 with an average increment rate of 3.4 Mt C per year over the recent decade (from 2000 to 2010) through vegetation restoration. The total carbon stabilized on slope systems through soil erosion controls (12 Mt C per year) was much higher than the direct carbon sequestration via vegetation restoration (3.4 Mt C per year), indicating the importance of horizontal carbon mobilization in carbon cycling, albeit a high estimate uncertainty.

  14. Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress.

    PubMed

    Liu, Shaobin; Zeng, Tingying Helen; Hofmann, Mario; Burcombe, Ehdi; Wei, Jun; Jiang, Rongrong; Kong, Jing; Chen, Yuan

    2011-09-27

    Health and environmental impacts of graphene-based materials need to be thoroughly evaluated before their potential applications. Graphene has strong cytotoxicity toward bacteria. To better understand its antimicrobial mechanism, we compared the antibacterial activity of four types of graphene-based materials (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene oxide (rGO)) toward a bacterial model-Escherichia coli. Under similar concentration and incubation conditions, GO dispersion shows the highest antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning electron microscope (SEM) and dynamic light scattering analyses show that GO aggregates have the smallest average size among the four types of materials. SEM images display that the direct contacts with graphene nanosheets disrupt cell membrane. No superoxide anion (O(2)(•-)) induced reactive oxygen species (ROS) production is detected. However, the four types of materials can oxidize glutathione, which serves as redox state mediator in bacteria. Conductive rGO and Gt have higher oxidation capacities than insulating GO and GtO. Results suggest that antimicrobial actions are contributed by both membrane and oxidation stress. We propose that a three-step antimicrobial mechanism, previously used for carbon nanotubes, is applicable to graphene-based materials. It includes initial cell deposition on graphene-based materials, membrane stress caused by direct contact with sharp nanosheets, and the ensuing superoxide anion-independent oxidation. We envision that physicochemical properties of graphene-based materials, such as density of functional groups, size, and conductivity, can be precisely tailored to either reducing their health and environmental risks or increasing their application potentials. © 2011 American Chemical Society

  15. 24 Hours of Sleep, Sedentary Behavior, and Physical Activity with Nine Wearable Devices

    PubMed Central

    Rosenberger, Mary E.; Buman, Matthew P.; Haskell, William L.; McConnell, Michael V.; Carstensen, Laura L.

    2015-01-01

    Getting enough sleep, exercising and limiting sedentary activities can greatly contribute to disease prevention and overall health and longevity. Measuring the full 24-hour activity cycle - sleep, sedentary behavior (SED), light intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) - may now be feasible using small wearable devices. PURPOSE This study compares nine devices for accuracy in 24-hour activity measurement. METHODS Adults (N=40, 47% male) wore nine devices for 24-hours: Actigraph GT3X+, activPAL, Fitbit One, GENEactiv, Jawbone Up, LUMOback, Nike Fuelband, Omron pedometer, and Z-Machine. Comparisons (to standards) were made for total sleep time (Z-machine), time spent in SED (activPAL), LPA (GT3x+), MVPA (GT3x+), and steps (Omron). Analysis included mean absolute percent error, equivalence testing, and Bland-Altman plots. RESULTS Error rates ranged from 8.1–16.9% for sleep; 9.5–65.8% for SED; 19.7–28.0% for LPA; 51.8–92% for MVPA; and 14.1–29.9% for steps. Equivalence testing indicated only two comparisons were significantly equivalent to standards: the LUMOback for sedentary behavior and the GT3X+ for sleep. Bland-Altman plots indicated GT3X+ had the closest measurement for sleep, LUMOback for sedentary behavior, GENEactiv for LPA, Fitbit for MVPA and GT3X+ for steps. CONCLUSIONS Currently, no device accurately captures activity data across the entire 24-hour day, but the future of activity measurement should aim for accurate 24-hour measurement as a goal. Researchers should continue to select measurement devices based on their primary outcomes of interest. PMID:26484953

  16. Association of COL1A1 polymorphisms with osteoporosis: a meta-analysis of clinical studies

    PubMed Central

    Xie, Peigen; Liu, Bin; Zhang, Liangming; Chen, Ruiqiang; Yang, Bu; Dong, Jianwen; Rong, Limin

    2015-01-01

    Objective: To conduct a meta-analysis of all association studies on two of the collagen 1 alpha 1 (COL1A1) gene polymorphisms, the -1997G/T (rs1107946) and the -1663indelT (rs2412298) polymorphisms and osteoporosis/BMD and fracture. Methods: PubMed/Medline and Web of Knowledge were searched for relevant association studies published in English. Pooled OR and its corresponding 95% CI or pooled MD and its corresponding 95% CI was calculated with the Cochrane Review Manager (Revman, version 5.2) using a random-effect or a fixed effect model. Results: No significant association between the -1997G/T polymorphism and Lumbar Spine (LS) and Femoral Neck (FN) BMD except for the Caucasian subpopulation wherein subjects with the T allele of the -1997G/T polymorphism was associated with significantly higher LS BMD. Our analysis did reveal that women, especially postmenopausal or perimenopausal women with the GG genotype, had significantly higher Total Hip (TH) BMD than those with the GT. Additionally, our meta-analysis did not show significant association between the -1997G/T polymorphism and risk of fracture, between the -1663indelT polymorphism and LS BMD in postmenopausal or perimenopausal women, or between the -1663indelT polymorphism and the risk of fracture. Conclusions: Our results suggested the possibility of the COL1A1 -1997G/T and the -1663indelT polymorphisms individually playing very little role in osteoporosis and fracture, although more studies are needed especially for the analysis of association between these two polymorphisms and fracture. Haplotype studies may become one important future direction of study to further elucidate whether and how various COL1A1 polymorphisms affect bone health, osteoporosis and fracture. PMID:26628959

  17. Enhanced osteogenic differentiation of MC3T3-E1 cells on grid-topographic surface and evidence for involvement of YAP mediator.

    PubMed

    Zhang, Yingying; Gong, He; Sun, Yan; Huang, Yan; Fan, Yubo

    2016-05-01

    Numerous studies have shown that surface topography can promote cell-substrate associations and deeply influence cell fate. The intracellular mechanism or how micro- or nano-patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes-associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3-E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3-E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates-induced MC3T3-E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates-induced MC3T3-E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering. © 2016 Wiley Periodicals, Inc.

  18. Performance of an online translation tool when applied to patient educational material.

    PubMed

    Khanna, Raman R; Karliner, Leah S; Eck, Matthias; Vittinghoff, Eric; Koenig, Christopher J; Fang, Margaret C

    2011-11-01

    Language barriers may prevent clinicians from tailoring patient educational material to the needs of individuals with limited English proficiency. Online translation tools could fill this gap, but their accuracy is unknown. We evaluated the accuracy of an online translation tool for patient educational material. We selected 45 sentences from a pamphlet available in both English and Spanish, and translated it into Spanish using GoogleTranslate™ (GT). Three bilingual Spanish speakers then performed a blinded evaluation on these 45 sentences, comparing GT-translated sentences to those translated professionally, along four domains: fluency (grammatical correctness), adequacy (information preservation), meaning (connotation maintenance), and severity (perceived dangerousness of an error if present). In addition, evaluators indicated whether they had a preference for either the GT-translated or professionally translated sentences. The GT-translated sentences had significantly lower fluency scores compared to the professional translation (3.4 vs. 4.7, P < 0.001), but similar adequacy (4.2 vs. 4.5, P = 0.19) and meaning (4.5 vs. 4.8, P = 0.29) scores. The GT-translated sentences were more likely to have any error (39% vs. 22%, P = 0.05), but not statistically more likely to have a severe error (4% vs. 2%, P = 0.61). Evaluators preferred the professional translation for complex sentences, but not for simple ones. When applied to patient educational material, GT performed comparably to professional human translation in terms of preserving information and meaning, though it was slightly worse in preserving grammar. In situations where professional human translations are unavailable or impractical, online translation may someday fill an important niche. Copyright © 2011 Society of Hospital Medicine.

  19. Stress perception and (GT)n repeat polymorphism in haem oxygenase 1 promoter are both risk factors in development of eating disorders.

    PubMed

    Slachtová, L; Kaminská, D; Chvál, M; Králík, L; Martásek, P; Papežová, H

    2013-01-01

    Haem oxygenase 1 (HO-1) plays a pivotal role in metabolic stress protecting cells in dependence on reactive oxygen species. This study investigated a potential gene environment interaction between the (GT)n repeat HO1 polymorphism and the stress perception in patients with eating disorder and in controls. Stress perception and (GT)n polymorphism were measured in 127 patients with eating disorders and in 78 healthy controls using Stress and Coping Inventory and genotyping. Based on the inventory, overall, specific and weighted stress scores were defined. Clinical stress score was generated according to the patient's history and interviews. According to our hypothesis, 1) all stress scores describing subjective stress perception were significantly higher in patients compared to controls (P ≤ 0.001; P ≤ 0.002; P ≤ 0.001), 2) the L/L genotype of GT promoter repeats (L < 25 GT repeats, S < 25 GT repeats) in the patients was associated with higher overall (P ≤ 0.001), specific (P ≤ 0.010) and weighted stress score (P ≤ 0.005) compared to the L/S variant, and 3) Pearson's correlation of clinical versus objective stress scores showed not very tight relationship (0.198; 0.287; 0.224, respectively). We assume potential risk of the L allele of HO1 promoter polymorphism for the stress response and contribution of the subjective stress perception together with the L/L genotype to the development of eating disorder. Decreased HO1 expression in the presence of L/L genotype plus more intensive stress perception in the patients can lead to secondary stress, with increasing severity of the symptoms and aggravation of the disease.

  20. Well-known surface and extracellular antigens of pathogenic microorganisms among the immunodominant proteins of the infectious microalgae Prototheca zopfii

    PubMed Central

    Irrgang, Alexandra; Murugaiyan, Jayaseelan; Weise, Christoph; Azab, Walid; Roesler, Uwe

    2015-01-01

    Microalgae of the genus Prototheca (P.) are associated with rare but severe infections (protothecosis) and represent a potential zoonotic risk. Genotype (GT) 2 of P. zopfii has been established as pathogenic agent for humans, dogs, and cattle, whereas GT1 is considered to be non-pathogenic. Since pathogenesis is poorly understood, the aim of this study was to determine immunogenic proteins and potential virulence factors of P. zopfii GT2. Therefore, 2D western blot analyses with sera and isolates of two dogs naturally infected with P. zopfii GT2 have been performed. Cross-reactivity was determined by including the type strains of P. zopfii GT2, P. zopfii GT1, and P. blaschkeae, a close relative of P. zopfii, which is known to cause subclinical forms of bovine mastitis. The sera showed a high strain-, genotype-, and species-cross-reactivity. A total of 198 immunogenic proteins have been analyzed via MALDI—TOF MS. The majority of the 86 identified proteins are intracellularly located (e.g., malate dehydrogenase, oxidoreductase, 3-dehydroquinate synthase) but some antigens and potential virulence factors, known from other pathogens, have been found (e.g., phosphomannomutase, triosephosphate isomerase). One genotype-specific antigen could be identified as heat shock protein 70 (Hsp70), a well-known antigen of eukaryotic pathogens with immunological importance when located extracellularly. Both sera were reactive to glyceraldehyde-3-phosphate-dehydrogenase of all investigated strains. This house-keeping enzyme is found to be located on the surface of several pathogens as virulence factor. Flow-cytometric analysis revealed its presence on the surface of P. blaschkeae. PMID:26484314

  1. γ-Tocotrienol Protects against Mitochondrial Dysfunction and Renal Cell Death

    PubMed Central

    Bakajsova, Diana; Hayes, Corey; Hauer-Jensen, Martin; Compadre, Cesar M.

    2012-01-01

    Oxidative stress is a major mechanism of a variety of renal diseases. Tocopherols and tocotrienols are well known antioxidants. This study aimed to determine whether γ-tocotrienol (GT3) protects against mitochondrial dysfunction and renal proximal tubular cell (RPTC) injury caused by oxidants. Primary cultures of RPTCs were injured by using tert-butyl hydroperoxide (TBHP) in the absence and presence of GT3 or α-tocopherol (AT). Reactive oxygen species (ROS) production increased 300% in TBHP-injured RPTCs. State 3 respiration, oligomycin-sensitive respiration, and respiratory control ratio (RCR) decreased 50, 63, and 47%, respectively. The number of RPTCs with polarized mitochondria decreased 54%. F0F1-ATPase activity and ATP content decreased 31 and 65%, respectively. Cell lysis increased from 3% in controls to 26 and 52% at 4 and 24 h, respectively, after TBHP exposure. GT3 blocked ROS production, ameliorated decreases in state 3 and oligomycin-sensitive respirations and F0F1-ATPase activity, and maintained RCR and mitochondrial membrane potential (ΔΨm) in injured RPTCs. GT3 maintained ATP content, blocked RPTC lysis at 4 h, and reduced it to 13% at 24 h after injury. Treatment with equivalent concentrations of AT did not block ROS production and cell lysis and moderately improved mitochondrial respiration and coupling. This is the first report demonstrating the protective effects of GT3 against RPTC injury by: 1) decreasing production of ROS, 2) improving mitochondrial respiration, coupling, ΔΨm, and F0F1-ATPase function, 3) maintaining ATP levels, and 4) preventing RPTC lysis. Our data suggest that GT3 is superior to AT in protecting RPTCs against oxidant injury and may prove therapeutically valuable for preventing renal injury associated with oxidative stress. PMID:22040679

  2. Quality of cancer family history and referral for genetic counseling and testing among oncology practices: a pilot test of quality measures as part of the American Society of Clinical Oncology Quality Oncology Practice Initiative.

    PubMed

    Wood, Marie E; Kadlubek, Pamela; Pham, Trang H; Wollins, Dana S; Lu, Karen H; Weitzel, Jeffrey N; Neuss, Michael N; Hughes, Kevin S

    2014-03-10

    Family history of cancer (CFH) is important for identifying individuals to receive genetic counseling/testing (GC/GT). Prior studies have demonstrated low rates of family history documentation and referral for GC/GT. CFH quality and GC/GT practices for patients with breast (BC) or colon cancer (CRC) were assessed in 271 practices participating in the American Society of Clinical Oncology Quality Oncology Practice Initiative in fall 2011. A total of 212 practices completed measures regarding CFH and GC/GT practices for 10,466 patients; 77.4% of all medical records reviewed documented presence or absence of CFH in first-degree relatives, and 61.5% of medical records documented presence or absence of CFH in second-degree relatives, with significantly higher documentation for patients with BC compared with CRC. Age at diagnosis was documented for all relatives with cancer in 30.7% of medical records (BC, 45.2%; CRC, 35.4%; P ≤ .001). Referall for GC/GT occurred in 22.1% of all patients with BC or CRC. Of patients with increased risk for hereditary cancer, 52.2% of patients with BC and 26.4% of those with CRC were referred for GC/GT. When genetic testing was performed, consent was documented 77.7% of the time, and discussion of results was documented 78.8% of the time. We identified low rates of complete CFH documentation and low rates of referral for those with BC or CRC meeting guidelines for referral among US oncologists. Documentation and referral were greater for patients with BC compared with CRC. Education and support regarding the importance of accurate CFH and the benefits of proactive high-risk patient management are clearly needed.

  3. Pain, not structural impairments may explain activity limitations in people with gluteal tendinopathy or hip osteoarthritis: A cross sectional study.

    PubMed

    Fearon, Angela; Neeman, Teresa; Smith, Paul; Scarvell, Jennie; Cook, Jill

    2017-02-01

    What are the functional differences between people with greater trochanteric pain syndrome (GT), hip osteoarthritis (OA) or an asymptomatic population as measured by walking, Time Up and Go, single leg standing and strength? Cross sectional study with blinded measurers. 38 participants with GT, 20 with end stage hip OA and 21 asymptomatic healthy control (AS) participants. All participants were women. Pain (numeric rating scale), Walking speed (m/s), cadence (steps/min) and step length (m) measured via the 10m walk test and the Timed Up and Go; balance via single leg stance (s) duration; and hip abduction, adduction, medial and lateral rotation strength, standardized to body mass (BM) via the body mass average index (BMavg), measured via a wall mounted dynamometer. The two symptomatic groups reported similar pain levels (p=0.226), more pain then the AS group (p<0.000). Compared to the AS participants, participants with GT or hip OA demonstrated lower walking speed (10mwt and TUG, p<0.001), lower cadence and shorter duration single leg stance on the affected leg (p<0.05). Participants with GT or hip OA also demonstrated bilaterally weaker hip abduction than the AS group (p≤0.005). Compared to AS and GT participants, participants with hip OA demonstrated adduction weakness on the affected side (p=0.008 and p=0.002 respectively). There is a significant level of dysfunction and impairments associated with GT and hip OA. As activity limitations do not appear to be differentiated by structural impairments, we suggest that pain, rather than the underlying pathology may be the driving impairment that leads to walking and single leg standing dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Negative emissions—Part 2: Costs, potentials and side effects

    NASA Astrophysics Data System (ADS)

    Fuss, Sabine; Lamb, William F.; Callaghan, Max W.; Hilaire, Jérôme; Creutzig, Felix; Amann, Thorben; Beringer, Tim; de Oliveira Garcia, Wagner; Hartmann, Jens; Khanna, Tarun; Luderer, Gunnar; Nemet, Gregory F.; Rogelj, Joeri; Smith, Pete; Vicente, José Luis Vicente; Wilcox, Jennifer; del Mar Zamora Dominguez, Maria; Minx, Jan C.

    2018-06-01

    The most recent IPCC assessment has shown an important role for negative emissions technologies (NETs) in limiting global warming to 2 °C cost-effectively. However, a bottom-up, systematic, reproducible, and transparent literature assessment of the different options to remove CO2 from the atmosphere is currently missing. In part 1 of this three-part review on NETs, we assemble a comprehensive set of the relevant literature so far published, focusing on seven technologies: bioenergy with carbon capture and storage (BECCS), afforestation and reforestation, direct air carbon capture and storage (DACCS), enhanced weathering, ocean fertilisation, biochar, and soil carbon sequestration. In this part, part 2 of the review, we present estimates of costs, potentials, and side-effects for these technologies, and qualify them with the authors’ assessment. Part 3 reviews the innovation and scaling challenges that must be addressed to realise NETs deployment as a viable climate mitigation strategy. Based on a systematic review of the literature, our best estimates for sustainable global NET potentials in 2050 are 0.5–3.6 GtCO2 yr‑1 for afforestation and reforestation, 0.5–5 GtCO2 yr‑1 for BECCS, 0.5–2 GtCO2 yr‑1 for biochar, 2–4 GtCO2 yr‑1 for enhanced weathering, 0.5–5 GtCO2 yr‑1 for DACCS, and up to 5 GtCO2 yr‑1 for soil carbon sequestration. Costs vary widely across the technologies, as do their permanency and cumulative potentials beyond 2050. It is unlikely that a single NET will be able to sustainably meet the rates of carbon uptake described in integrated assessment pathways consistent with 1.5 °C of global warming.

  5. GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan

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

    Wu, Meei-Maan, E-mail: mmwu@tmu.edu.t; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan

    2010-11-01

    Inorganic arsenic has been associated with increased risk of atherosclerotic vascular disease and mortality in humans. A functional GT-repeat polymorphism in the heme oxygenase-1 (HO-1) gene promoter is inversely correlated with the development of coronary artery disease and restenosis after clinical angioplasty. The relationship of HO-1 genotype with arsenic-associated cardiovascular disease has not been studied. In this study, we evaluated the relationship between the HO-1 GT-repeat polymorphism and cardiovascular mortality in an arsenic-exposed population. A total of 504 study participants were followed up for a median of 10.7 years for occurrence of cardiovascular deaths (coronary heart disease, cerebrovascular disease, andmore » peripheral arterial disease). Cardiovascular risk factors and DNA samples for determination of HO-1 GT repeats were obtained at recruitment. GT repeats variants were grouped into the S (< 27 repeats) or L allele ({>=} 27 repeats). Relative mortality risk was estimated using Cox regression analysis, adjusted for competing risk of cancer and other causes. For the L/L, L/S, and S/S genotype groups, the crude mortalities for cardiovascular disease were 8.42, 3.10, and 2.85 cases/1000 person-years, respectively. After adjusting for conventional cardiovascular risk factors and competing risk of cancer and other causes, carriers with class S allele (L/S or S/S genotypes) had a significantly reduced risk of cardiovascular mortality compared to non-carriers (L/L genotype) [OR, 0.38; 95% CI, 0.16-0.90]. In contrast, no significant association was observed between HO-1 genotype and cancer mortality or mortality from other causes. Shorter (GT)n repeats in the HO-1 gene promoter may confer protective effects against cardiovascular mortality related to arsenic exposure.« less

  6. "What Is a Step?" Differences in How a Step Is Detected among Three Popular Activity Monitors That Have Impacted Physical Activity Research.

    PubMed

    John, Dinesh; Morton, Alvin; Arguello, Diego; Lyden, Kate; Bassett, David

    2018-04-15

    (1) Background: This study compared manually-counted treadmill walking steps from the hip-worn DigiwalkerSW200 and OmronHJ720ITC, and hip and wrist-worn ActiGraph GT3X+ and GT9X; determined brand-specific acceleration amplitude (g) and/or frequency (Hz) step-detection thresholds; and quantified key features of the acceleration signal during walking. (2) Methods: Twenty participants (Age: 26.7 ± 4.9 years) performed treadmill walking between 0.89-to-1.79 m/s (2-4 mph) while wearing a hip-worn DigiwalkerSW200, OmronHJ720ITC, GT3X+ and GT9X, and a wrist-worn GT3X+ and GT9X. A DigiwalkerSW200 and OmronHJ720ITC underwent shaker testing to determine device-specific frequency and amplitude step-detection thresholds. Simulated signal testing was used to determine thresholds for the ActiGraph step algorithm. Steps during human testing were compared using bias and confidence intervals. (3) Results: The OmronHJ720ITC was most accurate during treadmill walking. Hip and wrist-worn ActiGraph outputs were significantly different from the criterion. The DigiwalkerSW200 records steps for movements with a total acceleration of ≥1.21 g. The OmronHJ720ITC detects a step when movement has an acceleration ≥0.10 g with a dominant frequency of ≥1 Hz. The step-threshold for the ActiLife algorithm is variable based on signal frequency. Acceleration signals at the hip and wrist have distinctive patterns during treadmill walking. (4) Conclusions: Three common research-grade physical activity monitors employ different step-detection strategies, which causes variability in step output.

  7. “What Is a Step?” Differences in How a Step Is Detected among Three Popular Activity Monitors That Have Impacted Physical Activity Research

    PubMed Central

    John, Dinesh; Arguello, Diego; Lyden, Kate; Bassett, David

    2018-01-01

    (1) Background: This study compared manually-counted treadmill walking steps from the hip-worn DigiwalkerSW200 and OmronHJ720ITC, and hip and wrist-worn ActiGraph GT3X+ and GT9X; determined brand-specific acceleration amplitude (g) and/or frequency (Hz) step-detection thresholds; and quantified key features of the acceleration signal during walking. (2) Methods: Twenty participants (Age: 26.7 ± 4.9 years) performed treadmill walking between 0.89-to-1.79 m/s (2–4 mph) while wearing a hip-worn DigiwalkerSW200, OmronHJ720ITC, GT3X+ and GT9X, and a wrist-worn GT3X+ and GT9X. A DigiwalkerSW200 and OmronHJ720ITC underwent shaker testing to determine device-specific frequency and amplitude step-detection thresholds. Simulated signal testing was used to determine thresholds for the ActiGraph step algorithm. Steps during human testing were compared using bias and confidence intervals. (3) Results: The OmronHJ720ITC was most accurate during treadmill walking. Hip and wrist-worn ActiGraph outputs were significantly different from the criterion. The DigiwalkerSW200 records steps for movements with a total acceleration of ≥1.21 g. The OmronHJ720ITC detects a step when movement has an acceleration ≥0.10 g with a dominant frequency of ≥1 Hz. The step-threshold for the ActiLife algorithm is variable based on signal frequency. Acceleration signals at the hip and wrist have distinctive patterns during treadmill walking. (4) Conclusions: Three common research-grade physical activity monitors employ different step-detection strategies, which causes variability in step output. PMID:29662048

  8. Estimating the supply and demand for deep geologic CO2 storage capacity over the course of the 21st Century: A meta-analysis of the literature

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

    Dooley, James J.

    2013-08-05

    Whether there is sufficient geologic CO2 storage capacity to allow CCS to play a significant role in mitigating climate change has been the subject of debate since the 1990s. This paper presents a meta- analysis of a large body of recently published literature to derive updated estimates of the global deep geologic storage resource as well as the potential demand for this geologic CO2 storage resource over the course of this century. This analysis reveals that, for greenhouse gas emissions mitigation scenarios that have end-of-century atmospheric CO2 concentrations of between 350 ppmv and 725 ppmv, the average demand for deepmore » geologic CO2 storage over the course of this century is between 410 GtCO2 and 1,670 GtCO2. The literature summarized here suggests that -- depending on the stringency of criteria applied to calculate storage capacity – global geologic CO2 storage capacity could be: 35,300 GtCO2 of “theoretical” capacity; 13,500 GtCO2 of “effective” capacity; 3,900 GtCO2, of “practical” capacity; and 290 GtCO2 of “matched” capacity for the few regions where this narrow definition of capacity has been calculated. The cumulative demand for geologic CO2 storage is likely quite small compared to global estimates of the deep geologic CO2 storage capacity, and therefore, a “lack” of deep geologic CO2 storage capacity is unlikely to be an impediment for the commercial adoption of CCS technologies in this century.« less

  9. How useful are ARFI elastography cut-off values proposed by meta-analysis for predicting the significant fibrosis and compensated liver cirrhosis?

    PubMed

    Bota, Simona; Sporea, Ioan; Sirli, Roxana; Popescu, Alina; Gradinaru-Tascau, Oana

    2015-06-01

    To evaluate how often do we "miss" chronic hepatitis C patients with at least significant fibrosis (F>/=2) and those with compensated cirrhosis, by using Acoustic Radiation Force Impulse (ARFI) elastography cut-off values proposed by meta-analysis. Our study included 132 patients with chronic hepatitis C, evaluated by means of ARFI and liver biopsy (LB), in the same session. Reliable measurements were defined as: median value of 10 liver stiffness (LS) measurements with a success rate>/=60% and an interquartile range interval<30%. For predicting F>/=2 and F=4 we used the LS cut-offs proposed in the last published meta-analysis: 1.35 m/s and 1.87 m/s, respectively. Reliable LS measurements by means of ARFI were obtained in 117 patients (87.9%). In our study, 58 patients (49.6%) had LS values <1.35 m/s; from these 75.8% had F>/=2 in LB. From the 59 patients (50.4%) with LS values>/=1.35 m/s, only 6.8% had F0 or F1 in LB. Also, in our study, 88 patients (75.3%) had LS values <1.87 m/s; from these only 2.2 % had F4 in LB. From the 29 patients (24.7%) with LS values>/=1.87 m/s, 41.3% had F4 in LB. Both for prediction of at least significant fibrosis and liver cirrhosis, higher aminotransferases levels were associated with wrongly classified patients, in univariate and multivariate analysis. ARFI elastography had a very good positive predictive value (93.2%) for predicting the presence of significant fibrosis and excellent negative predictive value (97.8%) for excluding the presence of compensated liver cirrhosis.

  10. Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

    PubMed Central

    Mack Correa, Mary Catherine; Mao, Guangru; Saad, Peter; Flach, Carol R; Mendelsohn, Richard; Walters, Russel M

    2014-01-01

    Plant-derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA-d34). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA-d34 and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose-dependent manner, with the highest increase from treatment with pure OA. OA-d34 penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA-d34 permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions. PMID:24372651

  11. National Utilization and Forecasting of Ototopical Antibiotics: Medicaid Data Versus "Dr. Google".

    PubMed

    Crowson, Matthew G; Schulz, Kristine; Tucci, Debara L

    2016-09-01

    To forecast national Medicaid prescription volumes for common ototopical antibiotics, and correlate prescription volumes with internet user search interest using Google Trends (GT). National United States Medicaid prescription and GT user search database analysis. Quarterly national Medicaid summary drug utilization data and weekly GT search engine data for ciprofloxacin-dexamethasone (CD), ofloxacin (OF), and Cortisporin (CS) ototopicals were obtained from January 2008 to July 2014. Time series analysis was used to assess prescription seasonality, Holt-Winter's method for forecasting quarterly prescription volumes, and Pearson correlations to compare GT and Medicaid data. Medicaid prescription volumes demonstrated sinusoidal seasonality for OF (r = 0.91), CS (r = 0.71), and CD (r = 0.62) with annual peaks in July, August, and September. In 2017, OF was forecasted to be the most widely prescribed ototopical, followed by CD. CS was the least prescribed, and volumes were forecasted to decrease 9.0% by 2017 from 2014. GT user search interest demonstrated analogous sinusoidal seasonality and significant correlations with Medicaid data prescriptions for CD (r = 0.38, p = 0.046), OF (r = 0.74, p < 0.001), CS (r = 0.49, p = 0.008). We found that OF, CD, and CS ototopicals have sinusoidal seasonal variation with Medicaid prescription volume peaks occurring in the summer. After 2012, OF was the most commonly prescribed ototopical, and this trend was forecasted to continue. CS use was forecasted to decrease. Google user search interest in these ototopical agents demonstrated analogous seasonal variation. Analyses of GT for interest in ototopical antibiotics may be useful for health care providers and administrators as a complementary method for assessing healthcare utilization trends.

  12. Scopolamine and amphetamine produce similar decision-making deficits on a rat gambling task via independent pathways.

    PubMed

    Silveira, Mason M; Malcolm, Emma; Shoaib, Mohammed; Winstanley, Catharine A

    2015-03-15

    Disorders characterized by disturbed cholinergic signaling, such as schizophrenia, exhibit impaired performance on measures of real-world cost/benefit decision-making. Whether the cholinergic system contributes to the choice deficits observed is currently unknown. We therefore determined the effects of broad-acting agonists and antagonists at the nicotinic and muscarinic receptor on decision making, as measured by the rodent gambling task (rGT). Given the anatomical and functional connectivity of the cholinergic and dopaminergic systems, we also sought to modulate amphetamine's previously reported effect on rGT performance via the cholinergic system. Male rats were trained on the rGT, during which animals chose from four different options. The optimal strategy on the rGT is to favor options associated with smaller immediate rewards and less punishment/loss. Impulsive action was also measured by recording the number of premature responses made. Performance on the rGT was assessed following acute treatment with the muscarinic receptor agonist oxotremorine, the muscarinic receptor antagonist scopolamine, nicotine, and the nicotinic receptor antagonist mecamylamine. Similar to the effect produced by amphetamine, muscarinic receptor antagonism with scopolamine (0.1mg/kg) impaired decision making, albeit to a lesser degree. Prior muscarinic agonism with oxotremorine was unable to attenuate amphetamine's effects on rGT performance. Oxotremorine, nicotine, and mecamylamine did not affect the choice profile. We therefore conclude that modulation of the muscarinic, but not nicotinic, receptor system can affect decision making under conditions of risk and uncertainty. Such findings contribute to a broader understanding of the cognitive deficits observed in disorders in which cholinergic signaling is compromised. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance

    PubMed Central

    2014-01-01

    Background Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood. Methods On days 0, 3, 7, and 14 after admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices. Results During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP. Conclusions The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels. PMID:24903748

  14. Anti-plaque effect of a synergistic combination of green tea and Salvadora persica L. against primary colonizers of dental plaque.

    PubMed

    Abdulbaqi, Hayder Raad; Himratul-Aznita, Wan Harun; Baharuddin, Nor Adinar

    2016-10-01

    Green tea (Gt), leafs of Camellia sinensis var. assamica, is widely consumed as healthy beverage since thousands of years in Asian countries. Chewing sticks (miswak) of Salvadora persica L. (Sp) are traditionally used as natural brush to ensure oral health in developing countries. Both Gt and Sp extracts were reported to have anti-bacterial activity against many dental plaque bacteria. However, their combination has never been tested to have anti-bacterial and anti-adherence effect against primary dental plaque colonizers, playing an initial role in the dental plaque development, which was investigated in this study. Two-fold serial micro-dilution method was used to measure minimal inhibitory concentration (MIC) of aqueous extracts of Gt, Sp and their combinations. Adsorption to hexadecane was used to determine the cell surface hydrophobicity (CSH) of bacterial cells. Glass beads were used to mimic the hard tissue surfaces, and were coated with saliva to develop experimental pellicles for the adhesion of the primary colonizing bacteria. Gt aqueous extracts exhibited better anti-plaque effect than Sp aqueous extracts. Their combination, equivalent to 1/4 and 1/2 of MIC values of Gt and Sp extracts respectively, showed synergistic anti-plaque properties with fractional inhibitory concentration (FIC) equal to 0.75. This combination was found to significantly reduce CSH (p<0.05) and lower the adherence ability (p<0.003) towards experimental pellicles. Combination between Gt and Sp aqueous extracts exhibited synergistic anti-plaque activity, and could be used as a useful active agent to produce oral health care products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Twenty-four Hours of Sleep, Sedentary Behavior, and Physical Activity with Nine Wearable Devices.

    PubMed

    Rosenberger, Mary E; Buman, Matthew P; Haskell, William L; McConnell, Michael V; Carstensen, Laura L

    2016-03-01

    Getting enough sleep, exercising, and limiting sedentary activities can greatly contribute to disease prevention and overall health and longevity. Measuring the full 24-h activity cycle-sleep, sedentary behavior (SED), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA)-may now be feasible using small wearable devices. This study compared nine devices for accuracy in a 24-h activity measurement. Adults (n = 40, 47% male) wore nine devices for 24 h: ActiGraph GT3X+, activPAL, Fitbit One, GENEactiv, Jawbone Up, LUMOback, Nike Fuelband, Omron pedometer, and Z-Machine. Comparisons (with standards) were made for total sleep time (Z-machine), time spent in SED (activPAL), LPA (GT3X+), MVPA (GT3X+), and steps (Omron). Analysis included mean absolute percent error, equivalence testing, and Bland-Altman plots. Error rates ranged from 8.1% to 16.9% for sleep, 9.5% to 65.8% for SED, 19.7% to 28.0% for LPA, 51.8% to 92% for MVPA, and 14.1% to 29.9% for steps. Equivalence testing indicated that only two comparisons were significantly equivalent to standards: the LUMOback for SED and the GT3X+ for sleep. Bland-Altman plots indicated GT3X+ had the closest measurement for sleep, LUMOback for SED, GENEactiv for LPA, Fitbit for MVPA, and GT3X+ for steps. Currently, no device accurately captures activity data across the entire 24-h day, but the future of activity measurement should aim for accurate 24-h measurement as a goal. Researchers should continue to select measurement devices on the basis of their primary outcomes of interest.

  16. Hymenobacter seoulensis sp. nov., isolated from river water.

    PubMed

    Lee, Jae-Jin; Lee, Yeon-Hee; Park, Su-Jin; Lee, Seung-Yeol; Park, Sangkyu; Kim, Myung Kyum; Ten, Leonid N; Jung, Hee-Young

    2017-04-01

    A Gram-stain-negative, aerobic, rod-shaped, non-motile and pink-pigmented bacterial strain, designated 16F7GT, was isolated from river water. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 16F7GT belongs to the genus Hymenobacter. The 16S rRNA gene sequence similarity to members of the genus Hymenobacter ranged from 90.5 to 97.4 %, and the most closely related strains were Hymenobacter rigui WPCB131T (97.4 %) and Hymenobacter xinjiangensis X2-1gT (97.3 %). Strain 16F7GT had <70 % DNA-DNA relatedness with H. rigui (32.8±7.8 %) and H. xinjiangensis (30.2±6.2 %), indicating that it represents a novel genospecies. Cells were catalase- and oxidase-positive. The genomic DNA G+C content was 56.6 mol%. The major fatty acids were summed feature 4 (C17 : 1iso I/C17 : 1 anteiso B; 19.8 %), summed feature 3 (C16 : 1ω7c/C16 : 1ω6c; 18.4 %), C15 : 0 iso (17.0 %), C16 : 1ω5c (11.8 %) and C15 : 0 anteiso (9.8 %). The major polar lipid was phosphatidylethanolamine and the predominant respiratory quinone was menaquinone 7 (MK-7). Based on the phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain 16F7GT represents a novel species within the genus Hymenobacter, for which the name Hymenobacter seoulensis sp. nov. is proposed. The type strain is 16F7GT (=KCTC 52197T=JCM 31655T).

  17. Development of teaching material to integrate GT-POWER into combustion courses for IC engine simulations.

    DOT National Transportation Integrated Search

    2009-02-01

    The main objective of this project was to develop instructional engineering projects that utilize the newly-offered PACE software GT-POWER for engine simulations in combustion-related courses at the Missouri University of Science and Technology. Stud...

  18. Applying Invitational Theory by Teachers of the Gifted to Regular Classroom Teachers.

    ERIC Educational Resources Information Center

    Russell, Donald W.

    1984-01-01

    The teacher of gifted students (G/T teacher) can use Invitational Theory to improve relations with regular classroom teachers. Through introspection, planned strategies, and practice, the G/T teacher can develop qualities and characteristics to promote a congenial professional atmosphere. (MM)

  19. Morphological control of gold nanorods via thermally driven bi-surfactant growth and application for detection of heavy metal ions.

    PubMed

    Huang, Hao; Li, Huiyi; Wang, Huaiyu; Li, Jia; Li, Penghui; Chen, Qidan; Chen, Yue; Chu, Paul K; Li, Bo; Yu, Xuefeng

    2018-05-22

    We report a modified synthesis route of colloidal gold nanorods (AuNRs) by combining the thermal re-shaping treatment and bi-surfactant modification using hexadecyltrimethylammonium bromide (CTAB) and sodium oleate (NaOL). Aspect ratios down to 1.3 ± 0.1 can be achieved in addition to good monodispersity, uniformity, and chemical stability of the materials. Furthermore, without needing post-treatment, metal ions directly interact with the AuNRs efficiently, allowing rapid and sensitive colorimetric detection of heavy metal ions such as Pb<sup>2+</sup> and Cu<sup>2+</sup> with a low concentration down to 2.5 μM. The detection performance in terms of selectivity, sensitivity and stability is systematically evaluated. The AuNRs with tunable aspect ratios as well as chemical stability have potential in surface-plasmon-based applications such as biochemical sensing, biochemical imaging, medical diagnostics, and cancer therapy. © 2018 IOP Publishing Ltd.

  20. Enhanced photodegradation of pentachlorophenol by single and mixed nonionic and anionic surfactants using graphene-TiO₂ as catalyst.

    PubMed

    Zhang, Yaxin; He, Xin; Zeng, Guangming; Chen, Tan; Zhou, Zeyu; Wang, Hongtao; Lu, Wenjing

    2015-11-01

    The photodegradation of pentachlorophenol (PCP) in a surfactant-containing (single and mixed) complex system using graphene-TiO2 (GT) as catalyst was investigated. The objective was to better understand the behavior of surfactants in a GT catalysis system for its possible use in remediation technology of soil contaminated by hydrophobic organic compounds (HOCs). In a single-surfactant system, surfactant molecules aggregated on GT via hydrogen bonding and electrostatic force; nonideal mixing between nonionic and anionic surfactants rendered GT surface with mixed admicelles in a mixed surfactant system. Both effects helped incorporating PCP molecules into surfactant aggregates on catalyst surface. Hence, the targeted pollutants were rendered easily available to photo-yielded oxidative radicals, and photodegradation efficiency was significantly enhanced. Finally, real soil washing-photocatalysis trials proved that anionic-nonionic mixed surfactant soil washing coupled with graphene-TiO2 photocatalysis can be one promising technology for HOC-polluted soil remediation.

  1. Historical warming reduced due to enhanced land carbon uptake

    PubMed Central

    Shevliakova, Elena; Stouffer, Ronald J.; Malyshev, Sergey; Krasting, John P.; Hurtt, George C.; Pacala, Stephen W.

    2013-01-01

    Previous studies have demonstrated the importance of enhanced vegetation growth under future elevated atmospheric CO2 for 21st century climate warming. Surprisingly no study has completed an analogous assessment for the historical period, during which emissions of greenhouse gases increased rapidly and land-use changes (LUC) dramatically altered terrestrial carbon sources and sinks. Using the Geophysical Fluid Dynamics Laboratory comprehensive Earth System Model ESM2G and a reconstruction of the LUC, we estimate that enhanced vegetation growth has lowered the historical atmospheric CO2 concentration by 85 ppm, avoiding an additional 0.31 ± 0.06 °C warming. We demonstrate that without enhanced vegetation growth the total residual terrestrial carbon flux (i.e., the net land flux minus LUC flux) would be a source of 65–82 Gt of carbon (GtC) to atmosphere instead of the historical residual carbon sink of 186–192 GtC, a carbon saving of 251–274 GtC. PMID:24062452

  2. Nanorheology of Entangled Polymer Melts

    DOE PAGES

    Ge, Ting; Grest, Gary S.; Rubinstein, Michael

    2018-02-01

    In this study, we use molecular simulations to probe the local viscoelasticity of an entangled polymer melt by tracking the motion of embedded nonsticky nanoparticles (NPs). As in conventional microrheology, the generalized Stokes-Einstein relation is employed to extract an effective stress relaxation function G GSE(t) from the mean square displacement of NPs. G GSE(t) for different NP diameters d are compared with the stress relaxation function G(t) of a pure polymer melt. The deviation of G GSE(t) from G(t) reflects the incomplete coupling between NPs and the dynamic modes of the melt. For linear polymers, a plateau in G GSE(t)more » emerges as d exceeds the entanglement mesh size a and approaches the entanglement plateau in G(t) for a pure melt with increasing d. For ring polymers, as d increases towards the spanning size R of ring polymers, G GSE(t) approaches G(t) of the ring melt with no entanglement plateau.« less

  3. Nanorheology of Entangled Polymer Melts

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

    Ge, Ting; Grest, Gary S.; Rubinstein, Michael

    In this study, we use molecular simulations to probe the local viscoelasticity of an entangled polymer melt by tracking the motion of embedded nonsticky nanoparticles (NPs). As in conventional microrheology, the generalized Stokes-Einstein relation is employed to extract an effective stress relaxation function G GSE(t) from the mean square displacement of NPs. G GSE(t) for different NP diameters d are compared with the stress relaxation function G(t) of a pure polymer melt. The deviation of G GSE(t) from G(t) reflects the incomplete coupling between NPs and the dynamic modes of the melt. For linear polymers, a plateau in G GSE(t)more » emerges as d exceeds the entanglement mesh size a and approaches the entanglement plateau in G(t) for a pure melt with increasing d. For ring polymers, as d increases towards the spanning size R of ring polymers, G GSE(t) approaches G(t) of the ring melt with no entanglement plateau.« less

  4. Inter- and intraobserver repeatability of the Salford Gait Tool: an observation-based clinical gait assessment tool.

    PubMed

    Toro, Brigitte; Nester, Christopher J; Farren, Pauline C

    2007-03-01

    To evaluate the inter- and intraobserver repeatability of the Salford Gait Tool (SF-GT), a new observation-based gait assessment tool for evaluating sagittal plane cerebral palsy (CP) gait. Masked comparative evaluation. University in the United Kingdom. A convenience sample of 23 pediatric physical therapists with varying degrees of clinical experience recruited from the Greater Manchester area. Participants viewed videotapes of the sagittal plane gait of 13 children and used the SF-GT to analyze their 13 different gait styles on 2 occasions. Eleven children had hemiplegic, diplegic, or quadriplegic CP and 2 were neurologically intact. Inter- and intraobserver repeatability of hip, knee, and ankle joint positions at 6 different phases of the gait cycle. The SF-GT demonstrated good interobserver (77%) and intraobserver (75%) repeatability. We have established that the SF-GT is a repeatable clinical assessment tool with which to guide the diagnosis, treatment planning, and evaluation of interventions by pediatric physical therapists of sagittal plane gait deviations in CP.

  5. Gamow-Teller Strength for the Mixed Ground State of ARGON-35 via the (proton, Neutron) Reaction.

    NASA Astrophysics Data System (ADS)

    Wagner, Anthony James

    1988-12-01

    Early asymmetry measurements of the mixed beta-decay of the ground state of ^{35}Ar to the ground state of ^{35}Cl showed an "anomalous" value of G_{rm V}. This anomalous value surprisingly would infer that unitary symmetry, believed to be spontaneously broken in nature, has been restored in this singular case. From the definition of rho^2, this "anomalous" value also infers a "anomalous" value for B(GT)/B(F). When the half-life data is used instead without the results of the asymmetry experiment, one obtains a different ("normal") value of B(GT)/B(F). The quantity rho^2 derived from the early asymmetry experiments is considered suspect. It has recently been shown that the (p,n) reaction at intermediate energies provides a strong interaction probe of the identical B(GT)/B(F) nuclear strength ratio that can be measured in beta-decay. The value of G_{rm A}/G _{rm V} has been determined very accurately from the beta -decay of the neutron. Thus, (p,n) can be used to determine via a totally independent measurement the value of B(GT)/B(F). The global proportionality constant E _{rm O} = 55 +/- 0.4 MeV is used to analyze the results of a 160 MeV Polarimeter experiment to distinguish between the normal and anomalous value. The results showed more spin-flip probability than was expected. A 120 MeV cross section experiment was required to check whether there was additional spin-flip probability due to a non-negligible DeltaL = 2 component. The results showed a negligible DeltaL = 2 component. The specific proportionality ({ sigma}_{rm GT} (Ground State) = {sigma} _{rm GT} (Excited State)) was then used to reanalyze the results of both experiments. The results showed a B(GT)/B(F) = 0.058 +/- 0.007. The specific proportionality gave a global proportionality constant of E_{rm O} = 32.2 +/- 1.9 MeV. The reason for this deviation in E_{rm O} is not understood.

  6. LU60645GT and MA132843GT Catalogues of Lunar and Martian Impact Craters Developed Using a Crater Shape-based Interpolation Crater Detection Algorithm for Topography Data

    NASA Technical Reports Server (NTRS)

    Salamuniccar, Goran; Loncaric, Sven; Mazarico, Erwan Matias

    2012-01-01

    For Mars, 57,633 craters from the manually assembled catalogues and 72,668 additional craters identified using several crater detection algorithms (CDAs) have been merged into the MA130301GT catalogue. By contrast, for the Moon the most complete previous catalogue contains only 14,923 craters. Two recent missions provided higher-quality digital elevation maps (DEMs): SELENE (in 1/16° resolution) and Lunar Reconnaissance Orbiter (we used up to 1/512°). This was the main motivation for work on the new Crater Shape-based interpolation module, which improves previous CDA as follows: (1) it decreases the number of false-detections for the required number of true detections; (2) it improves detection capabilities for very small craters; and (3) it provides more accurate automated measurements of craters' properties. The results are: (1) LU60645GT, which is currently the most complete (up to D>=8 km) catalogue of Lunar craters; and (2) MA132843GT catalogue of Martian craters complete up to D>=2 km, which is the extension of the previous MA130301GT catalogue. As previously achieved for Mars, LU60645GT provides all properties that were provided by the previous Lunar catalogues, plus: (1) correlation between morphological descriptors from used catalogues; (2) correlation between manually assigned attributes and automated measurements; (3) average errors and their standard deviations for manually and automatically assigned attributes such as position coordinates, diameter, depth/diameter ratio, etc; and (4) a review of positional accuracy of used datasets. Additionally, surface dating could potentially be improved with the exhaustiveness of this new catalogue. The accompanying results are: (1) the possibility of comparing a large number of Lunar and Martian craters, of e.g. depth/diameter ratio and 2D profiles; (2) utilisation of a method for re-projection of datasets and catalogues, which is very useful for craters that are very close to poles; and (3) the extension of the previous framework for evaluation of CDAs with datasets and ground-truth catalogue for the Moon.

  7. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

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

    Shin, Kwang-Soo, E-mail: shinks@dju.kr; Kim, Young Hwan; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found thatmore » the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus.« less

  8. Mass Changes of the Greenland and Antarctic Ice Sheets and Shelves and Contributions to Sea-level Rise: 1992-2002

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Giovinetto, Mario B.; Li, Jun; Cornejo, Helen G.; Beckley, Matthew A.; Brenner, Anita C.; Saba, Jack L.; Yi, Donghui

    2005-01-01

    Changes in ice mass are estimated from elevation changes derived from 10.5 years (Greenland) and 9 years (Antarctica) of satellite radar altimetry data from the European Remote-sensing Satellites ERS-1 and -2. For the first time, the dH/dt values are adjusted for changes in surface elevation resulting from temperature-driven variations in the rate of fun compaction. The Greenland ice sheet is thinning at the margins (-42 plus or minus 2 Gta(sup -1) below the equilibrium line altitude (ELA)) and growing inland (+53 plus or minus 2 Gt a(sup -1)above the ELA) with a small overall mass gain (+11 plus or minus 3 Gt a(sup -1); -0.03 mm a(sup -1) SLE (sea level equivalent)). The ice sheet in West Antarctica (WA) is losing mass (-47 (dot) 4 GT a(sup -1) and the ice sheet in East Antarctica (EA) shows a small mass gain (+16 plus or minus 11 Gt a(sup -1) for a combined net change of -31 plus or minus 12 Gt a(sup -1) (+0.08 mm a(sup -1) SLE)). The contribution of the three ice sheets to sea level is +0.05 plus or minus 0.03 mm a(sup -1). The Antarctic ice shelves show corresponding mass changes of -95 (dot) 11 Gt a(sup -1) in WA and +142 plus or minus 10 Gt a(sup -1) in EA. Thinning at the margins of the Greenland ice sheet and growth at higher elevations is an expected response to increasing temperatures and precipitation in a warming climate. The marked thinnings in the Pine Island and Thwaites Glacier basins of WA and the Totten Glacier basin in EA are probably ice-dynamic responses to long-term climate change and perhaps past removal of their adjacent ice shelves. The ice growth in the southern Antarctic Peninsula and parts of EA may be due to increasing precipitation during the last century.

  9. Ground and surface temperature variability for remote sensing of soil moisture in a heterogeneous landscape

    USGS Publications Warehouse

    Giraldo, M.A.; Bosch, D.; Madden, M.; Usery, L.; Finn, M.

    2009-01-01

    At the Little River Watershed (LRW) heterogeneous landscape near Tifton Georgia US an in situ network of stations operated by the US Department of Agriculture-Agriculture Research Service-Southeast Watershed Research Lab (USDA-ARS-SEWRL) was established in 2003 for the long term study of climatic and soil biophysical processes. To develop an accurate interpolation of the in situ readings that can be used to produce distributed representations of soil moisture (SM) and energy balances at the landscape scale for remote sensing studies, we studied (1) the temporal and spatial variations of ground temperature (GT) and infra red temperature (IRT) within 30 by 30 m plots around selected network stations; (2) the relationship between the readings from the eight 30 by 30 m plots and the point reading of the network stations for the variables SM, GT and IRT; and (3) the spatial and temporal variation of GT and IRT within agriculture landuses: grass, orchard, peanuts, cotton and bare soil in the surrounding landscape. The results showed high correlations between the station readings and the adjacent 30 by 30 m plot average value for SM; high seasonal independent variation in the GT and IRT behavior among the eight 30 by 30 m plots; and site specific, in-field homogeneity in each 30 by 30 m plot. We found statistical differences in the GT and IRT between the different landuses as well as high correlations between GT and IRT regardless of the landuse. Greater standard deviations for IRT than for GT (in the range of 2-4) were found within the 30 by 30 m, suggesting that when a single point reading for this variable is selected for the validation of either remote sensing data or water-energy models, errors may occur. The results confirmed that in this landscape homogeneous 30 by 30 m plots can be used as landscape spatial units for soil moisture and ground temperature studies. Under this landscape conditions small plots can account for local expressions of environmental processes, decreasing the errors and uncertainties in remote sensing estimates caused by landscape heterogeneity.

  10. The genetics of green thorax, a new larval colour mutant, non-linked with ruby - eye locus in the malaria mosquito, Anopheles stephensi.

    PubMed

    Sanil, D; Shetty, N J

    2009-06-01

    Anopheles stephensi, an important vector of malaria continues to be distributed widely in the Indian subcontinent. The natural vigour of the species combined with its new tolerance, indeed resistance to insecticides has made it obligatory that we look for control methods involving genetic manipulation. Hence, there is an immediate need for greater understanding of the genetics of this vector species. One of the requirements for such genetic studies is the establishment of naturally occurring mutants, establishment of the genetic basis for the same and use of such mutants in the genetic transformation studies and other genetic control programme(s). This paper describes the isolation and genetic studies of a larval colour mutant, green thorax (gt), and linkage studies involving another autosomal recessive mutant ruby- eye (ru) in An. stephensi. After the initial discovery, the mutant green thorax was crossed inter se and pure homozygous stock of the mutant was established. The stock of the mutant ruby- eye, which has been maintained as a pure stock in the laboratory. Crosses were made between the wild type and mutant, green thorax to determine the mode of inheritance of green thorax. For linkage studies, crosses were made between the mutant green thorax and another autosomal recessive mutant ruby-eye. The percentage cross-over was calculated for the genes linkage relationship for gt and gt ru. Results of crosses between mutant and wild type showed that the inheritance of green thorax (gt) in An. stephensi is monofactorial in nature. The gt allele is recessive to wild type and is autosomal. The linkage studies showed no linkage between ru and gt. The mutant gt represents an excellent marker for An. stephensi as it is expressed in late III instar stage of larvae and is prominent in IV instar and pupal stages with complete penetrance and high viability. The said mutant could be easily identified without the aid of a microscope. This mutant can be used extensively to conduct basic and applied research. The mutant has been maintained in two large cages in our laboratory.

  11. Mineral equilibria and zircon, garnet and titanite U-Pb ages constraining the PTt path of granite-related hydrothermal systems at the Big Bell gold deposit, Western Australia

    NASA Astrophysics Data System (ADS)

    Mueller, Andreas G.; McNaughton, Neal J.

    2018-01-01

    The Big Bell deposit (75 t gold) is located in a narrow spur of the Meekatharra greenstone belt, Yilgarn Craton, Western Australia. Two ore bodies are located in a calcic-potassic contact alteration zone overprinting lineated granodiorite dykes and amphibolite: almandine-cummingtonite-hornblende skarn (1-3 g/t Au, 1700 g/t As, 330 g/t W) and the muscovite-microcline gneiss (3-5 g/t Au, 580 g/t Sb, 620 g/t W) of the Main Lode. Genetic models vary from pre- to post-metamorphic replacement. Hornblende-plagioclase pairs in amphibolite constrain peak metamorphic temperature to 670 ± 50 °C. In contrast, garnet-biotite thermometry provides estimates of 578 ± 50 and 608 ± 50 °C for garnet-cordierite-biotite schist bordering the skarn and enveloping the Main Lode. Garnet-cordierite and garnet-hornblende pairs extend the range of fluid temperature to 540 ± 65 °C, well below peak metamorphic temperature. At 540-600 °C, the alteration assemblage andalusite + sillimanite constrains pressure to 300-400 MPa corresponding to 11-14 km crustal depth. Published U-Pb ages indicate that metamorphism took place in the aureole of the southeast granodiorite-tonalite batholith (2740-2700 Ma), followed by gold mineralization at 2662 ± 5 Ma and by the emplacement of biotite granite and Sn-Ta-Nb granite-pegmatite dykes at 2625-2610 Ma. Amphibolite xenoliths in granite northwest of the deposit record the lowest temperature (628 ± 50 °C), suggesting it lacks a metamorphic aureole. The rare metal dykes are spatially associated with epidote-albite and andradite-diopside skarns (≤1.5 g/t Au), mined where enriched in the weathered zone. We analysed hydrothermal zircon intergrown with andradite. Concordant U-Pb ages of 2612 ± 7 and 2609 ± 10 Ma confirm the presence of a second granite-related system. The zircons display oscillatory zoning and have low Th/U ratios (0.05-0.08). Low-Th titanite from an albite granite dyke has a concordant but reset U-Pb age of 2577 ± 7 Ma.

  12. Consumption of milk-protein combined with green tea modulates diet-induced thermogenesis.

    PubMed

    Hursel, Rick; Westerterp-Plantenga, Margriet S

    2011-08-01

    Green tea and protein separately are able to increase diet-induced thermogenesis. Although their effects on long-term weight-maintenance were present separately, they were not additive. Therefore, the effect of milk-protein (MP) in combination with green tea on diet-induced thermogenesis (DIT) was examined in 18 subjects (aged 18-60 years; BMI: 23.0 ± 2.1 kg/m(2)). They participated in an experiment with a randomized, 6 arms, crossover design, where energy expenditure and respiratory quotient (RQ) were measured. Green tea (GT)vs. placebo (PL) capsules were either given in combination with water or with breakfasts containing milk protein in two different dosages: 15 g (15 MP) (energy% P/C/F: 15/47/38; 1.7 MJ/500 mL), and 3.5 g (3.5 MP) (energy% P/C/F: 41/59/0; 146.4 kJ/100 mL). After measuring resting energy expenditure (REE) for 30 min, diet-induced energy expenditure was measured for another 3.5 h after the intervention. There was an overall significant difference observed between conditions (p < 0.001). Post-hoc, areas under the curve (AUCs) for diet-induced energy expenditure were significantly different (P ≤ 0.001) for GT + water (41.11 [91.72] kJ·3.5 h) vs. PL + water (10.86 [28.13] kJ·3.5 h), GT + 3.5 MP (10.14 [54.59] kJ·3.5 h) and PL + 3.5 MP (12.03 [34.09] kJ·3.5 h), but not between GT + 3.5 MP, PL + 3.5 MP and PL + water, indicating that MP inhibited DIT following GT. DIT after GT + 15 MP (167.69 [141.56] kJ·3.5 h) and PL + 15 MP (168.99 [186.56] kJ·3.5 h) was significantly increased vs. PL + water (P < 0.001), but these were not different from each other indicating that 15 g MP stimulated DIT, but inhibited the GT effect on DIT. No significant differences in RQ were seen between conditions for baseline and post-treatment. In conclusion, consumption of milk-protein inhibits the effect of green tea on DIT.

  13. Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil.

    PubMed

    Malta, Fernanda; Gaspareto, Karine Vieira; Lisboa-Neto, Gaspar; Carrilho, Flair José; Mendes-Correa, Maria Cássia; Pinho, João Renato Rebello

    2017-11-13

    Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.

  14. Population-based comparison of two feeding tube approaches for head and neck cancer patients receiving concurrent systemic-radiation therapy: is a prophylactic feeding tube approach harmful or helpful?

    PubMed

    Olson, Robert; Karam, Irene; Wilson, Gavin; Bowman, Angela; Lee, Christopher; Wong, Frances

    2013-12-01

    The purpose of this study is to compare patient outcomes between a therapeutic versus a prophylactic gastrostomy tube (GT) placement approach in patients treated with concurrent systemic and radiation (SRT) therapy for head and neck cancer (HNC). Outcomes were compared between all HNC patients treated with concurrent SRT from January 2001 to June 2009 from a center that only places GTs therapeutically when clinically necessary (center A) versus a center that generally places them prophylactically (center B). A total of 445 patients with HNC were identified, with 63 % from center A. As anticipated, GTs were placed less commonly in center A compared to B (31 versus 88 %; p < 0.001). Center B had a significantly higher number of GT complications (p < 0.001), including infection (16 versus 5 %), leakage (10 versus 2 %), and blockage (3 versus 1 %). Conversely, center A had a higher admission rate (27 versus 13 %, p = 0.001), most prominent for GT-related issues (15 versus 6 %). Center B had higher GT dependence at 90 days post-radiation therapy (34 versus 12 %; p < 0.001), but not at 1 year (11 versus 10 %; p = 0.74). There was no significant difference in the proportion of head and neck patients who had a 10 % weight loss at 1 year (compared to baseline) between centers A and B (42 versus 53 %, p = 0.07). There was no significant difference in the overall survival (A versus B, HR = 0.99; p = 0.96). A prophylactic GT approach results in exposing higher number of patients to GT complications. The higher rate of hospitalizations using a therapeutic approach suggests that patients are sicker when GTs are required. Given the similar weight loss and survival, a therapeutic approach at an earlier stage of need may be a preferable approach, when access to prompt GT placement is available.

  15. Intermediate Nuclear Structure for 2v 2{beta} Decay of {sup 48}Ca Studied by (p, n) and (n, p) Reactions at 300 MeV

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

    Sakai, H.; Yako, K.

    2009-08-26

    Angular distributions of the double differential cross sections for the {sup 48}Ca(p,n) and the {sup 48}Ti(n,p) reactions were measured at 300 MeV. A multipole decomposition technique was applied to the spectra to extract the Gamow-Teller (GT) transition strengths. In the (n, p) spectrum beyond 8 MeV excitation energy extra B(GT{sup +}) strengths which are not predicted by the shell model calculation. This extra B(GT{sup +}) strengths significantly contribute to the nuclear matrix element of the 2v2{beta}-decay.

  16. Clinical Utilisation and Usefullness of the Rating Scale of Mixed States, ("Gt-Msrs"): a Multicenter Study.

    PubMed

    Tavormina, Giuseppe; Franza, Francesco; Stranieri, Giuseppe; Juli, Luigi; Juli, Maria Rosaria

    2017-09-01

    The rating scale "G.T. MSRS" has been designed to improve the clinical effectiveness of the clinician psychiatrists, by enabling them to make an early "general" diagnosis of mixed states. The knowledge of the clinical features of the mixed states and of the symptoms of the "mixity" of mood disorders is crucial: to mis-diagnose or mis-treat patients with these symptoms may increase the suicide risk and make worse the evolution of mood disorders going to the dysphoric state. This study is the second validation study of the "G.T. MSRS" rating scale, in order to demonstrate its usefullness.

  17. Clinical utilisation of the "G.T. MSRS", the rating scale for mixed states: 35 cases report.

    PubMed

    Tavormina, Giuseppe

    2015-09-01

    The knowledge of the clinical features of the mixed states and of the symptoms of the "mixity" of mood disorders is crucial: to mis-diagnose or mis-treat patients with these symptoms may increase the suicide risk and make worse the evolution of mood disorders. The rating scale "G.T. MSRS" has been designed to improve the clinical effectiveness of both psychiatrists and GPs by enabling them to make an early "general" diagnosis of mixed states. This study presents some cases in which the "G.T. MSRS" scale has been used, in order to demonstrate its usefullness.

  18. [NRC/GT: Six Year One Research Studies.

    ERIC Educational Resources Information Center

    Gubbins, E. Jean, Ed.

    1992-01-01

    This newsletter focuses on six Year 1 research projects associated with the National Research Center on the Gifted and Talented (NRC/GT). The updates address: "Regular Classroom Practices With Gifted Students: Findings from the Classroom Practices Survey" (Francis X. Archambault, Jr. and others); "The Classroom Practices Study:…

  19. Landfill Methane

    USDA-ARS?s Scientific Manuscript database

    Landfill methane (CH4) accounts for approximately 1.3% (0.6 Gt) of global anthropogenic greenhouse gas emissions relative to total emissions from all sectors of about 49 Gt CO2-eq yr-1. For countries with a history of controlled landfilling, landfills can be one of the larger national sources of ant...

  20. Where Are the Grounds for Grounded Theory? A Troubled Empirical Methodology Meets Wittgenstein

    ERIC Educational Resources Information Center

    James, Fiona

    2018-01-01

    This article provides a critical exposition of the epistemological underpinnings of a recent redevelopment of Grounded Theory (GT) methodology, "Constructivist" GT. Although proffered as freed from the "objectivist" tenets of the original version, critical examination exposes the essentialism threaded through its integral…

  1. Effects of Ex Vivo y-Tocopherol on Airway Macrophage Function in Healthy and Mild Allergic Asthmatics

    EPA Science Inventory

    Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-med...

  2. Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds

    PubMed Central

    Mathew, Shilu; Fatima, Kaneez; Fatmi, M. Qaiser; Archunan, Govindaraju; Ilyas, Muhammad; Begum, Nargis; Azhar, Esam; Damanhouri, Ghazi; Qadri, Ishtiaq

    2015-01-01

    Background The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments. The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects. In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection. The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically. Aim We conducted this study to predict the 3D structure of the p7 protein from the HCV genotypes 3 and 4. Approximately 63 amino acid residues encoded in HCV render this channel sensitive to inhibitors, making p7 a promising target for novel therapies. HCV p7 protein forms a small membrane known as viroporin, and is essential for effective self-assembly of large channels that conduct cation assembly and discharge infectious virion particles. Method In this study, we screened drugs and flavonoids known to disrupt translation and production of HCV proteins, targeted against the active site of p7 residues of HCV genotype 3 (GT3) (isolatek3a) and HCV genotype 4a (GT4) (isolateED43). Furthermore, we conducted a quantitative structure–activity relationship and docking interaction study. Results The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225. A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4. Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds. Conclusions We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential. This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV. PMID:26030803

  3. A role for gamma-glutamyl transpeptidase and the amino acid transport system xc- in cystine transport by a human pancreatic duct cell line.

    PubMed Central

    Sweiry, J H; Sastre, J; Viña, J; Elsässer, H P; Mann, G E

    1995-01-01

    1. The roles of the gamma-glutamyl cycle and the anionic amino acid transport system xc- in mediating L-cystine uptake were investigated in cultured human pancreatic duct PaTu 8902 cells. This cell line exhibits morphological features of normal pancreatic duct cells and expresses gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2), an enzyme involved in the metabolism and regulation of intracellular glutathione (GSH). 2. Uptake of L-cystine (10 microM) was linear for up to 10 min, temperature dependent, Na+ independent, saturable (Michaelis-Menten constant (Km), 86 +/- 25 microM; maximal velocity (Vmax), 109 +/- 33 nmol (mg protein)-1 h-1) and reduced by 80-90% by a 50-fold excess concentration of L-glutamate and L-homocysteic acid, but not L-aspartate. These transport properties resemble those described for system xc-, which exchanges cystine for intracellular glutamate. 3. Acivicin, a known inhibitor of gamma-GT, decreased gamma-GT activity from 2.58 +/- 0.96 to 0.97 +/- 0.11 mU (mg protein)-1 and decreased the initial rates of L-cystine and L-glutamine uptake by 41-55%. Anthglutin (1-gamma-L-glutamyl-2-(2-carboxyphenylhyl)hydrazine), a structurally different inhibitor of gamma-GT, also caused a concentration-dependent (0.01-1 mM) decrease in gamma-GT activity and L-cystine uptake. 4. Neither acivicin nor anthglutin inhibited the uptake of L-glutamate, a poor substrate for gamma-GT. 5. In the presence of a 500-fold excess concentration of glutamate, which should abolish entry of cystine via system xc-, the remaining fraction of cystine transport was inhibited by 50% by acivicin, suggesting that transport is, in part, dependent on the activity of gamma-GT. 6. Cystine transport was also 60-80% inhibited by a series of gamma-glutamyl amino acids (5 mM) including gamma-glutamyl-glutamate, gamma-glutamyl-glutamine and gamma-glutamyl-glycine. alpha-Dipeptides inhibited cystine transport by only 6-22%. 7. These findings demonstrate that in human pancreatic duct PaTu 8902 cells, cystine uptake is mediated by system xc- (50-60%) and the gamma-glutamyl cycle. Our results provide the first evidence linking gamma-GT with cystine transport in human epithelial cells and are of relevance in view of the importance of cystine as a sulphur amino acid source for GSH synthesis in cells exposed to oxidative stress. Images Figure 1 PMID:7658371

  4. The Century-Long Challenge of Global Carbon Management

    NASA Astrophysics Data System (ADS)

    Socolow, R.

    2002-05-01

    The time scale of the global carbon management is a century, not a decade and not a millennium. A century is the ratio of 1000 billion metric tons of carbon [Gt(C)] to 10 Gt(C)/yr. 1000 Gt(C) is the future emissions that will lead to approximately a doubling of the pre-industrial atmospheric CO2 concentration, 280 ppm, assuming the total net ocean plus terrestrial sink remains at half the strength of this source - since 2.1 Gt (C) = 1 ppm, and the concentration today is already 370 ppm. Doubling is the most widely used boundary between acceptable and unacceptable Greenhouse-related environmental disruption, or, in the language of the Framework Convention on Climate Change, the onset of "dangerous anthropogenic interference with the climate system." And 10 Gt(C)/yr is a conservative estimate of the average annual fossil-fuel carbon source over the century; it is now between 6 and 7 Gt(C). Conventional oil and gas are not sufficiently abundant to generate a serious Greenhouse problem on their own. Well before their cumulative carbon emissions reach 1000 Gt(C), both are expected to become non-competitive as a result of growing costs of access (costs related to resources being very deep underground, or below very deep water, or very remote, or very small.) But several times 1000 Gt(C) of coal resources will probably be competitive with non-fossil fuel alternatives, as will "unconventional" oil and gas resources, such as tar sands. The world will not be saved from a serious Greenhouse problem by fossil fuel depletion. There are four mitigation strategies for avoiding dangerous interference with the climate system. Fossil fuels can cease to dominate the global energy system well before the end of the century, yielding large market share to some combination of renewable energy and nuclear (fission and fusion) energy sources. Fossil fuels can continue to dominate, but most of the carbon in the century's fossil fuels can be prevented from reaching the atmosphere (fossil-carbon sequestration). Carbon can be removed directly from the air by biological or chemical processes. Or the climate system can become so well understood that effective compensating actions can be implemented. If human beings implement none of these strategies, we will have chosen, in effect, to adapt to climate change. Not unlikely will be a mix of all four mitigation strategies plus adaptation. In recent years, as the intrinsic complexity and monumental scale of global carbon management has become better appreciated, new coalitions supportive of policies intended to mitigate climate change have emerged.

  5. Framing Climate Goals in Terms of Cumulative CO2-Forcing-Equivalent Emissions

    NASA Astrophysics Data System (ADS)

    Jenkins, S.; Millar, R. J.; Leach, N.; Allen, M. R.

    2018-03-01

    The relationship between cumulative CO2 emissions and CO2-induced warming is determined by the Transient Climate Response to Emissions (TCRE), but total anthropogenic warming also depends on non-CO2 forcing, complicating the interpretation of emissions budgets based on CO2 alone. An alternative is to frame emissions budgets in terms of CO2-forcing-equivalent (CO2-fe) emissions—the CO2 emissions that would yield a given total anthropogenic radiative forcing pathway. Unlike conventional "CO2-equivalent" emissions, these are directly related to warming by the TCRE and need to fall to zero to stabilize warming: hence, CO2-fe emissions generalize the concept of a cumulative carbon budget to multigas scenarios. Cumulative CO2-fe emissions from 1870 to 2015 inclusive are found to be 2,900 ± 600 GtCO2-fe, increasing at a rate of 67 ± 9.5 GtCO2-fe/yr. A TCRE range of 0.8-2.5°C per 1,000 GtC implies a total budget for 0.6°C of additional warming above the present decade of 880-2,750 GtCO2-fe, with 1,290 GtCO2-fe implied by the Coupled Model Intercomparison Project Phase 5 median response, corresponding to 19 years' CO2-fe emissions at the current rate.

  6. Cost-effectiveness of reducing emissions from tropical deforestation, 2016-2050

    NASA Astrophysics Data System (ADS)

    Busch, Jonah; Engelmann, Jens

    2017-12-01

    Reducing tropical deforestation is potentially a large-scale and low-cost strategy for mitigating climate change. Yet previous efforts to project the cost-effectiveness of policies to reduce greenhouse gas emissions from future deforestation across the tropics were hampered by crude available data on historical forest loss. Here we use recently available satellite-based maps of annual forest loss between 2001-2012, along with information on topography, accessibility, protected status, potential agricultural revenue, and an observed inverted-U-shaped relationship between forest cover loss and forest cover, to project tropical deforestation from 2016-2050 under alternative policy scenarios and to construct new marginal abatement cost curves for reducing emissions from tropical deforestation. We project that without new forest conservation policies 289 million hectares of tropical forest will be cleared from 2016-2050, releasing 169 GtCO2. A carbon price of US20/tCO2 (50/tCO2) across tropical countries would avoid 41 GtCO2 (77 GtCO2) from 2016-2050. By comparison, we estimate that Brazil’s restrictive policies in the Amazon between 2004-2012 successfully decoupled potential agricultural revenue from deforestation and reduced deforestation by 47% below what would have otherwise occurred, preventing the emission of 5.2 GtCO2. All tropical countries enacting restrictive anti-deforestation policies as effective as those in the Brazilian Amazon between 2004-2012 would avoid 58 GtCO2 from 2016-2050.

  7. Comparison of GT3X accelerometer and YAMAX pedometer steps/day in a free-living sample of overweight and obese adults.

    PubMed

    Barriera, Tiago V; Tudor-Locke, Catrine; Champagne, Catherine M; Broyles, Stephanie T; Johnson, William D; Katzmarzyk, Peter T

    2013-02-01

    The purpose of this study was to compare steps/day detected by the YAMAX SW-200 pedometer versus the Actigraph GT3X accelerometer in free-living adults. Daily YAMAX and GT3X steps were collected from a sample of 23 overweight and obese participants (78% female; age = 52.6 ± 8.4 yr.; BMI = 31.0 ± 3.7 m·kg-2). Because a pedometer is more likely to be used in a community-based intervention program, it was used as the standard for comparison. Percent difference (PD) and absolute percent difference (APD) were calculated to examine between-instrument agreement. In addition, days were categorized based on PD: a) under-counting (> -10 PD), b) acceptable counting (-10 to 10 PD), and c) over-counting (> 10 PD). The YAMAX and GT3X detected 8,025 ± 3,967 and 7131 ± 3066 steps/day, respectively, and the outputs were highly correlated (r = .87). Average PD was -3.1% ± 30.7% and average APD was 23.9% ± 19.4%. Relative to the YAMAX, 53% of the days detected by the GT3X were classified as under-counting, 25% acceptable counting, and 23% over-counting. Although the output of these 2 instruments is highly correlated, caution is advised when directly comparing or using their output interchangeably.

  8. Tissue-specific Requirements of β-Catenin in External Genitalia Development

    PubMed Central

    Lin, Congxing; Yin, Yan; Long, Fanxin; Ma, Liang

    2008-01-01

    SUMMARY External genitalia are body appendages specialized for internal fertilization. Its development can be divided into two phases, an early androgen-independent phase and a late androgen-dependant sexual differentiation phase. In the early phase, the embryonic anlage of external genitalia, the genital tubercle (GT), are morphologically identical in both sexes. Although congenital external genitalia malformations represent the second most common birth defect in humans, the genetic pathways governing early external genitalia development and urethra formation are poorly understood. Proper development of the GT requires coordinated outgrowth of the mesodermally-derived mesenchyme and extension of the endodermal urethra within an ectodermal epithelial capsule. Here we demonstrate that β-Catenin plays indispensable and distinct roles in each of the aforementioned three tissue layers in early androgen-independent GT development. WNT-β-Catenin signaling is required in the endodermal urethra to activate and maintain Fgf8 expression and direct GT outgrowth, as well as to maintain homeostasis of the urethra. Moreover, β-Catenin is required in the mesenchyme to promote cell proliferation. In contrast, β-Catenin is required in the ectoderm to maintain tissue integrity possibly through cell-cell adhesion during GT outgrowth. The fact that both endodermal and ectodermal β-Catenin knockout animals develop severe hypospadias in both sexes raises the possibility that deregulation of any of these functions can contribute to the etiology of congenital external genital defects in humans. PMID:18635608

  9. DNMT3B -579 G>T Promoter Polymorphism and the Risk of Gastric Cancer in the West of Iran.

    PubMed

    Ahmadi, Kulsom; Soleimani, Azam; Irani, Shiva; Kiani, Aliasghar; Ghanadi, Kourosh; Noormohamadi, Zahra; Sakinejad, Foroozan

    2018-06-01

    Many studies have suggested that modulation of DNMT3B function caused by single nucleotide polymorphisms of the DNMT3B promoter region may underlie the susceptibility to various cancers such as tumors of the digestive system. The aim of this study was to investigate the effect of -579 G>T polymorphism in the promoter of the DNMT3B gene on risk of gastric cancer in a population from West Iran. We conducted a case-control study in 100 gastric cancer patients and 112 cancer-free controls to assess the correlation between DNMT3B -579 G>T (rs1569686) polymorphism and the risk of gastric cancer. Detection of genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. There was no significant difference in the distribution of DNMT3B -579 G>T genotypes between the cases and controls. However, in the stratified analysis by clinicopathological characteristic types, we found that statistically, the risk susceptibility to gastric cancer was significantly associated with tumor grade II and GT/TT genotype of patients, compared to patients having GG genotype, (OR = 5.4737, 95% CI = 1.4746. 20.3184, P = 0.01). Our study suggested that the -579 T allele may increase the relative risk for the progression of clinicopathological characteristic of tumor grade of gastric cancer patients.

  10. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer

    PubMed Central

    Henning, Susanne M.; Wang, Piwen; Abgaryan, Narine; Vicinanza, Roberto; de Oliveira, Daniela Moura; Zhang, Yanjun; Lee, Ru-Po; Carpenter, Catherine L.; Aronson, William J.; Heber, David

    2013-01-01

    Scope Tea polyphenols are metabolized by the colonic microflora yielding phenolic metabolites, which may contribute to the health benefits of tea. We determined the serum and urine concentrations of phenolic acids, hippuric acid and polyhydroxyphenyl-γ-valerolactones during green tea (GT) and black tea (BT) administration. The effects of (−)-epigallocatechin gallate (EGCG) and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) alone and in combination on bioavailability, intracellular metabolism, and antiproliferative activity was determined in HCT-116 colon cancer cells. Methods and Results The concentration of phenolic metabolites was quantified by HPLC with electrochemical detection and MS. Urine concentrations of 4-hydroxyphenylacetic acid (4-HPAA), 3-hydroxyphenylacetic acid (3-HPAA) and polyhydroxy-γ-valerolactones were increased significantly in men drinking GT compared to control. Urine concentration of 3-O-methylgallic acid (3OMGA) was significantly increased in men drinking BT compared to control. Serum 3,4-DHPAA was significantly increased after consumption of GT and BT and 4-HPAA after GT consumption. In vitro treatment of HCT-116 colon cancer cells with 3,4-DHPAA and EGCG exhibited an additive antiproliferative effect, while methylation of 3,4-DHPAA was significantly decreased. 3OMGA exhibited the strongest antiproliferative activity among the phenolic acids. Conclusions The consumption of both, GT and BT, was associated with a significant increase in urinary and serum phenolic acids. PMID:23319439

  11. An analysis of the polymorphisms of the GLUT1 gene in urothelial cell carcinomas of the bladder and its correlation with p53, Ki67 and GLUT1 expressions.

    PubMed

    Xu, C; Yang, X; Wang, Y; Ding, N; Han, R; Sun, Y; Wang, Y

    2017-07-01

    Frequencies of two glucose transporter 1 (GLUT1) single-nucleotide polymorphisms (SNPs) (XbaI G>T and HaeIII T>C) were studied with urothelial cell carcinomas of the bladder (UCC) and 204 normal persons. And the expression of the p53, Ki67 and GLUT1 was assayed by immunohistochemistry. The frequency of the TT genotype and T allele of the XbaI G>T SNP was decreased in the patients with UCC. The frequency of the CC genotype and C allele of the HaeIII T>C SNP was decreased in the patients with UCC. The GLUT1 XbaI genotype GG was more frequent in higher tumor stage and higher tumor grade patients. In the XbaI G>T SNP, the GG genotype was significantly related to higher Remmele immunoreactive score (IRS) of Ki67 and higher IRS of GLUT1. In conclusion, the TT genotype in XbaI G>T SNP and CC genotype of HaeIII T>C SNP may have protective effect in the carcinogenesis process of UCC. In the XbaI G>T SNP, the GG genotype of was positively related to tumor proliferation, glucose metabolism, tumor grade and stage. Therefore, the variant might become a possible proliferation-related prognostic factor for UCC.

  12. Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse

    PubMed Central

    Carey, Amanda N.; Sypek, Elizabeth I.; Singh, Harminder D.; Kaufman, Marc J.; McLaughlin, Jay P.

    2012-01-01

    HIV-Tat protein has been implicated in the pathogenesis of HIV-1 neurological complications (i.e., neuroAIDS), but direct demonstrations of the effects of Tat on behavior are limited. GT-tg mice with a doxycycline (Dox)-inducible and brain-selective tat gene coding for Tat protein were used to test the hypothesis that the activity of Tat in brain is sufficient to impair learning and memory processes. Western blot analysis of GT-tg mouse brains demonstrated an increase in Tat antibody labeling that seemed to be dependent on the dose and duration of Dox pretreatment. Dox-treated GT-tg mice tested in the Barnes maze demonstrated longer latencies to find an escape hole and displayed deficits in probe trial performance, versus uninduced GT-tg littermates, suggesting Tat-induced impairments of spatial learning and memory. Reversal learning was also impaired in Tat-induced mice. Tat-induced mice additionally demonstrated long-lasting (up to one month) deficiencies in novel object recognition learning and memory performance. Furthermore, novel object recognition impairment was dependent on the dose and duration of Dox exposure, suggesting that Tat exposure progressively mediated deficits. These experiments provide evidence that Tat protein expression is sufficient to mediate cognitive abnormalities seen in HIV-infected individuals. Moreover, the genetically engineered GT-tg mouse may be useful for improving our understanding of the neurological underpinnings of neuroAIDS-related behaviors. PMID:22197678

  13. Spatial and temporal Antarctic Ice Sheet mass trends, glacio-isostatic adjustment, and surface processes from a joint inversion of satellite altimeter, gravity, and GPS data.

    PubMed

    Martín-Español, Alba; Zammit-Mangion, Andrew; Clarke, Peter J; Flament, Thomas; Helm, Veit; King, Matt A; Luthcke, Scott B; Petrie, Elizabeth; Rémy, Frederique; Schön, Nana; Wouters, Bert; Bamber, Jonathan L

    2016-02-01

    We present spatiotemporal mass balance trends for the Antarctic Ice Sheet from a statistical inversion of satellite altimetry, gravimetry, and elastic-corrected GPS data for the period 2003-2013. Our method simultaneously determines annual trends in ice dynamics, surface mass balance anomalies, and a time-invariant solution for glacio-isostatic adjustment while remaining largely independent of forward models. We establish that over the period 2003-2013, Antarctica has been losing mass at a rate of -84 ± 22 Gt yr -1 , with a sustained negative mean trend of dynamic imbalance of -111 ± 13 Gt yr -1 . West Antarctica is the largest contributor with -112 ± 10 Gt yr -1 , mainly triggered by high thinning rates of glaciers draining into the Amundsen Sea Embayment. The Antarctic Peninsula has experienced a dramatic increase in mass loss in the last decade, with a mean rate of -28 ± 7 Gt yr -1 and significantly higher values for the most recent years following the destabilization of the Southern Antarctic Peninsula around 2010. The total mass loss is partly compensated by a significant mass gain of 56 ± 18 Gt yr -1 in East Antarctica due to a positive trend of surface mass balance anomalies.

  14. Accuracy of intensity and inclinometer output of three activity monitors for identification of sedentary behavior and light-intensity activity.

    PubMed

    Carr, Lucas J; Mahar, Matthew T

    2012-01-01

    Purpose. To examine the accuracy of intensity and inclinometer output of three physical activity monitors during various sedentary and light-intensity activities. Methods. Thirty-six participants wore three physical activity monitors (ActiGraph GT1M, ActiGraph GT3X+, and StepWatch) while completing sedentary (lying, sitting watching television, sitting using computer, and standing still) light (walking 1.0 mph, pedaling 7.0 mph, pedaling 15.0 mph) intensity activities under controlled settings. Accuracy for correctly categorizing intensity was assessed for each monitor and threshold. Accuracy of the GT3X+ inclinometer function (GT3X+Incl) for correctly identifying anatomical position was also assessed. Percentage agreement between direct observation and the monitor recorded time spent in sedentary behavior and light intensity was examined. Results. All monitors using all thresholds accurately identified over 80% of sedentary behaviors and 60% of light-intensity walking time based on intensity output. The StepWatch was the most accurate in detecting pedaling time but unable to detect pedal workload. The GT3X+Incl accurately identified anatomical position during 70% of all activities but demonstrated limitations in discriminating between activities of differing intensity. Conclusions. Our findings suggest that all three monitors accurately measure most sedentary and light-intensity activities although choice of monitors should be based on study-specific needs.

  15. Model-Based Assessment of the CO2 Sequestration Potential of Coastal Ocean Alkalinization

    NASA Astrophysics Data System (ADS)

    Feng, E. Y.; Koeve, W.; Keller, D. P.; Oschlies, A.

    2017-12-01

    The potential of coastal ocean alkalinization (COA), a carbon dioxide removal (CDR) climate engineering strategy that chemically increases ocean carbon uptake and storage, is investigated with an Earth system model of intermediate complexity. The CDR potential and possible environmental side effects are estimated for various COA deployment scenarios, assuming olivine as the alkalinity source in ice-free coastal waters (about 8.6% of the global ocean's surface area), with dissolution rates being a function of grain size, ambient seawater temperature, and pH. Our results indicate that for a large-enough olivine deployment of small-enough grain sizes (10 µm), atmospheric CO2 could be reduced by more than 800 GtC by the year 2100. However, COA with coarse olivine grains (1000 µm) has little CO2 sequestration potential on this time scale. Ambitious CDR with fine olivine grains would increase coastal aragonite saturation Ω to levels well beyond those that are currently observed. When imposing upper limits for aragonite saturation levels (Ωlim) in the grid boxes subject to COA (Ωlim = 3.4 and 9 chosen as examples), COA still has the potential to reduce atmospheric CO2 by 265 GtC (Ωlim = 3.4) to 790 GtC (Ωlim = 9) and increase ocean carbon storage by 290 Gt (Ωlim = 3.4) to 913 Gt (Ωlim = 9) by year 2100.

  16. Informed Grounded Theory

    ERIC Educational Resources Information Center

    Thornberg, Robert

    2012-01-01

    There is a widespread idea that in grounded theory (GT) research, the researcher has to delay the literature review until the end of the analysis to avoid contamination--a dictum that might turn educational researchers away from GT. Nevertheless, in this article the author (a) problematizes the dictum of delaying a literature review in classic…

  17. Poor Results for High Achievers

    ERIC Educational Resources Information Center

    Bui, Sa; Imberman, Scott; Craig, Steven

    2012-01-01

    Three million students in the United States are classified as gifted, yet little is known about the effectiveness of traditional gifted and talented (G&T) programs. In theory, G&T programs might help high-achieving students because they group them with other high achievers and typically offer specially trained teachers and a more advanced…

  18. The Role of Foreign Languages in Gifted Education.

    ERIC Educational Resources Information Center

    Bartz, Walter

    Designed for school personnel, the booklet discusses identification strategies for elementary and secondary gifted and talented (G/T) students with specific recommendations for language learning. The role of foreign languages in the education of G/T students is discussed and identification of giftedness in language learning is surveyed. The…

  19. Preparing Preservice Teachers to Incorporate Geospatial Technologies in Geography Teaching

    ERIC Educational Resources Information Center

    Harte, Wendy

    2017-01-01

    This study evaluated the efficacy of geospatial technology (GT) learning experiences in two geography curriculum courses to determine their effectiveness for developing preservice teacher confidence and preparing preservice teachers to incorporate GT in their teaching practices. Surveys were used to collect data from preservice teachers at three…

  20. Global Carbon Budget 2016

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

    Le Quéré, Corinne; Andrew, Robbie M.; Canadell, Josep G.

    Accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates and consistency within and among components,more » alongside methodology and data limitations. CO 2 emissions from fossil fuels and industry ( E FF) are based on energy statistics and cement production data, respectively, while emissions from land-use change ( E LUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. The mean ocean CO 2 sink ( S OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink ( S LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models. We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1 σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2006–2015), E FF was 9.3 ± 0.5 GtC yr -1, E LUC 1.0 ± 0.5 GtC yr -1, G ATM 4.5 ± 0.1 GtC yr -1, S OCEAN 2.6 ± 0.5 GtC yr -1, and S LAND 3.1 ± 0.9 GtC yr -1. For year 2015 alone, the growth in E FF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr -1, showing a slowdown in growth of these emissions compared to the average growth of 1.8 % yr -1 that took place during 2006–2015. Also, for 2015, E LUC was 1.3 ± 0.5 GtC yr -1, G ATM was 6.3 ± 0.2 GtC yr -1, S OCEAN was 3.0 ± 0.5 GtC yr -1, and S LAND was 1.9 ± 0.9 GtC yr -1. G ATM was higher in 2015 compared to the past decade (2006–2015), reflecting a smaller S LAND for that year. The global atmospheric CO 2 concentration reached 399.4 ± 0.1 ppm averaged over 2015. For 2016, preliminary data indicate the continuation of low growth in E FF with +0.2 % (range of -1.0 to +1.8 %) based on national emissions projections for China and USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. In spite of the low growth of E FF in 2016, the growth rate in atmospheric CO 2 concentration is expected to be relatively high because of the persistence of the smaller residual terrestrial sink ( S LAND) in response to El Niño conditions of 2015–2016. From this projection of E FF and assumed constant E LUC for 2016, cumulative emissions of CO 2 will reach 565 ± 55 GtC (2075 ± 205 GtCO 2) for 1870–2016, about 75 % from E FF and 25 % from E LUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015b, a, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2016).« less

  1. Global Carbon Budget 2016

    DOE PAGES

    Le Quéré, Corinne; Andrew, Robbie M.; Canadell, Josep G.; ...

    2016-11-14

    Accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere – the “global carbon budget” – is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates and consistency within and among components,more » alongside methodology and data limitations. CO 2 emissions from fossil fuels and industry ( E FF) are based on energy statistics and cement production data, respectively, while emissions from land-use change ( E LUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. The mean ocean CO 2 sink ( S OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink ( S LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models. We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1 σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2006–2015), E FF was 9.3 ± 0.5 GtC yr -1, E LUC 1.0 ± 0.5 GtC yr -1, G ATM 4.5 ± 0.1 GtC yr -1, S OCEAN 2.6 ± 0.5 GtC yr -1, and S LAND 3.1 ± 0.9 GtC yr -1. For year 2015 alone, the growth in E FF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr -1, showing a slowdown in growth of these emissions compared to the average growth of 1.8 % yr -1 that took place during 2006–2015. Also, for 2015, E LUC was 1.3 ± 0.5 GtC yr -1, G ATM was 6.3 ± 0.2 GtC yr -1, S OCEAN was 3.0 ± 0.5 GtC yr -1, and S LAND was 1.9 ± 0.9 GtC yr -1. G ATM was higher in 2015 compared to the past decade (2006–2015), reflecting a smaller S LAND for that year. The global atmospheric CO 2 concentration reached 399.4 ± 0.1 ppm averaged over 2015. For 2016, preliminary data indicate the continuation of low growth in E FF with +0.2 % (range of -1.0 to +1.8 %) based on national emissions projections for China and USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. In spite of the low growth of E FF in 2016, the growth rate in atmospheric CO 2 concentration is expected to be relatively high because of the persistence of the smaller residual terrestrial sink ( S LAND) in response to El Niño conditions of 2015–2016. From this projection of E FF and assumed constant E LUC for 2016, cumulative emissions of CO 2 will reach 565 ± 55 GtC (2075 ± 205 GtCO 2) for 1870–2016, about 75 % from E FF and 25 % from E LUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015b, a, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2016).« less

  2. Global Carbon Budget 2015

    NASA Astrophysics Data System (ADS)

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.; Canadell, J. G.; Sitch, S.; Korsbakken, J. I.; Friedlingstein, P.; Peters, G. P.; Andres, R. J.; Boden, T. A.; Houghton, R. A.; House, J. I.; Keeling, R. F.; Tans, P.; Arneth, A.; Bakker, D. C. E.; Barbero, L.; Bopp, L.; Chang, J.; Chevallier, F.; Chini, L. P.; Ciais, P.; Fader, M.; Feely, R. A.; Gkritzalis, T.; Harris, I.; Hauck, J.; Ilyina, T.; Jain, A. K.; Kato, E.; Kitidis, V.; Klein Goldewijk, K.; Koven, C.; Landschützer, P.; Lauvset, S. K.; Lefèvre, N.; Lenton, A.; Lima, I. D.; Metzl, N.; Millero, F.; Munro, D. R.; Murata, A.; Nabel, J. E. M. S.; Nakaoka, S.; Nojiri, Y.; O'Brien, K.; Olsen, A.; Ono, T.; Pérez, F. F.; Pfeil, B.; Pierrot, D.; Poulter, B.; Rehder, G.; Rödenbeck, C.; Saito, S.; Schuster, U.; Schwinger, J.; Séférian, R.; Steinhoff, T.; Stocker, B. D.; Sutton, A. J.; Takahashi, T.; Tilbrook, B.; van der Laan-Luijkx, I. T.; van der Werf, G. R.; van Heuven, S.; Vandemark, D.; Viovy, N.; Wiltshire, A.; Zaehle, S.; Zeng, N.

    2015-12-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen-carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2005-2014), EFF was 9.0 ± 0.5 GtC yr-1, ELUC was 0.9 ± 0.5 GtC yr-1, GATM was 4.4 ± 0.1 GtC yr-1, SOCEAN was 2.6 ± 0.5 GtC yr-1, and SLAND was 3.0 ± 0.8 GtC yr-1. For the year 2014 alone, EFF grew to 9.8 ± 0.5 GtC yr-1, 0.6 % above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2 % yr-1 that took place during 2005-2014. Also, for 2014, ELUC was 1.1 ± 0.5 GtC yr-1, GATM was 3.9 ± 0.2 GtC yr-1, SOCEAN was 2.9 ± 0.5 GtC yr-1, and SLAND was 4.1 ± 0.9 GtC yr-1. GATM was lower in 2014 compared to the past decade (2005-2014), reflecting a larger SLAND for that year. The global atmospheric CO2 concentration reached 397.15 ± 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in EFF will be near or slightly below zero, with a projection of -0.6 [range of -1.6 to +0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of EFF and assumed constant ELUC for 2015, cumulative emissions of CO2 will reach about 555 ± 55 GtC (2035 ± 205 GtCO2) for 1870-2015, about 75 % from EFF and 25 % from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2015).

  3. Global Carbon Budget 2016

    NASA Astrophysics Data System (ADS)

    Le Quéré, Corinne; Andrew, Robbie M.; Canadell, Josep G.; Sitch, Stephen; Korsbakken, Jan Ivar; Peters, Glen P.; Manning, Andrew C.; Boden, Thomas A.; Tans, Pieter P.; Houghton, Richard A.; Keeling, Ralph F.; Alin, Simone; Andrews, Oliver D.; Anthoni, Peter; Barbero, Leticia; Bopp, Laurent; Chevallier, Frédéric; Chini, Louise P.; Ciais, Philippe; Currie, Kim; Delire, Christine; Doney, Scott C.; Friedlingstein, Pierre; Gkritzalis, Thanos; Harris, Ian; Hauck, Judith; Haverd, Vanessa; Hoppema, Mario; Klein Goldewijk, Kees; Jain, Atul K.; Kato, Etsushi; Körtzinger, Arne; Landschützer, Peter; Lefèvre, Nathalie; Lenton, Andrew; Lienert, Sebastian; Lombardozzi, Danica; Melton, Joe R.; Metzl, Nicolas; Millero, Frank; Monteiro, Pedro M. S.; Munro, David R.; Nabel, Julia E. M. S.; Nakaoka, Shin-ichiro; O'Brien, Kevin; Olsen, Are; Omar, Abdirahman M.; Ono, Tsuneo; Pierrot, Denis; Poulter, Benjamin; Rödenbeck, Christian; Salisbury, Joe; Schuster, Ute; Schwinger, Jörg; Séférian, Roland; Skjelvan, Ingunn; Stocker, Benjamin D.; Sutton, Adrienne J.; Takahashi, Taro; Tian, Hanqin; Tilbrook, Bronte; van der Laan-Luijkx, Ingrid T.; van der Werf, Guido R.; Viovy, Nicolas; Walker, Anthony P.; Wiltshire, Andrew J.; Zaehle, Sönke

    2016-11-01

    Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere - the "global carbon budget" - is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates and consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, respectively, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models. We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2006-2015), EFF was 9.3 ± 0.5 GtC yr-1, ELUC 1.0 ± 0.5 GtC yr-1, GATM 4.5 ± 0.1 GtC yr-1, SOCEAN 2.6 ± 0.5 GtC yr-1, and SLAND 3.1 ± 0.9 GtC yr-1. For year 2015 alone, the growth in EFF was approximately zero and emissions remained at 9.9 ± 0.5 GtC yr-1, showing a slowdown in growth of these emissions compared to the average growth of 1.8 % yr-1 that took place during 2006-2015. Also, for 2015, ELUC was 1.3 ± 0.5 GtC yr-1, GATM was 6.3 ± 0.2 GtC yr-1, SOCEAN was 3.0 ± 0.5 GtC yr-1, and SLAND was 1.9 ± 0.9 GtC yr-1. GATM was higher in 2015 compared to the past decade (2006-2015), reflecting a smaller SLAND for that year. The global atmospheric CO2 concentration reached 399.4 ± 0.1 ppm averaged over 2015. For 2016, preliminary data indicate the continuation of low growth in EFF with +0.2 % (range of -1.0 to +1.8 %) based on national emissions projections for China and USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the economy for the rest of the world. In spite of the low growth of EFF in 2016, the growth rate in atmospheric CO2 concentration is expected to be relatively high because of the persistence of the smaller residual terrestrial sink (SLAND) in response to El Niño conditions of 2015-2016. From this projection of EFF and assumed constant ELUC for 2016, cumulative emissions of CO2 will reach 565 ± 55 GtC (2075 ± 205 GtCO2) for 1870-2016, about 75 % from EFF and 25 % from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015b, a, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2016).

  4. Global Carbon Budget 2015

    DOE PAGES

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.; ...

    2015-12-07

    Accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We also discuss changes compared to previous estimates as well as consistency within and among components, alongside methodologymore » and data limitations. CO 2 emissions from fossil fuels and industry ( E FF) are based on energy statistics and cement production data, while emissions from land-use change ( E LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. Moreover, the mean ocean CO 2 sink ( S OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink ( S LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO 2, and land-cover change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2005–2014), E FF was 9.0 ± 0.5 GtC yr -1, E LUC was 0.9 ± 0.5 GtC yr -1, G ATM was 4.4 ± 0.1 GtC yr -1, S OCEAN was 2.6 ± 0.5 GtC yr -1, and S LAND was 3.0 ± 0.8 GtC yr -1. For the year 2014 alone, E FF grew to 9.8 ± 0.5 GtC yr -1, 0.6 % above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2 % yr -1 that took place during 2005–2014. Also, for 2014, E LUC was 1.1 ± 0.5 GtC yr -1, G ATM was 3.9 ± 0.2 GtC yr -1, S OCEAN was 2.9 ± 0.5 GtC yr -1, and S LAND was 4.1 ± 0.9 GtC yr -1. G ATM was lower in 2014 compared to the past decade (2005–2014), reflecting a larger S LAND for that year. The global atmospheric CO 2 concentration reached 397.15 ± 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in E FF will be near or slightly below zero, with a projection of -0.6 [range of -1.6 to +0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of E FF and assumed constant E LUC for 2015, cumulative emissions of CO 2 will reach about 555 ± 55 GtC (2035 ± 205 GtCO 2) for 1870–2015, about 75 % from E FF and 25 % from E LUC. Finally, this living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2015).« less

  5. Global Carbon Budget 2015

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

    Le Quéré, C.; Moriarty, R.; Andrew, R. M.

    Accurate assessment of anthropogenic carbon dioxide (CO 2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We also discuss changes compared to previous estimates as well as consistency within and among components, alongside methodologymore » and data limitations. CO 2 emissions from fossil fuels and industry ( E FF) are based on energy statistics and cement production data, while emissions from land-use change ( E LUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO 2 concentration is measured directly and its rate of growth ( G ATM) is computed from the annual changes in concentration. Moreover, the mean ocean CO 2 sink ( S OCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in S OCEAN is evaluated with data products based on surveys of ocean CO 2 measurements. The global residual terrestrial CO 2 sink ( S LAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO 2, and land-cover change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2005–2014), E FF was 9.0 ± 0.5 GtC yr -1, E LUC was 0.9 ± 0.5 GtC yr -1, G ATM was 4.4 ± 0.1 GtC yr -1, S OCEAN was 2.6 ± 0.5 GtC yr -1, and S LAND was 3.0 ± 0.8 GtC yr -1. For the year 2014 alone, E FF grew to 9.8 ± 0.5 GtC yr -1, 0.6 % above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2 % yr -1 that took place during 2005–2014. Also, for 2014, E LUC was 1.1 ± 0.5 GtC yr -1, G ATM was 3.9 ± 0.2 GtC yr -1, S OCEAN was 2.9 ± 0.5 GtC yr -1, and S LAND was 4.1 ± 0.9 GtC yr -1. G ATM was lower in 2014 compared to the past decade (2005–2014), reflecting a larger S LAND for that year. The global atmospheric CO 2 concentration reached 397.15 ± 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in E FF will be near or slightly below zero, with a projection of -0.6 [range of -1.6 to +0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of E FF and assumed constant E LUC for 2015, cumulative emissions of CO 2 will reach about 555 ± 55 GtC (2035 ± 205 GtCO 2) for 1870–2015, about 75 % from E FF and 25 % from E LUC. Finally, this living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quéré et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2015).« less

  6. GT-9 TEST - ASTRONAUT EDWARD H. WHITE -- MISCILANIES

    NASA Image and Video Library

    1965-06-03

    S65-19600 (3 June 1965) --- The prime crew for the Gemini-Titan 4 mission have an early morning breakfast prior to their historic flight which was launched at 10:16 a.m. (EST) on June 3, 1965. Shown here seated around the table (clockwise starting front center) are Dr. D. Owens Coons, chief, MSC Center Medical Office; astronaut James A. McDivitt, GT-4 command pilot; Dr. Eugene F. Tubbs, Kennedy Space Center; Rt. Rev. James Heiliky, McDivitt's priest at Cocoa Beach, Florida; Msgr. Irvine J. Nugent and astronaut Edward H. White II, GT-4 pilot. The group had a breakfast of tomato juice, broiled sirloin steak, poached eggs, toast, strawberry gelatin and coffee.

  7. Water Egress

    NASA Image and Video Library

    1965-07-21

    S65-39907 (21 July 1965) --- Prime crew for the Gemini-Titan 5 (GT-5) spaceflight, astronauts Charles Conrad Jr. (in water) and L. Gordon Cooper Jr. (in raft) practice survival techniques following successful egress from their Gemini Static Article 5 spacecraft in the Gulf of Mexico. Cooper is command pilot and Conrad is pilot for the GT-5 mission.

  8. WILLIAMS, CLIFTON C. ASTRONAUT - MISSION CONTROL CENTER (MCC) - GEMINI-TITAN (GT)-3 - MSC

    NASA Image and Video Library

    1965-03-23

    S65-18063 (23 March 1965) --- Astronaut Clifton C. Williams is shown at console in the Mission Control Center (MCC) in Houston, Texas during the Gemini-Titan 3 flight. The GT-3 flight was monitored by the MCC in Houston, but was controlled by the MCC at Cape Kennedy.

  9. 78 FR 20386 - Notice of Receipt of Petition for Decision That Nonconforming 2012 Porsche GT3RS Passenger Cars...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... Passenger Cars Are Eligible for Importation AGENCY: National Highway Traffic Safety Administration, DOT... passenger cars that were not originally manufactured to comply with all applicable Federal Motor Vehicle...-006) has petitioned NHTSA to decide whether nonconforming 2012 Porsche GT3RS passenger cars are...

  10. Georgia Tech Vertical Lift Research Center of Excellence

    DTIC Science & Technology

    2017-12-14

    Technical Project Summaries Task 1.1 (GT-1): Next Generation VABS for More Realistic Modeling of Composite Blades ...Methodology for the Prediction of Rotor Blade Ice Formation and Shedding ..................................................................... 20...software disclosures and technology transfer efforts. Task 1.1 (GT-1): Next Generation VABS for More Realistic Modeling of Composite Blades PIs

  11. The Arabidopsis Family GT43 Glycosyltransferases Form Two Functionally Nonredundant Groups Essential for the Elongation of Glucuronoxylan Backbone

    EPA Science Inventory

    There exist four members of family GT43 glycosyltransferases in the Arabidopsis (Arabidopsis thaliana) genome, and mutations of two of them, IRX9 and IRX14, have previously been shown to cause a defect in glucuronoxylan (GX) biosynthesis. However, it is currently unknown whether ...

  12. Environmental Education for the Gifted and Talented.

    ERIC Educational Resources Information Center

    Wright, Joe

    Designed for school personnel, the booklet suggests a framework for providing programs for the gifted and talented (G/T) students that will develop a concern for environmental problems. After a description of environmental education and a rationale for its place in the classroom, descriptions of three Indiana programs for G/T students are…

  13. Integrating University and Local Resources to Meet Varied Needs of Gifted and Talented Youth.

    ERIC Educational Resources Information Center

    Simmons, Wilber

    1978-01-01

    The article discusses the implementation of services to gifted and talented (G/T) public School students in Ohio including a schedule for establishing the program, definition of G/T, use of pre-existing resources in the schools, establishment of 10 task force groups, and community support. (PHR)

  14. The Uncertain Carbon Emissions in China (Invited)

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Guan, D.

    2013-12-01

    Anthropogenic fossil fuel emissions are considered as being well understood with a low uncertainty (9.1 × 0.5Gt C yr-1). By using full transparency emission inventory which the energy consumption, fuel heating values, carbon content and oxidation rate reported separately in sectoal level, here we found new 2.1 Gt C yr-1 (23% of global total) uncertainties of carbon emission inventory, which mainly contributed by the mass energy use and consumption coal quality in China and by misunderstanding of fuel quality in international fossil fuel trade. Increment of coal's carbon emission in China and India are equivalent to 130 % of global total coal's emission growth during 2008-2010, by using macro energy statistics and bottom up coal mine datasets, the difference carbon emission estimates from China and India can up to 1.32 C yr-1. Emissions from international trade of coal could produce another 0.08 Gt C yr-1 uncertainty. These new emerging 1.4 Gt C yr-1 uncertainties implies a significant mis-estimation of human induced carbon emissions and a new dominating factor in contributing the global carbon budget residual.

  15. Influence of support material on the electrocatalytic activity of nickel oxide nanoparticles for urea electro-oxidation reaction.

    PubMed

    Abdel Hameed, R M; Medany, Shymaa S

    2018-03-01

    Nickel oxide nanoparticles were deposited on different carbon supports including activated Vulcan XC-72R carbon black (NiO/AC), multi-walled carbon nanotubes (NiO/MWCNTs), graphene (NiO/Gr) and graphite (NiO/Gt) through precipitation step followed by calcination at 400 °C. To determine the crystalline structure and morphology of prepared electrocatalysts, X-ray diffraction (XRD) and transmission electron microscopy (TEM) were employed. The electrocatalytic activity of NiO/carbon support electrocatalysts was investigated towards urea electro-oxidation reaction in NaOH solution using cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy. Urea oxidation peak current density was increased in the following order: NiO/AC < NiO/MWCNTs < NiO/Gr < NiO/Gt. Chronoamperometry test also showed an increased steady state oxidation current density for NiO/Gt in comparison to other electrocatalysts. The increased activity and stability of NiO/Gt electrocatalyst encourage the application of graphite as an efficient and cost-saving support to carry metal nanoparticles for urea electro-oxidation reaction. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow-derived Progenitor Cells Mobilization and Homing to the Infarcted Heart.

    PubMed

    Meloni, Marco; Cesselli, Daniela; Caporali, Andrea; Mangialardi, Giuseppe; Avolio, Elisa; Reni, Carlotta; Fortunato, Orazio; Martini, Stefania; Madeddu, Paolo; Valgimigli, Marco; Nikolaev, Evgeni; Kaczmarek, Leszek; Angelini, Gianni D; Beltrami, Antonio P; Emanueli, Costanza

    2015-12-01

    Reparative response by bone marrow (BM)-derived progenitor cells (PCs) to ischemia is a multistep process that comprises the detachment from the BM endosteal niche through activation of osteoclasts and proteolytic enzymes (such as matrix metalloproteinases (MMPs)), mobilization to the circulation, and homing to the injured tissue. We previously showed that intramyocardial nerve growth factor gene transfer (NGF-GT) promotes cardiac repair following myocardial infarction (MI) in mice. Here, we investigate the impact of cardiac NGF-GT on postinfarction BM-derived PCs mobilization and homing at different time points after adenovirus-mediated NGF-GT in mice. Immunohistochemistry and flow cytometry newly illustrate the temporal profile of osteoclast and activation of MMP9, PCs expansion in the BM, and liberation/homing to the injured myocardium. NGF-GT amplified these responses and increased the BM levels of active osteoclasts and MMP9, which were not observed in MMP9-deficient mice. Taken together, our results suggest a novel role for NGF in BM-derived PCs mobilization/homing following MI.

  17. Comparison of pedometer and accelerometer derived steps in older individuals with Parkinson's disease or osteoporosis under free-living conditions.

    PubMed

    Wallén, Martin Benka; Dohrn, Ing-Mari; Ståhle, Agneta; Franzén, Erika; Hagströmer, Maria

    2014-10-01

    To compare self-reported pedometer steps with accelerometer steps under free-living conditions in individuals with Parkinson's disease (PD) or osteoporosis (OP). Seventy-three individuals with PD and 71 individuals with OP wore a pedometer (Yamax LS2000) and an accelerometer (ActiGraph GT1M/GT3X+) simultaneously for one week. Fifty-one individuals with PD (72.6 ± 5.3 years) and 61 with OP (75.6 ± 5.3 years) provided simultaneously recorded data for 3-7 consecutive days. Pedometer steps were significantly lower than accelerometer steps in the PD group (p = .002) but not in the OP group (p = .956). Bland-Altman plots demonstrated wide limits of agreement between the instruments in both PD (range = 6,911 steps) and OP (range = 6,794 steps). These results suggest that the ActiGraph GT1M/GT3X+ should be preferred over the Yamax LS2000 for the assessment of steps in both research and clinical evaluations, particularly in individuals with PD or altered gait.

  18. EXTRAVEHICULAR ACTIVITY (EVA) - GEMINI-TITAN (GT)-4

    NASA Image and Video Library

    1965-06-03

    S65-29766 (3 June 1965) --- Astronaut Edward H. White II, pilot for the Gemini-Titan 4 (GT-4) spaceflight, floats in the zero-gravity of space during the third revolution of the GT-4 spacecraft. White wears a specially designed spacesuit. His face is shaded by a gold-plated visor to protect him from unfiltered rays of the sun. In his right hand he carries a Hand-Held Self-Maneuvering Unit (HHSMU) that gives him control over his movements in space. White also wears an emergency oxygen chest pack; and he carries a camera mounted on the HHSMU for taking pictures of the sky, Earth and the GT-4 spacecraft. He is secured to the spacecraft by a 25-feet umbilical line and a 23-feet tether line. Both lines are wrapped together in gold tape to form one cord. Astronaut James A. McDivitt, command pilot, remained inside the spacecraft during the extravehicular activity (EVA). Photo credit: NASA EDITOR'S NOTE: Astronaut Edward H. White II died in the Apollo/Saturn 204 fire at Cape Kennedy on Jan. 27, 1967.

  19. Muscle Weakness and Fibrosis Due to Cell Autonomous and Non-cell Autonomous Events in Collagen VI Deficient Congenital Muscular Dystrophy.

    PubMed

    Noguchi, Satoru; Ogawa, Megumu; Malicdan, May Christine; Nonaka, Ikuya; Nishino, Ichizo

    2017-02-01

    Congenital muscular dystrophies with collagen VI deficiency are inherited muscle disorders with a broad spectrum of clinical presentation and are caused by mutations in one of COL6A1-3 genes. Muscle pathology is characterized by fiber size variation and increased interstitial fibrosis and adipogenesis. In this study, we define critical events that contribute to muscle weakness and fibrosis in a mouse model with collagen VI deficiency. The Col6a1 GT/GT mice develop non-progressive weakness from younger age, accompanied by stunted muscle growth due to reduced IGF-1 signaling activity. In addition, the Col6a1 GT/GT mice have high numbers of interstitial skeletal muscle mesenchymal progenitor cells, which dramatically increase with repeated myofiber necrosis/regeneration. Our results suggest that impaired neonatal muscle growth and the activation of the mesenchymal cells in skeletal muscles contribute to the pathology of collagen VI deficient muscular dystrophy, and more importantly, provide the insights on the therapeutic strategies for collagen VI deficiency. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Reduction of Hexavalent Chromium by Green Tea Polyphenols and Green Tea Nano Zero-Valent Iron (GT-nZVI).

    PubMed

    Chrysochoou, M; Reeves, K

    2017-03-01

    This study reports on the direct reduction of hexavalent chromium [Cr(VI)] by green tea polyphenols, including a green tea solution and pure epigallocatechin gallate (EGCG) solution. A linear trend was observed between the amount of reduced Cr(VI) and the amount of added polyphenols. The green tea solution showed a continued decrease in the observed stoichiometry with increasing pH, from a maximum of 1.4 mol per gallic acid equivalent (GAE) of green tea at pH 2.5, to 0.2 mol/GAE at pH 8.8. The EGCG solution exhibited different behavior, with a maximum stoichiometry of 2 at pH 7 and minimum of 1.6 at pH 4.4 and 8.9. When green tea was used to first react with Fe 3+ and form GT-nZVI, the amount of Cr(VI) reduced by a certain volume of GT-nZVI was double compared to green tea, and 6 times as high considering that GT-nZVI only contains 33 % green tea.

  1. Pharmacokinetics and Plasma Cellular Antioxidative Effects of Flavanols After Oral Intake of Green Tea Formulated with Vitamin C and Xylitol in Healthy Subjects.

    PubMed

    Son, Yu-Ra; Park, Tae-Sik; Shim, Soon-Mi

    2016-02-01

    This study aimed to test whether green tea formulated with vitamin C and xylitol (GTVX) could improve absorption of flavanols and total antioxidant activity (TAC) of plasma compared with green tea only (GT) in healthy subjects. The total radical-trapping antioxidant parameter method was used to measure the TAC of plasma. Cmax, Tmax, and area under the curve (AUC) of flavanols in plasma after consumption of GTVX were 5980.58 μg/mL, 2.14 h, and 18,915.56 h·μg/mL, respectively, indicating that GTVX showed significantly higher AUC than GT (13,855.43 μg/mL). The peak TACs occurred at 3 and 0.5 h after intake of GT and GTVX, respectively. The TAC of plasma was found to be significantly higher in GTVX than in GT at each time point. This study suggests that formulating green tea with vitamin C and xylitol could increase the absorption of flavanols in green tea, enhancing cellular antioxidative effects.

  2. Growth rate of crystalline ice and the diffusivity of supercooled water from 126 to 262 K

    DOE PAGES

    Xu, Yuntao; Petrik, Nikolay G.; Smith, R. Scott; ...

    2016-12-12

    Understanding deeply supercooled water is key to unraveling many of water’s anomalous properties. However, this has proven difficult due to rapid and uncontrolled crystallization. Using a pulsed laser heating technique, we measure the growth rate of crystalline ice, G(T), for 180 K < T < 262 K, i.e. deep within water’s “no man’s land.” The self-diffusion of supercooled liquid water, D(T), is obtained from G(T) using the Wilson-Frenkel model of crystal growth. For T > 237 K, G(T) and D(T) have super-Arrhenius (“fragile”) temperature dependences, but both crossover to Arrhenius (“strong”) behavior with a large activation energy in “no man’smore » land.” The fact that G(T) and D(T) are smoothly varying rules out the hypothesis that liquid water’s properties have a singularity at or near 228 K. However the results are consistent with a previous prediction for D(T) that assumed no thermodynamic transitions occur in “no man’s land.« less

  3. Neutrino-nucleus reactions based on recent structure studies

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

    Suzuki, Toshio; National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588

    2015-05-15

    Neutrino-nucleus reactions are studied with the use of new shell model Hamiltonians, which have proper tensor components in the interactions and prove to be successful in the description of Gamow-Teller (GT) strengths in nuclei. The new Hamiltonians are applied to obtain new neutrino-nucleus reaction cross sections in {sup 12}C, {sup 13}C, {sup 56}Fe and {sup 56}Ni induced by solar and supernova neutrinos. The element synthesis by neutrino processes in supernova explosions is discussed with the new cross sections. The enhancement of the production yields of {sup 7}Li, {sup 11}B and {sup 55}Mn is obtained while fragmented GT strength in {supmore » 56}Ni with two-peak structure is found to result in smaller e-capture rates at stellar environments. The monopole-based universal interaction with tensor force of π+ρ meson exchanges is used to evaluate GT strength in {sup 40}Ar and ν-induced reactions on {sup 40}Ar. It is found to reproduce well the experimental GT strength in {sup 40}Ar.« less

  4. ASTRONAUT EDWARD H. WHITE II - GEMINI-TITAN (GT)-IV - ZERO GRAVITY - OUTER SPACE

    NASA Image and Video Library

    2015-03-20

    S65-30427 (3 June 1965) --- Astronaut Edward H. White II, pilot for the Gemini-Titan 4 (GT-4) spaceflight, floats in the zero-gravity of space during the third revolution of the GT-4 spacecraft. White wears a specially designed spacesuit. His face is shaded by a gold-plated visor to protect him from unfiltered rays of the sun. In his right hand he carries a Hand-Held Self-Maneuvering Unit (HHSMU) that gives him control over his movements in space. White also wears an emergency oxygen chest pack; and he carries a camera mounted on the HHSMU for taking pictures of the sky, Earth and the GT-4 spacecraft. He is secured to the spacecraft by a 25-feet umbilical line and a 23-feet tether line. Both lines are wrapped together in gold tape to form one cord. Astronaut James A. McDivitt, command pilot, remained inside the spacecraft during the extravehicular activity (EVA). Photo credit: NASA EDITOR'S NOTE: Astronaut Edward H. White II died in the Apollo/Saturn 204 fire at Cape Kennedy on Jan. 27, 1967.

  5. Evaluation of cyclic flexural fatigue of M-wire nickel-titanium rotary instruments.

    PubMed

    Al-Hadlaq, Solaiman M S; Aljarbou, Fahad A; AlThumairy, Riyadh I

    2010-02-01

    This study was conducted to investigate cyclic flexural fatigue resistance of GT series X rotary files made from the newly developed M-wire nickel-titanium alloy compared with GT and Profile nickel-titanium files made from a conventional nickel-titanium alloy. Fifteen files, size 30/0.04, of each type were used to evaluate the cyclic flexural fatigue resistance. A simple device was specifically constructed to measure the time each file type required to fail under cyclic flexural fatigue testing. The results of this experiment indicated that the GT series X files had superior cyclic flexural fatigue resistance than the other 2 file types made from a conventional nickel-titanium alloy (P = .004). On the other hand, the difference between the Profile and the GT files was not statistically significant. The findings of this study suggest that size 30/0.04 nickel-titanium rotary files made from the newly developed M-wire alloy have better cyclic flexural fatigue resistance than files of similar design and size made from the conventional nickel-titanium alloy. Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  6. A dynamic approach to assess international competitiveness of Vietnam's garment and textile industry.

    PubMed

    Vu, Huong Thanh; Pham, Lam Cat

    2016-01-01

    Garment and textile (G&T) industry has been playing as a driving force for the socio-economic development of Vietnam. With the international integration process and rising challenges from the global market, there is a need to examine international competitiveness of Vietnam's G&T industry to find out what Vietnam should focus on to enhance its position in the global market place. This paper, by using the Generalized Double Diamond Model (GDDM), analyzed international competitiveness of Vietnam's G&T industry and compared it with China. The results showed that Vietnam was less competitive than China in all four attributes of the GDDM. The lowest competitiveness of Vietnam in comparison with China was Related and Supporting industries, followed by Factor Conditions. Therefore, the paper argued that although Vietnam should improve all of the four attributes in the long term, Vietnam must put a high priority on developing Related and Supporting Industries and then enhance Factor Conditions while maintaining its strengths over China in terms of G&T export growths and favorable business context.

  7. Shell-model method for Gamow-Teller transitions in heavy deformed odd-mass nuclei

    NASA Astrophysics Data System (ADS)

    Wang, Long-Jun; Sun, Yang; Ghorui, Surja K.

    2018-04-01

    A shell-model method for calculating Gamow-Teller (GT) transition rates in heavy deformed odd-mass nuclei is presented. The method is developed within the framework of the projected shell model. To implement the computation requirement when many multi-quasiparticle configurations are included in the basis, a numerical advancement based on the Pfaffian formula is introduced. With this new many-body technique, it becomes feasible to perform state-by-state calculations for the GT nuclear matrix elements of β -decay and electron-capture processes, including those at high excitation energies in heavy nuclei which are usually deformed. The first results, β- decays of the well-deformed A =153 neutron-rich nuclei, are shown as the example. The known log(f t ) data corresponding to the B (GT- ) decay rates of the ground state of 153Nd to the low-lying states of 153Pm are well described. It is further shown that the B (GT) distributions can have a strong dependence on the detailed microscopic structure of relevant states of both the parent and daughter nuclei.

  8. Spectral mineral mapping for characterization of subtle geothermal prospects using ASTER data

    NASA Astrophysics Data System (ADS)

    Abubakar, A. J.; Hashim, M.; Pour, A. B.

    2017-05-01

    In this study, the performance of ASTER data is evaluated for mapping subtle geothermal prospects in an unexplored tropical region having a number of thermal springs. The study employed a simple Decorrelation stretch with specific absorptions to highlight possible alteration zones of interest related to Geothermal (GT) systems. Hydrothermal alteration minerals are subsequently mapped using Spectral Angle Mapper (SAM) and Linear Spectral Unmixing (LSU) algorithms to target representative minerals such as clays, carbonates and AL-OH minerals as indicators of GT activity. The results were validated through field GPS survey, rock sampling and laboratory analysis using latest smart lab X-Ray Diffractometer technology. The study indicates that ASTER broadband satellite data could be used to map subtle GT prospects with the aid of an in-situ verification. However, it also shows that ASTER could not discriminate within specie minerals especially for clays using SWIR bands. Subsequent studies are aimed at looking at both ASTER and Hyperion hyperspectral data in the same area as this could have significant implications for GT resource detection in unmapped aseismic and inaccessible tropical regions using available spaceborne data.

  9. Effects of seasonal change and experimental warming on the temperature dependence of photosynthesis in the canopy leaves of Quercus serrata.

    PubMed

    Yamaguchi, Daisuke P; Nakaji, Tatsuro; Hiura, Tsutom; Hikosaka, Kouki

    2016-10-01

    The effects of warming on the temperature response of leaf photosynthesis have become an area of major concern in recent decades. Although growth temperature (GT) and day length (DL) affect leaf gas exchange characteristics, the way in which these factors influence the temperature dependence of photosynthesis remains uncertain. We established open-top canopy chambers at the canopy top of a deciduous forest, in which average daytime leaf temperature was increased by 1.0 °C. We conducted gas exchange measurements for the canopy leaves of deciduous trees exposed to artificial warming during different seasons. The carbon dioxide assimilation rate at 20 °C (A 20 ) was not affected by warming, whereas that at 25 °C (A 25 ) tended to be higher in leaves exposed to warming. Warming increased the optimal temperature of photosynthesis by increasing the activation energy for the maximum rate of carboxylation. Regression analysis indicated that both GT and DL strongly influenced gas exchange characteristics. Sensitivity analysis revealed that DL affected A without obvious effects on the temperature dependence of A, whereas GT almost maintained constant A 20 and strongly influenced the temperature dependence. These results indicate that GT and DL have different influences on photosynthesis; GT and DL affect the 'slope' and intercept' of the temperature dependence of photosynthesis, respectively. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Hand and nickel-titanium root canal instrumentation performed by dental students: a micro-computed tomographic study.

    PubMed

    Peru, M; Peru, C; Mannocci, F; Sherriff, M; Buchanan, L S; Pitt Ford, T R

    2006-02-01

    The aim of this study was to evaluate root canals instrumented by dental students using the modified double-flared technique, nickel-titanium (NiTi) rotary System GT files and NiTi rotary ProTaper files by micro-computed tomography (MCT). A total of 36 root canals from 18 mesial roots of mandibular molar teeth were prepared; 12 canals were prepared with the modified double-flared technique, using K-flexofiles and Gates-Glidden burs; 12 canals were prepared using System GT and 12 using ProTaper rotary files. Each root was scanned using MCT preoperatively and postoperatively. At the coronal and mid-root sections, System GT and ProTaper files produced significantly less enlarged canal cross-sectional area, volume and perimeter than the modified double-flared technique (P < 0.05). In the mid-root sections there was significantly less thinning of the root structure towards the furcation with System GT and ProTaper (P < 0.05). The rotary techniques were both three times faster than the modified double-flared technique (P < 0.05). Qualitative evaluation of the preparations showed that both ProTaper and System GT were able to prepare root canals with little or no procedural error compared with the modified double-flared technique. Under the conditions of this study, inexperienced dental students were able to prepare curved root canals with rotary files with greater preservation of tooth structure, low risk of procedural errors and much quicker than with hand instruments.

  11. Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

    PubMed

    Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

    2015-01-01

    We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

  12. Mass Gains of the Antarctic Ice Sheet Exceed Losses

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Li, Jun; Robbins, John; Saba, Jack L.; Yi, Donghui; Brenner, Anita; Bromwich, David

    2012-01-01

    During 2003 to 2008, the mass gain of the Antarctic ice sheet from snow accumulation exceeded the mass loss from ice discharge by 49 Gt/yr (2.5% of input), as derived from ICESat laser measurements of elevation change. The net gain (86 Gt/yr) over the West Antarctic (WA) and East Antarctic ice sheets (WA and EA) is essentially unchanged from revised results for 1992 to 2001 from ERS radar altimetry. Imbalances in individual drainage systems (DS) are large (-68% to +103% of input), as are temporal changes (-39% to +44%). The recent 90 Gt/yr loss from three DS (Pine Island, Thwaites-Smith, and Marie-Bryd Coast) of WA exceeds the earlier 61 Gt/yr loss, consistent with reports of accelerating ice flow and dynamic thinning. Similarly, the recent 24 Gt/yr loss from three DS in the Antarctic Peninsula (AP) is consistent with glacier accelerations following breakup of the Larsen B and other ice shelves. In contrast, net increases in the five other DS of WA and AP and three of the 16 DS in East Antarctica (EA) exceed the increased losses. Alternate interpretations of the mass changes driven by accumulation variations are given using results from atmospheric-model re-analysis and a parameterization based on 5% change in accumulation per degree of observed surface temperature change. A slow increase in snowfall with climate waRMing, consistent with model predictions, may be offsetting increased dynamic losses.

  13. Antimicrobial Activity of Pomegranate and Green Tea Extract on Propionibacterium Acnes, Propionibacterium Granulosum, Staphylococcus Aureus and Staphylococcus Epidermidis.

    PubMed

    Li, Zhaoping; Summanen, Paula H; Downes, Julia; Corbett, Karen; Komoriya, Tomoe; Henning, Susanne M; Kim, Jenny; Finegold, Sydney M

    2015-06-01

    We used pomegranate extract (POMx), pomegranate juice (POM juice) and green tea extract (GT) to establish in vitro activities against bacteria implicated in the pathogenesis of acne. Minimum inhibitory concentrations (MIC) of 94 Propionibacterium acnes, Propionibacterium granulosum, Staphylococcus aureus, and Staphylococcus epidermidis strains were determined by Clinical and Laboratory Standards Institute-approved agar dilution technique. Total phenolics content of the phytochemicals was determined using the Folin-Ciocalteu method and the polyphenol composition by HPLC. Bacteria were identified by 16S rRNA sequence analysis. GT MIC of 400 μg/ml or less was obtained for 98% of the strains tested. 64% of P. acnes strains had POMx MICs at 50 μg/ml whereas 36% had MIC >400 μg/ml. POMx, POM juice, and GT showed inhibitory activity against all the P. granulosum strains at ≤100 μg/ml. POMx and GT inhibited all the S. aureus strains at 400 μg/ml or below, and POM juice had an MIC of 200 μg/ml against 17 S. aureus strains. POMx inhibited S. epidermidis strains at 25 μg/ml, whereas POM juice MICs were ≥200 μg/ml. The antibacterial properties of POMx and GT on the most common bacteria associated with the development and progression of acne suggest that these extracts may offer a better preventative/therapeutic regimen with fewer side effects than those currently available.

  14. Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats.

    PubMed

    Popa, Daniela-Saveta; Bolfa, Pompei; Kiss, Bela; Vlase, Laurian; Păltinean, Ramona; Pop, Anca; Cătoi, Cornel; Crişan, Gianina; Loghin, Felicia

    2014-02-01

    To evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA). Adult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection. The severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation. GT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  15. Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-ζ and PP2A pathway

    PubMed Central

    Caraballo, Juan Carlos; Yshii, Cecilia; Butti, Maria L.; Westphal, Whitney; Borcherding, Jennifer A.; Allamargot, Chantal

    2011-01-01

    During pulmonary edema, the alveolar space is exposed to a hypoxic environment. The integrity of the alveolar epithelial barrier is required for the reabsorption of alveolar fluid. Tight junctions (TJ) maintain the integrity of this barrier. We set out to determine whether hypoxia creates a dysfunctional alveolar epithelial barrier, evidenced by an increase in transepithelial electrical conductance (Gt), due to a decrease in the abundance of TJ proteins at the plasma membrane. Alveolar epithelial cells (AEC) exposed to mild hypoxia (Po2 = 50 mmHg) for 30 and 60 min decreased occludin abundance at the plasma membrane and significantly increased Gt. Other cell adhesion molecules such as E-cadherin and claudins were not affected by hypoxia. AEC exposed to hypoxia increased superoxide, but not hydrogen peroxide (H2O2). Overexpression of superoxide dismutase 1 (SOD1) but not SOD2 prevented the hypoxia-induced Gt increase and occludin reduction in AEC. Also, overexpression of catalase had a similar effect as SOD1, despite not detecting any increase in H2O2 during hypoxia. Blocking PKC-ζ and protein phosphatase 2A (PP2A) prevented the hypoxia-induced occludin reduction at the plasma membrane and increase in Gt. In summary, we show that superoxide, PKC-ζ, and PP2A are involved in the hypoxia-induced increase in Gt and occludin reduction at the plasma membrane in AEC. PMID:21257729

  16. Oceanobacillus neutriphilus sp. nov., isolated from activated sludge in a bioreactor.

    PubMed

    Yang, Jun-Yi; Huo, Ying-Yi; Xu, Xue-Wei; Meng, Fan-Xu; Wu, Min; Wang, Chun-Sheng

    2010-10-01

    A Gram-stain-positive, neutrophilic, rod-shaped bacterium, strain A1g(T), was isolated from activated sludge of a bioreactor and was subjected to a polyphasic taxonomic characterization. The isolate grew in the presence of 0-17.0 % (w/v) NaCl and at pH 6.0-9.0; optimum growth was observed in the presence of 3.0-5.0 % (w/v) NaCl and at pH 7.0. Strain A1g(T) was motile, formed cream-coloured colonies, was catalase- and oxidase-positive and was able to hydrolyse aesculin, Tween 40 and Tween 60. Chemotaxonomic analysis revealed menaquinone-7 as the predominant respiratory quinone and anteiso-C₁₅:₀, anteiso-C₁₇:₀, iso-C₁₆:₀ and iso-C₁₅:₀ as major fatty acids. The genomic DNA G+C content of strain A1g(T) was 36.3 mol%. Comparative 16S rRNA gene sequence analysis revealed that the new isolate belonged to the genus Oceanobacillus and exhibited closest phylogenetic affinity to the type strains of Oceanobacillus oncorhynchi subsp. incaldanensis (97.9 % similarity) and O. oncorhynchi subsp. oncorhynchi (97.5 %), but less than 97 % sequence similarity with respect to the type strains of other recognized Oceanobacillus species. Levels of DNA-DNA relatedness between strain A1g(T) and reference strains O. oncorhynchi subsp. incaldanensis DSM 16557(T), O. oncorhynchi subsp. oncorhynchi JCM 12661(T) and Oceanobacillus iheyensis DSM 14371(T) were 29, 45 and 38 %, respectively. On the basis of phenotypic and genotypic data, strain A1g(T) is considered to represent a novel species of the genus Oceanobacillus, for which the name Oceanobacillus neutriphilus sp. nov. is proposed. The type strain is A1g(T) (=CGMCC 1.7693(T) =JCM 15776(T)).

  17. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity.

    PubMed

    Bellassoued, Khaled; Ghrab, Ferdaws; Makni-Ayadi, Fatma; Van Pelt, Jos; Elfeki, Abdelfattah; Ammar, Emna

    2015-01-01

    Kombucha (KT) is claimed to have various beneficial effects on human health, but there is very little scientific evidence available in the literature. The present study investigates the effects of Camellia sinensis (GT) Linn. (Theaceae) and KT, two natural drinks, on cholesterol and antioxidant status using a hypercholesterolemia rat model. The present study compared the free-radical scavenging abilities and polyphenol levels of GT and KT. Wistar rats fed cholesterol-rich diets were given KT or GT (5 mL/kg body weight per day, po) for 16 weeks, then fasted overnight and sacrificed. The plasma lipid levels, thiobarbituric acid reactive substances (TBARS) and aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGT) serum levels, antioxidant activities of superoxide dismutase (SOD) and catalase (CAT), and creatinine and urea rats were examined. KT had a phenolic compound of 955 ± 0.75 mg GAE/g) followed, by GT (788.92 ± 0.02 mg GAE/g). The free radical scavenging activity of KT was higher than GT. Compared with GT, KT induced lowered serum levels of TC, TG, VLDL-C, and LDL-C by 26, 27, 28, and 36%, respectively, and increased the serum level of high-density lipoprotein cholesterol (HDL-C). KT induced a 55% decrease of TBARS level in liver and 44% in kidney, compared with those of rats fed a cholesterol-rich diet alone. Moreover, CAT and SOD activities were reduced by 29 and 33%, respectively, in liver and 31 and 35%, respectively, in kidney, after oral administration of KT, compared with those of HCD-fed rats. The findings revealed that KT administration induced attractive curative effects on hypercholesterolemic, particularly in terms of liver-kidney functions in rats. Its effect on humans needs to be studied further.

  18. Ledipasvir/sofosbuvir regimens for chronic hepatitis C infection: Insights from a work productivity economic model from the United States.

    PubMed

    Younossi, Zobair M; Jiang, Yushan; Smith, Nathaniel J; Stepanova, Maria; Beckerman, Rachel

    2015-05-01

    Patients with chronic hepatitis C (CHC) exhibit reduced work productivity owing to their disease. Historically, most regimens indicated for CHC genotype 1 (GT1) patients were administered with pegylated interferon (Peg-IFN) and/or ribavirin (RBV), which further compromised work productivity during treatment. The aim of this study was to model the impact of LDV/SOF (ledipasvir/sofosbuvir), the first Peg-IFN- and RBV-free regimen for CHC GT1 patients, on work productivity from an economic perspective, compared to receiving no treatment. The WPAI-SHP (Work Productivity and Activity Index-Specific Health Problem) questionnaire was administered to patients across the ION clinical trials (N = 1,923 U.S. patients). Before initiation of treatment, patients with CHC GT1 in the ION trials exhibited absenteeism and presenteeism impairments of 2.57% and 7.58%, respectively. Patients with cirrhosis exhibited greater work productivity impairment than patients without cirrhosis. In total, 93.21% of U.S. patients in the ION trials achieved SVR; these patients exhibited absenteeism and presenteeism impairments of 2.62% (P = 0.76, when compared to baseline) and 3.53% (P < 0.0001), respectively. Monetizing these data to the entire U.S. population, our model projects an annual societal cost of $7.1 billion owing to productivity loss in untreated GT1 CHC patients. Our model projects that, when compared to no treatment, treating all CHC GT1 patients with a regimen with very high viral eradication rates (LDV/SOF) would translate to annual productivity loss savings of $2.7 billion over a 1-year time horizon. Patients with untreated HCV impose a substantial societal burden owing to reduced work productivity. As a result of improvements in work productivity, treatment of CHC GT1 patients with LDV/SOF-based regimens is likely to result in significant cost savings from a societal perspective, relative to no treatment. © 2015 by the American Association for the Study of Liver Diseases.

  19. Twenty-Five Years of Gene Therapy for ADA-SCID: From Bubble Babies to an Approved Drug.

    PubMed

    Ferrua, Francesca; Aiuti, Alessandro

    2017-11-01

    Twenty-five years have passed since first attempts of gene therapy (GT) in children affected by severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) defect, also known by the general public as bubble babies. ADA-SCID is fatal early in life if untreated. Unconditioned hematopoietic stem cell (HSC) transplant from matched sibling donor represents a curative treatment but is available for few patients. Enzyme replacement therapy can be life-saving, but its chronic use has many drawbacks. This review summarizes the history of ADA-SCID GT over the last 25 years, starting from first pioneering studies in the early 1990s using gamma-retroviral vectors, based on multiple infusions of genetically corrected autologous peripheral blood lymphocytes. HSC represented the ideal target for gene correction to guarantee production of engineered multi-lineage progeny, but it required a decade to achieve therapeutic benefit with this approach. Introduction of low-intensity conditioning represented a crucial step in achieving stable gene-corrected HSC engraftment and therapeutic levels of ADA-expressing cells. Recent clinical trials demonstrated that gamma-retroviral GT for ADA-SCID has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions in patients >13 years after treatment. No abnormal clonal proliferation or leukemia development have been observed in >40 patients treated experimentally in five different centers worldwide. In 2016, the medicinal product Strimvelis™ received marketing approval in Europe for patients affected by ADA-SCID without a suitable human leukocyte antigen-matched related donor. Positive safety and efficacy results have been obtained in GT clinical trials using lentiviral vectors encoding ADA. The results obtained in last 25 years in ADA-SCID GT development fundamentally contributed to improve patients' prognosis, together with earlier diagnosis thanks to newborn screening. These advances open the way to further clinical development of GT as treatment for broader applications, from inherited diseases to cancer.

  20. Analysis of hepatitis C NS5A resistance associated polymorphisms using ultra deep single molecule real time (SMRT) sequencing.

    PubMed

    Bergfors, Assar; Leenheer, Daniël; Bergqvist, Anders; Ameur, Adam; Lennerstrand, Johan

    2016-02-01

    Development of Hepatitis C virus (HCV) resistance against direct-acting antivirals (DAAs), including NS5A inhibitors, is an obstacle to successful treatment of HCV when DAAs are used in sub-optimal combinations. Furthermore, it has been shown that baseline (pre-existing) resistance against DAAs is present in treatment naïve-patients and this will potentially complicate future treatment strategies in different HCV genotypes (GTs). Thus the aim was to detect low levels of NS5A resistant associated variants (RAVs) in a limited sample set of treatment-naïve patients of HCV GT1a and 3a, since such polymorphisms can display in vitro resistance as high as 60000 fold. Ultra-deep single molecule real time (SMRT) sequencing with the Pacific Biosciences (PacBio) RSII instrument was used to detect these RAVs. The SMRT sequencing was conducted on ten samples; three of them positive with Sanger sequencing (GT1a Q30H and Y93N, and GT3a Y93H), five GT1a samples, and two GT3a non-positive samples. The same methods were applied to the HCV GT1a H77-plasmid in a dilution series, in order to determine the error rates of replication, which in turn was used to determine the limit of detection (LOD), as defined by mean + 3SD, of minority variants down to 0.24%. We found important baseline NS5A RAVs at levels between 0.24 and 0.5%, which could potentially have clinical relevance. This new method with low level detection of baseline RAVs could be useful in predicting the most cost-efficient combination of DAA treatment, and reduce the treatment duration for an HCV infected individual. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Cleaning effectiveness and shaping ability of rotary ProTaper compared with rotary GT and manual K-Flexofile.

    PubMed

    Liu, Sheng-Bo; Fan, Bin; Cheung, Gary S P; Peng, Bing; Fan, Ming-Wen; Gutmann, James L; Song, Ya-Ling; Fu, Qiang; Bian, Zhuan

    2006-12-01

    To compare the cleaning efficacy and shaping ability of engine-driven ProTaper and GT files, and manual preparation using K-Flexofile instruments in curved root canals of extracted human teeth. 45 canals of maxillary and mandibular molars with curvatures between 25 degrees and 40 degrees were divided into three groups. The groups were balanced with regard to the angle and the radius of canal curvature. Canals in each group were prepared to an apical size of 25 with either the rotary ProTaper or GT system, or manually with K-Flexofile using the modified double-flared technique. Irrigation was done with 2 mL 2.5% NaOCl after each instrument and, as the final rinse, 10 mL 2.5% NaOCl then 10 mL 17% EDTA and finally 5 mL distilled water. The double-exposure radiographic technique was used to examine for the presence of apical transportation. The time required to complete the preparation, as well as any change in working length after preparation were recorded. The roots were then grooved and split longitudinally. The amounts of debris and smear layer were evaluated at the apical, middle and coronal regions under the scanning electron microscope. Data were analyzed either parametrically with the F-test or non-parametrically using the Kruskal-Wallis test, where appropriate. Two GT files but none of the K-Flexofile and ProTaper instruments separated. For debris removal, the ProTaper group achieved a better result than GT (P < 0.05) but not the K-Flexofile group at all three regions (apical, middle and coronal). K-Flexofiles produced significantly less smear layer than ProTaper and GT files only in the middle third of the canal (P < 0.01). Both NiTi rotary instruments maintained the original canal shape better than the K-Flexofiles (P < 0.05) and required significantly less time to complete the preparation.

  2. High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

    PubMed

    Mariño, Zoe; Pascasio-Acevedo, Juan M; Gallego, Adolfo; Diago, Moisés; Baliellas, Carme; Morillas, Rosa; Prieto, Martín; Moreno, José M; Sánchez-Antolín, Gloria; Vergara, Mercedes; Forné, Montserrat; Fernández, Inmaculada; Castro, María A; Pascual, Sonia; Gómez, Alexandra; Castells, Lluis; Montero, José L; Crespo, Javier; Calleja, José L; García-Samaniego, Javier; Carrión, Jose A; Arencibia, Ana C; Blasco, Alejandro; López-Núñez, Carmen; Sánchez-Ruano, Juan J; Gea-Rodríguez, Francisco; Giráldez, Álvaro; Cabezas, Joaquín; Hontangas, Vanessa; Torras, Xavier; Castellote, Jose; Romero-Gómez, Manuel; Turnes, Juan; de Artaza, Tomás; Narváez, Isidoro; Cuervas-Mons, Valentín; Forns, Xavier

    2017-12-01

    Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×10 9 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. [In vitro comparison of root canal preparation with step-back technique and GT rotary file--a nickel-titanium engine driven rotary instrument system].

    PubMed

    Krajczár, Károly; Tóth, Vilmos; Nyárády, Zoltán; Szabó, Gyula

    2005-06-01

    The aim of the authors' study was to compare the remaining root canal wall thickness and the preparation time of root canals, prepared either with step-back technique, or with GT Rotary File, an engine driven nickel-titanium rotary instrument system. Twenty extracted molars were decoronated. Teeth were divided in two groups. In Group 1 root canals were prepared with step-back technique. In Group 2 GT Rotary File System was utilized. Preoperative vestibulo-oral X-ray pictures were taken from all teeth with radiovisiograph (RVG). The final preparations at the mesiobuccal canals (MB) were performed with size #30 and palatinal/distal canals with size #40 instruments. Postoperative RVG pictures were taken ensuring the preoperative positioning. The working time was measured in seconds during each preparation. The authors also assessed the remaining root canal wall thickness at 3, 6 and 9 mm from the radiological apex, comparing the width of the canal walls of the vestibulo-oral projections on pre- and postoperative RVG pictures both mesially and buccally. The ratios of the residual and preoperative root canal wall thickness were calculated and compared. The largest difference was found at the MB canals of the coronal and middle third level of the root, measured on the distal canal wall. The ratio of the remaining dentin wall thickness at the coronal and the middle level in the case of step-back preparation was 0.605 and 0.754, and 0.824 and 0.895 in the cases of GT files respectively. The preparation time needed for GT Rotary File System was altogether 68.7% (MB) and 52.5% (D/P canals) of corresponding step-back preparation times. The use of GT Rotary File with comparison of standard step-back method resulted in a shortened preparation time and excessive damage of the coronal part of the root canal could be avoided.

  4. Real-World Effectiveness of Elbasvir/Grazoprevir in HCV-Infected Patients in the US Veterans Affairs Healthcare System.

    PubMed

    Kramer, Jennifer R; Puenpatom, Amy; Erickson, Kevin; Cao, Yumei; Smith, Donna; El-Serag, Hashem; Kanwal, Fasiha

    2018-05-31

    Elbasvir/grazoprevir (EBR/GZR) is an all-oral direct-acting antiviral agent (DAA) with high sustained virologic response (SVR) in clinical trials. This study's primary objective was to evaluate effectiveness of EBR/GZR among HCV-infected patients in a real-world clinical setting. We conducted a nationwide retrospective observational cohort study of HCV-infected patients in the US Department of Veterans Affairs (VA) using the VA Corporate Data Warehouse. The study population included patients with positive HCV RNA who initiated EBR/GZR from February 1 to August 1, 2016. We calculated the 95% confidence interval for binomial proportions for SVR overall and by demographic subgroups. Clinical and demographic characteristics were also evaluated. We included 2,436 patients in the study cohort. Most were male (96.5%), African-American (57.5%), with mean age of 63.5 (SD=5.9), and 95.4% infected with genotype (GT) 1 [GT1a (34.7%), GT1b (58.6%)]. Other comorbidities included diabetes (53.2%), depression (57.2%), and HIV (3.0%). More than 50% had history of drug or alcohol abuse (53.9% and 60.5%, respectively). 33.2% of the cohort had cirrhosis. A total of 95.6% (2,328/2,436; 95% CI: 94.7%-96.4%) achieved SVR. The SVR rates by subgroups were: male, 95.5% (2245/2350); female, 96.5% (83/86); GT1a, 93.4%, GT1b, 96.6%, GT4, 96.9%, African-American, 95.9% (1,342/1,400); treatment-experienced, 96.3% (310/322); cirrhosis, 95.6% (732/766); stage 4-5 CKD, 96.3% (392/407); and HIV, 98.6% (73/74). SVR rates were high overall and across patient subgroups regardless of gender, race/ethnicity, cirrhosis, renal impairment, or HIV. This study provided important data regarding the effectiveness of EBR/GZR in a large clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Effect of suppression of arabinoxylan synthetic genes in wheat endosperm on chain length of arabinoxylan and extract viscosity.

    PubMed

    Freeman, Jackie; Lovegrove, Alison; Wilkinson, Mark David; Saulnier, Luc; Shewry, Peter Robert; Mitchell, Rowan Andrew Craig

    2016-01-01

    Arabinoxylan (AX) is the dominant component within wheat (Triticum aestivum L.) endosperm cell walls, accounting for 70% of the polysaccharide. The viscosity of aqueous extracts from wheat grain is a key trait influencing the processing for various end uses, and this is largely determined by the properties of endosperm AX. We have previously shown dramatic effects on endosperm AX in transgenic wheat by down-regulating either TaGT43_2 or TaGT47_2 genes (orthologues to IRX9 and IRX10 in Arabidopsis, respectively) implicated in AX chain extension and the TaXAT1 gene responsible for monosubstitution by 3-linked arabinose. Here, we use these transgenic lines to investigate the relationship between amounts of AX in soluble and insoluble fractions, the chain-length distribution of these measured by intrinsic viscosity and the overall effect on extract viscosity. In transgenic lines expressing either the TaGT43_2 or TaGT47_2 RNAi transgenes, the intrinsic viscosities of water-extractable (WE-AX) and of a water-insoluble alkaline-extracted fraction (AE-AX) were decreased by between 10% and 50% compared to control lines. In TaXAT1 RNAi lines, there was a 15% decrease in intrinsic viscosity of WE-AX but no consistent effect on that of AE-AX. All transgenic lines showed decreases in extract viscosity with larger effects in TaGT43_2 and TaGT47_2 RNAi lines (by up to sixfold) than in TaXAT1 RNAi lines (by twofold). These effects were explained by the decreases in amount and chain length of WE-AX, with decreases in amount having the greater influence. Extract viscosity from wheat grain can therefore be greatly decreased by suppression of single gene targets. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  6. Greenland Ice Sheet Mass Balance: Distribution of Increased Mass Loss with Climate Warming; 2003-07 Versus 1992-2002

    NASA Technical Reports Server (NTRS)

    Zwally, H. Jay; Li, Jun; Benner, Anita C.; Beckley, Matthew; Cornejo, Helen G.; DiMarzio, John; Giovinetto, Mario B.; Neumann, Thomas A.; Robbins, John; Saba, Jack L.; hide

    2011-01-01

    We derive mass changes of the Greenland ice sheet (GIS) for 2003-07 from ICESat laser altimetry and compare them with results for 1992-2002 from ERS radar and airborne laser altimetry. The GIS continued to grow inland and thin at the margins during 2003 07, but surface melting and accelerated flow significantly increased the marginal thinning compared with the 1990s. The net balance changed from a small loss of 7 plus or minus 3 Gt a 1(sup -1) in the 1990s to 171 plus or minus 4 Gt a (sup -1) for 2003-07, contributing 0.5 mm a(sup -1) to recent global sea-level rise. We divide the derived mass changes into two components: (1) from changes in melting and ice dynamics and (2) from changes in precipitation and accumulation rate. We use our firn compaction model to calculate the elevation changes driven by changes in both temperature and accumulation rate and to calculate the appropriate density to convert the accumulation-driven changes to mass changes. Increased losses from melting and ice dynamics (17-206 Gt a(sup-1) are over seven times larger than increased gains from precipitation (10 35 Gt a(sup-1) during a warming period of approximately 2 K (10 a)(sup -1) over the GIS. Above 2000m elevation, the rate of gain decreased from 44 to 28 Gt a(sup-1), while below 2000m the rate of loss increased from 51 to 198 Gt a(sup-1). Enhanced thinning below the equilibrium line on outlet glaciers indicates that increased melting has a significant impact on outlet glaciers, as well as accelerating ice flow. Increased thinning at higher elevations appears to be induced by dynamic coupling to thinning at the margins on decadal timescales.

  7. Comparability of activity monitors used in Asian and Western-country studies for assessing free-living sedentary behaviour.

    PubMed

    Kurita, Satoshi; Yano, Shohei; Ishii, Kaori; Shibata, Ai; Sasai, Hiroyuki; Nakata, Yoshio; Fukushima, Noritoshi; Inoue, Shigeru; Tanaka, Shigeho; Sugiyama, Takemi; Owen, Neville; Oka, Koichiro

    2017-01-01

    This study aims to compare the outputs of the waist-worn Active style Pro HJA-350IT (ASP; used in studies with Asian populations), the waist-worn ActiGragh™GT3X+ using the normal filter (GT3X+) and the thigh-worn activPAL3 (AP) in assessing adults' sedentary behaviour (total sedentary time, number of breaks) under free-living conditions. Fifty healthy workers wore the three monitors simultaneously during their waking hours on two days, including a work day and a non-work day. Valid data were at least 10 hours of wearing time, and the differences between monitors on the sedentary outputs using the AP as criterion measurement were analyzed by ANOVA. The number of participants who had complete valid data for work day and non-work day was 47 and 44, respectively. Total sedentary time and breaks estimated by the AP were respectively 466.5 ± 146.8 min and 64.3 ± 24.9 times on the work day and 497.7 ± 138.3 min and 44.6 ± 15.4 times on the non-work day. In total sedentary time, the ASP estimated 29.7 min (95%CI = 7.9 to 51.5) significantly shorter than the AP on the work day but showed no significant difference against the AP on the non-work day. The GT3X+ estimated 80.1 min (54.6 to 105.6) and 52.3 (26.4 to 78.2) significantly longer than the AP on the work day and the non-work day, respectively. For the number of breaks from sedentary time, on both days, the ASP and the GT3X+ estimated significantly more than the AP: 14.1 to 15.8 times (6.3 to 22.5) for the ASP and 27.7 to 28.8 times (21.8 to 34.8) for the GT3X+. Compared to the AP as the criterion, the ASP can underestimate total sedentary time and the GT3X+ can overestimate it, and more so at the lower levels of sedentary time. For breaks from sedentary time, compared to the AP, both the GT3X+ the ASP can overestimate.

  8. Overview of Hole GT2A: Drilling middle gabbro in Wadi Tayin massif, Oman ophiolite

    NASA Astrophysics Data System (ADS)

    Takazawa, E.; Kelemen, P. B.; Teagle, D. A. H.; Coggon, J. A.; Harris, M.; Matter, J. M.; Michibayashi, K.

    2017-12-01

    Hole GT2A (UTM: 40Q 655960.7E / 2529193.5N) was drilled by the Oman Drilling Project (OmDP) into Wadi Gideah of Wadi Tayin massif in the Samail ophiolite, Oman. OmDP is an international collaboration supported by the International Continental Scientific Drilling Program, the Deep Carbon Observatory, NSF, IODP, JAMSTEC, and the European, Japanese, German and Swiss Science Foundations, with in-kind support in Oman from the Ministry of Regional Municipalities and Water Resources, Public Authority of Mining, Sultan Qaboos University, and the German University of Technology. Hole GT2A was diamond cored in 25 Dec 2016 to 18 Jan 2017 to a total depth of 406.77 m. The outer surfaces of the cores were imaged and described on site before being curated, boxed and shipped to the IODP drill ship Chikyu, where they underwent comprehensive visual and instrumental analysis. 33 shipboard scientists were divided into six teams (Igneous, Alteration, Structural, Geochem, Physical Properties, Paleomag) to describe and analyze the cores. Hole GT2A drilled through the transition between foliated and layered gabbro. The transition zone occurs between 50 and 150 m curation corrected depth (CCD). The top 50 m of Hole GT2A is foliated gabbro whereas the bottom 250 m consists of layered gabbro. Brittle fracture is observed throughout the core. Intensity of alteration vein decreases from the top to the bottom of the hole. On the basis of changes in grain size and/or modal abundance and/or appearance/disappearance of igneous primary mineral(s) five lithological units are defined in Hole GT2A (Unit I to V). The uppermost part of Hole GT2A (Unit I) is dominated by fine-grained granular olivine gabbro intercalated with less dominant medium-grained granular olivine gabbro and rare coarse-grained varitextured gabbro. The lower part of the Hole (Units II, III and V) is dominated by medium-grained olivine gabbro, olivine melagabbro and olivine-bearing gabbro. Modally-graded rhythmic layering with olivine melagabbro and olivine-bearing gabbro is well conspicuous in the bottom part of Unit II. The Unit IV occurs between 284.25 m and 293.92 m CCD from the top of the hole and is characterized by orthopyroxene-bearing lithologies such as fine-grained gabbronorite and coarse-grained troctolite. Discrete orthopyroxene crystals occur in these lithologies.

  9. An appraisal of Indonesia's immense peat carbon stock using national peatland maps: uncertainties and potential losses from conversion.

    PubMed

    Warren, Matthew; Hergoualc'h, Kristell; Kauffman, J Boone; Murdiyarso, Daniel; Kolka, Randall

    2017-12-01

    A large proportion of the world's tropical peatlands occur in Indonesia where rapid conversion and associated losses of carbon, biodiversity and ecosystem services have brought peatland management to the forefront of Indonesia's climate mitigation efforts. We evaluated peat volume from two commonly referenced maps of peat distribution and depth published by Wetlands International (WI) and the Indonesian Ministry of Agriculture (MoA), and used regionally specific values of carbon density to calculate carbon stocks. Peatland extent and volume published in the MoA maps are lower than those in the WI maps, resulting in lower estimates of carbon storage. We estimate Indonesia's total peat carbon store to be within 13.6 GtC (the low MoA map estimate) and 40.5 GtC (the high WI map estimate) with a best estimate of 28.1 GtC: the midpoint of medium carbon stock estimates derived from WI (30.8 GtC) and MoA (25.3 GtC) maps. This estimate is about half of previous assessments which used an assumed average value of peat thickness for all Indonesian peatlands, and revises the current global tropical peat carbon pool to 75 GtC. Yet, these results do not diminish the significance of Indonesia's peatlands, which store an estimated 30% more carbon than the biomass of all Indonesian forests. The largest discrepancy between maps is for the Papua province, which accounts for 62-71% of the overall differences in peat area, volume and carbon storage. According to the MoA map, 80% of Indonesian peatlands are <300 cm thick and thus vulnerable to conversion outside of protected areas according to environmental regulations. The carbon contained in these shallower peatlands is conservatively estimated to be 10.6 GtC, equivalent to 42% of Indonesia's total peat carbon and about 12 years of global emissions from land use change at current rates. Considering the high uncertainties in peatland extent, volume and carbon storage revealed in this assessment of current maps, a systematic revision of Indonesia's peat maps to produce a single geospatial reference that is universally accepted would improve national peat carbon storage estimates and greatly benefit carbon cycle research, land use management and spatial planning.

  10. Günther Tulip and Celect IVC filters in multiple-trauma patients.

    PubMed

    Rosenthal, David; Kochupura, Paul V; Wellons, Eric D; Burkett, Allison B; Methodius-Rayford, Walaya C

    2009-08-01

    To evaluate results with the retrievable Günther Tulip (GT) and Celect inferior vena cava filters (IVCFs) placed at the intensive care unit (ICU) bedside under "real-time" intravascular ultrasound (IVUS) guidance in multiple-trauma patients. Between December 2004 and December 2008, 187 multiple-trauma patients (109 men; mean age 44+/-2 years, range 17-71) with contraindications to low-dose anticoagulation therapy or sequential compression devices had Günther Tulip (n = 97) or Celect (n = 90) retrievable IVCFs placed under real-time IVUS guidance. Günther Tulip filters were inserted using a "double-puncture" technique. The Celect IVCFs were placed with a simplified single-puncture technique in which the filter introducer sheath was advanced until the radiopaque tip "covered" the IVUS image of the renal vein, indicating that the filter sheath was in position for filter deployment. The 2 filter groups were compared on the endpoints of technical implantation success, retrievability, prevention of PE, and procedure-related deep vein thrombosis (DVT). As verified by abdominal radiography, 93.1% (174/187) of IVCFs were placed without complications; 6 IVCFs (all GT; p = 0.03 versus Celect) were misplaced in the iliac vein but uneventfully retrieved and replaced in the IVC within 24 hours. Two insertion site femoral vein DVTs (both in the dual puncture group; p>0.2) and 5 groin hematomas occurred during follow-up. GT filters were in place a mean of 107 days and Celect 97 days. In this time, 2 pulmonary embolisms occurred (1 in each group; p>0.2). Of the 115 filters scheduled for retrieval (50 Günther Tulip, 65 Celect), 33 (23 Günther Tulip, 10 Celect) could not be retrieved (p = 0.0004). Vena cavography identified filter tilting (>20 degrees ) in 21 cases (15 GT, 6 Celect), while 12 filters (8 GT, 4 Celect) had extended indwell times (mean 187 days) and excessive tissue ingrowth covering the retrieval hook. Subjectively, the Celect filters were clinically "easier" to retrieve; they also had fewer cases of significant tilt (>20%) than the GT filters, but the difference was not statistically significant. GT and Celect IVCFs placed at the ICU bedside under IVUS guidance in multiple-trauma patients was simple, safe, and avoided transporting critically ill patients out of the ICU. Further investigation of the single sheath IVUS technique and the role of retrievable IVCFs in multi-trauma patients is warranted.

  11. Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels.

    PubMed

    Avihingsanon, Anchalee; Jitmitraparp, Salyavit; Tangkijvanich, Pisit; Ramautarsing, Reshmie A; Apornpong, Tanakorn; Jirajariyavej, Supunee; Putcharoen, Opass; Treeprasertsuk, Sombat; Akkarathamrongsin, Srunthron; Poovorawan, Yong; Matthews, Gail V; Lange, Joep M A; Ruxrungtham, Kiat

    2014-09-01

    Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  12. Intelligent Command and Control Systems for Satellite Ground Operations

    NASA Technical Reports Server (NTRS)

    Mitchell, Christine M.

    1999-01-01

    This grant, Intelligent Command and Control Systems for Satellite Ground Operations, funded by NASA Goddard Space Flight Center, has spanned almost a decade. During this time, it has supported a broad range of research addressing the changing needs of NASA operations. It is important to note that many of NASA's evolving needs, for example, use of automation to drastically reduce (e.g., 70%) operations costs, are similar requirements in both government and private sectors. Initially the research addressed the appropriate use of emerging and inexpensive computational technologies, such as X Windows, graphics, and color, together with COTS (commercial-off-the-shelf) hardware and software such as standard Unix workstations to re-engineer satellite operations centers. The first phase of research supported by this grant explored the development of principled design methodologies to make effective use of emerging and inexpensive technologies. The ultimate performance measures for new designs were whether or not they increased system effectiveness while decreasing costs. GT-MOCA (The Georgia Tech Mission Operations Cooperative Associate) and GT-VITA (Georgia Tech Visual and Inspectable Tutor and Assistant), whose latter stages were supported by this research, explored model-based design of collaborative operations teams and the design of intelligent tutoring systems, respectively. Implemented in proof-of-concept form for satellite operations, empirical evaluations of both, using satellite operators for the former and personnel involved in satellite control operations for the latter, demonstrated unequivocally the feasibility and effectiveness of the proposed modeling and design strategy underlying both research efforts. The proof-of-concept implementation of GT-MOCA showed that the methodology could specify software requirements that enabled a human-computer operations team to perform without any significant performance differences from the standard two-person satellite operations team. GT-VITA, using the same underlying methodology, the operator function model (OFM), and its computational implementation, OFMspert, successfully taught satellite control knowledge required by flight operations team members. The tutor structured knowledge in three ways: declarative knowledge (e.g., What is this? What does it do?), procedural knowledge, and operational skill. Operational skill is essential in real-time operations. It combines the two former knowledge types, assisting a student to use them effectively in a dynamic, multi-tasking, real-time operations environment. A high-fidelity simulator of the operator interface to the ground control system, including an almost full replication of both the human-computer interface and human interaction with the dynamic system, was used in the GT-MOCA and GT-VITA evaluations. The GT-VITA empirical evaluation, conducted with a range of'novices' that included GSFC operations management, GSFC operations software developers, and new flight operations team members, demonstrated that GT-VITA effectively taught a wide range of knowledge in a succinct and engaging manner.

  13. Classical, Generalizability, and Multifaceted Rasch Detection of Interrater Variability in Large, Sparse Data Sets.

    ERIC Educational Resources Information Center

    MacMillan, Peter D.

    2000-01-01

    Compared classical test theory (CTT), generalizability theory (GT), and multifaceted Rasch model (MFRM) approaches to detecting and correcting for rater variability using responses of 4,930 high school students graded by 3 raters on 9 scales. The MFRM approach identified far more raters as different than did the CTT analysis. GT and Rasch…

  14. SPECT and fMRI Analysis of Motor and Cognitive Indices of Early Parkinson’s Disease: The Relationship of Striatal Dopamine and Cortical Function

    DTIC Science & Technology

    2005-09-01

    MC. Predicting white matter targets for direct neurostimulation therapy. Epilepsy Research 2010;PMID:20728313. Shukla D, Kaiser CC, Stebbins GT...Predicting white matter targets for direct neurostimulation therapy. Epilepsy Research 2010;PMID:20728313. Shukla D, Kaiser CC, Stebbins GT, Feinstein

  15. Gemini 6 crew during press conference

    NASA Image and Video Library

    1965-04-06

    S65-19406 (6 April 1965) --- Astronauts Thomas P. Stafford (left), pilot; and Walter M. Schirra Jr., command pilot, have been named as the prime crew for the Gemini-Titan 6 spaceflight. Schirra and Stafford served as the GT-3 backup crew. Their selection for the GT-6 flight was announced at an MSC news conference on April 6, 1965.

  16. 46 CFR 128.310 - Fuel.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Fuel. 128.310 Section 128.310 Shipping COAST GUARD... Main and Auxiliary Machinery § 128.310 Fuel. (a) OSVs of less than 6,000 GT ITC (500 GRT if GT ITC is... main propulsion or for auxiliaries, must be driven by a fuel having a flashpoint of not lower than 43...

  17. Mass Disinfection of Documents Affected by Microorganisms: One Practical Experience.

    ERIC Educational Resources Information Center

    Dobrusina, Svetlana; Velikova, Tatiana

    This paper presents the results of disinfecting treatment of more than 200,000 documents damaged by microorganisms in connection with moving the documents from depositories to a new building of the National Library of Russia. For disinfection, a preparation Metatin GT made by a Swedish firm ACIMA was applied. Metatin GT meets three basic…

  18. Gifted and Talented Programs in Charter Schools

    ERIC Educational Resources Information Center

    Buchanan, Nina K.; Fox, Robert A.; Martin, Darlene E.

    2006-01-01

    The fact that the reform movement in public education has directed greater attention to the needs of underperforming students than to those of gifted and talented (G/T) students is both well documented and not surprising in the current political climate. Some advocates for G/T education greeted the growth of charter schools as promising a more…

  19. First Monte Carlo Global Analysis of Nucleon Transversity with Lattice QCD Constraints

    DOE PAGES

    Lin, Huey-Wen; Melnitchouk, Wally; Prokudin, Alexei; ...

    2018-04-11

    We report on the first global QCD analysis of the quark transversity distributions in the nucleon from semi-inclusive deep-inelastic scattering (SIDIS), using a new Monte Carlo method based on nested sampling and constraints on the isovector tensor chargemore » $$g_T$$ from lattice QCD. A simultaneous fit to the available SIDIS Collins asymmetry data is compatible with $$g_T$$ values extracted from a comprehensive reanalysis of existing lattice simulations, in contrast to previous analyses, which found significantly smaller $$g_T$$ values. The contributions to the nucleon tensor charge from $u$ and $d$ quarks are found to be $$\\delta u = 0.3(2)$$ and $$\\delta d = -0.7(2)$$ at a scale $Q^2 = 2$ GeV$^2$.« less

  20. First Monte Carlo Global Analysis of Nucleon Transversity with Lattice QCD Constraints

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

    Lin, Huey-Wen; Melnitchouk, Wally; Prokudin, Alexei

    We report on the first global QCD analysis of the quark transversity distributions in the nucleon from semi-inclusive deep-inelastic scattering (SIDIS), using a new Monte Carlo method based on nested sampling and constraints on the isovector tensor chargemore » $$g_T$$ from lattice QCD. A simultaneous fit to the available SIDIS Collins asymmetry data is compatible with $$g_T$$ values extracted from a comprehensive reanalysis of existing lattice simulations, in contrast to previous analyses, which found significantly smaller $$g_T$$ values. The contributions to the nucleon tensor charge from $u$ and $d$ quarks are found to be $$\\delta u = 0.3(2)$$ and $$\\delta d = -0.7(2)$$ at a scale $Q^2 = 2$ GeV$^2$.« less

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