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Sample records for histopatologia viii diagnostico

  1. HISTOPATOLOGIA DA ADENOMIOSE EM VACAS ABATIDAS NO NORTE FLUMINENSE

    Directory of Open Access Journals (Sweden)

    Eulógio Carlos Queiróz de Carvalho

    2006-10-01

    patologia, além do estudo mais profundo desta, nesta espécie. PALAVRAS-CHAVES: Adenomiose, histopatologia, vacas

  2. Haemophilus influenzae biotype VIII.

    OpenAIRE

    Sottnek, F O; Albritton, W L

    1984-01-01

    Six Haemophilus influenzae strains could not be classified as biotypes I through VII. The strains were indole, urease, and ornithine decarboxylase negative. We propose that they be classified as biotype VIII, a previously unreported biotype.

  3. Clima organizacional y su diagnostico: una aproximacion conceptual

    National Research Council Canada - National Science Library

    Garcia Solarte, Monica

    2009-01-01

    El clima organizacional es hoy un factor clave en el desarrollo empresarial, y su estudio en profundidad, diagnostico y mejoramiento incide de manera directa en el denominado espiritu de la organizacion...

  4. Diagnosis of factor VIII deficiency.

    NARCIS (Netherlands)

    Verbruggen, B.; Meijer, P.; Novakova, I.; Heerde, W. Van

    2008-01-01

    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show

  5. Diagnostico del estado situacional de la comunicacion interna en Amanco-Costa Rica

    National Research Council Canada - National Science Library

    Lobo Rojas, Paola

    2009-01-01

    El presente articulo resume el trabajo de graduacion titulado "Diagnostico del estado situacional de los procesos de comunicacion interna generados por el Departamento de Recursos Humanos de Amanco...

  6. Diagnosis of factor VIII deficiency.

    Science.gov (United States)

    Verbruggen, B; Meijer, P; Novákova, I; Van Heerde, W

    2008-07-01

    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, one-stage and two-stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one-stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one-stage and two-stage assays are reviewed and discussed.

  7. Diagnostico del modelo de organizacion: caso empresa comercial de acabados para construccion

    National Research Council Canada - National Science Library

    Lopez Orozco, Gilberto; Gil Montelongo, Maria Dolores; Fleitas Triana, Maria Sonia

    2010-01-01

    Este articulo presenta el resultado de investigacion sobre el diagnostico del modelo de organizacion de una organizacion cuyo giro principal es la compra y venta de materiales para acabados de construccion...

  8. Desarrollo de tecnicas serologicas para el diagnostico de la Neosporosis canina

    National Research Council Canada - National Science Library

    Romeral Requena, Natalia; Aguado Martinez, Adriana

    2007-01-01

    .... El diagnostico laboratorial incluye, por un lado, la deteccion directa de ooquistes en las muestras de heces y, por otro, la deteccion de anticuerpos especificos en muestras de suero que permite...

  9. Stark broadening parameter tables for Ar VIII

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1999-01-01

    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 9 Ar VIII transitions as a function of temperature and perturber density.

  10. Stark broadening parameter tables for Kr VIII

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1999-01-01

    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 6 Kr VIII multiplets as a function of temperature and perturber density.

  11. Trypanosoma (Herpetosoma rangeli Tejera, 1920: nota prévia sobre a histopatologia em camundongos infectados experimentalmente

    Directory of Open Access Journals (Sweden)

    Cecilia de Scorza

    1986-10-01

    Full Text Available Ratones machos (cepa NMRI de 3 y 5 gr, inoculados i.p. con 8 x 10(6 y 9 x 10(4 metatripo- mastigotes/gr cosechados de cultivo LIT de 12 días de repique de la cepa "Perro-82" de Trypanosoma rangeli fueron procesados, em determinados períodos postinoculación, para seccionar y teñir con hematoxilina-eosina y Giemsa-colofonio trozos de corozón, hígado, bazo, pulmones, fémur, riñon, intestino, estómago, cerebro, cerebelo, esternón y columna vertebral. Se detallan los resultados preliminares sobre la histopatologia provocada por el T. rangeli en los cinco primeros órganos citados. Los tejidos conjuntivos subcutáneo, periosteal, intersticial y peribronquial, así como las miocélulas del corazón fueron altamente parasitados por amastigotes y tripomastigotes. Se discuten las posibles razones de la disminución del parasitismo tisular cuando la parasitemia se encontró en sus niveles máximos, así como la escasa inflamación obtenida en los tejidos parasitados. Las observaciones de varios autores sobre el comportamiento del protozoario en humanos y en animales de laboratorio así como los resultados descritos en este trabajo, plantean la posibilidad de que determinadas cepas de T. rangeli, en condiciones particulares, podrían causar alteraciones patológicas en el mamífero.

  12. Razonamiento cientifico y conocimientos conceptuales de mecanica: un diagnostico de alumnos de primer ingreso a licenciaturas en ingenieria

    National Research Council Canada - National Science Library

    Rodriguez, Maria D; Mena, Daniel A; Rubio, Carlos M

    2010-01-01

    Se presenta un diagnostico del grado de razonamiento cientifico de cinco grupos de estudiantes de primer ingreso a licenciaturas en ingenieria aplicando la prueba de aula de razonamiento cientifico de Lawson...

  13. Una propuesta para configurar el algoritmo FastICA en el diagnostico de fallos en sistemas industriales

    National Research Council Canada - National Science Library

    Quinones Grueiro, M; Prieto-Moreno, A; Llanes Santiago, O

    2014-01-01

    El Analisis de Componentes Independientes (ICA) es una tecnica estadistica que ha sido ampliamente aplicada en los ultimos diez anos para la reduccion de la dimension en el diagnostico de fallos en sistemas industriales...

  14. Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII.

    Science.gov (United States)

    Schmidbauer, Stefan; Witzel, Reinhild; Robbel, Lars; Sebastian, Petra; Grammel, Nicolas; Metzner, Hubert J; Schulte, Stefan

    2015-08-01

    rVIII-SingleChain is a novel recombinant single-chain factor VIII (FVIII) construct, comprising covalently bonded heavy and light chains. Post-translational modifications of FVIII affect physicochemical parameters, including hydrophobicity and charge. The most relevant post-translational modifications of FVIII products are N-glycosylation of asparagine residues and tyrosine sulphations. Here, the physicochemical properties, thrombin cleavage products and post-translational modifications of rVIII-SingleChain were investigated and compared against commercially available recombinant FVIII (rFVIII) products with a predominant two-chain structure (B-domain deleted rFVIII and full-length rFVIII). rVIII-SingleChain was expressed in Chinese hamster ovary (CHO) cells and purified by chromatographic methods. Physicochemical properties of rVIII-SingleChain or thrombin-derived cleavage products were assessed using size-exclusion chromatography, reversed-phase chromatography and sodium dodecyl sulphate polyacrylamide gel electrophoresis. Analysis of the respective carbohydrate structures was performed after release of N-glycans by PNGase F followed by fluorescence labelling and high-performance liquid chromatography. Proteolysis by trypsin generated the corresponding peptides, which were analysed for sulphated tyrosines by liquid chromatography-electrospray ionisation time of flight-mass spectrometry. rVIII-SingleChain was shown to be of high purity and homogeneity, and presented a well-defined single-chain molecule with predominant β-sheet conformation. The coagulation-relevant thrombin-activation products of rVIII-SingleChain were comparable with those obtained by activation of commercially available rFVIII products. rVIII-SingleChain post-translational modifications were similar to other CHO cell-derived rFVIII products for N-glycopattern and tyrosine sulphation. In conclusion, rVIII-SingleChain is of high homogeneity and purity, and provides an expected cleavage pattern on

  15. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  16. Reasoning based in cases applied to diagnosis of electric generators; Razonamiento basado en casos aplicado al diagnostico de generadores electricos

    Energy Technology Data Exchange (ETDEWEB)

    De la Torre Vega, H. Octavio; Garcia Tevillo, Arturo; Campuzano Martinez, Roberto [Instituto de Investigaciones Electricas, Temixco, Morelos (Mexico); Lopez Azamar, Ernesto [Comision Federal de Electricidad (Mexico)

    2000-07-01

    The development of a system for the diagnosis of electrical generators that apply techniques of artificial intelligence, is presented, as it is the reasoning based on cases, to support the work of the diagnosis engineer. This system is part of a system called CADIS, dedicated to the diagnosis of electrical generators out of line and reason of previous articles. In this occasion the characteristics of the reasoning module based on experiences (SirBE) are emphasized, indicating how to make a diagnosis using similar cases and how to edit the system base of experience, using the interactive editor of cases. It is included, in addition, a summarized example which represents a case for SirBE and how the system helps to make a diagnosis. [Spanish] Se presenta el desarrollo de un sistema de diagnostico de generadores electricos que aplica tecnicas de inteligencia artificial, como es el razonamiento basado en casos, para apoyar la labor del ingeniero de diagnostico. Este sistema es parte de un sistema denominado CADIS, dedicado al diagnostico de generadores electricos fuera de linea y motivo de articulos anteriores. En esta ocasion se resaltan las caracteristicas del modulo de razonamiento basado en experiencias (SirBE), indicando como realizar un diagnostico utilizando casos similares y como editar la base de experiencia del sistema utilizando el editor interactivo de casos. Se incluye, ademas, un ejemplo resumido de lo que representa un caso para SiRBE y como el sistema ayuda a realizar un diagnostico.

  17. Heat transfer burnout of Mark VIII fuel

    Energy Technology Data Exchange (ETDEWEB)

    Bernath, L.

    1956-08-01

    The operating conditions to which the special Mark VIII quatrefoils will be exposed during the proposed piloting program have been compared with the conditions required to cause burnout, using an established method of calculating these conditions. The results of this comparison permit the following conclusions to be drawn: (1) With normal flow of coolant through the special elements the heat flux to be encountered in the R-8 cycle (1400 MW) will be 70% or that required to cause burnout (30% margin from burnout). (2) With a reduction of coolant flow to 82% of normal through one tube of a special element, burnout of that fuel column is possible in the R-8 cycle. (3) In the R-6 cycle (1280 MW), the margin from burnout in the special Mark VIII quatrefoils is 42% with full flow and 20% with the above reduced coolant flow. A similar comparison of operating conditions predicted for the L-3 cycle (full Mark VIII charge) shows that, even at the highest power level (1250 MW), the margin from burnout is greater than 55% with normal flow and 40% with reduced flow.

  18. Online monitoring and diagnosis of power transformers; Monitoreo y diagnostico en linea de transformadores de potencia

    Energy Technology Data Exchange (ETDEWEB)

    Linan, Roberto; Alvarez, Rafael; Jimenez, Leon; Nunez, Arturo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico); Contreras, Francisco A. [Comision Federal de Electricidad, Mexico, D. F. (Mexico)

    1997-12-31

    In this article are presented three diagnosis techniques for power transformers. The first one consists in a non-invasive technique for detecting mechanical failure in taps with load in power transformers utilizing vibration sensors. The second one consists in an online diagnosis to detect the presence of arcing and partial discharges in the power transformer based in the recording and analysis of the signals using ultrasonic sensors that detect the noise that these phenomena emit from the outside of the transformer tank. The third technique consists in analyzing the dissolved gases in the transformer insulating oil, with it and in accordance with the levels and the existing relationships, it is possible to determine the involved deteriorating process. The results of the application of the three mentioned diagnosis techniques, which were used for the evaluation of some transformers in different Comision Federal de Electricidad (CFE) substations, are presented. [Espanol] En el presente articulo se reportan tres tecnicas de diagnostico para transformadores de potencia. La primera consiste en una tecnica no invasiva para detectar fallas mecanicas en cambiadores de derivacion con carga de transformadores de potencia utilizando sensores de vibracion. La segunda consiste en un diagnostico en linea para detectar la presencia de arqueos y descargas parciales en el transformador de potencia basada en el registro y analisis de senales usando sensores ultrasonicos que detectan el sonido que emiten esos fenomenos desde el exterior del tanque del transformador. La tercer tecnica consisten en analizar los gases disueltos en el aceite aislante de los transformadores, con la cual y de acuerdo con los niveles y relaciones existentes, es posible determinar el proceso de deterioro involucrado. Se presentan resultados de la aplicacion de las tres tecnicas de diagnostico mencionadas, las cuales se usaron para evaluar algunos transformadores en diferentes subestaciones de la Comision

  19. The 7 steps for the power diagnosis; Los 7 pasos del diagnostico energetico

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Osorio, Javier [Director de Ahorro de Energia en el Transporte, Comision Nacional para el Ahorro de Energia (CONAE) (Mexico)

    2005-07-01

    This study explains in detail the 7 steps to perform energy diagnose, which are: the balance (the expenses against the income); the traffic operations; the assets (vehicles and technology); the operation of the vehicles; the maintenance; the fuel management; the information and administration. [Spanish] Este estudio explica detalladamente los 7 pasos para realizar un diagnostico energetico, que son: el balance (los gastos contra los ingresos), las operaciones de trafico, el parque (vehiculos y tecnologia), la operacion de los vehiculos, el mantenimiento, la gestion de combustible, e informacion y administracion.

  20. Sindrome de ovario poliquistico: del diagnostico clinico y ecografico al molecular.(Perspectiva general de la enfermedad/trastorno)

    National Research Council Canada - National Science Library

    Martinez-Sanchez, Lina Maria; Agudelo-Velez, Camilo Andres; Rendon-Pereira, Gabriel Jaime

    2010-01-01

    ... a los trastornos menstruales (oligomenorreas o amenorreas) y a los signos de hiperandrogenismo (hirsutismo y acne) y/o a la hiperandrogenemia; pero no incluia como criterio diagnostico la presencia ecografica de ovarios poliquisticos (3). El abordaje conceptual se desarrollara en dos tiempos. El primero da cuenta de la descripcion general de los principios d...

  1. Preparing for ENDF/B-VIII

    Science.gov (United States)

    Brown, David

    2017-09-01

    Although the next major release of the ENDF/B library is not due until the 2017-2018 time frame, ENDF/B-VIII is already positioned to become the most important release of the library in some time. ENDF/B-VIII will be built around the Neutron Reaction Standards as well as the 1H, 16O, 56Fe, 235U, 238U and 239Pu evaluations developed as part of the Coordinated International Evaluation Library Organization (CIELO) pilot project. In this contribution, we summarize these improvements as well as the many other improvements to ENDF that have already been made or are scheduled to be made in the next year. Improvements already included in the ENDF/B-VIII beta releases: • Aggressive use of the flexible and physically correct LRF=7 resolved resonance format in 12 updated evaluations (35,37Cl, 40Ca, 54,56,57Fe, 63,65Cu and 182,183,184,186W) • Thermal capture gammas from the EGAF project (6,7Li, 11B, 19F, 23Na, 27Al, 28Si, 35,37Cl) • Thermal Scattering Law evaluations from NCSU (α and β phase SiO2, SiC, lucite, BeO, and polyethylene) and from the CAB-CNL collaboration (heavy and light water) • Many new evaluations in the neutron sublibrary (n, 12,13C, 40Ar, 54,57,58Fe, 58,59,60,61,62,64Ni, 63,65Cu, 73As, 120Sn, 236m1Np) Inclusion of Red Cullen's EPICS2014 library, updating the photo-atomic, electron and atomic-relaxation sublibraries. Many improvements are planned in the next year including new evaluations such as charged particle evaluations translated from LLNL's ECPL. In addition to these major changes, ENDF/B-VIII will be the first official library released simultaneously in the legacy ENDF-6 and the newly developed Generalized Nuclear Data (GND) formats.

  2. Diagnostico y tratamiento de los trastornos tiroideos durante el embarazo: un enfoque para el cuidado integral del binomio madre-hijo

    National Research Council Canada - National Science Library

    Cordoba Ramirez, Nathalia; Builes Barrera, Carlos Alfonso; Garcia Botina, Hernan David

    2013-01-01

    ...., se anaden las modificaciones en el eje tiroideo que a lo largo de la gestacion presenta diferentes estados, lo que hace aun mas dificil el diagnostico y tratamiento correctos en los casos patologicos...

  3. Evaluacion de la restrictividad de dispositivos residenciales para personas con un diagnostico psiquiatrico en el modelo de salud mental comunitaria en Chile

    National Research Council Canada - National Science Library

    Bustos Navarrete, Claudio; Tapia Cardenas, Carolina; Cova Solar, Felix; Grandon Fernandez, Pamela

    2015-01-01

    Los hogares y residencias protegidas son elementos centrales de la red asistencial que atiende a personas con un diagnostico de trastorno mental severo, dentro del modelo de salud mental comunitaria...

  4. ROTURA DE ANEURISMA DE AORTA ABDOMINAL: SU IMPORTANCIA COMO DIAGNOSTICO DIFERENCIAL EN ABDOMEN AGUDO

    Directory of Open Access Journals (Sweden)

    Vanessa Orellana-Villazón

    2012-02-01

    Full Text Available El aneurisma aórtico abdominal (AAA roto es una forma de presentación poco frecuente de los AAA. Presentamos un caso de rotura de aneurisma de aorta abdominal (AAAr de un paciente varón de 76 años de edad que ingresa al servicio de emergencias del Hospital Elizabeth Setón por presentar dolor abdominal punzante en región lumbar derecha de inicio súbito e intensidad creciente, llegando a perder el conocimiento. La impresión diagnóstica inicial incluye cólico ureteral e hipertensión arterial; sin embargo después realizar una ecografía abdominal y posteriormente una tomografía abdominal se concluye con el diagnostico de AAAr. El paciente es sometido a cirugía de emergencia, y después de permanecer tres días en terapia intensiva y tres días en sala, es dado de alta. Consideramos importante informar este caso clínico por la frecuencia con que se le confunde con patologías renales o abdomen agudo, pese a la sintomatología característica que presenta, que en muchos casos lleva a un diagnostico retrasado y posteriormente a la muerte.

  5. Acquired Factor VIII Inhibitors: Three Cases

    Directory of Open Access Journals (Sweden)

    Tay Za Kyaw

    2013-03-01

    Full Text Available Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients’ ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed.

  6. 12 CFR 611.1137 - Title VIII service corporations.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Title VIII service corporations. 611.1137 Section 611.1137 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM ORGANIZATION Service... authorities granted under title VIII of the Act to act as an agricultural mortgage marketing facility. (b) How...

  7. The influence of prophylactic factor VIII in severe hemophilia A

    Science.gov (United States)

    Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

    2013-01-01

    Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

  8. Energy diagnoses to the small company; Diagnosticos energeticos a la pequena empresa

    Energy Technology Data Exchange (ETDEWEB)

    Ambriz Garcia, Juan Jose; Ortega Navarro, Hermilio Oscar [Universidad Autonoma Metropolitana, Mexico D.F. (Mexico)

    2005-07-01

    In this work are presented some results of the application of energy diagnoses to small companies. These diagnoses use the methodology developed by the Department of Energy of the United States of America and are performed by advanced students of engineering and university professors. The results of four energy diagnoses applied to companies of different branches are presented. In the studies the energy saving alternatives are evaluated, as well as their economic impact and their economic viability. The annual energy saving according to the company goes from 25,600 to 596,000 MJ (from 1.2 to 10.5%), which means a saving from $5,300 to $165,000 Mexican Currency (1.43 to 9.27%). The simple rate of return goes of 0.5 to 9.3 years. From the work it is concluded that the application of that methodology of energy diagnoses in Mexico is very feasible, since with very low costs opportunities of energy savings are identified and evaluated for this section of companies that traditionally have not been taken care of by the official programs and allows them to give launch to a solid program of energy improvement. [Spanish] En este trabajo se presentan algunos resultados de la aplicacion de diagnosticos energeticos a pequenas empresas. Se utiliza la metodologia desarrollada por el Departamento de Energia de los Estados Unidos de America, en donde, los estudios los realizan alumnos avanzados de ingenieria y profesores de universidades. Como ejemplo se presentan los resultados de cuatro diagnosticos energeticos aplicados a empresas de distintas ramas. En los estudios se evaluan las alternativas de ahorro de energia, tanto en la energia ahorrada, como su impacto economico, asi como su viabilidad economica. El ahorro anual de energia segun la empresa va de 25,600 a 596,000 MJ (de 1.2 a 10.5%), lo que significa un ahorro de $5,300 a $165,000 (1.43 a 9.27%). La tasa simple de retorno va de 0.5 a 9.3 anos. Del trabajo se concluye que la aplicacion de esa metodologia de diagnosticos

  9. Bilateral Renal Vein Thrombosis due to Elevated Factor VIII Levels.

    Science.gov (United States)

    Patole, Shalom; Ramya, I

    2015-08-01

    Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use. © Journal of the Association of Physicians of India 2011.

  10. Factoring in Factor VIII With Acute Ischemic Stroke.

    Science.gov (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  11. Estudo comparativo entre citopatologia e histopatologia no diagnóstico de neoplasias caninas A comparative study between cytology and histopathology for the diagnosis of canine neoplasms

    Directory of Open Access Journals (Sweden)

    Adelaide M. Magalhães

    2001-03-01

    Full Text Available Foi realizado um estudo comparativo entre os diagnósticos citológico e histopatológico em diversas neoplasias de 150 cães, pelas colorações de Wright, May-Grünwald-Giemsa, Novo Azul de Metileno e Papanicolau. Colorações histológicas como Hematoxilina-Eosina, van Gieson, Sudan, Azul de Toluidina e Ácido Periódico de Schiff também foram empregadas. Os dados revelaram uma eficácia de ordem de 85,3% no diagnóstico citopatológico, considerando-se os resultados histopatológicos como corretos. Em 4,0% dos casos somente a origem embrionária das neoplasias foi estabelecida. Em 1,3% das neoplasias apenas o prognóstico foi determinado; o diagnóstico citológico diferiu da histopatologia em 8,1% dos casos. Em dois casos (1,3% o diagnóstico citológico diferiu do histológico, mas um reexame determinou que o primeiro estava correto, o que elevou a sua eficácia para 86,6%. Entre as técnicas utilizadas, a punção aspirativa por agulha fina foi o melhor método para obter amostras. A citologia não foi adequada para o diagnóstico de neoplasias mamárias, dadas às variações morfológicas em diferentes áreas. A impressão em lâmina não é recomendada para análise de tumores mesenquimais e deve ser substituída pela citologia esfoliativa. O Wright revelou-se o método de coloração mais eficiente. As colorações adaptadas da histopatologia, van Gieson em leiomiomas e leiomiossarcomas, Sudan em lipomas e lipossarcomas, e Ácido Periódico de Schiff e Azul de Toluidina em mastocitomas, foram empregadas com sucesso fornecendo assim maior clareza de detalhes para as diversas neoformações de origem epitelial e mesenquimal.A comparative study between cytology and histopathology of various neoplasms from 150 dogs was carried out. Several staining methods including Wright, May-Grünwald-Giemsa, New-Methylene Blue and Papanicolau, and histological staining methods such as Hematoxilin & Eosin, van Gieson, Sudan, Toluidine Blue and

  12. Diagnosis and treatment for sick building; Diagnostico y tratamiento para edificios saludables

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Maria M; Salomon, Jorge A; Lazcano, Alejandro S [Facultad de Ingenieria UADY, Merida Yucatan (Mexico)

    2000-07-01

    In recent years, the indoor air quality (IAQ) in work spaces have acquired special importance. Health symptoms refer to a productivity and economic loss. IAQ health symptoms associated with acute discomfort that improve while away from work. More common, however, are apparent outbreaks of illness within work spaces in which neither environmental causes non recognized diseases can be identified. Usually reported within the last years, these events are often called sick building syndrome. To determine a sick building diagnosis and treatment, it is necessary to plan methodology based on environment comfort, habitability, energy efficiency use and nature preservation. Hereby it is presented a methodology to determine a sick building diagnosis and treatment which was applied in Superior Court of Justice building (Tribunales Primero y Segundo del Decimocuarto Circuito del Poder Judicial de la Federacion), where employees have expressed diseases as sleepiness, cold and difficulty breathing. [Spanish] En los ultimos anos, la calidad del aire en el ambiente de trabajo ha adquirido especial interes debido a la importancia que representa para el bienestar, eficiencia y productividad de los empleados. Los edificios carentes de esa calidad del aire ocasionan trastornos de salud relacionados con la falta de confort que prevalece en el ambiente de trabajo, es comun encontrar en los empleados que alli laboran, brotes de sintomas como dolores de cabeza, letargo y resfriados, entre otros. Usualmente encontrados en los ultimos anos en ambientes de oficinas a estos sintomas se les llama sindrome del edificio enfermo. Para lograr el diagnostico y tratamiento de un edificio enfermo es necesario plantear una metodologia basada en criterios de confort ambiental, habitabilidad, uso eficiente de la energia y preservacion del medio ambiente. En este trabajo presentamos una metodologia para el diagnostico y tratamiento de edificios con ese sindrome y presentamos un estudio de casos de los

  13. Automatic diagnosis of steam turbines in line; Diagnostico automatico de turbinas de vapor en linea

    Energy Technology Data Exchange (ETDEWEB)

    Pensado Vassallo, Enlai

    2008-05-15

    o confiabilidad. De esta manera, siendo la energia nuclear la unica alternativa viable para sustituir la quema de combustibles fosiles en plantas termoelectricas, con antecedentes como el accidente de Three Mile Island en 1979 o el desastre de Chernobil en 1986, han llevado a no despreciar los riesgos relacionados. Lo cual complica su manejo y en consecuencia ha limitado la proliferacion de mas centrales nucleares. Bajo esta realidad, la problematica se concentra en dos tares: aumentar el rendimiento de las plantas termoelectricas y reducir la emision de contaminantes, tanto gases como liquidos. Por todo esto, y en cumplimiento con los valores expresados en la mision y vision del Instituto de Investigaciones Electrica (IIE), se ha seleccionado desarrollar una herramienta de apoyo para el estudio del estado de equipos rotativos remotos. Para ello, tomando como base la experiencia del IIE en el diagnostico de turbinas de vapor, se ha desarrollado una plataforma capaz de determinar la presencia de fallas a traves del modelado de la turbina y sus elementos, se representa el comportamiento esperado y, mediante la transformacion de las senales recolectadas del sistema, se calcula el comportamiento real del equipo. Con ambos resultados se procede a aplicar una tecnica de diagnostico que permita detectar las desviaciones e inferir los desperfectos existentes. Buscando mejorar la certeza y calidad de los resultados del analisis, como complemento, se ejecuta revision de las reglas de diagnostico, con base en el registro historico de diagnosis realizada y empleando un algoritmo genetico para la inclusion de reglas nuevas, las cuales se evaluan como candidatas para la mejora del producto. Este documento representa los esfuerzos de mas de un ano en el area de diagnostico, en busca de la adecuada arquitectura para una infraestructura de diagnostico remoto que permita la deteccion de fallas en centrales con turbina de vapor. El principal reto de crear esta infraestructura es la

  14. Stark broadening parameter tables for K VIII and K IX

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.

    1998-01-01

    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 4 K VIII and 30 K IX multiplets as a function of temperature and perturber density.

  15. Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish.

    Science.gov (United States)

    Aspatwar, Ashok; Tolvanen, Martti E E; Jokitalo, Eija; Parikka, Mataleena; Ortutay, Csaba; Harjula, Sanna-Kaisa E; Rämet, Mika; Vihinen, Mauno; Parkkila, Seppo

    2013-02-01

    Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema and abnormal movement patterns. Histologic examination revealed gross morphologic defects in the cerebellar region and in the muscle. Electron microscopy studies showed increased neuronal cell death in developing larvae injected with CA8 antisense morpholinos. These data suggest a pivotal role for CARP VIII during embryonic development. Furthermore, suppression of CA8 expression leads to defects in motor and coordination functions, mimicking the ataxic human phenotype. This work reveals an evolutionarily conserved function of CARP VIII in brain development and introduces a novel zebrafish model in which to investigate the mechanisms of CARP VIII-related ataxia and mental retardation in humans.

  16. Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking

    OpenAIRE

    Ebberink, Eduard H T M; Bouwens, Eveline A. M.; Bloem, Esther; Boon-Spijker, Mariëtte; van den Biggelaar, Maartje; Voorberg, Jan; Alexander B. Meijer; Mertens, Koen

    2017-01-01

    Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study, we addressed the contribution of individual factor VIII C-domains in intrace...

  17. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

    Science.gov (United States)

    Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John

    2017-12-28

    Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with

  18. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  19. Computerized system for energy diagnosis in domestic users; Sistema computarizado para diagnostico energetico en usuarios domesticos

    Energy Technology Data Exchange (ETDEWEB)

    Ramos N, Gaudencio; Heard, Cristopher; Fiscal E, Raul; Maqueda Z, Martin [Instituto de Investigaciones Electricas, Temixco, Morelos (Mexico)

    1999-07-01

    The scope of a computerized system is presented to make an energy diagnosis to homes and a simulation of scenarios of cost/benefit, due to the implementation of energy saving measures and the efficient use of electrical energy. The FIPATERM (trust for the heat insulation of the house in Mexicali), provides economic and technical support so that the domestic users diminish their expense for the electrical energy, implementing programs of Demand Side Management (DSM). The current effective programs are: thermal insulation, substitution of the existent air conditioning units for efficient ones, reduction of infiltration, leveled plan of payments, interruption of the air conditioning equipment. In order to participate in one or several of the programs of energy efficiency, an energy diagnosis is made to the user. It is from a survey of the equipment and characteristics of the house, as well as a description on the part of the user of his habits of use of the equipment, that scenarios are simulated, which allow the user to identify the most profitable measures. [Spanish] Se presenta el alcance de un sistema computarizado para realizar diagnostico energetico a casas habitacion y simulacion de escenarios de beneficio/costo, debido a la implantacion de medidas de ahorro y uso eficiente de energia electrica. El FIPATERM (fideicomiso para el aislamiento termico de la vivienda en Mexicali), proporciona apoyo economico y tecnico para que los usuarios domesticos minimicen su gasto de energia electrica, implementando programas de Administracion por el Lado de la Demanda (ALD). Los programas actualmente vigentes son: aislamiento termico, sustitucion del aire acondicionado actual por uno eficiente, reduccion de infiltracion, plan nivelado de pagos, interrupcion del equipo de aire acondicionado. Para participar en uno o varios de los programas de eficiencia energetica, al usuario se le realiza un diagnostico energetico. Es a partir de una encuesta del equipamiento y caracteristicas

  20. LA TELEMEDICINA EN EL DIAGNOSTICO Y TRATAMIENTO DE LOS TRASTORNOS RESPIRATORIOS DEL SUEÑO

    Directory of Open Access Journals (Sweden)

    José Cordero Guevara.

    2004-01-01

    Full Text Available We review the current state of the diagnosis and treatment of the sleep-apnea syndrome in relation to the instrument telematics available. The advance poligraphy systems, the not supervised polysomnography at home, combined with videoconference could be effective with an inferior cost in the diagnosis and treatment of the sleep apnea syndrome (SAS. The importance of the research, development and technological innovation in this area, will allow to introduce systems that allow a greater yield of the laboratory polysomnography, approaching the average east population of diagnose and treatment. RESUMEN: Se revisa el estado actual del diagnóstico y tratamiento del síndrome de apnea e hipopnea del sueño en relación con los medios telemáticos disponibles. Los sistemas de poligrafia avanzada, tipo polisomnografía domiciliaria no supervisada (PSG-DNS apoyado con teleconsulta por videoconferencia podria ser eficaz con un coste inferior en el diagnóstico y tratamiento del síndrome de apneas hipopneas del sueño (SAHS. La importancia de la investigacion, desarrollo e innovación tecnológica en este área, permitirá implantar sistemas que permitan un mayor rendimiento de las Unidades del Sueño, acercando a la población este medio de diagnostico y tratamiento.

  1. Histopathology of human American cutaneous leishmaniasis before and after treatment Histopatologia de leishmaniose tegumentar americana humana, antes e após o tratamento

    Directory of Open Access Journals (Sweden)

    A.C.C. Botelho

    1998-02-01

    Full Text Available Chemical therapy for the treatment of leishmaniasis is still inadequate, and a number of drugs and therapeutic programs are being tested. Besides treatment, the ultimate goal is an effective cure, and histopathological analyses of the lesion cicatrices constitute an important measure of treatment success, or otherwise, in this respect. In this paper, we describe histopathological patterns in cases of American cutaneous leishmaniasis in 32 patients from the municipality of Caratinga, Minas Gerais, Brazil, before and after treatment with the following therapeutic methodos: l leishvacin + glucantime; 2 leishvacin + BCG associated with glucantime; 3 glucantime; 4 leishvacin + BCG. Lesion fragments were collected from all patients by biopsy prior to, and approximately 30 days after, each treatment which resulted in a clinical diagnosis of cure. Following the analysis of slides, the preparations were described from a histopathological point of view and grouped taking into account the prevalence or significance of the characteristic elements. This process resulted in the following classification: 1. exsudative reaction (ER; 2. exsudative giant cell reaction (EGCR; 3. exsudative productive reaction (EPR; 4. exsudative productive giant cell reaction (EPGCR; 5. exsudative productive necrotic reaction (EPNR; 6. necrotic exsudative reaction (NER; 7. productive exsudative reaction (PER, 8. productive giant cell reaction (PGCR; 9. productive exsudative giant cell reaction (PEGCR; 10. productive exsudative giant cell granulomatous reaction (PEGCGR; 11. productive reaction (PR and 12. productive cicatricial (cure reaction (PCR. After this analysis, it was noted that clinical cure did not always coincide with histopathological cure.A quimioterapia para a leishmaniose não é satisfatória e existem hoje, várias drogas e esquemas terapêuticos em teste. Além do tratamento ideal, busca-se um critério de cura efetivo, onde a análise da histopatologia da

  2. Igor Zabel 14. VIII 1958 - 23. VII 2005

    Index Scriptorium Estoniae

    2005-01-01

    Igor Zabel oli Ida-Euroopa tuntumaid kunstiteoreetikuid ja kuraatoreid. Töötas 1986. aastast Ljubljana moodsa kunsti muuseumi kuraatorina. 9. VIII avatakse seal viimane I. Zabeli kureeritud näitus "Territories, Identities, Nets-Slovene Art 1995-2005"

  3. What history tells us VIII. The progressive construction of a ...

    Indian Academy of Sciences (India)

    2007-02-09

    Feb 9, 2007 ... Home; Journals; Journal of Biosciences; Volume 32; Issue 2. What history tells us VIII. The progressive construction of a mechanism for prion diseases. Michel Morange. Series Volume 32 Issue 2 March 2007 pp 223-227. Fulltext. Click here to view fulltext PDF. Permanent link:

  4. The labour ward analgesic service at King Edward VIII Hospital ...

    African Journals Online (AJOL)

    dence of shivering9 and an improved sense of maternal well-being.lo. In summary, the study presented here shows that the analgesia service provided ro the labour ward at King. Edward VIII Hospital is at present grossly inadequate. In particular, a high proportion (76%) of mothers with a specific indication for epidural ...

  5. Functional regions in coagulation factor VIII explored by mass spectrometry

    NARCIS (Netherlands)

    Bloem, E.

    2013-01-01

    The molecular mechanisms behind the function of factor VIII (FVIII) have remained poorly understood. FVIII acts in the blood coagulation cascade as cofactor for activated factor IX (FIXa) in the membrane bound activated factor X generating (FXase) complex. A functional absence in FVIII leads to the

  6. Comparison of factor VIII transgenes bioengineered for improved expression in gene therapy of hemophilia A.

    Science.gov (United States)

    Dooriss, Kerry L; Denning, Gabriela; Gangadharan, Bagirath; Javazon, Elisabeth H; McCarty, David A; Spencer, H Trent; Doering, Christopher B

    2009-05-01

    Successful gene therapy of hemophilia A depends on the sustained expression of therapeutic levels of factor VIII (fVIII). Because of mRNA instability, interactions with resident endoplasmic reticulum (ER) chaperones, and the requirement for carbohydrate-facilitated transport from the ER to the Golgi apparatus, fVIII is expressed at much lower levels from mammalian cells than other proteins of similar size and complexity. A number of bioengineered forms of B domain-deleted (BDD) human fVIII have been generated and shown to have enhanced expression. Previously, we demonstrated that recombinant BDD porcine fVIII exhibits high-level expression due to specific sequence elements that increase biosynthesis via enhanced posttranslational transit through the secretory pathway. In the current study, high-expression recombinant fVIII constructs were compared directly in order to determine the relative expression of the various bioengineered fVIII transgenes. The data demonstrate that BDD porcine fVIII expression is superior to that of any of the human fVIII variant constructs tested. Mean fVIII expression of 18 units/10(6) cells/24 hr was observed from HEK-293 cells expressing a single copy of the porcine fVIII transgene, which was 36- to 225-fold greater than that of any human fVIII transgene tested. Furthermore, greater than 10-fold higher expression was observed in human cells transduced with BDD porcine fVIII versus BDD human fVIII-encoding lentiviral vectors, even at low proviral copy numbers, supporting its use over other human fVIII variants in future hemophilia A gene therapy clinical trials.

  7. TT virus contaminates first-generation recombinant factor VIII concentrates.

    Science.gov (United States)

    Azzi, A; De Santis, R; Morfini, M; Zakrzewska, K; Musso, R; Santagostino, E; Castaman, G

    2001-10-15

    Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein-free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.

  8. The online diagnosis of steam turbines; El diagnostico en linea de turbinas de vapor

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez S, J. Antonio; Rivera G, Juan J; Cristalinas N, Victor M; Marino L, Carlos A [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2004-07-01

    To maintain the efficiency values, power and unit thermal consumption of the electrical generation units near the design levels, has been always one of the objectives of the operation and maintenance personnel of the power plants of the Comision Federal de Electricidad (CFE). A way to obtain this objective is through the systematic analysis of the equipment operating conditions and of the diagnosis of the deviations causes of the normal operation way. The Gerencia de Operacion de Maquinaria (Management of Turbo-Machinery) through projects contracted with the Unidad de Investigacion y Desarrollo (Unit of Investigation and Development) of the CFE has made the thermal evaluation of different generation units. These evaluations have allowed to identify which internal components are causing the deviations and to improve the planning of the maintenance activities required to bring back the unit to its best working conditions. In this article the methodology for the online thermal evaluation of the steam turbines and its heat transfer auxiliary equipment is described -water condenser and heaters- and some of the obtained results are also presented. [Spanish] Mantener cercanos a los niveles de diseno los valores de eficiencia, potencia y consumo termico unitario de las unidades de generacion electrica ha sido siempre uno de los objetivos del personal de operacion y mantenimiento de las plantas de la Comision Federal de Electricidad (CFE). Una manera de lograr este objetivo es a traves del analisis sistematico de las condiciones de operacion de los equipos y del diagnostico de las causas de las desviaciones del modo normal de operacion. La Gerencia de Turbomaquinaria a traves de proyectos contratados con la Unidad de Investigacion y Desarrollo de la CFE ha realizado la evaluacion termica de diferentes unidades de generacion. Estas evaluaciones han permitido identificar cuales componentes internos estan provocando las desviaciones y mejorar la planeacion de las actividades

  9. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P. (Univ. of Vermont, Burlington (USA))

    1989-09-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO{sub 4}/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated {sup 125}I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function.

  10. 40 CFR Appendix Viii to Part 600 - Fuel Economy Label Formats

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Fuel Economy Label Formats VIII... POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Pt. 600, App. VIII Appendix VIII to Part 600—Fuel Economy Label Formats EC01MY92.117 EC01MY92.118 EC01MY92.119 EC01MY92.120...

  11. Localization of collagen type VIII in normal and pathological human cornea

    OpenAIRE

    Zenklová, Kateřina

    2007-01-01

    The aim of this work was to localize collagen type VIII in different layers of the cornea and to compare it's localization in normal corneas with pathological corneas obtained from patients with Fuchs endothelial dystrophy, posterior polymorphous dystrophy or keratoconus.The only comercially available antibody did not proove sufficient specifiky for collagen type VIII. With use of the antibody 9H3 anti alCVIII was collagen VIII evidenced in the cornea. This antibody can be used for detection ...

  12. System of diagnosis of generators computer aided integrated into a movable laboratory; Sistema de diagnostico de generadores asistido por computadora integrado a un laboratorio movil

    Energy Technology Data Exchange (ETDEWEB)

    De la Torre Vega, H. Octavio; Escorsa Morales, Oscar; Castaneda Parra, Adelina; Garcia- Colon H, Rodolfo [Instituto de Investigaciones Electricas, Temixco, Morelos (Mexico); Lopez Azamar, Ernesto [Comision Federal de Electricidad (Mexico)

    1999-07-01

    The development of the Movable Laboratory is presented, which will allow to combine and document the knowledge acquired by more than ten years of experience in diagnosis of electrical generators. The development of the project is divided into three main parts: laboratory design, data acquisition system (Datec) and system of diagnosis of generators computer aided (Cadis). [Spanish] Se presenta el desarrollo del Laboratorio Movil, el cual permitira conjuntar y documentar el conocimiento adquirido por mas de diez anos de experiencia en diagnostico de generadores electricos. El desarrollo del proyecto se divide en tres grandes partes: diseno de laboratorio, sistema de adquisicion de datos (Datec) y sistema de diagnostico de generadores asistido por computadora (Cadis).

  13. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin.

    OpenAIRE

    Hill-Eubanks, D C; Parker, C G; Lollar, P

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. We isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as ...

  14. War and peace: Factor VIII and the adaptive immune response.

    Science.gov (United States)

    Georgescu, Maria T; Lai, Jesse D; Hough, Christine; Lillicrap, David

    2016-03-01

    The development of neutralizing anti-factor VIII (FVIII) antibodies (inhibitors) remains a major challenge for FVIII replacement therapy in hemophilia A patients. The adaptive immune response plays a crucial role in the development and maintenance of inhibitors. In this review, we focus on our current understanding of FVIII interactions with cells of the adaptive immune system and the phenotype of the resultant response. Additionally, we examine both current and novel FVIII tolerance induction methods that function at the level of the adaptive immune response. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Factor VIII therapy for hemophilia A: current and future issues.

    Science.gov (United States)

    Aledort, Louis; Ljung, Rolf; Mann, Kenneth; Pipe, Steven

    2014-06-01

    Hemophilia A is a congenital, recessive, X-linked bleeding disorder that is managed with infusions of plasma-derived or recombinant factor (F) VIII. The primary considerations in FVIII replacement therapy today are the: 1) immunogenicity of FVIII concentrates, 2) role of longer-acting FVIII products, 3) prophylactic use of FVIII in children and adults with severe hemophilia A, and 4) affordability and availability of FVIII products. Improving patient outcomes by increasing the use of FVIII prophylaxis, preventing or eliminating FVIII inhibitors, and expanding access to FVIII concentrates in developing countries are the major challenges confronting clinicians who care for patients with hemophilia A.

  16. Factor VIII and transmissible spongiform encephalopathy: the case for safety.

    Science.gov (United States)

    Cervenakova, L; Brown, P; Hammond, D J; Lee, C A; Saenko, E L

    2002-03-01

    Haemophilia A is the most common inherited bleeding disorder, caused by a deficiency in coagulation factor VIII (FVIII). Current treatment of haemophilia A is based on repeated infusions of plasma-derived FVIII concentrate or of recombinant FVIII, which may be exposed to plasma-derived material of human or animal origin used in its tissue culture production process. We review epidemiological and experimental studies relevant to blood infectivity in the transmissible spongiform encephalopathies (TSEs, or 'prion' diseases), and evaluate the hypothetical risk of TSE transmission through treatment with plasma-derived or recombinant FVIII.

  17. PENERAPAN METODE PENEMUAN TERBIMBING DI KELAS VIII SMP

    Directory of Open Access Journals (Sweden)

    Toni Hidayat

    2017-08-01

    Full Text Available This study was a classroom action research which aims to investigate how the implementation of guided discovery learning can improve students’ activeness and attainment in the class VIII of Laboraturium UM Senior High School Malang city. The study subject was Class VIII that consists of 36 students, year 2016/2017. This study consisted of two cycles, and the data was collected from the result of the final test, observation, and interview. Based on the research of cycle I, the students’ activeness with mean scores of the meeting I, II, III was 78.88%, 79%, 86.6% respectively. The students’ activeness on cycle II, the mean scores of analyst meeting V and VI were 89.22% and 92.24% respectively. The result of Mathematics learning was increased, it is shown on the test mean of the cycle I that was achieved by 36 students with the percentage of successful learning 83 %. On the cycle test II, the average of 36 gained 82 (score with 7.2 increased from the score mean of the cycle I and with classical mastery learning cycle II 88.88%. Penelitian ini merupakan Penelitian Tindakan Kelas (PTK yang bertujuan untuk mengetahui bagaimana penerapan metode penemuan terbimbing yang dapat meningkatan keaktifan dan hasil belajar siswa kelas VIII SMP Laboratorium UM Kota Malang. Subjek penelitian ini ialah siswa kelas VIII yang berjumlah 36 siswa tahun pelajaran 2016/2017. Penelitian ini terdiri atas dua siklus dan data dikumpulkan dari hasil tes akhir tindakan, observasi, dan wawancara. Berdasarakan hasil penelitian pada siklus I, keaktifan siswa siswa dengan skor rata-rata pertemuan I, II, III adalah 78,88% 79,%, dan 86,6%. Aktivitas siswa pada siklus II, rata-rata skor pengamat pertemuan V dan VI berturut-turut 89,22 % dan 92,24%. Hasil belajar matematika siswa meningkat, hal ini terlihat bahwa rata-rata tes siklus I yang diperoleh 36 siswa sebesar 74,8 dengan presentase keberhasilan belajar 83,33%. Pada tes siklus II rata-rata nilai menjadi 82 dengan

  18. A rare combination: Combined factor V and factor VIII deficiency

    Directory of Open Access Journals (Sweden)

    Başak Ünver Koluman

    2014-06-01

    Full Text Available Combined factor V (FV and factor VIII (FVIII deficiency is a rare factor deficiency with mild-moderate hemorrhage. It is an autosomal recessive coagulation disorder . Prolonged prothrombin time and partial thromboplastic time is characteristic, platelet count remains in normal ranges. The main stay of treatment is to control the hemorrhage. Fresh frozen plasma, desmopressin, specific FVIII concentrates (plasma- derived or recombinant may be used. Being very rare in the general population, we present a case with a combined FV and FVIII deficiency. J Clin Exp Invest 2014; 5 (2: 323-325

  19. Evidence for the formation of sodium hassate(VIII)

    Energy Technology Data Exchange (ETDEWEB)

    Zweidorf, A. von [Inst. fuer Kernchemie, Johannes Gutenberg-Univ. Mainz, Mainz (Germany); Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany); Angert, R.; Bruechle, W.; Buerger, S.; Eberhardt, K.; Eichler, R.; Hummrich, H.; Jaeger, E.; Kling, H.O.; Kratz, J.V.; Kuczewski, B.; Langrock, G.; Mendel, M.; Rieth, U.; Schaedel, M.; Schausten, B.; Schimpf, E.; Thoerle, P.; Trautmann, N.; Tsukada, K.; Wiehl, N.; Wirth, G.

    2004-07-01

    Hassium, element 108, was produced in the fusion reaction between {sup 26}Mg and {sup 248}Cm. The hassium recoils were oxidized in-situ to a highly volatile oxide, presumably HsO{sub 4}, and were transported in a mixture of He and O{sub 2} to a deposition and detection system. The latter consisted of 16 silicon PIN-photodiodes facing a layer of NaOH, which served, in the presence of a certain partial pressure of water in the transport gas, as reactive surface for the deposition of the volatile tetroxides. Six correlated {alpha}-decay chains of Hs were detected in the first 5 detectors centred around detection position 3. In analogy to OsO{sub 4}, which forms Na{sub 2}[OsO{sub 4}(OH){sub 2}], an osmate(VIII), with aqueous NaOH, HsO{sub 4} presumably was deposited as Na{sub 2}[HsO{sub 4}(OH){sub 2}], a hassate(VIII). (orig.)

  20. Aristóteles y las series causales infinitas en Física VII y VIII

    Directory of Open Access Journals (Sweden)

    Alberto Ross

    2013-11-01

    Full Text Available The aim of this paper is to show that we have at least two different arguments that prove the First Motor's existence. Even though there are coincidences between Physics VII 1 and VIII 5, their arguments are not identical. Physics VII argue the impossibility of an infinite movement in a finite time and VIII 5 the necessity of a "principal" cause.

  1. Effectiveness of Mind Mapping in English Teaching among VIII Standard Students

    Science.gov (United States)

    Hallen, D.; Sangeetha, N.

    2015-01-01

    The aim of the study is to find out the effectiveness of mind mapping technique over conventional method in teaching English at high school level (VIII), in terms of Control and Experimental group. The sample of the study comprised, 60 VIII Standard students in Tiruchendur Taluk. Mind Maps and Achievement Test (Pretest & Posttest) were…

  2. 40 CFR Appendix Viii to Part 85 - Vehicle and Engine Parameters and Specifications

    Science.gov (United States)

    2010-07-01

    .... a. Control parameters and calibrations. b. EGR valve flow calibration. 3. Catalytic converter system.... a. Control parameters and calibrations. b. EGR valve flow calibration. 3. Catalytic converter system... Specifications VIII Appendix VIII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  3. 40 CFR Appendix Viii to Part 266 - Organic Compounds for Which Residues Must Be Analyzed

    Science.gov (United States)

    2010-07-01

    ... AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VIII Appendix VIII to Part 266... residues collected from areas downstream of the combustion chamber (e.g., ductwork, boiler tubes, heat...

  4. diagnóstico da infecção pelo HPV em lesões do colo do útero em mulheres HIV+: acuidade da histopatologia Histopathology accuracy for the diagnosis of HPV in cervical lesions of HIV-seropositive women

    Directory of Open Access Journals (Sweden)

    Néli Sueli Teixeira de Souza

    2001-07-01

    Full Text Available Objetivo: comparar a acurácia do estudo histopatológico e da reação em cadeia por polimerase (PCR no diagnóstico da infecção pelo papilomavírus humano (HPV em lesões do colo uterino de mulheres infectadas pelo vírus da imunodeficiência humana (HIV. Métodos: foram estudadas 52 mulheres soropositivas para o HIV com lesões cervicais clinicamente suspeitas de HPV nas quais se realizou raspado ectocervical para a PCR e biópsia dirigida pela colposcopia, para o estudo histopatológico. As amostras de três pacientes se mostraram sem qualidade para a PCR, reduzindo a população estudada para 49. Resultados: a prevalência de HPV foi de 53% pela histopatologia e de 85,7% pela PCR. Dentre as 42 pacientes com HPV detectado pela PCR, 26 foram confirmadas pela histopatologia (sensibilidade = 61,9%. Esta, por sua vez, não demonstrou nenhum resultado falso-positivo (especificidade = 100%, com predição positiva de 100%. Comparando-se os dois resultados, encontrou-se para a histopatologia: valor preditivo positivo = 100% e valor preditivo negativo = 30,4%. Das 26 pacientes com histopatologia positiva para HPV, 15 (57,6% apresentaram neoplasias intra-epiteliais cervicais (NIC. O risco relativo de uma paciente com HPV apresentar NIC foi de 13,3. Conclusão: a histopatologia mostrou 100% de acerto para o diagnóstico de HPV, o que significa dizer que, quando a biópsia for positiva o HPV certamente estará presente, confirmando a suspeita clínica. No entanto, a baixa sensibilidade retira da histopatologia o valor como exame de rastreamento nesse grupo de mulheres.Purpose: to compare histopathology and polymerase chain reaction (PCR for the diagnosis of human papillomavirus (HPV in cervical lesions of human immunodeficiency virus (HIV-seropositive women. Methods: fifty-two HIV-seropositive women with suspected HPV cervical lesions were studied. Cervical scrapes were collected for PCR and colposcopy-guided biopsy was made for the histopathologic

  5. Maternally transferred anti-factor VIII IgG reduce the anti-factor VIII humoral immune response in factor VIII-deficient mice.

    Science.gov (United States)

    Meslier, Yann; André, Sébastien; Teyssandier, Maud; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2010-12-01

    Replacement therapy with exogenous factor VIII (FVIII) to treat haemorrhages or used in prophylaxis induces inhibitory anti-FVIII immunoglobulin G (IgG) in some patients with haemophilia A. Therapeutic strategies to prevent the onset of the deleterious anti-FVIII immune response are still lacking. Maternal IgG is transferred to the offspring during fetal and neonatal life. While protecting the offspring from bacterial and viral infections, maternal IgG may alter the repertoires of T and B lymphocytes, and may impair vaccination in early infancy. Using haemophilic mice, we demonstrate that the transfer of maternal anti-FVIII IgG modulates the onset of anti-FVIII inhibitory IgG in early adulthood. The protective effect is reproduced upon reconstitution of naive mice with anti-FVIII IgG, suggesting that the reduced ability to mount an anti-FVIII immune response is the result of an interference between circulating anti-FVIII IgG and the administered FVIII rather than to a profound remodelling of lymphocyte repertoires occurring during the ontogeny of the immune system. © 2010 The Authors. Immunology © 2010 Blackwell Publishing Ltd.

  6. Comparação entre a citopatologia por biopsia com agulha fina e a histopatologia no diagnóstico das neoplasias cutâneas e subcutâneas de cães

    Directory of Open Access Journals (Sweden)

    Paulo H. Braz

    2016-03-01

    Full Text Available Resumo: Os neoplasmas cutâneos estão entre os mais diagnosticados em medicina veterinária, diante disso busca-se que o diagnóstico desses tumores seja rápido e eficaz. Em medicina veterinária o uso da citopatologia como método para diagnóstico tornou-se crescente. Diante disso, é necessário que estudos comprovem a eficiência da técnica para que a mesma possa ser usada de maneira isolada. Este trabalho teve como objetivo comparar o diagnóstico obtido pelas técnicas citopatológica e histopatológica de tumores cutâneos e subcutâneos de cães, determinar qual o tipo neoplásico mais facilmente diagnosticado pela citopatologia e a neoplasia mais prevalente nesses animais, atendidos em dois hospitais veterinários de Campo Grande/MS, no período de março de 2012 a dezembro de 2013. Foram coletadas amostras celulares de tumores de 91 cães, através de punção aspirativa por agulha fina e punch cirúrgico Os resultados citopatológicos demonstraram uma eficácia de 69,69%, em relação à histopatologia. Para a diferenciação entre tumores neoplásicos e não neoplásicos, a eficiência aumenta, com resultados iguais em 91,91%. Para diferenciar tumores benignos de malignos, foi possível chegar a uma concordância na ordem de 68,13%. Os tumores mais prevalentes foram o mastocitoma, seguido do lipoma, fibrossarcoma e tumor de célula basal.

  7. Acquired factor VIII inhibitor syndrome: A rare cause of hematuria

    Directory of Open Access Journals (Sweden)

    Muthuvel Seral Kannan

    2015-01-01

    Full Text Available A 50-year-old woman presented with gross hematuria for 1 month. Clinical examinations, laboratory investigations, ultrasound and contrast computed tomography were normal, except anemia. Cystoscopy revealed bloody efflux from the right side. Retrograde pyelogram showed filling defect in the renal pelvis and biopsy was inconclusive. Renal angiogram was normal. She developed ecchymosis on the right thigh and arm with elevated activated partial thromboplastin time. The partial thromboplastin time correction study and Bethesda study confirmed the presence of acquired factor VIII inhibitor (acquired hemophilia. With flexible ureterorenoscopy, the mass in the renal pelvis was removed and its histopathology revealed clotted blood. The patient was subsequently managed with steroids and Factor eight inhibitor bypass activity.

  8. A bispecific antibody mimicking factor VIII in hemophilia A therapy.

    Science.gov (United States)

    Nogami, Keiji

    2016-06-01

    Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.

  9. Agnostic Stacking of Intergalactic Doublet Absorption: Measuring the Ne VIII Population

    Science.gov (United States)

    Frank, Stephan; Pieri, Matthew M.; Mathur, Smita; Danforth, Charles W.; Michael Shull, J.

    2018-02-01

    We present a blind search for doublet intergalactic metal absorption with a method dubbed `agnostic stacking'. Using a forward-modelling framework we combine this with direct detections in the literature to measure the overall metal population. We apply this novel approach to the search for Ne VIII absorption in a set of 26 high-quality COS spectra. We probe to an unprecedented low limit of log N>12.3 at 0.47≤z ≤1.34 over a pathlength Δz = 7.36. This method selects apparent absorption without requiring knowledge of its source. Stacking this mixed population dilutes doublet features in composite spectra in a deterministic manner, allowing us to measure the proportion corresponding to Ne VIII absorption. We stack potential Ne VIII absorption in two regimes: absorption too weak to be significant in direct line studies (12.3 13.7). We do not detect Ne VIII absorption in either regime. Combining our measurements with direct detections, we find that the Ne VIII population is reproduced with a power law column density distribution function with slope β = -1.86+0.18-0.26 and normalisation log f_{13.7} = -13.99+0.20-0.23, leading to an incidence rate of strong Ne VIII absorbers dn/dz =1.38+0.97-0.82. We infer a cosmic mass density for Ne VIII gas with 12.3 constituting 4% of the total baryonic mass.

  10. Methodology for energy diagnosis in distribution steam lines; Metodologia para diagnostico de energia en lineas de distribucion de vapor

    Energy Technology Data Exchange (ETDEWEB)

    Almanza, M.; Ambriz, J. J.; Romero P, H. [Universidad Autonoma Metropolitana Iztapalapa, Mexico, D. F. (Mexico)

    1992-12-31

    This paper shows a methodology that results of great advantage in the development of the energy analysis of an industrial facility that utilizes steam as a mean of energy transport and where the steam operated equipment is physically located in a remote place, away from the generation site. Mention is made here of the equipment characteristics that can be used for such purpose, the most important parameters to identify in a rapid and efficient way the faults presented in the steam distribution system in the industrial plants and the formats that contribute to keep the corresponding records for efficiently maintain in operation the steam pipeline net in conjunction with the involved accessories. [Espanol] En el presenta trabajo se muestra una metodologia que resulta de gran utilidad en el desarrollo del analisis energetico de una planta industrial, en la cual se emplee el vapor como medio de transporte de la energia y en donde el equipo que utiliza el vapor se encuentre fisicamente en un lugar apartado de la zona de generacion. Aqui se mencionan las caracteristicas del equipo que se puede utilizar para dicho diagnostico, los parametros de mayor importancia para identificar en forma rapida y eficiente las fallas que se presentan en el sistema de distribucion de vapor en las plantas industriales y los formatos que contribuyen a llevar los registros correspondientes para mantener operando eficientemente la red de vapor, en conjunto con los accesorios que en ella se involucran.

  11. Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

    DEFF Research Database (Denmark)

    Hansen, N. U. B.; Willumsen, N.; Bülow Sand, Jannie Marie

    2016-01-01

    Objectives Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...... performance, and in relevant disease cohorts. The developed ELISA was applied for the assessment of type VIII collagen in serum from patients diagnosed with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and various cancers. Results The C8-C ELISA was technically stable...

  12. Evaluación de una prueba rápida para el diagnostico de Malaria en áreas endémicas del Perú

    Directory of Open Access Journals (Sweden)

    Nancy Arrospide V

    2006-04-01

    Full Text Available Objetivos: Evaluar la sensibilidad, especificidad y valores predictivos de la prueba rapida basada en la deteccion de la pLDH (OptiMALR kit individual para el diagnostico de malaria en areas endemicas del Peru. Materiales y metodos: Estudio transversal realizado con pacientes febriles atendidos en centros de salud de la selva norte del Peru (San Martin y Loreto, de abril a diciembre de 2001. A cada paciente se le realizo la gota gruesa, la prueba OptiMALR y densidad parasitaria en forma ciega, por personal local capacitado y luego en el Laboratorio Nacional de Referencia de Malaria. Se calculo la sensibilidad (S, especificidad (E, valor predictivo positivo (VPP y valor predictivo negativo(VPN de la prueba OptiMALR en relacion a la gota gruesa para el diagnostico de malaria global y segun especie (P.falciparum y P.vivax. Resultados: Se incluyeron 346 muestras, 170 positivas. La prueba OptiMALR tuvo niveles de S=95,7%, E=97,1%, VPP=97,7%, VPN=95,3% independientemente de la especie. Para P.falciparum tuvo S=90,5%, E=97,3%, VPP=67,9 y VPN=99.4%; en tanto que para P.vivax S=92,0%, E=99,0%, VPP=98,7% y VPN=93,5%. Las sensibilidades estratificadas por parasitemia fueron 97,0% (5000 parasitos/¥ìL, 99% (100-5000 p/¥ìL y 50% (<100p/¥ìL. Conclusiones: La prueba rapida OptiMALR es un metodo con buena sensibilidad y especificidad para el diagnostico de malaria y puede ser usado en lugares donde no se dispone de laboratorios o microscopistas.

  13. Diagnosis technique for the detection of mechanical faults in power breakers; Tecnica de diagnostico para la deteccion de fallas mecanicas en interruptores de potencia

    Energy Technology Data Exchange (ETDEWEB)

    Linan, Roberto; Perez, Marciano; Estrada, J. Manuel [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1996-12-31

    This article reports a non-invasive diagnosis technique for the detection of mechanical faults in power breakers, supporting it with the recording and analysis of vibration signals of the equipment under test. Also, an assessment of four breakers using this technique is presented. [Espanol] En el presente articulo se reporta una tecnica de diagnostico no invasiva para detectar fallas mecanicas en interruptores de potencia, apoyandose en el registro y analisis de senales de vibracion del equipo bajo prueba. Asimismo, se presenta la evaluacion de cuatro interruptores usando esta tecnica.

  14. Monitoring and diagnosis of condensation systems in thermoelectric power stations: behavior indicators; Monitoreo y diagnostico de sistemas de condensacion en centrales termoelectricas: indicadores de comportamiento

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Martinez, Hugo; Sanchez Sanchez, Ramon [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2009-07-01

    In this article are described the basic characteristics, capacities and benefits of a computer system for the monitoring and operation diagnosis of the main equipment of a condensation system of thermoelectric power plants. The system monitors the process variables in real time and, with base in these variables, it can realize a diagnosis of the cooling tower, the condenser, the circulation water and the circulating water pumps, deducting the possible problems (deficiency causes) and raising alternatives to improve the system performance or to solve the problem. It is important to mention that with base in the raised alternatives, the user can take decisions to diminish or eliminate the problem. The essential content of the article focuses in the description of the basic procedures for the calculation of the performance and diagnosis indicators of the condensation system of the equipment. The equipment evaluation is carried out by means of the comparison between the indicators values and the expected ones, whereas the diagnosis is realized by means of an expert system. [Spanish] En este articulo se describen las caracteristicas principales, capacidades y beneficios de un sistema computacional para el monitoreo y diagnostico del funcionamiento de los equipos principales de un sistema de condensacion de plantas termoelectricas. El sistema monitorea las variables del proceso en tiempo real y, con base en dichas variables, puede realizar un diagnostico de la torre de enfriamiento, el condensador y las bombas de agua de circulacion, deduciendo los posibles problemas (causas de las deficiencias) y planteando alternativas para mejorar el desempeno del sistema o solucionar el problema. Es importante mencionar que con base en las alternativas planteadas, el usuario puede tomar decisiones para reducir o eliminar el problema. El contenido esencial del articulo se enfoca en la descripcion de los procedimientos basicos para el calculo de los indicadores de desempeno y

  15. DIAGNOSTICO DE DISPLASIA DE CADERA POR EL METODO DE ANGULO DE NORBERG, ANGULO DE INCLINACION Y CARACTERISTICAS FENOTIPICAS DE CADERA EN PERROS MESTIZOS DE LA CIUDAD DE PUNO

    OpenAIRE

    DE LA CRUZ PEREZ, ABIGAIL; Universidad Nacional del Altiplano; ESPEZUA FLORES, OSCAR HENRY; Universidad Nacional del Altiplano

    2013-01-01

    Se determino la frecuencia de presentación de displasia de cadera en caninos de la ciudad de Puno en 64 ejemplares de ambos sexos entre uno y tres años de edad y un peso promedio de 18.5 kg. Se siguieron los lineamientos de la Federación Cinologica Internacional, usando el examen radiológico y empleando el método de diagnostico cuantitativo del Angulo de Norberg, ángulo de inclinación y características fenotípicas de la cadera según la Orthopedic Foundation for Animals. Los resultados muestra...

  16. Influencia de la sedación sobre el diagnostico y complicaciones en los pacientes sometidos a fibrobroncoscopia en el Instituto Nacional de Cancerología

    OpenAIRE

    Camargo Mendoza, Juan Pablo

    2013-01-01

    Objetivo: identificar si la sedación influye en el diagnostico y en las complicaciones en los pacientes sometidos a fibrobroncoscopia. Diseño: estudio de corte transversal de pacientes sometidos a fibrobroncoscopia del Instituto Nacional de Cancerología de marzo del 2011 a junio 2012. Materiales y métodos: las características de base se compararon según utilización o no de sedación. Descripciones univariada y bivariada dependiendo del tipo y distribución de las variables. Para estudiar la aso...

  17. AnGel System for the diagnosis of generators in operation; Sistema AnGeL para el diagnostico de generadores en operacion

    Energy Technology Data Exchange (ETDEWEB)

    De la Torre V, H. Octavio; Ramirez N, J. Tomas; Pascacio de los S, Alberth; Reyes M, Oscar A; Carrillo C, Jaime; Iturbe F, Marlene [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Ponce de Leon V, Eugenio [Comision Federal de Electricidad (Mexico)

    2005-07-01

    The continuous monitoring of the electrical variables of a generator allows the knowing of the operating status of the main components of the equipment, which is helpful at the time of emitting a diagnosis of the same one. System of diagnosis for generators of operation, denominated AnGel System (acronym of Analysis of Generators in Line). The system was developed by the Management of Electrical equipment of the Instituto de Investigaciones Electricas (IIE) and implemented in the six units of generation of the Manzanillo Thermoelectric Unit. The present article includes a description of the main components and functions. The world-wide tendency in monitoring systems of the fault statistics, were key elements in defining the variable to be monitored: Partial discharges (PD), Shaft current (SC), Neutral current (NC), Tangential Magnetic (TM) flux, Voltages and currents of line (as reference to the operation point). The main processes of deterioration that are intended to be observed with each one of these variables are described with greater thoroughness in the article Sistema AnGel: Aspectos teorico-practicos para el diagnostico de generadores en operacion (AnGel System: Theoretical-practical aspects for the diagnosis of generators in operation), contained in the section of Research Activities in this same issue of the IIE bulletin. [Spanish] La monitorizacion continua de las variables electricas de un generador permite conocer el estado operativo de los principales componentes del equipo, lo que es de ayuda a la hora de emitir un diagnostico del mismo. Sistema de diagnostico para generadores de operacion, denominado Sistema AnGeL (acronimo de Analisis de Generadores en Linea). El sistema fue desarrollado por la Gerencia de Equipos Electricos del IIE e implementado en las seis unidades de generacion del Complejo Termoelectrico Manzanillo. El presente articulo incluye una descripcion de los principales componentes y funciones. La tendencia mundial en sistemas de

  18. Historia y globalización. VIII Conversaciones Internacionales de Historia [Reseña

    OpenAIRE

    Olábarri-Gortázar, I. (Ignacio)

    2013-01-01

    Reseña de Francisco Javier Caspistegui (ed.), Historia y globalización. VIII Conversaciones Internacionales de Historia. Universidad de Navarra. Pamplona, 7-9 de octubre de 2010, Pamplona, EUNSA, 2012. 318 pp. ISBN: 9788431328801.

  19. THE APPEARANCE OF THE INHIBITORS TO FACTOR VIII IN AN ELDER PATIENT WITH MILD HAEMOPHILIA A

    Directory of Open Access Journals (Sweden)

    Barbara Faganel

    2004-12-01

    Full Text Available Background. The inhibitors to F VIII are unusual in case of a mild haemophilia because the replacement therapy is seldom necessary. In case of severe trauma, when prolonged replacement therapy of F VIII is needed, the appearance of the inhibitors is more frequent. The mild form of the disease becomes a severe one and the haemorrhages are frequent.Patient and methods. In case of our patient with mild form of haemophilia, the inhibitors to F VIII developed after prolonged replacement therapy for treatement of subdural haemorrhage. In the article we describe recurrent haemorrhages and treatement of them with FEIBA and rF VIIa.Conclusions. Due to poor compliance of an elder patient we didn’t decide to treat the inhibitors for F VIII actively.

  20. A Cranial Trauma was the Cause of Death of Charles VIII of France (1470-1498).

    Science.gov (United States)

    Markatos, Konstantinos; Karamanou, Marianna; Arkoudi, Konstantina; Konstantinidi, Apostolia; Androutsos, Georgios

    2017-09-01

    This article summarizes the reign, life and death, of Charles VIII of France. Also we intend to investigate current views on his cause of death, contradictions and opinions of his biographers. Poisoning, disease, and injury are the possible causes of his death but, according to the literature, cranial trauma was the most probable cause of death of the King Charles VIII of France. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. PENGARUH KONSELING KELOMPOK TERHADAP KONFORMITAS SISWI KELAS VIII SMPIT BINA AMAL SEMARANG

    OpenAIRE

    sudyastuti sudyastuti; heru mugiarso

    2017-01-01

    This research was conducted based on the phenomenon that happens to grade VIII SMPIT Bina Amal Semarang which has the social conformity low. The purpose of this research is to proof  the influence of counseling service groups towards the conformity. The type of this research is experimental research. The research was conducted with seven times the grant of preferential treatment on grade VIII SMPIT Bina Amal Semarang, research subject with 8 students. The data collection method used is the ps...

  2. Type VIII collagen has a restricted distribution in specialized extracellular matrices

    OpenAIRE

    1988-01-01

    A pepsin-resistant triple helical domain (chain 50,000 Mr) of type VIII collagen was isolated from bovine corneal Descemet's membrane and used as an immunogen for the production of mAbs. An antibody was selected for biochemical and tissue immunofluorescence studies which reacted both with Descemet's membrane and with type VIII collagen 50,000-Mr polypeptides by competition ELISA and immunoblotting. This antibody exhibited no crossreactivity with collagen types I-VI by competition ELISA. The m...

  3. Implications of an updated ultraviolet background for the ionization mechanisms of intervening Ne VIII absorbers

    Science.gov (United States)

    Hussain, Tanvir; Khaire, Vikram; Srianand, Raghunathan; Muzahid, Sowgat; Pathak, Amit

    2017-04-01

    Ne VIII absorbers seen in QSO spectra are useful tracers of warm ionized gas, when collisional ionization is the dominant ionization process. While photoionization by the ultraviolet background (UVB) is a viable option, it tends to predict large line-of-sight thickness for the absorbing gas. Here, we study the implications of the recently updated UVB at low z to understand the ionization mechanisms of intervening Ne VIII absorbers. With the updated UVB, one typically needs higher density and metallicity to reproduce the observed ionic column densities under photoionization. Both reduce the inferred line-of-sight thicknesses of the absorbers. We find a critical density of ≥5 × 10-5 cm-3 above which the observed N({Ne VIII})/N({O VI}) can be reproduced by pure collisional processes. If the gas is of near solar metallicity (as measured for the low ions) then the cooling time-scales will be small (inferred low ion metallicity is near solar or supersolar. If we assume the Ne VIII phase to have similar metallicities then photoionization can reproduce the observed N({Ne VIII})/N({O VI}) without the line-of-sight thickness being unreasonably large and avoids cooling issues related to the collisional ionization at these metallicities. However, the indication of broad Lyα absorption in a couple of systems, if true, suggests that the Ne VIII phase is distinct from the low ion phase having much lower metallicity.

  4. Serology and histopathology of Toxoplasma gondii and Neospora caninum in dogs with neurologic disorders/ Sorologia e histopatologia de Toxoplasma gondii e Neospora caninum em cães portadores de distúrbios neurológicos

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    Thiago Neves Batista

    2002-05-01

    Full Text Available The evolvement of Toxoplasma gondii and Neospora caninum on etiology of clinical-neurological signs in dogs was investigated in this work. Ninety-eight urban dogs with neurologic disturbances were divided into two groups: Group I consisted of 67 dogs examined by the Animal Neurologic Service of Universidade Estadual de Londrina, between 1987 and 1990. Group II consisted of 31 dogs examined on the same University between 2000 and 2001. Dogs were serological evaluated for evidence of T. gondii or N. caninum. The serological results for T. gondii were 82,5% and 35.4% on groups I and II, respectively. Histologic lesions compatible with distemper on the two groups were observed. T. gondii cysts were observed in two dogs by histopathology and immunohistochemistry. Neosporosis was not observed in these dogs, possibly because their urban origin.Neste trabalho estudou-se a participação do Toxoplasma gondii e Neospora caninum na etiologia de sinais neurológicos em cães. Foram utilizados 98 cães com distúrbios neurológicos provenientes da área urbana divididos em dois grupos: Grupo I constituído de 67 animais atendidos no período de 1987 a 1990 pelo Serviço de Neurologia Animal da Universidade Estadual de Londrina, onde se utilizaram os tecidos emblocados em parafina e Grupo II com 31 animais atendidos no período de 2000 a 2001 nesta mesma instituição. Os animais foram avaliados sorologicamente para pesquisa de anticorpos contra T. gondii e N. caninum. Os resultados da sorologia para T. gondii obtidos no grupo I e II foram 82,5% e 35.4%, respectivamente. Foram observadas lesões histológicas compatíveis com cinomose nos dois grupos. Cistos de T. gondii foram diagnosticados em dois cães através da histopatologia e imuno-histoquímica. A neosporose não foi diagnosticada em nenhum animal, provavelmente devido à procedência urbana dos animais estudados.

  5. Functional mapping of factor VIII C2 domain.

    Science.gov (United States)

    Pellequer, Jean-Luc; Chen, Shu-wen W; Saboulard, Didier; Delcourt, Marc; Négrier, Claude; Plantier, Jean-Luc

    2011-07-01

    The factor VIII (FVIII) is a cofactor of the coagulation cascade. The FVIII C2 domain is a critical domain that participates in the interactions with the von Willebrand factor and the phospholipidic surfaces. To assess the importance of each residue of this domain in the maintenance of the structure and the function of FVIII, a number (n=139) of mutants were generated by substituting the original residues, from Ser2173 to Gly2325, by an alanine. Mutants were built within a complete B domain-deleted FVIII and expressed in COS-1 cells. Mutant antigen levels and procoagulant activities were measured. Two in silico analyses, a sliding average procedure and an analysis of the mutation energy cost were conducted in parallel on the FVIII structure. Both results were in agreement with the functional data, and illustrated the benefit of using such strategies prior to targeting specific residues in the aim of generating active recombinant molecules. The functional assays identify the residues that are important to maintaining the structure of the C2 domain, mainly those forming β-sheet, and those that can afford substitution, establishing a detailed functional relation with the available crystallographic data. This study provided a comprehensive functional mapping of the FVIII C2 domain and discussed the implication of specific residues in respect to the maintenance in the activity and structure stability, the efficiency in secretion, the binding to phospholipids and the formation of epitope.

  6. piggyBac-mediated phenotypic correction of factor VIII deficiency

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    Janice M Staber

    2014-01-01

    Full Text Available Hemophilia A, caused by a deficiency in factor VIII (FVIII, is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integrated transgene offers the possibility of long term expression. We engineered the DNA transposon-based vector, piggyBac (PB, to carry a codon-optimized B-domain deleted human FVIII cDNA. Evaluation of gene transfer efficiency in FVIII null mice demonstrated that PB containing the FVIII cDNA, delivered via hydrodynamic injection to immunocompetent hemophilia mice, conferred persistent gene expression, attaining mean FVIII activity of approximately 60% with 3/19 developing inhibitors. In addition to efficacious expression, a goal of gene transfer-based therapies is to develop vectors with low toxicity. To assess endoplasmic reticulum stress in hepatocytes stably expressing the transgene, we evaluated levels of ER stress markers via qPCR and found no evidence of cell stress. To evaluate phenotypic correction, a tail clip assay performed at the end of the study revealed reduced blood loss. These data demonstrate that PB can be used to achieve sustained FVIII expression and long-term therapeutic benefit in a mouse model.

  7. Factor VIII and fibrinogen recovery in plasma after Theraflex methylene blue-treatment: effect of plasma source and treatment time.

    Science.gov (United States)

    Rapaille, André; Reichenberg, Stefan; Najdovski, Tome; Cellier, Nicolas; de Valensart, Nicolas; Deneys, Véronique

    2014-04-01

    The quality of fresh-frozen plasma is affected by different factors. Factor VIII is sensitive to blood component storage processes and storage as well as pathogen-reduction technologies. The level of fibrinogen in plasma is not affected by the collection processes but it is affected by preparation and pathogen-reduction technologies. The quality of plasma from whole blood and apheresis donations harvested at different times and treated with a pathogen-reduction technique, methylene blue/light, was investigated, considering, in particular, fibrinogen and factor VIII levels and recovery. The mean factor VIII level after methylene blue treatment exceeded 0.5 IU/mL in all series. Factor VIII recovery varied between 78% and 89% in different series. The recovery of factor VIII was dependent on plasma source as opposed to treatment time. The interaction between the two factors was statistically significant. Mean levels of fibrinogen after methylene blue/light treatment exceeded 200 mg/dL in all arms. The level of fibrinogen after treatment correlated strongly with the level before treatment. There was a negative correlation between fibrinogen level before treatment and recovery. Pearson's correlation coefficient between factor VIII recovery and fibrinogen recovery was 0.58. These results show a difference in recovery of factor VIII and fibrinogen correlated with plasma source. The recovery of both factor VIII and fibrinogen was higher in whole blood plasma than in apheresis plasma. Factor VIII and fibrinogen recovery did not appear to be correlated.

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

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    Bhavya S Doshi

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

  9. Recombinant factor VIII in the management of hemophilia A: current use and future promise

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    Jerry S Powell

    2009-05-01

    Full Text Available Jerry S PowellDivision of Hematology and Oncology, University of California Davis Cancer Center, Sacramento, CA, USAAbstract: Hemophilia A is a rare inherited bleeding disorder due to mutation of the gene that encodes the coagulation protein factor VIII. Historically, prior to the availability of treatment with factor VIII preparations, most boys died from uncontrolled bleeding, either spontaneous bleeding or after injury, before reaching 20 years of age. One of the most impressive triumphs of modern medicine is that with current recombinant factor VIII replacement therapy, a boy born in the 21st century with severe hemophilia A can anticipate a normal life expectancy with essentially no permanent complications from bleeding. For severe hemophilia A, current optimal treatment should have two goals: first, to provide sufficient factor VIII to prevent spontaneous bleeding, and second, to provide sufficient factor VIII to have normal coagulation function after any trauma. However, the replacement therapy requires tremendous resources for effective use, and remains extraordinarily expensive. Thus there are opportunities for further advances in therapy for hemophilia A. Two major concerns continue to trouble current optimal treatment approaches: some patients will develop neutralizing antibodies during the first 50 infusions of therapeutic factor VIII, and second, to administer therapeutic factor VIII every other day in young boys often requires placement of a central venous access device, and such use carries the life-threatening risks of infection and thrombosis. Because of the effectiveness of current therapy, any new developments in treatment will require significant concerns for safety, both immediate and in the long term. A number of research groups seek to prolong the biological efficacy of infused recombinant factor VIII. Currently, one such promising development is in the advanced stages of clinical trial. The goals will be to improve

  10. The F309S mutation increases factor VIII secretion in human cell line

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    Daianne Maciely Carvalho Fantacini

    2016-06-01

    Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

  11. Desenvolvimento de inibidores do fator VIII na hemofilia A Development of factor VIII inhibitors in hemophilia A

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    Daniel G. Chaves

    2009-01-01

    Full Text Available A hemofilia A é uma coagulopatia genética com herança recessiva ligada ao cromossomo X que afeta 1-2 a cada 10 mil indivíduos do sexo masculino nascidos vivos. Estes indivíduos têm baixas concentrações ou ausência do fator VIII (FVIII da coagulação no plasma e apresentam quadros hemorrágicos leves, moderados e graves, dependendo da atividade de FVIII circulante. Estes pacientes necessitam de constante reposição proteica e aproximadamente 30% deles desenvolvem aloanticorpos contra a proteína exógena. A síntese dos anticorpos anti-FVIII é iniciada quando o FVIII exógeno é endocitado por células apresentadoras de antígeno, degradado e apresentado às células T CD4+ na forma de peptídeos ligados a moléculas do complexo maior de histocompatibilidade (MHC de classe II. Alguns fatores de risco (paciente/tratamento podem ser relacionados ao desenvolvimento desta resposta imune. Neste contexto, as mutações no gene do FVIII e polimorfismos em genes envolvidos na resposta imune são candidatos moleculares como determinantes imunogenéticos na predisposição para o desenvolvimento de inibidores. Por não ser completamente entendido e controlado, o desenvolvimento desta resposta imune contra o FVIII constitui o maior problema decorrente do tratamento de indivíduos portadores de hemofilia A e faz-se necessária busca de opções que visem minimizar suas ações deletérias. Algumas alternativas de tratamento têm se mostrado eficazes no tratamento (anti-CD20, plasmaférese, concentrado de complexo protrombínico (PCCs, concentrado de complexo protrombínico ativado (APCCs, fator VII humano ativado, mas a retirada ou neutralização específica dos inibidores de FVIII ainda não foram alcançadas.Hemophilia A, which affects 1-2:10,000 live-born male neonates, is a genetic coagulopathy with recessive inheritance linked to the X chromosome. These individuals have low concentrations or no coagulation factor VIII (FVIII in the plasma

  12. Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.

    Science.gov (United States)

    Johnston, J M; Denning, G; Doering, C B; Spencer, H T

    2013-06-01

    We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

  13. Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor.

    Science.gov (United States)

    Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan

    2016-10-01

    Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.

  14. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit.

    Science.gov (United States)

    Gerstenberger, Brian S; Trzupek, John D; Tallant, Cynthia; Fedorov, Oleg; Filippakopoulos, Panagis; Brennan, Paul E; Fedele, Vita; Martin, Sarah; Picaud, Sarah; Rogers, Catherine; Parikh, Mihir; Taylor, Alexandria; Samas, Brian; O'Mahony, Alison; Berg, Ellen; Pallares, Gabriel; Torrey, Adam D; Treiber, Daniel K; Samardjiev, Ivan J; Nasipak, Brian T; Padilla-Benavides, Teresita; Wu, Qiong; Imbalzano, Anthony N; Nickerson, Jeffrey A; Bunnage, Mark E; Müller, Susanne; Knapp, Stefan; Owen, Dafydd R

    2016-05-26

    The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays.

  15. Histopathology of Anticarsia gemmatalis Hübner (Lepidoptera; Noctuidae treated with Nucleopolyhedrovirus and Bacillus thuringiensis serovar kurstaki Histopatologia de Anticarsia gemmatalis Hübner (Lepidoptera; Noctuidae tratadas com Virus de Poliedrose Nuclear e Bacillus thuringiensis sorovar kurstaki

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    Neiva Knaak

    2005-06-01

    . gemmatalis, após a interação dos entomopatógenos Btk e VPNAg, representados nas formulações Dipel e Baculovirus anticarsia, respectivamente. As avaliações foram realizadas com lagartas de 2º ínstar, onde a mortalidade foi avaliada diariamente, e a histopatologia foi realizada com lagartas coletadas nos períodos de 1, 3, 6, 12 e 24 horas após a aplicação dos tratamentos. Os resultados dos ensaios in vivo, revelam que o tratamento referente à associação VPNAg/Btk (98.68% de mortalidade foi mais eficiente que VPNAg (81.28% de mortalidade isoladamente, porém o Btk isoladamente causou 100% de mortalidade. Os tratamentos mostraram diferenças significativas (P <0,05 entre AgNPV e Btk,AgNPV e AgNPV/Btk. As análises de patogenicidade do VPNAg e Btk em lagartas de A. gemmatalis sugerem que os produtos Dipel e Baculovirus anticarsia foram mais eficientes, quando utilizados simultaneamente, pois a ação do VPNAg foi intensificada quando utilizada em associação com Btk, provocando alterações no intestino médio das lagartas a partir de 6 horas após os tratamentos. Quando os entomopatógenos foram utilizados isoladamente, as alterações das células intestinais foram observadas apenas 12 horas após a aplicação dos tratamentos.

  16. Histopatologia da infecção por Yersinia pestis em roedores de focos de peste do Nordeste brasileiro Histopathology of Yersinia pestis infection in rodents from plague foci of Brazilian Northeast

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    Eridan M. Coutinho

    1982-06-01

    Full Text Available O presente trabalho mostra a histopatologia da infecção pela Yersinia pestis, entre as diferentes espécies de roedores silvestres e comensais (cricetídeos, equimídeos, murídeos e cavídeos que ocorrem na zona endêmica de peste do Nordeste do Brasil. Estes roedores foram encontrados naturalmente infectados nos campos ou inoculados experimentalmente no laboratório (vias percutânea, subcutânea ou picada de pulgas com cepas locais e/ou estrangeiras de Yersiniapestis. Quase todos os animais, exceto alguns dos cavídeos, desenvolveram a forma bubosepticêmica da peste. Entre as lesões encontradas, a necrose coagulativa multifocal do fígado, a pneumonite intersticial aguda difusa e a atrofia linfoide do baço, podem, por sua constância, ser consideradas como os principais indicadores histológicos da infecção pestosa, embora estas lesões não sejam exclusivas da peste. A diversidade e a intensidade das lesões entre os Zygodontomys lasiurus pixuna, podem explicar a mortalidade elevada desta espécie e a disseminação da peste nos focos naturais do Nordeste brasileiro. Cricetídeos e murídeos mostraram alterações histopatológicas qualitativamente semelhantes. A resistência dos cavídeos à infecção pestosa foi evidenciada pela sobrevida desses roedores à fase aguda da infecção e pelo desenvolvimento de uma reação histiocitária interna, delimitando as áreas abscedadas. è possível que estas lesões crônicas abriguem bacilos virulentos, que permitirão a reinfecção periódica das pulgas e conseqüente reativação do processo epizoótico.In this paper, the histopathological aspects of plague infection in different species of wild and domestic rodents (cricetidae, echymidae, muridae and cavidae are described. All of them had been trapped in endemic plague areas and harboured natural infection, while others were laboratory infected by different routes (percutaneous, subcutaneous rout, fleas bite. Several national and

  17. Oral tumors in dogs: clinical aspects, exfoliative cytology and histopathology Neoplasias orais em cães: avaliação dos aspectos clínicos, histopatologia e citologia esfoliativa

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    Cláudia Ronca Felizzola

    1999-09-01

    Full Text Available In order to establish the diagnosis and prognosis of tumors of the oral cavity, a comparative study was carried out in 130 dogs considering age, sex, breed, clinical aspects, exfoliative cytology as well as histopathology. Exfoliative cytology revealed: 100% negative for benign non-odontogenic tumors, 97.91% negative benign odontogenic tumors and 77.92% positive for malignant tumors. Histopathology showed: 59.23% malignant tumors (33.08% malignant melanoma, 9.23% squamous cell carcinoma, 5.38% osteosarcoma, 2.31% fibrosarcoma, 2.31% angiosarcoma, 1.54% malignant mesenchymal tumors, 1.54% malignant fibrohistiocytoma, 1.54% lymphoma, 0.77% leyomyosarcoma, 0.77%% epithelioid sarcoma and 0.77% angiofibrosarcoma; 36.92% benign odontogenic tumors (25.38% peripheral odontogenic fibroma, 10.0% ossifyng fibroma and 1.54% odontoma in addition to 3.85% benign non-odontogenic tumors (1.54% fibroma, 0.77% plasmocytoma, 0.77% pilomatrixoma and 0.77% giant tumor cells. These results permit us to conclude that exfoliative cytology was an efficient, safe, quick and noninvasive method and could be used for early evaluation of oral cancer.Objetivou-se o estudo comparativo em tumores de cavidade bucal de animais de espécie canina de acordo com sexo, faixa etária, raça, aspectos clínicos, citologia esfoliativa e histopatologia, para estabelecer diagnóstico dessas neoplasias, tendo sido utilizados 130 cães, encaminhados ao Hospital Veterinário (HOVET da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo. Os resultados obtidos na citologia esfoliativa foram: 100% de negativos para neoplasias benignas não odontogênicas; 97,91% de negativos para neoplasias benignas odontôgenicas e 77,92% de positivos para neoplasias malignas. Obtiveram-se os seguintes resultados no exame histopatológico: neoplasias malignas - 59,23% (melanoma 33,08%, carcinoma epidermóide 9,23%, osteossarcoma 5,38%, fibrossarcoma 2,31%, angiossarcoma 2

  18. Drevnerusskij pamflet na Mihaila VIII Paleologa v svete germenevtičeskogo analiza

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    Demincev Mihail

    2015-01-01

    Full Text Available In the article the perception of the image of Michael VIII Palaeologus by literate citizens of Tsardom of Russia is considered. The study is based on analysis of writings that date back to XVII century. The study focuses on identifying the symbols and latent ideas, that point to a semantic connection of the studied writings with The Old Testament, Apocalypse and some antique texts. In the end of the article the authjr makes a conclusion, that the perception of the image of Michael VIII Palaeologus in Tsardom of Russia was negative.

  19. Wavelengths and energy levels of Xe VII and Xe VIII obtained by collision-based spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, M.O. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Gonzalez, A.M. [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Madrid (Spain). Inst. de Investigacion Basica; Hallin, R. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Heijkenskjoeld, F. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Hutton, R. [Lund Univ. (Sweden). Dept. of Physics; Langereis, A. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Nystroem, B. [Lund Univ. (Sweden). Dept. of Physics; O`Sullivan, G. [University Coll., Dublin (Ireland). Dept. of Physics; Waennstroem, A. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics

    1995-01-01

    The Xe VII and Xe VIII spectra have been investigated by collision-based spectroscopy. The radiation emitted following electron capture by 10q keV Xe{sup q+} ions (q = 6-8) impinging on a He (Ar) gas target has, with some exceptions, been recorded in the 350-8000 (1200-2500) A wavelength region. The xenon ions were provided by the Uppsala University ECR ion source. Many of the observed, previously unreported spectral lines have been identified. In total, nine new energy levels of Xe VII and Xe VIII have been established, of which two are tentative. The analysis was supported by Hartree-Fock calculations. (orig.).

  20. Acquired factor VIII inhibitor (acquired hemophilia A) presenting as spontaneous blood-filled scrotum.

    Science.gov (United States)

    Verma, Rajanshu; Noack, Jill; Vemuri, Radhakrishna; Loehrke, Mark E

    2011-05-01

    Acquired hemophilia A, also known as acquired factor VIII deficiency, is an exceedingly rare bleeding diathesis that does not require any personal or family history of bleeding or clotting disorder. Because treatment is available, misdiagnosing or completely missing this diagnosis can be life threatening for patients. Clinicians should be aware that acquired forms of hemophilia do exist and are associated with high morbidity and mortality in elderly adults. We present a case of a 74-year-old man who was diagnosed with acquired factor VIII inhibitor during an admission for community-acquired pneumonia.

  1. Advances in the research line of diagnosing of faults in fossil fuel power plants; Avances en la linea de investigacion de diagnostico de fallas en centrales termoelectricas

    Energy Technology Data Exchange (ETDEWEB)

    Ruz H, Jose A [Universidad Autonoma del Carmen, Campeche (Mexico); Sanchez C, Edgar N [Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional, Mexico, D.F. (Mexico); Suarez Cerda, Dionisio A; Quintero R, Agustin [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2006-07-01

    This article deals with a research in progress searching to take care of the faults that occur with greatest frequency in the fossil fuel power plants of Mexico with the aid of tools of computational intelligence such as the neuronal networks and the fuzzy logic, for the online recognition of the dynamic behavior patterns of variable groups. What this research looks for is the development of individual systems, in relation to the computational intelligence techniques that continuously supervise the functioning of the unit and inform the operator of the eventual faults in the understanding that on time attention to the faults will result in a minimum cost. The advantages of these diagnosis mechanisms are established in comparison to alternative diagnosis methods, such as their associative memory useful to store fault patterns. [Spanish] Se trata de una investigacion en progreso que busca atender las fallas que ocurren con mayor frecuencia en las unidades termoelectricas de Mexico con la ayuda de herramientas de inteligencia computacional como las redes neuronales y la logica difusa, para el reconocimiento en linea de patrones de comportamiento dinamico de grupos de variables. Lo que esta investigacion busca es desarrollar sendos sistemas, en relacion a las tecnicas de inteligencia computacional, que supervisen continuamente el funcionamiento de la unidad e informen al operador de fallas eventuales, en el entendido que la oportuna atencion a fallas redituara en un costo minimo. Las ventajas de estos mecanismos de diagnostico se establecen en comparacion a metodos de diagnostico alternativos, como su memoria asociativa util para almacenar patrones de falla.

  2. 46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of division 1 of section VIII of the ASME... division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. (a) Pressure vessels shall be designed, constructed, and inspected in accordance with section VIII of the ASME Boiler and Pressure Vessel...

  3. Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations

    NARCIS (Netherlands)

    Loomans, J.I.; Velzen, A.S. van; Eckhardt, C.L.; Peters, M.; Makipernaa, A.; Holmstrom, M.; Brons, P.P.T.; Dors, N.; Haya, S.; Voorberg, J.; Bom, J.G. Van Der; Fijnvandraat, K.

    2017-01-01

    Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels.

  4. Desain Pembelajaran Materi Luas Permukaan Prisma Menggunakan Pendekatan PMRI bagi Siswa Kelas VIII

    Directory of Open Access Journals (Sweden)

    Djuwita Trisnawati

    2015-08-01

    Full Text Available Penelitian ini bertujuan menghasilkan lintasan belajar untuk membantu siswa dalam pembelajaran luas permukaan prisma menggunakan kemasan produk di kelas VIII SMP. Penelitian ini berdasarkan PMRI yang dikaitkan dengan pembelajaran Kurikulum 2006/KTSP. Metode yang digunakan dalam penelitian ini adalah design research type validation study yang bertujuan untuk membuktikan teori-teori pembelajaran. Penelitian ini dilaksanakan di SMP Negeri 24 Palembang dengan melibatkan siswa kelas VIII yang berjumlah 31 siswa. Aktivitas-aktivitas pembelajaran yang dilakukan siswa meliputi: 1 memahami bentuk dan sifat prisma, 2 menemukan dan memahami konsep luas permukaan prisma, dan 3 menyelesaikan permasalahan dalam kehidupan sehari-hari yang berhubungan dengan luas permukaan prisma. Hasil dari penelitian ini menunjukkan bahwa melalui serangkaian aktivitas yang telah dilakukan membantu siswa dalam pembelajaran luas permukaan prisma.This research aimed to produce learning trajectory in learning surface area of prism using product packaging in class VIII. This study was based PMRI associated with learning curriculum 2006 / KTSP. The method used was design research of type validation study that aimed to prove the theories of learning. The research was conducted on 31 students of class VIII SMPN 24 Palembang. Students learning activities that were conducted including: (1 comprehending the shape and the characteristic of prism, (2 finding and comprehending the concept surface area of prism, and (3 solving the problems in daily life related to the surface area of prism. The results of this study indicate that a series of activities can help students in learning surface area of prism.

  5. A natural anatoxin, Amm VIII, induces neutralizing antibodies against the potent scorpion alpha-toxins.

    Science.gov (United States)

    Martin-Eauclaire, M-F; Alami, M; Giamarchi, A; Missimilli, V; Rosso, J-P; Bougis, P E

    2006-03-15

    In this study, we have used Amm VIII, a natural anatoxin from the scorpion Androctonus mauretanicus mauretanicus, to elicit specific polyclonal antibodies in rabbit. Using liquid-phase radioimmunoassay, we have studied its selectivity and its neutralizing activity both in vitro and in vivo for the most lethal scorpion alpha-toxins described, in particular the alpha-toxin of reference AaH II. We have shown that the anti-Amm VIII serum prevents the association of 125I-AaH II with its receptor and is able to remove 125I-AaH II already bound to its site (the half-life of the complex 125I-AaH II-receptor site was 12 min in the absence of anti-Amm VIII serum but decreased to only 2 min in the presence of anti-Amm VIII serum). In vivo, the serum also has a protective effect in mice: 42 LD50 of AaH II by millilitre are neutralized, measured by subcutaneous injection.

  6. Analysis of mutations in the entire coding sequence of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Bidichadani, S.I.; Lanyon, W.G.; Connor, J.M. [Glascow Univ. (United Kingdom)] [and others

    1994-09-01

    Hemophilia A is a common X-linked recessive disorder of bleeding caused by deleterious mutations in the gene for clotting factor VIII. The large size of the factor VIII gene, the high frequency of de novo mutations and its tissue-specific expression complicate the detection of mutations. We have used a combination of RT-PCR of ectopic factor VIII transcripts and genomic DNA-PCRs to amplify the entire essential sequence of the factor VIII gene. This is followed by chemical mismatch cleavage analysis and direct sequencing in order to facilitate a comprehensive search for mutations. We describe the characterization of nine potentially pathogenic mutations, six of which are novel. In each case, a correlation of the genotype with the observed phenotype is presented. In order to evaluate the pathogenicity of the five missense mutations detected, we have analyzed them for evolutionary sequence conservation and for their involvement of sequence motifs catalogued in the PROSITE database of protein sites and patterns.

  7. In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A

    NARCIS (Netherlands)

    Vossebeld, P. J. M.; Tissing, M. H.; van den Berg, H. M.; Leebeek, F. W. G.; de Goede-Bolder, A.; Novakova, I. R. O.; Gerrits, W. B. J.; Peters, M.; Koopman, M. M. W.; Faber, A.; Hiemstra, H.; Grob, P.; Strengers, P. F. W.

    2003-01-01

    AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance

  8. Intercombination lines of AlVIII, AlIX, and AlX ions

    Science.gov (United States)

    Denne, B.; Hinnov, E.

    1984-06-01

    Several aluminum lines observed in the Princeton Large Torus tokamak discharges have been identified as intersystem transitions, establishing the energies of the Al VIII 2s2p35S, Al IX 2s2p24P, and Al X 2s2p3P terms. Some observations of isoelectronic transitions in scandium and titanium ions are also reported.

  9. Living in a physical world VIII. Gravity and life in water

    Indian Academy of Sciences (India)

    2006-07-31

    Jul 31, 2006 ... Home; Journals; Journal of Biosciences; Volume 31; Issue 3. Living in a physical world VIII. Gravity and life in water. Steven Vogel. Series Volume 31 Issue 3 September 2006 pp 309-322. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jbsc/031/03/0309-0322 ...

  10. Idiopathic factor VIII inhibitor autoantibody in a man presented after accident.

    NARCIS (Netherlands)

    Mansouritorghabeh, H.; Lak, M.; Heerde, W.L. van

    2009-01-01

    Acquired hemophilia A is a rare but severe autoimmune bleeding disorder caused by autoantibodies against factor VIII activity and is a potentially life-threatening hemorrhagic disorder. The incidence of acquired hemophilia A has been estimated as 1.48 cases per million per year. The overall rate of

  11. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    DEFF Research Database (Denmark)

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

    2017-01-01

    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  12. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  13. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  14. Endocytic receptor for pro-coagulant factor VIII: relevance to inhibitor formation.

    Science.gov (United States)

    Navarrete, Ana-Maria; Dasgupta, Suryasarathi; Teyssandier, Maud; Repesse, Yohann; Delignat, Sandrine; André, Sébastien; Bayry, Jagadeesh; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2010-12-01

    The immunogenicity of therapeutic factor VIII (FVIII) in patients with haemophilia A remains a critical issue in patient management. This review describes the immunological processes involved in the activation of the immune system against FVIII, with a particular focus on the role of endocytic receptors for the recognition of FVIII by antigen-presenting cells.

  15. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII

    NARCIS (Netherlands)

    van Haren, Simon D.; Wroblewska, Aleksandra; Herczenik, Eszter; Kaijen, Paul H.; Ruminska, Aleksandra; ten Brinke, Anja; Meijer, Alexander B.; Voorberg, Jan

    2013-01-01

    The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the

  16. Molecular characterization of a novel family VIII esterase from burkholderia multivorans UWC10

    CSIR Research Space (South Africa)

    Rashamuse, KJ

    2007-02-01

    Full Text Available was identified. Full-length sequencing of the DNA insert showed that it consisted of a single open reading frame (ORF1) encoding a predicted protein of 398 amino acids. ORF1 (termed EstBL) had a high protein sequence identity to family VIII esterases. The Est...

  17. VIII Olimpíada Brasileira de Astronomia e Astronáutica

    Science.gov (United States)

    Garcia Canalle, João Batista; Villas da Rocha, Jaime Fernando; Wuensche de Souza, Carlos Alexandre; Pereira Ortiz, Roberto; Aguilera, Nuricel Villalonga; Padilha, Maria De Fátima Catta Preta; Pessoa Filho, José Bezerra; Soares Rodrigues, Ivette Maria

    2007-07-01

    Neste trabalho apresentamos as motivações pelas quais organizamos, em conjunto, pela primeira vez, a Olimpíada Brasileira de Astronomia incluindo a Astronáutica, em colaboração com a Agência Espacial Brasileira. Esta ampliação contribuiu para atrair ainda mais alunos, professores, escolas e patrocinadores para participarem desta Olimpíada. Em 2005 participaram da VIII Olimpíada Brasileira de Astronomia e Astronáutica (VIII OBA) 187.726 alunos distribuídos por 3.229 escolas, pertencentes a todos os estados brasileiros, incluindo o Distrito Federal. O crescimento em número de alunos participantes foi 52,4% maior do que em 2004. Em abril de 2005 organizamos, em Itapecerica da Serra, SP, um curso para os 50 alunos previamente selecionados e participantes da VII OBA e ao final selecionamos, dentre eles, uma equipe de 5 alunos, os quais representaram o Brasil na X Olimpíada Internacional de Astronomia, na China, em outubro de 2005. Ganhamos, pela primeira vez, uma medalha de ouro naquele evento. Em Agosto de 2005, organizamos a VIII Escola de Agosto para 50 alunos e respectivos professores, em Águas de Lindóia, SP, juntamente com a XXXI reunião anual da Sociedade Astronômica Brasileira (SAB). Em novembro de 2005 realizamos a I Jornada Espacial, em São José dos Campos, com 22 alunos e 22 professores selecionados dentre os participantes que melhores resultados obtiveram nas questões de Astronáutica da VIII OBA. Neste trabalho detalhamos os resultados da VIII OBA bem como as ações subseqüentes.

  18. RELATIONSHIP OF INTEREST, LEARNING MOTIVATION AND ATTITUDE WITH RESULTS LEARNING CLASS VIII SMP STATE 13 MAKASSAR

    Directory of Open Access Journals (Sweden)

    Putri Athirah Azis

    2016-12-01

    Full Text Available The study aims at examining (1 the correlation of learning interest towards learning result of grade students, (2 the correlation of learning motivation towards learning result of grade students, (3 the correlation of students attitude towards learning result, (4 the correlationof interest, learning motivation, and attitude collaboratively towards learning result. The study is an ex post facto. The population of the study was grade VIII at SMPN 13 Makassar. Samples were 105 students taken by employing random sampling technique. Data were collected through questionnaire and documentation. Data were analyzed using regression test. The result of study reveal that (1 there is significant correlation (p<0,01 of interest towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,718 and its effectiveness contribution (R2 is 51,5%, (2 there is significant correlation (p<0,01 of motivation towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,775 and its effectiveness contribution (R2 is 60,1%, (3 there is significant correlation (p<0,01 of attitude towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,737 and its effectiveness contribution (R2 is 54,4%, (4 there is significant correlation (p<0,01 of interest, motivation and attitude collaboratively towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,861 and its effectiveness contribution (R2 is 74,1%,

  19. Macroscopia, histopatologia e bacteriologia de fígados de frangos (Gallus gallus condenados no abate Gross, microscopic and bacteriologic evaluations of broiler chicken livers (Gallus gallus condemned at slaughter

    Directory of Open Access Journals (Sweden)

    Aleverson da Silva Barcelos

    2006-04-01

    Full Text Available Este trabalho avaliou, através da macroscopia, histopatologia e bacteriologia, fígados de frangos (Gallus gallus condenados no abate. Cem fígados de frango foram coletados na linha de inspeção. Noventa deles tinham sido condenados por apresentarem alterações macroscópicas. Dez fígados não apresentavam alterações macroscópicas. As coletas foram feitas em dois abatedouros localizados no Estado do Rio Grande do Sul. No laboratório, fez-se detalhada descrição das alterações macroscópicas dos fígados condenados e exames histopatológicos e bacteriológicos complementares. Para a descrição macroscópica, os seguintes parâmetros foram avaliados: forma, coloração, tamanho, consistência, odor e presença de lesões visíveis. Foram observados fígados com alterações na cor, forma, tamanho e/ou consistência em 47/90 amostras; fígados marrom-pálidos e com outras alterações macroscópicas associadas perfizeram 19/90 amostras; 5/90 fígados estavam amarelos ou amarelados e com outras alterações macroscópicas associadas; 19/90 fígados estavam verdes ou esverdeados e com outras alterações macroscópicas associadas. Os principais diagnósticos histopatológicos foram de colângio-hepatite heterofílica multifocal, degeneração e/ou necrose hepatocelular centrolobular e em ponte, hepatite necrosante aleatória, pericolangite heterofílica multifocal e peri-hepatite fibrinosa subaguda difusa acentuada. A bacteriologia foi direcionada para pesquisa de Escherichia coli, Salmonella spp. e Staphylococcus sp. Utilizando-se cultivo direto das amostras de fígado em meios de cultura seletivos, isolou-se E. coli em 26/100 amostras e Staphylococcus sp. em 24/100 amostras. Para pesquisa de salmonelas, utilizou-se a metodologia convencional preconizada para esta bactéria, entretanto não houve isolamento de nenhuma espécie deste gênero. Através das avaliações realizadas pode-se confirmar o predomínio de lesões sugestivas de

  20. 75 FR 26196 - Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII...

    Science.gov (United States)

    2010-05-11

    ..., (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, Forest Service, USDA. ACTION... 39269. SUPPLEMENTARY INFORMATION: The Federal Recreation Lands Enhancement Act (Title VII, Pub. L. 108...

  1. DAMPAK POSITIF DAN NEGATIF SOSIAL MEDIA TERHADAP PENDIDIKAN AKHLAK ANAK (Studi Kasus di SMP Negeri 2 Kelas VIII Banda Aceh)

    National Research Council Canada - National Science Library

    NISA KHAIRUNI

    2016-01-01

    The author examines the positive and negative effects of social media on the moral education of children in school SMPN 2 class VIII Banda Aceh, it is very interesting because of the many children who abuse social media...

  2. A novel approach in potential anticoagulants from peptides epitope 558-565 of A2 subunit of factor VIII.

    Science.gov (United States)

    Anastasopoulos, C; Sarigiannis, Y; Stavropoulos, G

    2013-04-01

    Factor VIII, a human blood plasma protein, plays an important role during the intrinsic pathway of blood coagulation cascade after its activation by thrombin. The activated form of FVIII acts as cofactor to the serine protease Factor IXa, in the conversion of the zymogen Factor X to the active enzyme Factor Xa. The Ser558-Gln565 region of the A2 subunit of Factor VIII has been shown to be crucial for FVIIIa-FIXa interaction. Based on this, a series of linear peptides, analogs of the 558-565 loop of the A2 subunit of the heavy chain of Factor VIII were synthesized using the acid labile 2-chlorotrityl chloride resin and biologically evaluated in vitro by measuring the chronic delay of activated partial thromboplastin time and the inhibition of Factor VIII activity, as potential anticoagulants.

  3. Haga su diagnostico

    OpenAIRE

    Rivelli,Victoria; Domínguez,Liz; Gorostiaga,Graciela; Mendoza,Gloria; Aldama,Arnaldo

    2008-01-01

    Comunicamos un paciente joven, que presentaba una inmunodepresión atribuida al alcohol y la desnutrición, que consultó por numerosas lesiones. Luego de los estudios auxiliares se llegó al diagnóstico y mostró buena respuesta al tratamiento convencional para esta leishmaniasis. Las lesiones polimorfas obligaron a varios diagnósticos diferenciales, entre ellos histoplasmosis, paracoccidioidomicosis, ectima, linfoma.

  4. KEEFEKTIFAN PAIRED STORYTELLING DAN JIGSAW DALAM PENINGKATAN KOMPETENSI BERBICARA SISWA KELAS VIII SMP NEGERI 3 SLEMAN

    Directory of Open Access Journals (Sweden)

    Nurmiyati Nurmiyati

    2014-10-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui: (1 apakah ada perbedaan keefektifan antara teknik paired storytelling, jigsaw, dan konvensional dalam meningkatkan kompetensi berbicara siswa, (2 teknik pembelajaran berbicara yang paling efektif antara ketiga teknik penelitian itu dalam meningkatkan kompetensi berbicara siswa kelas VIII SMP Negeri 3 Sleman. Penelitian ini menggunakan jenis penelitian eksperimen semu dengan nonequivalent control-group design. Hasil penelitian menunjukkan bahwa: (1 Ada perbedaan keefektifan antara teknik paired storytelling, jigsaw, and konvensional itu dalam meningkatkan kompetensi berbicara siswa dengan nilai F sebesar 3,532 dan signifikan dengan P < 0,05, yaitu sebesar 0,033, dan (2 teknik paired storytelling adalah teknik keterampilan berbicara yang paling efektif diantara ketiga teknik itu dalam meningkatkan kompetensi berbicara siswa kelas VIII SMP Negeri 3 Sleman dengan mean tertinggi sebesar 74,3492. Kata kunci: teknik paired storytelling, teknik jigsaw, teknik konvensional, kompetensi berbicara

  5. Genomic characterisation of the toxin Amm VIII from the scorpion Androctonus mauretanicus mauretanicus.

    Science.gov (United States)

    Alami, Meriem; Céard, Brigitte; Legros, Christian; Bougis, Pierre E; Martin-Eauclaire, Marie-France

    2006-04-01

    The genomic DNA sequence encoding the scorpion toxin Amm VIII was amplified from genomic DNA of the scorpion Androctonus mauretanicus mauretanicus from Morocco, subcloned and sequenced. An intron, with a high A+T content (73.5%), split a Gly codon at the end of the precursor signal peptide and the consensus GT/AG splice junction was identified in the Amm VIII gene. This intron of only 166 bp is the smallest intron described so far for a long-chain scorpion toxin gene. In addition, this study led to the identification of three new toxin-related genes. From the deduced amino acid sequences of the encoded precursor proteins, we found that the mature putative toxins were highly similar to the scorpion toxins Leiurus quinquestriatus quinquestriatus IV and Odonthobuthus doriae 1.

  6. Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey

    2013-01-01

    Full Text Available Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs. An indirect intracellular staining (ICS method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels.

  7. Acquired hemophilia A caused by factor VIII inhibitors: report of a case.

    Science.gov (United States)

    Hosoya, Yoshinori; Matsumura, Miho; Madoiwa, Seiji; Zuiki, Toru; Matsumoto, Shiro; Nunomiya, Shin; Lefor, Alan; Sata, Naohiro; Yasuda, Yoshikazu

    2013-06-01

    We report a case of acquired hemophilia A (AHA) after esophageal resection. The patient was an 80-year-old woman whose preoperative activated partial-thromboplastin time (APTT) was well within the normal range, at 34.9 s. She underwent thoracic esophagectomy and gastric pull-up for superficial esophageal cancer (operative time, 315 min; intraoperative blood loss, 245 ml). Intrathoracic and subcutaneous bleeding occurred spontaneously on postoperative day (POD) 39. The APTT was prolonged, at 140 s, and factor VIII inhibitor was 36 Bethesda U/ml. Treatment with recombinant activated factor VII, prednisolone, and cyclophosphamide resulted in remission within 2 months. This case supports an association between surgery and the triggering of factor VIII inhibitors. The diagnosis of AHA requires clinical acumen and must be considered in any patient with bleeding and a prolonged APTT.

  8. Treatment of radiation osteomyelitis of the mandible in a patient with acquired factor VIII inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Arimoto, Takamasa; Kishimoto, Hiromitsu; Matsumoto, Suwako; Kawanaka, Masao; Urabe, Masahiro; Yoshioka, Wataru [Hyogo Coll. of Medicine, Nishinomiya (Japan)

    1996-07-01

    A case of radiation osteomyelitis of mandible in a 56-year-old man with acquired factor VIII inhibitor is presented. He had undergone radiation therapy for malignant lymphoma of the tonsilar region seven years earlier, and also had received steroids to treat acquired factor VIII inhibitor for a year. On initial examination, he was given a diagnosis of phlegmon of the cheek caused by pericoronitis of the left lower wisdom tooth. To prevent the recurrence of inflammation, the wisdom tooth was extracted carefully, but radiation osteomyelitis occurred in association with a pathological fracture of the condylar head. After mini-pulse therapy with methylpredonisolone, segmental mandibulectomy and reconstruction with a titanium metal plate were performed. The postoperative course was satisfactory with no complications such as bleeding or infection. (author)

  9. Pengembangan Modul Matematika Untuk Pembelajaran Berbasis Masalah (Problem Based Learning) Pada Materi Pokok Persamaan Garis Lurus Kelas VIII SMP

    OpenAIRE

    Khayati, Fitrotul; Sujadi, Imam; Sari Saputro, Dewi Retno

    2016-01-01

    Absrtact:The objectives of this research were to investigate: (1) how to develop of Mathematics module development for problem-based learning on the topic of discussion of Linear Equation of Straight Line for Grade VIII of Junior Secondary School; and (2) the effectiveness of result of Mathematics module development for problem-based learning on the topic of discussion of Linear Equation of Straight Line for Grade VIII of Junior Secondary School. This research consisted of two phases. The fi...

  10. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A.

    Science.gov (United States)

    Goudemand, Jenny; Rothschild, Chantal; Demiguel, Virginie; Vinciguerrat, Christine; Lambert, Thierry; Chambost, Hervé; Borel-Derlon, Annie; Claeyssens, Ségolène; Laurian, Yves; Calvez, Thierry

    2006-01-01

    Inhibitor development is the major treatment complication in children with severe hemophilia A. It is not clear whether the risk of inhibitors is higher with recombinant factor VIII or with plasma-derived factor VIII. We used multivariate analysis to compare 2 cohorts of previously untreated patients (PUPs) with severe hemophilia A: 62 patients treated with the same brand of high-purity plasma-derived FVIII (pFVIII) containing von Willebrand factor (VWF) and 86 patients treated with full-length recombinant FVIII (rFVIII). In addition to the usual end points (all inhibitors, high inhibitors), we also examined a third end point (high inhibitors and/or immune tolerance induction). The risk of inhibitor development was higher in patients treated with rFVIII than in patients treated with pFVIII, regardless of other risk factors (F8 genotype; nonwhite origin; history of inhibitors in patients with a family history of hemophilia; age at first FVIII infusion). The adjusted relative risk (RRa) for inhibitor development with rFVIII versus pFVIII was 2.4 (all inhibitors), 2.6 (high inhibitors), and 3.2 (high inhibitors and/or immune tolerance induction), respectively, depending on the end point (above). The pathophysiology of this large effect must be understood in order to improve the characteristics of recombinant products and to reduce the incidence of inhibitors to FVIII.

  11. IMPLEMENTASI PENDEKATAN KONFLIK KOGNITIF DALAM PEMBELAJARAN FISIKA UNTUK MENUMBUHKAN KEMAMPUAN BERPIKIR KRITIS SISWA SMP KELAS VIII

    OpenAIRE

    A. Setyowati; B. Subali; Mosik -

    2012-01-01

    Tujuan dari penelitian ini adalah untuk mengetahui pengaruh implementasi pendekatan konflik kognitif dalam pembelajaran fisikapokok bahasan tekanan pada siswa kelas VIII terhadap kemampuan berpikir kritis, pemahaman konsep dan hasil belajar kognitifsiswa. Penelitian ini merupakan penelitian eksperimen. Setelah dilakukan pengambilan sampel secara random sampling,diperoleh kelas VIIIB sebagai kelas eksperimen dan kelas VIIIC sebagai kelas kontrol. Dari analisis uji rata-rata dua pihak atau uji ...

  12. Construction of a mouse model of factor VIII deficiency by gene targeting

    Energy Technology Data Exchange (ETDEWEB)

    Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.

  13. Historical intensity VIII earthquakes along the Rhone valley (Valais, Switzerland): primary and secondary effects

    Energy Technology Data Exchange (ETDEWEB)

    Fritsche, S.; Faeh, D.; Schwarz-Zanetti, G.

    2012-06-15

    In recent years the upper Rhone Valley has been one of the most intensively investigated regions by the Swiss Seismological Service. The high seismicity in the region encourages research in the seismological field and one main focus has been historical seismology. This report presents the state of the art of our historical investigations by giving an overview of the effects of four damaging earthquakes with intensity larger than VII, for which a fairly large number of documents could be found and analyzed. The overview includes the events of 1584 (Aigle, epicentral intensity VIII), 1755 (Brig, epicentral intensity VIII), 1855 (Visp, epicentral intensity VIII), and 1946 (Sierre, epicentral intensity VIII for the main shock and intensity VII for the largest aftershock). The paper focuses mainly on primary and secondary effects in the epicentral region, providing the key data and a general characterization of the event. Generally, primary effects such as the reaction of the population and impact on buildings took more focus in the past. Thus building damage is more frequently described in historic documents. However, we also found a number of sources describing secondary effects such as landslides, snow avalanches, and liquefaction. Since the sources may be useful, we include citations of these documents. The 1584 Aigle event, for example, produced exceptional movements in the Lake of Geneva, which can be explained by an expanded sub aquatic slide with resultant tsunami and seiche. The strongest of the aftershocks of the 1584 event triggered a destructive landslide covering the villages Corbeyrier and Yvorne, Vaud. All macroseismic data on the discussed events are accessible through the web page of the Swiss Seismological Service (http://www.seismo.ethz.ch). (authors)

  14. The impact of von Willebrand factor on factor VIII memory immune responses

    OpenAIRE

    Chen, Juan; Schroeder, Jocelyn A.; Luo, Xiaofeng; Shi, Qizhen

    2017-01-01

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis...

  15. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia

    OpenAIRE

    Sejersted, Yngve; Hildrestrand, Gunn A.; Kunke, David; Rolseth, Veslemøy; Krokeide, Silje Z.; Neurauter, Christine G.; Suganthan, Rajikala; Atneosen-Åsegg, Monica; Fleming, Aaron M.; Saugstad, Ola D.; Burrows, Cynthia J.; Luna, Luisa; Bjørås, Magnar

    2011-01-01

    Neural stem/progenitor cell proliferation and differentiation are required to replace damaged neurons and regain brain function after hypoxic-ischemic events. DNA base lesions accumulating during hypoxic-ischemic stress are removed by DNA glycosylases in the base-excision repair pathway to prevent cytotoxicity and mutagenesis. Expression of the DNA glycosylase endonuclease VIII-like 3 (Neil3) is confined to regenerative subregions in the embryonic and perinatal brains. Here we show profound n...

  16. Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Boyko, Konstantin M., E-mail: kmb@inbi.ras.ru [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Gorbacheva, Marina A.; Korzhenevskiy, Dmitry A. [National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Alekseeva, Maria G.; Mavletova, Dilara A.; Zakharevich, Natalia V.; Elizarov, Sergey M.; Rudakova, Natalia N.; Danilenko, Valery N. [Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina str. 3, Moscow, 119333 (Russian Federation); Popov, Vladimir O. [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation)

    2016-09-02

    Aminoglycoside phosphotransferases represent a broad class of enzymes that promote bacterial resistance to aminoglycoside antibiotics via the phosphorylation of hydroxyl groups in the latter. Here we report the spatial structure of the 3′-aminoglycoside phosphotransferase of novel VIII class (AphVIII) solved by X-ray diffraction method with a resolution of 2.15 Å. Deep analysis of APHVIII structure and its comparison with known structures of aminoglycoside phosphotransferases of various types reveals that AphVIII has a typical two-domain fold and, however, possesses some unique characteristics that distinguish the enzyme from its known homologues. The most important difference is the presence of the activation loop with unique Ser146 residue. We demonstrate that in the apo-state of the enzyme the activation loop does not interact with other parts of the enzyme and seems to adopt catalytically competent state only after substrate binding. - Highlights: • 3D structure of the novel aminoglycoside phosphotransferase AphVIII was obtained. • AphVIII activation loop is clearly identified in the electron density. • AphVIII has some unique structural features in its substrate C-ring binding pocket.

  17. Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII.

    Science.gov (United States)

    Hu, Chuhong; Cela, Racel G; Suzuki, Masataka; Lee, Brendan; Lipshutz, Gerald S

    2011-02-01

    Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential "cure." Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.

  18. A close insight to factor VIII inhibitor in the congenital hemophilia A.

    Science.gov (United States)

    Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan

    2016-09-01

    Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

  19. [Structure and function of the factor VIII/von Willebrand factor complex].

    Science.gov (United States)

    Müller, G

    1990-03-01

    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated.

  20. PENINGKATAN PEMBELAJARAN MENULIS PUISI BEBAS MELALUI MEDIA LAGU MEDLEY SISWA KELAS VIII SMP SINTANG

    Directory of Open Access Journals (Sweden)

    Rohanawati Silalahi

    2015-05-01

    Full Text Available Penelitian ini bertujuan untuk meningkatkan pembelajaran menulis puisi bebas melalui media lagu medley siswa kelas VIII B SMP Sintang. Subjek penelitian adalah siswa kelas VIII B SMP Sintang. Penelitian ini merupakan Penelitian Tindakan Kelas (PTK. Prosedur pelaksanaan dan implementasi penelitian dilaksanakan dalam dua siklus. Teknik pengumpulan data berupa obsevasi, wawancara, catatan lapangan, angket, evaluasi dan dokumentasi. Instrumen pengumpulan data meliputi lembar wawancara, lembar catatan lapangan, lembar angket, lembar tes hasil belajar dan lembar portofolio serta dokumentasi foto kegiatan. Teknik analisis data yang digunakan adalah analisis data kuantitatif dan kualitatif. Hasil penelitian ini menunjukkan bahwa penggunaan media lagu medley dapat meningkatkan pembelajaran menulis puisi bebas. Peningkatan hasil atau produk dapat dilihat dari perbandingan skor rata-rata keterampilan menulis puisi bebas siswa pada setiap siklus. Nilai rata-rata siswa pada tahap pratindakan adalah 55,23, pada saat siklus I meningkat menjadi 71,18, dan pada siklus II meningkat menjadi 73,4. ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ DEVELOPING THE TEACHING OF FREE VERSE WRITING THROUGH MEDLEY SONG MEDIA TO GRADE VIII STUDENTS OF SMP SINTANG   Abstract This study aims to improve the teaching of free verse writing through medley song media to Grade VIII B students of SMP Sintang. The research subjects were Grade VIII B students of SMP Sintang,. This was a classroom action research (CAR. The research procedure and implementation were conducted in two cycles. The data were collected through observations, field notes, questionnaires, evaluations, and documentations. The data collecting instruments included interview sheets, field note sheets

  1. The insulation condition diagnosis of high tension generator stators; Diagnostico del estado de aislamiento de estatores de generadores de alta tension

    Energy Technology Data Exchange (ETDEWEB)

    Robles Pimentel, Edgar Guillermo; Rosales Sedano, Inocente [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1989-12-31

    The high tension electrical generators are very high cost equipment, therefore they need to be very reliable. The generators preventive maintenance based in diagnosis techniques of the insulation condition might mean substantial savings for the user. In this article the most common techniques employed all over the world are presented, the greatest part of them already implemented in Mexico by the authors. The techniques and the equipment employed are analyzed and are exemplified with the results obtained in some field experiences. [Espanol] Los generadores electricos de alta tension son equipos de muy alto costo, por lo que necesitan ser muy confiables. El mantenimiento preventivo de los generadores basado en tecnicas de diagnostico del estado del aislamiento puede significar ahorros sustanciales al usuario. En este articulo se presentan las tecnicas mas comunes empleadas en el mundo, la mayor parte de ellas ya implantadas en Mexico por los autores. Se analizan las tecnicas y el equipo empleado, y se ejemplifica con resultados obtenidos de algunas de las experiencias en el campo.

  2. Diagnosis of feed water, condensate and circulation pumps in electric power plants; Diagnostico de bombas de agua de alimentacion, condensado y circulacion en centrales termoelectricas

    Energy Technology Data Exchange (ETDEWEB)

    Colin Castellanos, Carlos [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1991-12-31

    This article encompasses the analysis and the diagnosis of the pump`s performance that belong to the feed water, condensate and circulation systems of a fossil fuel power plant (FFPP). For this analysis pressure, temperature and flow data were collected by means of field installed instrumentation, as well as these pumps` motors current consumption and voltage values. Later on, the capacity and the pump efficiency are calculated and compared with the design values, to obtain the actual performance of the equipment with the aid of their characteristic curves (Q vs {Delta}H, Q vs {pi}, etc.). [Espanol] Este articulo comprende el analisis y el diagnostico de comportamiento de las bombas, las cuales forman parte de los sistemas de agua de alimentacion, condensado y circulacion de una central termoelectrica (CT). Para el analisis se recopilan datos de presion, temperatura y flujo de la instrumentacion instalada en campo, asi como de los valores de consumo de corriente y de voltaje en los motores de dichas bombas. Posteriormente, se calcula la capacidad y la eficiencia de las bombas en operacion real y se comparan con los valores de diseno, para obtener el comportamiento real del equipo con ayuda de las curvas caracteristicas (Q vs {Delta}H, Q vs {pi}, etcetera).

  3. Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in acquired and congenital hemophilia A.

    Science.gov (United States)

    Kahle, Joerg; Orlowski, Aleksander; Stichel, Diana; Healey, John F; Parker, Ernest T; Jacquemin, Marc; Krause, Manuela; Tiede, Andreas; Schwabe, Dirk; Lollar, Pete; Königs, Christoph

    2017-08-10

    Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study, the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178). The domain specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins. The analysis with HSA-fVIII domain proteins confirmed the results of the HSM approach but resulted in higher detection levels. The higher detection levels with HSA-fVIII domain proteins are a result of antibody cross-reactivity with human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-, and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63). Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed overlapping epitopes with murine C1-specific group A mAbs including 2A9. Mutational analyses identified distinct crucial binding residues for LE2E9 (E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies was particularly observed in patients with AHA. Overall, our study demonstrates that the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral anti-fVIII immune response in acquired and congenital hemophilia inhibitor patients. © 2017 by The American Society of Hematology.

  4. Dry-heat treatment process for enhancing viral safety of an antihemophilic factor VIII concentrate prepared from human plasma.

    Science.gov (United States)

    Kim, In Seop; Choi, Yong Woon; Kang, Yong; Sung, Hark Mo; Shin, Jeong Sup

    2008-05-01

    Viral safety is a prerequisite for manufacturing clinical antihemophilic factor VIII concentrates from human plasma. With particular regard to the hepatitis A virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of factor VIII activity during dry-heat treatment was of about 5%. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor VIII compared with those of the factor VIII before dry-heat treatment. The dry-heat-treated factor VIII was stable for up to 24 months at 4oC. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and human immunodeficiency virus (HIV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the treatment. However porcine parvovirus (PPV) was slightly resistant to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13 for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat treatment improves the virus safety of factor VIII concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.

  5. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

    2008-01-01

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  6. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

    2008-06-03

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  7. Analysis of inversions in the factor VIII gene in Spanish hemophilia A patients and families

    Energy Technology Data Exchange (ETDEWEB)

    Domenech, M.; Tizzano, E.; Baiget, M. [Hospital de Sant Pau, Barcelona (Spain); Altisent, C. [Hospital Vall d`Hebron, Barcelona (Spain)

    1994-09-01

    Intron 22 is the largest intron of the factor VIII gene and contains a CpG island from which two additional transcripts originate. One of these transcripts corresponds to the F8A gene which have telomeric extragenic copies in the X chromosome. An inversion involving homologous recombination between the intragenic and the distal or proximal copies of the F8A gene has been recently described as a common cause of severe hemophilia A (HA). We analyzed intron 22 rearrangements in 195 HA patients (123 familial and 72 sporadic cases). According to factor VIII levels, our sample was classified as severe in 114 cases, moderate in 29 cases and mild in 52 cases. An intron 22 (F8A) probe was hybridized to Southern blots of BcII digested DNA obtained from peripheral blood. A clear pattern of altered bands identifies distal or proximal inversions. We detected an abnormal pattern identifying an inversion in 49 (25%) of the analyzed cases. 43% of severe HA patients (49 cases) showed an inversion. As expected, no inversion was found in the moderate and mild group of patients. We found a high proportion (78%) of the distal rearrangement. From 49 identified inversions, 33 were found in familial cases (27%), while the remaining 15 were detected in sporadic patients (22%) in support that this mutational event occurs with a similar frequency in familial or sporadic cases. In addition, we detected a significant tendency of distal inversion to occur more frequently in familial cases than in sporadic cases. Inhibitor development to factor VIII was documented in approximately 1/3 of the patients with inversion. The identification of such a frequent molecular event in severe hemophilia A patients has been applied in our families to carrier and prenatal diagnosis, to determine the origin of the mutation in the sporadic cases and to detect the presence of germinal mosaicism.

  8. AKTIVITAS FISIK, ASUPAN ENERGI DAN STATUS GIZI WANITA PEMETIK TEH DI PTPN VIII BANDUNG, JAWA BARAT

    Directory of Open Access Journals (Sweden)

    Venny Agustiani Mahardikawati

    2012-03-01

    Full Text Available 800x600 Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Quality of human resources is very important to improve productivity. The worker productivity is correlated with nutritional status and health status. The objective of the research is to analyze physical activity, energy intake, nutritional status, of women workers at Tea Plantation PTPN VIII Bandung, West Java. The cross sectional design was used in this study to elaborate physical activity, nutritional status, and productivity of tea picker’s women. The criteria of study sample were tea picker’s women at cluster area of Malabar tea plantation of PTPN VIII Bandung, having infant and they were willing to be interviewed. The total number of 92 women sample was chosen randomly. Primary data consisted of physical activity recall (2x24 hours, food consumption recall (2x24 hours, anthropometry data (weight and height, and productivity (passage of tea sprout. Secondary data were included data of PT Perkebunan Nusantara VIII Bandung, West Java. The result showed that more than a half of samples having active or moderate physical activity level (PAL. The physical activity level of samples during work day (average PAL=1.87 was higher than holiday (average PAL=1.69 (p2362 kcal and 2134 kcal. The average energy adequacy level during workday and day off according to Schofield and Oxford equation were not significantly different, respectively 97,2% and 103,3%. The majority of samples had normal nutritional status, and 30.4% of the sample was overweight. The energy adequacy level according to Schofield and Oxford equation are related to nutritional status of women workers. Keywords: physical activity, energy expenditure, nutritional status, plantation women

  9. IMPLIKASI YURIDIS PUTUSAN MK NOMOR 46/PUU- VIII/ 2010 TERHADAP AKTA KELAHIRAN ANAK LUAR KAWIN

    Directory of Open Access Journals (Sweden)

    Djumikasih Djumikasih

    2014-08-01

    Full Text Available Abstract This paper aims to identify and analyze what the juridical implications of the publication of the decision of the Constitutional Court No. 46/PUU-VIII / 2010 on Child Outside Marriage Deed which has been published by the Department of Population and Civil Registration prior to the establishment of the Constitutional Court's decision . The method used in this study is a normative juridical approach legislation. From the discussion, it can be concluded that the Constitutional Court 46/PUU-VIII/2010 Number of Tests on Article 43 paragraph ( 1 Marriage Act ( Act No. 1 of 1974 when viewed from the angle of legal certainty it will lead to legal certainty . But the decision will not have any juridical implications of the child's birth certificate that has been published outside of marriage and illegitimate child who was born before the date of February 17, 2012, as if enacted would be contrary to the principle of legality is interpreted Article 47 of the Law on the Constitutional Court and Article 28 ( i of the 1945 Constitution . Likewise, if the terms of the fairness and usefulness , especially for justice seekers / applicant , the timing of this decision is not fair and not useful , because although the Court granted the petition but the Constitutional Court can not be applied to her .   Key words: yuridical implication, birth certificate, children who are born outside of marriage   Abstrak   Tulisan ini bertujuan untuk mengetahui dan menganalisis apa implikasi yuridis dari terbitnya putusan MK Nomor 46/PUU-VIII/ 2010 terhadap Akta Anak Luar Kawin yang sudah diterbitkan oleh Dinas Kependudukan dan Catatan Sipil sebelum lahirnya putusan MK tersebut. Metode yang digunakan dalam penelitian ini adalah yuridis normative dengan pendekatan perundang-undangan. Dari pembahasan dapat disimpulkan bahwa Putusan MK Nomer 46/PUU-VIII/2010 tentang Pengujian terhadap Pasal 43 ayat (1 UU Perkawinan (UU NO 1 Tahun 1974 jika dilihat dari sudut kepastian

  10. Underground Test Area Subproject Phase I Data Analysis Task. Volume VIII - Risk Assessment Documentation Package

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-12-01

    Volume VIII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the risk assessment documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  11. Comercio Internacional mediterráneo en el siglo VIII a.C.

    Directory of Open Access Journals (Sweden)

    Paloma Cabrera Bonet

    2018-01-01

    Full Text Available The VIII century B.C. saw, for the first time after the breakdown of the system in the Late Bronze Age, the revival of a true intemational trade at a growing scale, especíally protagonized by Phoenicians and Greeks. In this article we analyze sorne aspects of this phenomenon, from the Aegean to the Far West, which made possíble, through a vaste network of trading routes, a large multinational ínteractíon. We understand the international trade as a key factor in the proccess of economic, social and political changes of the Mediterranean areas submerged in this complex "world-system".

  12. Production of Lentiviral Vectors Encoding Recombinant Factor VIII Expression in Serum-Free Suspension Cultures

    Directory of Open Access Journals (Sweden)

    Angelo Luis Caron

    2015-12-01

    Full Text Available ABSTRACT Lentiviral vector-mediated gene transfer offers several advantages over other gene delivery vectors when considering gene and cell therapy applications. However, using these therapies in clinical applications involves large-scale vector production in an efficient and cost-effective manner. Here we describe a high yield production of a lentivirus encoding recombinant factor VIII in a scalable and GMP-compliant culture system, based on serum free suspension cultures and transient transfection with an inexpensive reagent, polyethylenimine (PEI, reaching a total viral yield of 2.48x108 particles.

  13. Measurements of Sheath Currents and Equilibrium Potential on the Explorer VIII Satellite (1960 xi)

    Science.gov (United States)

    Bourdeau, R. E.; Donley, J. L.; Serbu, G. P.; Whipple, E. C., Jr.

    1961-01-01

    Experimental data were obtained from the Explorer VIII satellite on five parameters pertinent to the problem of the interaction of space vehicles with an ionized atmosphere. The five parameters are: photoemission current due to electrons emitted from the satellite surfaces as a result of solar radiation; electron and positive ion currents due to the diffusion of charged particles from the medium to the spacecraft; the vehicle potential relative to the medium, and the ambient electron temperature. Included in the experimental data is the aspect dependence of the photoemission and diffusion currents. On the basis of the observations, certain characteristics of the satellite's plasma sheath are postulated.

  14. Methodology for the location diagnosis of electrical faults in electric power systems; Metodologia para el diagnostico de ubicacion de fallas en sistema electricos de potencia

    Energy Technology Data Exchange (ETDEWEB)

    Rosas Molina, Ricardo

    2008-08-15

    tareas mas afectada por esta situacion es la operacion de los sistemas electricos frente a la presencia de fallas, donde la primera labor a realizar por parte del personal de operacion de la red es la pronta ubicacion del lugar de falla dentro del sistema. En el presente trabajo se aborda el problema del diagnostico de ubicacion de fallas electricas en sistemas de potencia, desde la perspectiva de los operadores de los centros de control de energia de una empresa electrica. El objetivo de este trabajo de tesis es describir una metodologia de analisis de operacion de protecciones como base para el desarrollo de un sistema de diagnostico de ubicacion de fallas, que permita estimar los posibles lugares de falla dentro del sistema asi como una justificacion de la operacion de las protecciones ante un disturbio como apoyo a los operadores de los Centros de Control de Energia. La metodologia esta disenada para utilizar distintos tipos de informacion, discreta, continua y controles. Sin embargo, en el desarrollo de la presente etapa de la metodologia propuesta se hace uso exclusivamente de la informacion de tipo discreta de los estados de interruptores y operacion de relevadores, asi como de la conectividad de los elementos de la red. La metodologia de analisis consiste en determinar el grupo de elementos donde pudo haber ocurrido la falla, utilizando las zonas de cobertura de las protecciones asociadas a los interruptores operados. Posteriormente, estas alternativas de falla se ordenan en forma descendentes de posibilidad utilizando indices de clasificacion y analisis basados en logica difusa.

  15. KEEFEKTIFAN MODEL TGT DENGAN PENDEKATAN SCIENTIFIC BERBANTUAN CD PEMBELAJARAN TERHADAP KEMAMPUAN PEMECAHAN MASALAH SISWA SMP KELAS VIII PADA MATERI LINGKARAN

    Directory of Open Access Journals (Sweden)

    Singgih Baswendro

    2015-11-01

    Full Text Available Artikel ini dibuat berdasarkan penelitian skripsi yang telah dilaksanakan. Tujuan penelitian ini adalah (1 untuk mengetahui hasil kemampuan pemecahan masalah siswa kelas VIII pada materi lingkaran dengan menggunakan model TGT mencapai KKM, dan (2 untuk mengetahui rata-rata kemampuan pemecahan masalah siswa dengan model TGT lebih tinggi daripada dengan model ekspositori. Penelitian ini dilaksanakan di SMP Negeri 3 Ungaran dengan populasi siswa kelas VIII tahun ajaran 2014/2015. Pengambilan kelas sampel menggunakan teknik cluster random sampling. Untuk mengetahui hasil penelitian ini, data hasil akhir diuji dengan uji proporsi dan uji perbedaan rata-rata. Hasil penelitan ini menunjukkan bahwa (1 hasil kemampuan pemecahan masalah siswa kelas VIII pada materi lingkaran dengan menggunakan model TGT mencapai KKM, dan (2 rata-rata kemampuan pemecahan masalah siswa dengan model TGT lebih tinggi daripada dengan model ekspositori. Dengan ini maka model TGT dengan pendekatan scientific berbantuan CD pembelajaran efektif terhadap kemampuan pemecahan masalah siswa.

  16. Methodology for carrying out energy diagnosis in auxiliaries systems in thermal electrical central stations; Metodologia para realizar un diagnostico energetico en sistemas auxiliares de centrales termoelectricas

    Energy Technology Data Exchange (ETDEWEB)

    Nebradt Garcia, Jesus [Comision Federal de Electricidad (CFE), Mexico, D. F. (Mexico); Rojas Hidalgo, Ismael; Huante Perez, Liborio [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1998-12-31

    One of the potential areas for energy saving in Central Electric Power Plants are the auxiliaries system, so as to based in a preliminary energy diagnosis and considering that energy saving measures would be taken, going from the instrumentation, operational changes in equipment, as well as in using velocity variators in motors, it turns out to be that the energy consumption of auxiliaries at 75% load in a 150 MW thermal power plant varies from 3% to 4% and for the case of a 350 MW power plant the energy consumption of the auxiliaries represents 2 to 3.5%. Nowadays this consumption are above 6%. Considering that the country has 40 units with capacities varying from 150 to 350 MW, the economical and the fuel saving would be substantial. This paper will present a summary of the methodology to be used to carry out this type of projects. [Espanol] Una de las areas potenciales de ahorro de energia en centrales termoelectricas son los sistemas auxiliares, de tal manera que basados en un diagnostico energetico preliminar y considerando que se aplicarian las medidas de ahorro de energia que van desde la instrumentacion, cambios operativos en equipos, asi como el uso de variadores de velocidad en motores, se tienen que los consumos de auxiliares para un 75% de carga en una central termoelectrica de 150 MW varian desde un 3% hasta un 4% y para el caso de una central termoelectrica de 350 MW, el consumo de auxiliares representa del 2 al 3.5%. Hoy en dia dichos consumos estan por encima del 6%. Si consideramos que el pais cuenta con 40 unidades que varian desde 150 MW hasta 350 MW, entonces los ahorros economicos y de combustible serian impactantes. La presente ponencia mostrara un resumen de la metodologia a emplear para la realizacion de este tipo de proyectos.

  17. Advances in the diagnosis of substations primary equipment by means of high sensitivity techniques; Avances en el diagnostico de equipo primario de subestaciones mediante tecnicas de alta sensibilidad

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Colon H, V. Rodolfo; Nava G, J. Armando; Azcarraga R, Carlos G [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2005-07-01

    In an electrical system, the substations primary equipment is integrated by the power transformers, the instrument transformers, the breakers and the interconnection circuits (energy cables). At the present time, the described primary equipment has been integrated in an arrangement denominated encapsulated substation that presents dimensional and aesthetic advantages in the conventional substations. Nevertheless, the isolation involved in this type of substations means new challenges when carrying out its diagnosis in a planned way or after the appearance of a fault. In this sense, the insulating and electromechanical system of the primary equipment of substations must be evaluated in a programmed way or be constantly monitored. This with the final purpose of detecting incipient problems that could evolve towards a fault or to the diminution of the electrical system reliability. [Spanish] En un sistema electrico, el equipo primario de subestaciones esta integrado por los transformadores de potencia, los transformadores de instrumento, los interruptores y los circuitos de interconexion (cables de energia). En la actualidad, el equipo primario descrito se ha integrado en un arreglo denominado subestacion encapsulada que presenta ventajas dimensionales y esteticas sobre las subestaciones convencionales. Sin embargo, el aislamiento involucrado en este tipo de subestaciones significa nuevos retos al efectuar su diagnostico de manera planeada o despues de presentarse una falla. En este sentido, el sistema aislante y electromecanico del equipo primario de subestaciones debe ser evaluado de manera programada o monitoreado constantemente. Ello con la finalidad de detectar problemas incipientes que pudieran evolucionar hacia una falla o la disminucion de la confiabilidad del sistema electrico.

  18. Indonesian Interference on English Language in VIII Grade Junior High School Students

    Directory of Open Access Journals (Sweden)

    Agustia Km Tri Sutrisna

    2018-01-01

    Full Text Available This study aims to determine the type of Indonesian interference found in English language among class VIII SMPK 2 Harapan Untal-Untal students. This research is done by analyzing the result of simple text translation done by the students of class VIII SMPK 2 Harapan Untal-Untal, then from the translation result will be analyzed what kind of interference that appeared. Methods of data collection in this study using observational research methods and literature. The data that have been collected in the form of simple translations from the students will be analyzed descriptively using related theories to find out what kind of interference found in the analysis. Further, in relating to interference, it will find a way out to reduce and even eliminate Indonesian interference itself. The results to be achieved in this research is recognize the level of Indonesian language interference in the use of English among the junior high school students, then find the practical efforts to be done so that interference does not increased. So, the use and English understanding can be done as much as possible. The finding of the paper found that 6 interference such as grammar structure, subject pronoun, adjectives, auxiliaries, preposition and word order.

  19. PENGEMBANGAN PERANGKAT AJAR MODEL CORE PENDEKATAN METAKOGNITIF UNTUK MENINGKATKAN KEMAMPUAN PEMECAHAN MASALAH GEOMETRI KELAS VIII

    Directory of Open Access Journals (Sweden)

    Daroinis Sa’adah

    2017-02-01

    Full Text Available The objectives of this study are to develop teaching aids, to test the validity and practically teaching aids, and to test the effectiveness of learning process using CORE (Connecting, Organizing, Reflecting, and Extending model with metacognitive approach to improve the ability in Geometri problem solving. This research and development design is adapted from Plomp model by using several phases: (1 preliminary investigation; (2 design; (3 realization/construction; (4 test, evaluation and revision. This study developed some teaching aids; a part of syllabus, lesson plan, students book, students’ work sheet, and test of problem solving ability. The subject of the try out is eighth graders of MTs NU Nurul Huda Kudus. The research data to test the validity, practically, and effectiveness are collected by: (1 validation sheet; (2 observation sheet; (3 problem solving test. The results of research showed that development teaching aids using CORE model with metacognitive approach for Geometry material of VIII grade is valid and practical, and learning CORE model with metacognitive approach for Geometry material of VIII grade is effective.

  20. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

    Directory of Open Access Journals (Sweden)

    Alexandra Sherman

    2017-11-01

    Full Text Available Hemophilia A (coagulation factor VIII deficiency is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors” remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg, in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A.

  1. The head that wears the crown: Henry VIII and traumatic brain injury.

    Science.gov (United States)

    Ikram, Muhammad Qaiser; Sajjad, Fazle Hakim; Salardini, Arash

    2016-06-01

    Henry VIII of England is one of the most controversial figures in European history. He was born on 28 June 1491 as the second son of Henry VII and Elizabeth of York and became the heir to the English throne after his elder brother died prematurely. A contradictory picture of Henry's character emerges from history: the young Henry was a vigorous, generous and intelligent king who saw early military and naval successes. In contrast, in his later years he became cruel, petty and tyrannical. His political paranoia and military misjudgements are in direct contrast to his earlier successes and promise. Several hypotheses have been put forward regarding his transformation from a renaissance king to a later medieval tyrant, including endocrinopathies, psychiatric illnesses and traumatic brain injury. In this paper we examine the historical evidence linking the change in Henry's personality and health problems to traumatic brain injury. To our knowledge this is the first systematic neurological study of traumatic brain injury in Henry VIII. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Detection of Fibrinogen and Coagulation Factor VIII in Plasma by a Quartz Crystal Microbalance Biosensor

    Directory of Open Access Journals (Sweden)

    Chunyan Yao

    2013-05-01

    Full Text Available A quartz crystal microbalance (QCM biosensor with nanogram sensitivity has been constructed through a reasonable designing and biological processing of the piezoelectric quartz crystals. Due to its highly sensitivity, real time detection and low cost, the proposed QCM biosensor has a promising potential in blood coagulation research. In the current study, the QCM biosensor was used to determine the activated partial thromboplastin time (APTT for 120 anticoagulated plasma specimens. A good linear relationship was found in a double-logarithmic plot of APTT versus fibrinogen concentration in the range of 1.58–6.30 g/L. For factor VIII, the detection range by the QCM biosensor is 0.0185–0.111 mg/L. The QCM biosensor results were compared with those obtained by commercial optical coagulometry and a good agreement (correlation coefficient is 0.949 for fibrinogen, and 0.948 for factor VIII was reached. Furthermore, the QCM determination can be completed within 10 min. Our study suggested that the proposed QCM biosensor could provide for more convenient and time saving operations, which may be useful in clinical situations for rapid monitoring of anticoagulant therapy using small volume (20 μL plasma specimens.

  3. Improving attitudes toward mathematics learning with problem posing in class VIII

    Science.gov (United States)

    Vionita, Alfha; Purboningsih, Dyah

    2017-08-01

    This research is classroom action research which is collaborated to improve student's behavior toward math and mathematics learning at class VIII by using problem posing approach. The subject of research is all of students grade VIIIA which consist of 32 students. This research has been held on two period, first period is about 3 times meeting, and second period is about 4 times meeting. The instrument of this research is implementation of learning observation's guidance by using problem posing approach. Cycle test has been used to measure cognitive competence, and questionnaire to measure the students' behavior in mathematics learning process. The result of research shows the students' behavior has been improving after using problem posing approach. It is showed by the behavior's criteria of students that has increasing result from the average in first period to high in second period. Furthermore, the percentage of test result is also improve from 68,75% in first period to 78,13% in second period. On the other hand, the implementation of learning observation by using problem posing approach has also improving and it is showed by the average percentage of teacher's achievement in first period is 89,2% and student's achievement 85,8%. These results get increase in second period for both teacher and students' achievement which are 94,4% and 91,11%. As a result, students' behavior toward math learning process in class VIII has been improving by using problem posing approach.

  4. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

    Science.gov (United States)

    Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.

    2017-01-01

    Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

  5. A new recombinant factor VIII: from genetics to clinical use

    Directory of Open Access Journals (Sweden)

    Santagostino E

    2014-12-01

    Full Text Available Elena Santagostino Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy Abstract: Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake of understanding of the new biochemical characteristics of FVIII, namely its protein structure, and glycosylation and sulfating patterns. Culture conditions and a five-step purification process have been developed to optimize the safety of turoctocog alfa. The results of two pilot clinical trials using turoctocog alfa confirmed high safety levels, with no patient developing inhibitors during the period of observation. The purpose of this review is to describe briefly the molecular and biological properties of turoctocog alfa, together with details of its clinical development, with emphasis on the needs of patients with hemophilia A. Keywords: hemophilia A, recombinant factor VIII, turoctocog alfa, purification, inhibitor, safety

  6. KEANEKARAGAMAN HYMENOPTERA PARASITOID PADA PERKEBUNAN KELAPA SAWIT PTPN VIII CINDALI, BOGOR

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    Ichsan Luqmana Indra Putra

    2016-09-01

    Full Text Available Diversity of parasitic Hymenoptera in PTPN VIII oil palm plantation Cindali, Bogor. One group of important natural enemies in oil palm plantation is parasitic Hymenoptera. The purpose of this research is to know the diversity and fluctuation of parasitic Hymenoptera PTPN VIII Cindali oil palm plantation. This research was conducted in 6 blocks of oil palm in September 2014 – June 2015. There were 5 plots in every observation blocks 39.2 x 39.2 m in size, and used direct and indirect method. Direct method done by 5 plants in every plots was taken randomized to observed and taken the herbivore insects to reared until the parasitic Hymenoptera came out. Observation of cover crops conducted by 3 subplots determined diagonally in every plots 9.8 x 9.8 m in size and herbivore insects was observed and collected. Indirect methods used sweep net and yellow pan trap. The result of this research, 26 parasitic Hymenoptera families was found, with the Braconidae was the most morphospecies found and the most individual amount was Scelionidae. The abundance of parasitoid in every month fluctuated.

  7. PENGARUH KONSELING KELOMPOK TERHADAP KONFORMITAS SISWI KELAS VIII SMPIT BINA AMAL SEMARANG

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    sudyastuti sudyastuti

    2017-03-01

    Full Text Available This research was conducted based on the phenomenon that happens to grade VIII SMPIT Bina Amal Semarang which has the social conformity low. The purpose of this research is to proof  the influence of counseling service groups towards the conformity. The type of this research is experimental research. The research was conducted with seven times the grant of preferential treatment on grade VIII SMPIT Bina Amal Semarang, research subject with 8 students. The data collection method used is the psychology scale. Data analysis techniques using deskriptif analysis of percentage and wilcoxon test. The results showed incoming students conformity category is middle (59,75%. After being given the treatment through the counseling of the group, a significant unchanged in conformity of students. Conformity of the students in a middle category (60,37%. It shows that conformity of student can’t be influenced through the counseling service groups. Conformity of students not depend on one cause but the another thing to establish it as cohesion,the pretension to change, and the environmental support.

  8. PROSES BERPIKIR SISWA KELAS VIII DALAM MENYELESAIKAN SOAL MATEMATIKA TIMSS MATERI BESAR SUDUT DALAM BENTUK GEOMETRIS

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    Nurul Hidayati Arifani

    2017-07-01

    Full Text Available This study aims to describe the students' thinking process in solving TIMSS math problem on measurement of angle in geometric shapes based on Polya’s problem solving step associated with Swartz’s thinking process theory. The subject of the research was a grade VIII student in SMP Negeri 4 Malang who was classified as intelligent but made many mistakes when completing the test. Data collection methods used were test and interview methods. The results show that students go through the step of generating ideas, clarifying ideas, assessing the reasonableness of ideas, and thinking complex on every step of problem solving, but at the look back step, students do not clarify the idea. Penelitian ini bertujuan untuk mendeskripsikan proses berpikir siswa dalam menyelesaikan soal matematika TIMSS materi besar sudut dalam bentuk geometris berdasarkan langkah penyelesaian masalah Polya yang dikaitkan dengan teori proses berpikir Swartz. Subjek penelitian adalah seorang siswa kelas VIII di SMP Negeri 4 Malang yang tergolong pandai, tetapi banyak melakukan kesalahan saat menyelesaikan soal tes. Metode pengumpulan data yang digunakan adalah metode tes dan wawancara. Hasil penelitian menunjukkan bahwa siswa dalam menyelesaikan soal TIMSS melalui tahap menghasilkan ide, mengklarifikasi ide, menilai kelayakan ide, dan berpikir kompleks pada setiap langkah penyelesaian masalah. Namun, pada tahap memeriksa kembali, siswa tidak melakukan pengklarifikasian ide.

  9. Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a new scorpion toxin that discriminates between neuronal and skeletal sodium channels.

    Science.gov (United States)

    Alami, Meriem; Vacher, Hélène; Bosmans, Frank; Devaux, Christiane; Rosso, Jean-Pierre; Bougis, Pierre E; Tytgat, Jan; Darbon, Hervé; Martin-Eauclaire, Marie-France

    2003-11-01

    The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion alpha-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v)1.2 or rat skeletal muscle Na+ channel rNa(v)1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29+/-5 and 416+/-14 nM respectively for AmmVIII and 2.6+/-0.3 nM and 2.2+/-0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the X-ray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.

  10. Evaluation of B&W UO2/ThO2 VIII experimental core: criticality and thermal disadvantage factor analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carlo Parisi; Emanuele Negrenti

    2017-02-01

    In the framework of the OECD/NEA International Reactor Physics Experiment (IRPHE) Project, an evaluation of core VIII of the Babcock & Wilcox (B&W) Spectral Shift Control Reactor (SSCR) critical experiment program was performed. The SSCR concept, moderated and cooled by a variable mixture of heavy and light water, envisaged changing of the thermal neutron spectrum during the operation to encourage breeding and to sustain the core criticality. Core VIII contained 2188 fuel rods with 93% enriched UO2-ThO2 fuel in a moderator mixture of heavy and light water. The criticality experiment and measurements of the thermal disadvantage factor were evaluated.

  11. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    Science.gov (United States)

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Epitope mapping of inhibitory antibodies targeting the C2 domain of coagulation factor VIII by hydrogen-deuterium exchange mass spectrometry

    Science.gov (United States)

    Sevy, Alexander M.; Healey, John F.; Deng, Wei; Spiegel, P. Clint; Meeks, Shannon L.; Li, Renhao

    2014-01-01

    Summary Background The development of anti-factor VIII (fVIII) antibodies (inhibitors) is a significant complication in the management of patients with hemophilia A, leading to significant increases in morbidity and treatment cost. Using a panel of anti-fVIII monoclonal antibodies (MAbs) to different epitopes on fVIII, we recently have shown that epitope specificity, inhibitor kinetics, and time to maximum inhibition are more important than inhibitor titer in predicting response to fVIII and the combination of fVIII and recombinant factor VIIa. In particular, a subset of high-titer inhibitors responded to high dose fVIII, which would not be predicted based on their inhibitor titer alone. Thus the ability to quickly map the epitope spectrum of patient plasma using a clinically feasible assay may fundamentally change how clinicians approach the treatment of high-titer inhibitor patients. Objectives To map the epitopes of anti-fVIII MAbs, of which 3 are classical inhibitors and one non-classical, using hydrogen-deuterium exchange coupled with liquid chromatography-mass spectrometry (HDX-MS). Methods Binding epitopes of 4 MAbs targeting fVIII C2 domain were mapped using HDX-MS. Results The epitopes determined by HDX-MS are consistent with those obtained earlier through structural characterization and antibody competition assays. In addition classical and non-classical inhibitor epitopes could be distinguished using a limited subset of C2-derived peptic fragments. Conclusion Our results demonstrate the effectiveness and robustness of the HDX-MS method for epitope mapping and suggest a potential role of rapid mapping of fVIII inhibitor epitopes in facilitating individualized treatment of inhibitor patients. PMID:24152306

  13. Keefektifan Experiential Learning Berbantuan Origami Terhadap Kemampuan Keruangan Siswa Kelas VIII

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    Isnaeni Umi Machromah

    2014-11-01

    Full Text Available AbstrakPenelitian eksperimen ini bertujuan untuk mengetahui keefektifan pembelajaran Experiential Learning berbantuan origami terhadap kemampuan keruangan siswa dengan kualifikasi keefektifan yang telah ditentukan. Populasi yaitu siswa kelas VIII SMP Negeri 3 Colomadu tahun pelajaran 2012/2013. Sampel diambil secara simple random sampling. Hasil penelitian ini yaitu: (1 Uji proporsi ketuntasan belajar menunjukkan siswa kelompok eksperimen telah mencapai ketuntasan belajar; (2 Uji perbedaan dua rata-rata menghasilkan simpulan bahwa rata-rata hasil post-test kemam-puan keruangan siswa kelompok eksperimen lebih dari kelompok kontrol; (3 Analisis re-gresi menunjukkan bahwa motivasi belajar siswa memberikan pengaruh positif sebesar 49,3% terhadap kemampuan keruangan siswa; (4 Uji gain ternormalisasi menunjukkan terdapat peningkatan kemampuan keruangan siswa secara signifikan pada kategaori sedang untuk kelompok eksperimen dan kategori rendah untuk kelompok kontrol. Simpulan yang diperoleh yaitu Experiential Learning berbantuan origami efektif terhadap kemampuan keruangan siswa kelas VIII. AbstractThis experiment research aims to determine the effectiveness of Experiential Learning with Origami to the students’s spatial abilities by the criteria of effectiveness. The population of this research is students of grade VIII of SMP Negeri 3 Colomadu 2012/2013 academic year. Independent variables used in this research are learning by Experiential Learning with origami and student’s motivation. While the dependent variable is the student’s spatial abilities. This research is using documentation, spatial abilities’s test, dan motivation’s scale for collecting data method. Result of this research are: (1 proportion test show that the experiment group has reached mastering of learning clasically and personally; (2 result of spatial ablities’s post test in experiment group better than control group; (3 result of regretion shows that student

  14. Analysis of factor VIII gene inversions in 164 unrelated hemophilia A families

    Energy Technology Data Exchange (ETDEWEB)

    Vnencak-Jones, L.; Phillips, J.A. III; Janco, R.L. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others

    1994-09-01

    Hemophilia A is an X-linked recessive disease with variable phenotype and both heterogeneous and wide spread mutations in the factor VIII (F8) gene. As a result, diagnostic carrier or prenatal testing often relies upon laborious DNA linkage analysis. Recently, inversion mutations resulting from an intrachromosomal recombination between DNA sequences in one of two A genes {approximately}500 kb upstream from the F8 gene and a homologous A gene in intron 22 of the F8 gene were identified and found in 45% of severe hemophiliacs. We have analyzed banked DNA collected since 1986 from affected males or obligate carrier females representing 164 unrelated hemophilia A families. The disease was sporadic in 37%, familial in 54% and in 10% of families incomplete information was given. A unique deletion was identified in 1/164, a normal pattern was observed in 110/164 (67%), and 53/164 (32%) families had inversion mutations with 43/53 (81%) involving the distal A gene (R3 pattern) and 10/53 (19%) involving the proximal A gene (R2 pattern). While 19% of all rearrangements were R2, in 35 families with severe disease (< 1% VIII:C activity) all 16 rearrangements seen were R3. In 18 families with the R3 pattern and known activities, 16 (89%) had levels < 1%, with the remaining 2 families having {le} 2.4% activity. Further, 18 referrals specifically noted the production of inhibitors and 8/18 (45%) had the R3 pattern. Our findings demonstrate that the R3 inversion mutation patterns is (1) only seen with VIII:C activity levels of {le} 2.4%, (2) seen in 46% of families with severe hemophilia, (3) seen in 45% of hemophiliacs known to have inhibitors, (4) not correlated with sporadic or familial disease and (5) not in disequilibrium with the Bcl I or Taq I intron 18 or ST14 polymorphisms. Finally, in families positive for an inversion mutation, direct testing offers a highly accurate and less expensive alternative to DNA linkage analysis.

  15. Hemophilia A gene therapy via intraosseous delivery of factor VIII-lentiviral vectors.

    Science.gov (United States)

    Miao, Carol H

    2016-01-01

    Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect. However, ex vivo HSC gene therapy requires pre-conditioning which is highly undesirable for hemophilia patients. The recently developed novel methodology of direct intraosseous (IO) delivery of LVs can efficiently transduce bone marrow cells, generating high levels of transgene expression in HSCs. IO delivery of E-F8-LV utilizing a ubiquitous EF1α promoter generated initially therapeutic levels of FVIII, however, robust anti-FVIII antibody responses ensued neutralized functional FVIII activity in the circulation. In contrast, a single IO delivery of G-FVIII-LV utilizing a megakaryocytic-specific GP1bα promoter achieved platelet-specific FVIII expression, leading to persistent, partial correction of HemA in treated animals. Most interestingly, comparable therapeutic benefit with G-F8-LV was obtained in HemA mice with pre-existing anti-FVIII inhibitors. Platelets is an ideal IO delivery vehicle since FVIII stored in α-granules of platelets is protected from high-titer anti-FVIII antibodies; and that even relatively small numbers of activated platelets that locally excrete FVIII may be sufficient to promote efficient clot formation during bleeding. Additionally, combination of pharmacological agents improved transduction of LVs and persistence of transduced cells and transgene expression. Overall, a single IO infusion of G-F8-LV can generate long-term stable

  16. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Voorberg, Jan; Mertens, Koen

    2011-01-01

    Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both

  17. Requirements for cellular co-trafficking of factor VIII and von Willebrand factor to Weibel-Palade bodies

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bierings, R.; Storm, G.; Voorberg, J.; Mertens, K.

    2007-01-01

    von Willebrand factor (VWF) serves a critical role as a carrier of factor (F)VIII in circulation. While it is generally believed that FVIII and VWF assemble in circulation after secretion from different cells, an alternative view is that cells should exist that co-express FVIII and VWF. In this

  18. Effectiveness of Peer Tutoring in Learning English among Tutors and Tutees of Class VIII Students in Kancheepuram DT

    Science.gov (United States)

    Marieswari, M.; Prema, N.

    2016-01-01

    The peer who teaches to their mates is peer tutoring. It is a common instructional strategy used in classrooms. The aim of this study is to know whether there is any improvement in achievement marks of tutors and tutees after the process of peer tutoring. Class VIII students were selected as the sample for the present experimental study. The…

  19. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  20. Mediastinal, subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient.

    Science.gov (United States)

    Omura, Yuka; Kusama, Yoshiki; Takeuchi, Noriko; Ishiwada, Naruhiko

    2018-01-17

    We report a case of mediastinal subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient. The patient arrived at the hospital with the chief complaint of immobility, and blood examination results suggested an acute infection and poorly controlled diabetes mellitus. Group B streptococcal bacteria were cultured from the patient's blood, and identified as serotype VIII upon further analysis. The patient recovered without any sequelae after percutaneous drainage, antibiotic therapy, and intensive glycemic control. Although the incidence of group B streptococcal infection in non-pregnant adults has recently increased in many developed countries, information on serotype VIII infection is quite limited. The reason is that serotype VIII group B streptococci are a Japan-specific serotype, and rarely cause invasive infections, even in Japan. Therefore, further surveillance and case reports should be documented in the future. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Factor VIII genotype and inhibitor development in patients with haemophilia A: highest risk in patients with splice site mutations.

    NARCIS (Netherlands)

    Boekhorst, J.; Lari, G.R.; D'Oiron, R.; Costa, J.M.; Novakova, I.R.O.; Ala, F.A.; Lavergne, J.M.; Heerde, W.L. van

    2008-01-01

    The appearance of inhibitory antibodies against factor VIII (FVIII) is the most severe and costly complication of replacement therapy in patients with haemophilia A (HA). To determine the relationship between FVIII genotype and inhibitor development, baseline FVIII activity, genotype and inhibitor

  2. 77 FR 42696 - Notice of New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2012-07-20

    ... Forest Service Notice of New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... Laws, Recreation Fee Coordinator, 406-283-7648 SUPPLEMENTARY INFORMATION: The Federal Recreation Lands... advance notice in the Federal Register whenever new recreation fee areas are established. This new fee...

  3. 78 FR 19445 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2013-04-01

    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... and maintenance of these recreation sites. Lake Canyon Recreation Area is a fee campground with 54... is to keep the site fees consistent with other campsites in the Lake Canyon Recreation Area. The fee...

  4. 75 FR 2850 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-01-19

    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... and recreation experiences. A financial analysis is being completed to determine fee rates. The.... Recreation Passes such as the Northwest Forest Pass would cover day use fees for this trailhead. Northwest...

  5. 76 FR 36518 - Notice of Meeting; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2011-06-22

    .... 2. An increase of fees for the Shelf Road Recreation Area in the Royal Gorge Field Office of the BLM..., Bureau of Land Management staff and Committee members. Persons who wish to bring recreation fee matters... Forest Service Notice of Meeting; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447...

  6. 75 FR 21583 - Notice of Proposed New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L...

    Science.gov (United States)

    2010-04-26

    ... Forest Service Notice of Proposed New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub... improve the recreation experience. An analysis of the campground shows that the proposed fees are..., Moab/Monticello Recreation Fee Coordinator, 435-636-3367. Information about proposed fee changes can...

  7. 78 FR 52499 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2013-08-23

    ... Forest Service Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: Monongahela National Forest, Forest Service, USDA. ACTION: Notice of new fee site... new recreation fee areas are established. This new fee will be reviewed by the Eastern Region...

  8. 78 FR 41783 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2013-07-11

    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... comments can be compiled, analyzed and shared with a Recreation Resource Advisory Committee. New fees would... advance notice in the Federal Register whenever new recreation fee areas are established. Once public...

  9. 75 FR 80789 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2010-12-23

    ... Forest Service Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108... Agriculture to publish a six month advance notice in the Federal Register whenever new recreation fee areas are established. This new fee will be reviewed by the Colorado Recreation Resource Advisory Committee...

  10. Chromosome VIII disomy influences the nonsense suppression efficiency and transition metal tolerance of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zadorsky, S P; Sopova, Y V; Andreichuk, D Y; Startsev, V A; Medvedeva, V P; Inge-Vechtomov, S G

    2015-06-01

    The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation termination factor eRF3. Mutations in this gene lead to the suppression of nonsense mutations and a number of other pleiotropic phenotypes, one of which is impaired chromosome segregation during cell division. Similar effects result from replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic and epigenetic changes that occur in the sup35 background result in partial compensation for this suppressor effect. In this study we showed that in S. cerevisiae strains in which the SUP35 orthologue from the yeast Pichia methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results in decreased efficiency of nonsense suppression. This antisuppressor effect is not associated with decreased stop codon read-through. We identified SBP1, a gene that localizes to chromosome VIII, as a dosage-dependent antisuppressor that strongly contributes to the overall antisuppressor effect of chromosome VIII disomy. Disomy of chromosome VIII also leads to a change in the yeast strains' tolerance of a number of transition metal salts. Copyright © 2015 John Wiley & Sons, Ltd.

  11. 75 FR 5759 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-02-04

    ... Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII... Recreation Fee Sites. SUMMARY: The Soda Springs Ranger District of the Caribou-Targhee National Forest is... appreciate and enjoy the availability of developed recreation campground and picnicking facilities. This...

  12. 75 FR 4340 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-01-27

    ... Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII.... SUPPLEMENTARY INFORMATION: The Federal Recreation Lands Enhancement Act (Title VII, Pub. L. 108-447) directed... new recreation fee areas are established. The Caribou-Targhee National Forest currently has nine other...

  13. 75 FR 26711 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L...

    Science.gov (United States)

    2010-05-12

    ... No: 2010-11040] DEPARTMENT OF AGRICULTURE Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, USDA Forest Service. ACTION: Notice of New Recreation Fee Site. SUMMARY: Bethel Motorcycle and Bethel...

  14. 75 FR 26714 - Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII...

    Science.gov (United States)

    2010-05-12

    ... No: 2010-11042] DEPARTMENT OF AGRICULTURE Forest Service Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, USDA Forest Service. ACTION: Notice of Proposed New Recreation Fee Site. SUMMARY: Rattlesnake Bay...

  15. Symposium by NATO Defense Research Group Panel VIII on Computer-Based Instruction in Military Environments

    CERN Document Server

    Weddle, Peter

    1987-01-01

    This collection of papers is the result of a symposium sponsored by NATO's Defense Research Group Panel VIII in the Spring of 1985. The symposium came into being when it became obvious to the NATO countries that research, development and utilization of advanced technologies for training was the best means of increasing both training effectiveness and efficiency. This symposium was the second in a series of three devoted to training. The series was structured to cover all aspects of training. The first series addressed the value of training, the second one dealt with the application of training technologies and the third and last of the series focused on academic issues concerned with the effect of prior learning on subsequent learning. The fact that a major American publisher has determined that computer based instruction is the technology of greatest interest to the NATO community is not surprising. Advances in microprocessor technology have revolutionized both how and where we train. During this symposium t...

  16. PENERAPAN PENDEKATAN CINEMATHERAPY UNTUK MENINGKATKAN PERILAKU PROSOSIAL PADA SISWA KELAS VIII DI BOSOWA INTERNATIONAL SCHOOL MAKASSAR

    Directory of Open Access Journals (Sweden)

    Haeruddin Niva

    2016-06-01

    Full Text Available The objectives of the research are: (i to know the prosocial behavioral level of the students in Bosowa International School Makassar before and after giving cinematography approach, and (ii to know whether or not the approach is able to enhance the prosocial behavior of the students in Bosowa International School Makassar. The research is a quantitative research using experimental method. The research design used is quasi experimental design with non-equivalent control group design. The data collection technique applied is scale and FGD (Focus Group Discussion. The findings shows that (i the prosocial behavioral level of the students was low in pretest while after giving treatment there were significant increase to the prosocial behavior in the experimental group, and (ii the cinematography approach was able to increase the prosocial behavior of the Grade VIII students in Bosowa Internatinal School Makassar. 

  17. Naked DNA transfer of Factor VIII induced transgene-specific, species-independent immune response in hemophilia A mice.

    Science.gov (United States)

    Ye, Peiqing; Thompson, Arthur R; Sarkar, Rita; Shen, Zhenping; Lillicrap, David P; Kaufman, Randal J; Ochs, Hans D; Rawlings, David J; Miao, Carol H

    2004-07-01

    The development of antibodies to a previously unexpressed protein product may limit the success of human gene therapy approaches. We inserted B-domain-deleted factor VIII (FVIII) cDNA of human, canine, or murine origin into the multiple cloning site of a liver-specific vector, pBS-HCRHPI-A, to yield plasmids pBS-HCRHPI-FVIIIA, pBS-HCRHPI-cFVIIIA, and pBS-HCRHPI-mFVIIIA, respectively. Fifty micrograms of each plasmid in 2 ml of solution was rapidly injected into the tail vein of three groups of hemophilia A mice. Factor VIII levels ranging from 3 to 12 IU/ml were obtained from all three groups (normal is 1 IU/ml in human plasma) 3 days after treatment. These initial very high levels of functional human, canine, or murine factor VIII, however, fell gradually to undetectable levels within 2-3 weeks, and their disappearance correlated with the generation of high-titer, inhibitory anti-FVIII antibodies. Notably, this immune response occurred independent of the species of origin of the exogenous factor VIII. Antibody titers to factor VIII were detected beginning at 2 weeks, reached a plateau and remained at high levels for over 6 months. The majority of anti-hFVIII IgG was IgG1 isotype specific, suggesting a humoral response mediated by Th2-induced signals. Consistent with this idea, in a separate group of mice treated with pBS-HCRHPI-FVIIIA, transient immunosuppression by cyclophosphamide significantly delayed (5/6) or abolished (1/6) inhibitory antibody formation against the transgene.

  18. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

    Science.gov (United States)

    Al-Allaf, Faisal A.; Taher, Mohiuddin M.; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M.; Abalkhail, Halah A.; Owaidah, Tarek MA.

    2017-01-01

    Background Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. Methods For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Results Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. Conclusion The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia. PMID:28270892

  19. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies.

    Science.gov (United States)

    Al-Allaf, Faisal A; Taher, Mohiuddin M; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M; Abalkhail, Halah A; Owaidah, Tarek Ma

    2017-04-01

    Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia.

  20. Heat transfer equipment performance diagnosis of auxiliary systems in electric power stations; Diagnostico de comportamiento de equipo de transferencia de calor de sistemas auxiliares de centrales termoelectricas

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Esparza Gutierrez, Rogelio [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1990-12-31

    In this article the methodology followed to diagnose the performance of the equipment where heat is transferred from the feed water, condensate and circulation water systems in fossil power plants (FPP). The data collection is made with the unit in normal operation, using local instrumentation without taking the equipment out of service for its installation. The equipment diagnosis is made through the analysis of the collected data in actual operation and the design data; for this purpose a thermal balance of the interested systems is performed to obtain all the conditions an operation data. Later on the performance indicative parameters (PIP) of actual operation and design are calculated and compared one against the other. Such a comparison reveals the performance deterioration and the possible equipment faults. The data obtained and the supplementary information are stored in a data base whose objective is that Comision Federal de Electricidad has on hand a prompt access to them in order to control the performance, compare them among similar units and power stations, and inclusively verify possible recurrent causes of low availability in the referred systems. [Espanol] En este articulo se presenta la metodologia seguida para diagnosticar el comportamiento de equipos en los que se transfiere calor de los sistemas de agua de alimentacion, condensado y circulacion de las centrales termoelectricas (CTE). La toma de datos se realiza con la unidad en operacion normal, utilizando instrumentacion local sin necesidad de sacar de servicio a los equipos para su instalacion, ya que se ocupan los mismos puntos para instrumentos con que cuentan por diseno. El diagnostico de los equipos se realiza mediante el analisis de los datos recopilados, tanto de operacion real como de diseno; para ello, se efectua un balance termico de los sistemas de interes para obtener todas las condiciones y los datos de operacion. Posteriormente, se calculan los parametros indicativos de

  1. Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery

    Directory of Open Access Journals (Sweden)

    Harrison C Brown

    2014-01-01

    Full Text Available Clinical data support the feasibility and safety of adeno-associated viral (AAV vectors in gene therapy applications. Despite several clinical trials of AAV-based gene transfer for hemophilia B, a unique set of obstacles impede the development of a similar approach for hemophilia A. These include (i the size of the factor VIII (fVIII transgene, (ii humoral immune responses to fVIII, (iii inefficient biosynthesis of human fVIII, and (iv AAV vector immunity. Through bioengineering approaches, a novel fVIII molecule, designated ET3, was developed and shown to improve biosynthetic efficiency 10- to 100-fold. In this study, the utility of ET3 was assessed in the context of liver-directed, AAV-mediated gene transfer into hemophilia A mice. Due to the large size of the expression cassette, AAV-ET3 genomes packaged into viral particles as partial genome fragments. Despite this potential limitation, a single peripheral vein administration of AAV-ET3 into immune-competent hemophilia A mice resulted in correction of the fVIII deficiency at lower vector doses than previously reported for similarly oversized AAV-fVIII vectors. Therefore, ET3 appears to improve vector potency and mitigate at least one of the critical barriers to AAV-based clinical gene therapy for hemophilia A.

  2. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011.

    Science.gov (United States)

    Collins, Peter W; Palmer, Benedict P; Chalmers, Elizabeth A; Hart, Daniel P; Liesner, Ri; Rangarajan, Savita; Talks, Katherine; Williams, Michael; Hay, Charles R M

    2014-11-27

    The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands. © 2014 by The American Society of Hematology.

  3. Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy.

    Science.gov (United States)

    Peng, Baowei; Ye, Peiqing; Rawlings, David J; Ochs, Hans D; Miao, Carol H

    2009-11-12

    One major obstacle in gene therapy is the generation of immune responses directed against transgene product. Five consecutive anti-CD3 treatments concomitant with factor VIII (FVIII) plasmid injection prevented the formation of inhibitory antibodies against FVIII and achieved persistent, therapeutic levels of FVIII gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is applicable in tolerized mice without eliciting immune responses. Anti-CD3 treatment significantly depleted both CD4+ and CD8+ T cells, whereas increased transforming growth factor-beta levels in plasma and the frequency of both CD4+CD25+FoxP3+ and CD4+CD25-Foxp3+ regulatory T cells in the initial few weeks after treatment. Although prior depletion of CD4+CD25+ cells did not abrogate tolerance induction, adoptive transfer of CD4+ cells from tolerized mice at 6 weeks after treatment protected recipient mice from anti-FVIII immune responses. Anti-CD3-treated mice mounted immune responses against both T-dependent and T-independent neo-antigens, indicating that anti-CD3 did not hamper the immune systems in the long term. Concomitant FVIII plasmid + anti-CD3 treatment induced long-term tolerance specific to FVIII via a mechanism involving the increase in transforming growth factor-beta levels and the generation of adaptive FVIII-specific CD4+Foxp3+ regulatory T cells at the periphery. Furthermore, anti-CD3 can reduce the titers of preexisting anti-FVIII inhibitory antibodies in hemophilia A mice.

  4. Opportunities for energy conservation detected in a diagnosis made for the smelting industry; Oportunidades de ahorro de energia detectadas en un diagnostico efectuado en la industria de la fundicion

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez Bautista, Rolando; Magana Castro, Rogelio [Fideicomiso de Apoyo al Programa de Ahorro de Energia del Sector Electrico (FIDE), Mexico, D. F. (Mexico)

    1993-12-31

    The smelting industry is one of the main industrial branches in the utilization of electric power at national level, for this reason an energy diagnosis was made in representative industries of this process in which excellent results were obtained regarding opportunity areas, with potentials ranging from 15% up to 40% of energy saving in relation to the energy consumption, with actions recoverable in less than 15 months. [Espanol] La industria de la fundicion es una de las principales ramas industriales en la utilizacion de la energia electrica a nivel nacional, por esta razon se realizo un diagnostico energetico en empresas representativas de este proceso y en las cuales se obtuvieron excelentes resultados en cuanto a areas de oportunidad, teniendo potenciales que van desde un 15% hasta un 40% de ahorro con relacion al consumo de energia, con medidas que se recuperan en menos de 15 meses.

  5. Advance of the National Program of Radiological Protection and Safety for medical diagnostic with X-rays; Avance del Programa Nacional de Proteccion y Seguridad Radiologica para diagnostico medico con rayos X

    Energy Technology Data Exchange (ETDEWEB)

    Verdejo S, M. [Direccion de Riesgos Radiologicos, Direccion General de Salud Ambiental (Mexico)

    1999-07-01

    The National Program of Radiological Protection and Safety for medical diagnostic with X-ray (Programa Nacional de Proteccion y Seguridad Radiologica para diagnostico medico con rayos X) was initiated in the General Direction of Environmental Health (Direccion General de Salud Ambiental) in 1995. Task coordinated with different dependences of the Public Sector in collaboration between the Secretary of Health (Secretaria de Salud), the National Commission of Nuclear Safety and Safeguards (Comision Nacional de Seguridad Nuclear y Salvaguardias) and, the National Institute of Nuclear Research (Instituto Nacional de Investigaciones Nucleares). The surveillance to the fulfilment of the standardization in matter of Radiological Protection and Safety in the medical diagnostic with X-rays has been obtained for an important advance in the Public sector and it has been arousing interest in the Private sector. (Author)

  6. PENGEMBANGAN MODEL PEMBELAJARAN BERBASIS MASALAH YANG BERMUATAN NILAI-NILAI PENDIDIKAN KARAKTER DALAM PEMBELAJARAN MENULIS CERPEN PADA KELAS VIII SMP

    Directory of Open Access Journals (Sweden)

    Aditya Dwi Haryawan

    2014-08-01

    Full Text Available Menulis merupakan suatu keterampilan yang harus dimiliki peserta didik sekolah menengah pertama. Melaluitulisan, peserta didik dapat menyampaikan pengalaman, pikiran, perasaan, atau keinginan. Masalah penelitianini adalah (1 bagaimanakah kebutuhan pengembangan model pembelajaran berbasis masalah yang bermuatannilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen berdasarkan persepsi guru dan pesertadidik kelas VIII SMP?; (2 bagaimanakah prinsip-prinsip pengembangan model pembelajaran berbasis masalahyang bermuatan nilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen pada peserta didik kelasVIII SMP? (3 bagaimanakah pengembangan prototipe model pembelajaran berbasis masalah yang bermuatannilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen pada kelas VIII SMP?; (4 bagaimanakahkeberterimaan penerapan pengembangan model pembelajaran berbasis masalah yang bermuatan nilai-nilaipendidikan karakter dalam pembelajaran menulis cerpen pada kelas VIII SMP. Dalam penelitian ini digunakandesain Research and Development. Tahapan yang dilakukan dalam penelitian ini adalah studi pustaka, analisiskebutuhan, pengembangan model yang dikembangkan, uji validasi, revisi, implementasi, revisi akhir,pengembangan model/produk akhir. Pengumpulan data dilakukan dengan observasi, angket, wawancara, tes,dan dokumentasi foto. Writing is a skill that must be owned by middle school students. Through writing, students canconvey experiences, thoughts, feelings, or desires. The research problem is (1 How can the needsof the development of PBL model that charged the values of character education in learning towrite short stories on the perceptions of teachers and students of class VIII?; (2 How do thecharacteristics of the development of PBL model value-laden -the value of character education inlearning to write short stories at the high school of learner assessment system class?; (3 How isthe development of a prototype model of PBL  charged

  7. Histopatologia de fígado, rim e baço de piaractus mesopotamicus, prochilodus lineatus e pseudoplatystoma fasciatum parasitados por myxosporídios, capturados no Rio Aquidauana, Mato Grosso do Sul, Brasil Histopathology of liver, kidney and spleen of Piaractus mesopotamicus, Prochilodus lineatus and Pseudoplatystoma fasciatum infected by myxosporean parasite, caugth in Aquidauana River, Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Cristiane M. de Campos

    2008-12-01

    Full Text Available Este estudo descreveu a histopatologia de rim, baço e fígado de Piaractus mesopotamicus, Prochilodus lineatus e Pseudoplatystoma fasciatum, parasitados por mixosporídios, capturados no Rio Aquidauana, MS. Após necropsia, amostras do fígado, rim cefálico e baço foram colhidas, fixadas em formalina a 10 % tamponada e processadas de acordo com a rotina histológica. Os cortes foram feitos à espessura de 5 μm e corados com hematoxilina-eosina. Foram encontrados Myxobolus porofilus em P. lineatus, M. colossomatis em P. mesopotamicus e Myxobolus spp. nas três espécies de hospedeiros. Cistos de mixosporídios no exame histopatológico foram vistos no fígado e baço de P. mesopotamicus. Mais de 50% das amostras de fígado de P mesopotamicus e P lineatus apresentou hepatodistrofia difusa. Mais de 80 % das amostras de fígado de P. fasciatum apresentou formações hialinas concêntricas e esteatose em 50% das amostras. Em 95,23 % das amostras de rins de P. mesopotamicus, foram observadas alterações teciduais, e em mais de 60 % dos casos nefrodistrofia difusa moderada e congestão de sinusóides glomerulares. Alterações teciduais nas amostras de rins de P. lineatus foram observadas em menos de 20 % da amostra. No baço dos peixes ora examinados não foram encontradas lesões dignas de relato.Histological analysis of kidney, spleen and liver of Piaractus mesopotamicus, Prochilodus lineatus and Pseudoplatystoma fasciatum, infected by myxosporean, caugth in Aquidauana river, MS, was studied. After necropsy, samples of liver, previous kidney and spleen were fixed in 10 % buffered formalin and processed followed histological routine methods. Sections of 5 μm were stained with hematoxylin and eosin. Myxobolusporofilus, M. colossomatis and were found in P. lineatus, in P. mesopotamicus respectively and Myxobolus spp. Were also found in all three species of fish. Myxosporideans cysts in the liver and spleen of P mesopotamicus were also related. Up

  8. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  9. Potential role of a new PEGylated recombinant factor VIII for hemophilia A

    Directory of Open Access Journals (Sweden)

    Wynn TT

    2016-06-01

    Full Text Available Tung Thanh Wynn,1 Burak Gumuscu,2,3 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Florida, Gainesville, FL, 2Pediatric Hematology-Oncology, Bon Secours Health System, St. Mary’s Hospital, Richmond, VA, 3Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Virginia, Charlottesville, VA, USA Abstract: Hemophilia A, a deficiency in the activity of coagulation factor (F VIII, is an X-linked bleeding disorder with an approximate incidence of one in 5,000 male infants. Bleeding-related complications often result in greater severity of disease, poor quality of life, surgical interventions for severe joint destruction, and shortened life span. With the availability of plasma-derived and recombinant FVIII products, the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies. Current hemophilia research is focusing on the creation of new factor replacement therapies with longer half-lives; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing ­activity; and limiting the immunogenicity of the protein. PEGylation involves the covalent attachment of polyethylene glycol (PEG to a protein, peptide, or a small molecule drug. PEG effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce susceptibility of the molecule to proteolytic activity and degradation. It is also believed that PEGylation changes the surface charge of the protein that ultimately interferes with some receptor-mediated clearance processes. The half-life of PEGylated factor is more prolonged when compared to non-PEGylated full-length recombinant FVIII. The dawn of a new era in the care of hemophilia patients is upon us with the release of recombinant FVIII products with extended half-lives, and products with even more extended half

  10. ANALISIS KEMAMPUAN BERPIKIR ALJABAR DALAM MATEMATIKA PADA SISWA SMP KELAS VIII

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    Ahmad Badawi

    2017-03-01

    Full Text Available Berpikir aljabar merupakan representasi dari aktivitas maupun kemampuan dalam mempelajari aljabar sekolah. Tujuan penelitian ini adalah untuk mengetahui kemampuan berpikir aljabar siswa SMP Kelas VIII. Metode penelitian yang digunakan adalah dengan pendekatan deskriptif kualitatif. Penelitian ini dilakukan dengan memberikan tes kemampuan berpikir aljabar pada siswa. Selanjutnya berdasarkan hasil tes, siswa dikelompokkan berdasarkan kemampuan berpikir aljabar mereka yang terdiri dari kelompok tingkat tinggi, kelompok tingkat sedang, dan kelompok tingkat rendah. Dari masing-masing kelompok tersebut dipilih dua subjek sebagai perwakilan untuk diwawancara lebih lanjut terkait kemampuan berpikir aljabar mereka. Hasil analisis dari penelitian ini menunjukkan bahwa kemampuan generasional, transformasional, dan level-meta global sudah terlihat pada sebagian siswa kelas VIII. Siswa yang termasuk dalam kelompok tingkat tinggi mempunyai kemampuan generasional, transformasional, dan level-meta global yang cenderung tinggi. Sedangkan siswa dalam kelompok rendah mempunyai kemampuan transformasional yang cenderung rendah, kemampuan generasional yang rendah sampai sedang, dan kemampuan level-meta global yang rendah sampai sedang.   Algebraic thinking is a representation of activities and abilities to learn school algebraic. The aim of this research was to determine the ability of eighth grade junior high school students in algebraic thinking. The method used in this research was the qualitative descriptive approach. This research was conducted with giving a test of algebraic thinking skills to the students. Furthermore, based on test results, students are grouped according to their algebraic thinking skills which consists of a high­level group, moderate­level group and low­level group. From each group, two subjects were selected to be interviewed more related their algebraic thinking skills, as a representative for their each group. Analytical results from

  11. PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

    Directory of Open Access Journals (Sweden)

    Apri Dwi Astuti

    2012-10-01

    Full Text Available Kemandirian belajar membantu siswa untuk bertanggung jawab dan menumbuhkan kesadaran belajar. Penggunaan uang saku menumbuhkan jiwa mandiri, jujur dan komitmen. Adapun hasil observasi awal menunjukkan masih ada siswa kels VII dan VIII SMP Semesta untuk kompetensi dasar ekonomi dibawah KKM. Tujuan penelitian ini untuk mengetahui pengaruh kemandirian belajar dn penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta. Populasi penelitian ini adalah semua siswa kelas VII dan VIII SMP Semesta Boarding School Semarang. Variabel penelitian ini adalah kemandirian belajar dan penggunaan uang saku sebagai variabel bebas, sedangkan untuk� variabel terikat adalah prestasi belajar kompetensi dasar ekonomi. Data diambil dengan metode wawancara, kuesioner dan dokumentasi guru. Analisis data menggunakan analisis regresi linear berganda.Berdasarkan penelitian secara simultan menunjukkan adanya pengaruh antara kemandirian belajar dan penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 51,3%. Secara parsial, pengaruh kemandirian belajar terhadap prestasi belajar kompetensi dasar ekonomi sebesar 66,2% dan pengaruh penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 62,5%.Berdasarkan hasil penelitian diatas disimpulkan bahwa kemandirian belajar dan penggunaan uang saku berpengaruh positif baik secara simultan maupun parsial terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta Boarding school semarang tahun pelajaran 2011/2012. Saran yang berkaitan dengan penelitian ini yaitu : 1 Sekolah disarankan untuk memberikan batasan siswa pulang ke rumah agar dapat membantu siswa beradaptasi dengan cepat dan mudah tinggal di asrama. 2 Orang tua disarankan untuk memberikan uang saku yang disesuaikan dengan kebutuhan siswa. 3 Siswa disarankan untuk meningkatkan kemandirian dalam aspek belajar terutama bagi mata pelajaran yang masih kurang dari

  12. Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A.

    Science.gov (United States)

    Gomperts, Edward

    2015-08-01

    Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). 'Bypassing' therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

  13. [Detection of hemophilia A carriers by PCR analysis of hind III polymorphism in the factor VIII gene].

    Science.gov (United States)

    Wu, S; Li, Y; Cui, H; Xie, Y; Zheng, J; Pan, X; Zhang, H; Zhao, R; Zhang, Q

    1998-04-10

    To explore a scheme of using PCR analysis in the detection of carriers of Hind III polymorphism of factor VIII gene of hemophilia A. Implicating intron 19 of the factor VIII gene of 6 patients with the hemophilia A and 207 unrelated X-chromosomes were amplified by PCR and were analysed by means of Amp-RFLPs of Hind III. The incidence of the polymorphic Hind III sites in the given population was found to be 0.29. The frequence of the Hind III heterozygotes in women calculated according to Hardy-Weinberg equation was 0.41, which proved to be informative enough for carrier detection and prenatal diagnosis of hemophilia A. 2 out of 6 families (33%)examined in this study were informative. The new scheme proved to be effective for hemophilia A carrier detection and prenatal diagnosis.

  14. Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides presented by monocyte-derived dendritic cells.

    Science.gov (United States)

    Peyron, Ivan; Hartholt, Robin B; Pedró-Cos, Laura; van Alphen, Floris; Ten Brinke, Anja; Lardy, Neubury; Meijer, Sander; Voorberg, Jan

    2017-10-12

    The development of anti-factor VIII antibodies represents a major complication in the treatment of patients with hemophilia A. Generation of high affinity anti-factor VIII antibodies is dependent on help provided by CD4+ T cells that recognize factor VIII-derived peptides presented on class II major histocompatibility complex on the surface of antigen presenting cells. In order to identify the immune-dominant epitopes that can be presented to CD4+ T cells, we previously developed a mass-spectrometry based method to identify factor VIII derived peptides that are presented on human leucocyte antigen (HLA)-DR. In the present work, we compared the repertoire of FVIII-derived peptide presented on HLA-DR and HLA-DQ. Monocyte-derived dendritic cells from 9 HLA-typed healthy donors were pulsed with recombinant factor VIII. HLA-DR and HLA-DQ molecules were purified using monoclonal antibodies. Our data show that HLA-DQ and HLA-DR present a similar repertoire of factor VIII-derived peptides. However, the number of peptides associated with HLA-DQ was lower when compared to HLA-DR. We also identified a peptide, within the acidic a3 domains of factor VIII that is presented with higher frequency on HLA-DQ. Interestingly, this peptide was found to have a higher predicted affinity for HLA-DQ when compared to HLA-DR. Taken together, our data suggest that HLA-DQ participates in the presentation of factor VIII peptides, thereby contributing to the development of inhibitory antibodies in a proportion of patients with severe hemophilia A. Copyright © 2017, Ferrata Storti Foundation.

  15. Development of Integrated Natural Science Teaching Materials Webbed Type with Applying Discourse Analysis on Students Grade VIII in Physics Class

    Science.gov (United States)

    Sukariasih, Luh

    2017-05-01

    This study aims to produce teaching materials integrated natural science (IPA) webbed type of handout types are eligible for use in integrated science teaching. This type of research IS a kind of research and development / Research and Development (R & D) with reference to the 4D development model that is (define, design, develop, and disseminate). Data analysis techniques used to process data from the results of the assessment by the validator expert, and the results of the assessment by teachers and learners while testing is limited (12 students of class VIII SMPN 10 Kendari) using quantitative descriptive data analysis techniques disclosed in the distribution of scores on the scale of five categories grading scale that has been determined. The results of due diligence material gain votes validator material in the category of “very good” and “good”, of the data generated in the feasibility test presentation obtained the category of “good” and “excellent”, from the data generated in the feasibility of graphic test obtained the category of “very good “and” good “, as well as of the data generated in the test the feasibility of using words and language obtained the category of“very good “and” good “, so with qualifications gained the teaching materials IPA integrated type webbed by applying discourse analysis on the theme of energy and food for Junior High School (SMP) grade VIII suitable as teaching materials. In limited testing, data generated in response to a science teacher at SMPN 10 Kendari to product instructional materials as “excellent”, and from the data generated while testing is limited by the 12 students of class VIII SMPN 10 Kendari are more students who score indicates category “very good”, so that the qualification obtained by the natural science (IPA) teaching material integrated type webbed by applying discourse analysis on the theme of energy and food for SMP / class VIII fit for use as teaching material.

  16. Pengembangan Materi Luas Permukaan Dan Volum Limas Yang Sesuai Dengan Karakteristik Pmri Di Kelas VIII SMP Negeri 4 Palembang

    OpenAIRE

    Hariyati, Hariyati; Indaryanti, Indaryanti; Zulkardi, Zulkardi

    2008-01-01

    Penelitian ini bertujuan mengembangkan materi luas permukaan dan volum limas dengan pendekatan PMRI. Subjek dalam penelitian ini adalah siswa kelas VIII SMP Negeri 4 Palembang. Dalam mengembangkan materi terdapat proses evaluasi formatif dan uji coba terhadap materi, yaitu expert review, one-to-one evaluation, small group, dan field test. Dari tiga tahap pertama, materi dinyatakan valid. Kemudian materi diujicobakan di lapangan (field test). Dari hasil uji coba diperoleh simpulan yaitu mengha...

  17. PENGARUH VIRTUAL LABORATORY BERBASIS FLASH ANIMATION TERHADAP PEMAHAMAN KONSEP DAN KETERAMPILAN BERPIKIR KRITIS PESERTA DIDIK TEMA OPTIK KELAS VIII SMP

    Directory of Open Access Journals (Sweden)

    Nuzul Andri Permana

    2017-02-01

    ___________________________________________________________________ Availability of practical tools in learning of science subject is needed to achieve the learning objectives. Based on observations in Junior High School 10 Semarang, practicum low intensity because of practical tools ara not available that support learning activities. The intensity of practicum is low, it make critical thinking skills of students is low. Critical thinking skills to be one of the variables that influence of understanding concept of learners. Availability of practicum tools that incomplete requires teachers to achieve the learning objectives by using media that can support learners to be able to do practicum virtually. Media that can support to do practicum virtually is a virtual laboratory. This study aims to determine the influence of virtual laboratory based flash animation againts understanding concepts and critical thinking skills of students in grade VIII SMP in optical theme. The population used in this study were all students of grade VIII Junior High School 10 Semarang academic year 2015/2016. Sampling technique used is purposive sampling and obtained VIII C as the experimental class and VIII F as the control class. The design of study is nonequivalent control group design. The results showed that the correlation value of understanding concept of students is 0.660 which shows in the strong category and correlation analysis of students' critical thinking skills of 0,729 based on observational data and 0.69 based on the posttest data that shows in the strong category. The influence of the use of virtual laboratory-based flash animation againts understanding concept of students is 43.53%, whereas the influence the use of virtual laboratory based flash animation againts the critical thinking skills of students is 53.14% based on observational data and 47.06% based on the posttest data. The conclusion is there are infuence of virtual laboratory based flash animation againts

  18. Neurotology findings in patients with diagnosis of vascular loop of cranial nerves VIII in magnetic resonance imaging

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    Grocoske, Francisco Luiz Busato

    Full Text Available Introduction: The vascular compression by redundant vessels under the VIII cranial nerves has been studied since the 80's, and many authors proposed correlations between the compression and the otoneurological findings (vertigo, tinnitus, hypoacusis, audiometry and electrophysiological findings. Objective: Analyze and correlate the different signs and otoneurological symptoms, the audiological findings and its incidence over individuals with Vascular Loop (VL diagnosis of VIII cranial nerves by magnetic resonance imaging (MRI. Method: Retrospective study through the analysis of medical records of 47 patients attended in the otoneurology clinic of Clinical Hospital of UFPR. All the patients have MRI exams with compatible pictures of VL of the VIII cranial nerves. Results: The tinnitus was the most frequent symptom, in 83% of the patients, followed by hypoacusis (60% and vertigo (36%. The audiometry presented alterations in 89%, the brainstem evoked auditory potential in 33% and the vecto-electronystagmography in 17% of the patients. Was not found statistically significant relation between the buzz or hypoacusis, and the presence of VL in MRI. Only 36% of patients had complaints of vertigo, the main symptom described in theory of vascular compression of the VIII pair of nerve. As in the audiometry and in brainstem evoked auditory potential was not found a statistically significant relation between the exam and the presence of the VL in the RMI. Conclusion: The results show independence between the findings of the RMI, clinical picture and audiological results (p>0,05 suggesting that there are no exclusive and direct relation between the diagnosis of vascular loop in the MRI and the clinical picture matching.

  19. Pengaruh Model Pembelajaran Berbasis Masalah terhadap Prestasi Belajar Matematika dan Keterampilan Berpikir Kritis Siswa Kelas VIII SMP Negeri 2 Abang

    OpenAIRE

    KD ARYA UTAMA JAYA; PROF.DR. NASWAN SUHARSONO, M.Pd; DRA. NI NYOMAN PARWATI, M.Pd

    2015-01-01

    Tujuan penelitian ini adalah untuk mendeskripsikan perbedaan prestasi belajar matematika dan keterampilan berpikir kritis antara siswa yang belajar dengan menerapkan model pembelajaran berbasis masalah dan siswa yang belajar dengan menerapkan model pembelajaran konvensional. Penelitian ini merupakan penelitian quasi experiment dengan pretest-posttest non-equivalent control group design. Sampel penelitian adalah dua kelas VIII di SMP Negeri 2 Abang tahun pelajaran 2015/2016 yang ditentukan den...

  20. MX Siting Investigation. Geotechnical Evaluation. Volume VIII. Nevada - Utah Verification Studies, FY 79. Geotechnical Data Big Smoky CDP, Nevada.

    Science.gov (United States)

    1979-08-24

    Angular - particles have sharp edges and relatively plane sides with unpolished surfaces. wfl . AT#UNL, EWE. FN-TR-27-VIII 6-5 Subangular - particles... GEM ~GIC UNIT My ’All .’j GP T-3 C-33 St FACE ELEV TION: 492j * 1500m) SM jSIRFICIAL GE LOGIC UNIT: AMy A3 SW-SM F -6 C-34 SURFACE ELEVATION: 4938

  1. MENINGKATKAN PEMBELAJARAN HOCKEY MELALUI PERMAINAN 4 GAWANG KECIL PADA SISWA KELAS VIII 3 SMP MUHAMMADIYAH 4 SEMARANG TAHUN 2015

    Directory of Open Access Journals (Sweden)

    Muhammad Taufiq

    2016-02-01

    Full Text Available The purpose of this result the study learning of hockey games through the 4 Small Wicket Game in Grade VIII 3 students of Smp Muhammadiyah 4 Semarang. In this case the right is 4 semarang. research method. In practice consists of two cycles. Based on the results of the research, it showed the percentage of passing students study result in the first cycle, students who got pass score are 58.33% (21 students and who did not pass are 41.66% (15 students. In the second cycle students who got pass score are 88.88% (34 students and students who did not pass are 11.11% (4 students. It indicates an increase completeness of student study result is 30.55%.Based on the research’s result, it can be concluded that the use of 4 Small Wicket Game in Grade VIII 3 students is right to improve the study result of grade VIII 3 students of SMP Muhammadiyah 4 Semarang in learning hockey.

  2. Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Young, M.; Antonarakis, S.E. [Univ. of Geneva (Switzerland); Inaba, Hiroshi [Tokyo Medical College (Japan)] [and others

    1997-03-01

    Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A{sub 8}TA{sub 2} sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient`s plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) {open_quotes}ribosomal frameshifting{close_quotes} resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A{sub 10} instead of A{sub 8}TA{sub 2}, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. 36 refs., 6 figs.

  3. Functional mapping of the A2 domain from human factor VIII.

    Science.gov (United States)

    Plantier, Jean-Luc; Saboulard, Didier; Pellequer, Jean-Luc; Négrier, Claude; Delcourt, Marc

    2012-02-01

    Coagulation factor VIII (FVIII) is a multidomain glycoprotein in which the FVIII A2 domain is a key structural element. We aimed at identifying residues within FVIII A2 domain that are crucial for the maintenance of the cofactor function. A high number (n=206) of mutants were generated by substituting original residues with alanine. The mutants were expressed in COS-1 cells and their antigen levels and procoagulant activities were measured. The residues were classified in three categories: those with a non-detrimental alteration of their activities (activity >50 % of control FVIII; n=98), those with a moderate alteration (15 %maintenance of the A2 domain structure. In contrast, residues resistant to mutations formed external loops without well- defined structures suggesting that these loops were not crucial for the process of factor X activation. This study provided a detailed map of the FVIII A2 domain between residues 371 and 649, identifying residues crucial for maintaining FVIII function and residues that can be mutated without jeopardising the coagulant activity.

  4. Characteristics of rabbit transgenic mammary gland expressing recombinant human factor VIII.

    Science.gov (United States)

    Chrenek, P; Makarevich, A V; Pivko, J; Massanyi, P; Lukac, N

    2009-02-01

    The objective of this research was to compare (i) the content of milk protein and recombinant human factor VIII (rhFVIII) in the milk of transgenic and non-transgenic rabbit females at three lactations and (ii) histological structure, ultrastructural morphology and occurrence of apoptosis in rabbit transgenic and non-transgenic mammary gland during third lactation and involution. Significant differences (t(0.05)) in milk protein content were found between transgenic and non-transgenic at all three lactations. The percentage of apoptotic cells was significantly higher (t(0.01)) in non-transgenic ones compared with transgenic mammary gland tissues (6.5% versus 2.4%) taken at the involution stage. Morphometrical analysis of histological preparations at the involution stage detected a significantly higher (t(0.05)) relative volume of lumen in transgenic animals compared with non-transgenic ones (60.00 versus 46.51%). Ultrastructural morphology of the transgenic mammary gland epithelium at the involution stage revealed an increased relative volume of protein globules (t(0.05)); at the lactation stage, a significantly higher volume of mitochondria (13.8%) compared with the non-transgenic (9.8%) ones was observed. These results, although revealing differences in some parameters of ultrastructure and histology, indicate no harmful effect of the mouse whey acid protein-hFVIII transgene expression on the state of mammary gland of transgenic rabbit females.

  5. [Organoleptic and physicochemical characteristics of propolis in the Province Of Nuble, VIII Region-Chile].

    Science.gov (United States)

    Hernández, M S; Lazo, C S; Junod, J M; Arancibia, J M; Flores, R S; Valencia, A E; Valenzuela, E V

    2005-12-01

    Propolis ("bee-glue") is a gummy resinous substance elaborated by honey bees (Apis mellifera) from different types of plant resins. The chemical composition of propolis is very complex and variable as it depends on the botanical source and the environmental conditions prevailing at the location where the resin is collected by bees. The objective [corrected] of this study was to determine the propolis organoleptic and physicochemical properties of different types in the Province of Nuble (VIII Región, Chile). Samples were collected at different sites located in the Central Valley, ranging from the coast to the mountain skirts. Analyses included humidity, ashes, wax content, total phenolics content, total flavonoids, mechanical impurities, oxidation time, and solubility in ethanol. Results showed that propolis extracts from coastal sites are better quality than those collected at mountain skirts, and these in turn are better than propolis obtained from the Central Valley. All propolis analyzed in this study can be classified according to the Brazilian norm as high flavonoid content. The same homogeneity is observed in the amounts of total phenolics found in the samples. In general terms, properties of the propolis samples analyzed fulfill the quality requirements of the current international standards.

  6. IMPROVING WRITING DESCRIPTIVE TEXT BY USING NLP STRATEGY AT VIII GRADE OF SMPN 11 DURI

    Directory of Open Access Journals (Sweden)

    Dahler Dahler

    2017-07-01

    Full Text Available This research is based on the problem faced by the students such as: difficulty inunderstanding the generic structures of descriptive text and the difficulties in developingparagraph. The purpose of this research was to improve the students’ writing skill by usingNeuro Linguistics Programming (NLP strategy at VIII grade of SMPN 11 Mandau Duri. Theresearch design was Classroom Action Research (CAR consisted of two cycles. The datawere collected by using test, field note, observation sheet, and interview. Then, the datacollected were analyzed by using scoring rubric of writing descriptive text. The result showedthat students’ ability in writing descriptive text could be improved. It could be seen frombased score of students writing skill was 38 (failed improve to 51 (failed in cycle 1 to 70(Pass in cycle II. It was caused by some factors, those were the teacher gave motivation,created enjoyfull experience, comfortable class and used various media. In conclusion, theuse of NLP strategy has many beneficial.Keywords:Writing skill, Descriptive Text and NLP strategy.

  7. [Determinants of the elevated factor VIII activity in patients following venous thromboembolism].

    Science.gov (United States)

    Lech, Monika; Kościelniak, Barbara; Bryk, Agata; Undas, Anetta

    2016-01-01

    Activity of factor VIII (FVIII) increased above 150% of reference range predisposes to venous thromboembolism (VTE). The aim of this study was to identify predictors of increased FVIII activity in patients following VTE. 241 (38% men) patients presented due to objectively documented VTE episode at least 3 months ago were included in this study. FVIII activity was measured using a clotting assay on the analyzer BCS XP. Among 241 patients with VTE, activity of FVIII above 150% (FVIII ≥ 150%) was observed in 96 (40%). These patients were older (p = 0.035) and their concentrations of fibrinogen and C-reactive protein (CRP) were higher by 12% and 88% (p 200%) and this group was also older (p = 0.015), more patients in that group had obesity (p = 0.015), idiopathic VTE (p = 0.043), less of them had positive family history (p = 0.010) and they were characterized by fibrinogen and CRP increased by 28% (p 200% (p = 0.016). The activity of FVIII in patients after VTE episode is influenced by age, concentration of fibrinogen, bilirubin, hemoglobin, glucose, CRP and homocysteine. Our results suggest the role of environmental factors, mainly inflammatory response in maintaining elevated FVIII activity following VTE.

  8. PENGGUNAAN MIND MAP DIIRINGI MUSIK KLASIK DALAM PEMBELAJARAN MATEMATIKA UNTUK SISWA KELAS VIII SMPN 1 SAWAHLUNTO

    Directory of Open Access Journals (Sweden)

    Rezky Ramadhona

    2016-06-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui apakah motivasi dan hasil belajar belajar matematika siswa kelas VIII SMPN 1 Sawahlunto setelah menggunakan mind map dan musik klasik lebih baik dari sebelum menggunakan mind map dan musik klasik. Jenis penelitian ini adalah penelitian eksperimen dengan menggunakan dua model rancangan yaitu One Group Pretest Posttest Design untuk melihat dampak perlakuan terhadap motivasi belajar dan Randomized Control Group Only Design untuk melihat dampak perlakuan terhadap hasil belajar. Pengumpulan data dalam penelitian ini menggunakan angket dan tes akhir berupa soal essai. Data yang diperoleh dianalisis dengan menggunakan Uji-t. Hasil penelitian menunjukkan bahwa motivasi belajar matematika siswa cenderung meningkat. Jadi disimpulkan bahwa motivasi belajar matematika siswa setelah menggunakan mind map dan musik klasik lebih baik dari pada sebelum menggunakan mind map dan musik klasik. Dari hasil uji hipotesis untuk data hasil belajar pada selang kepercayaan α = 0,05 diperoleh P-value = 0,022. Jadi dapat disimpulkan bahwa hasil belajar matematika siswa yang menggunakan mind map dan musik klasik lebih baik dari hasil belajar matematika siswa yang tidak menggunakan mind map dan musik klasik. Kata Kunci: Mind Map, Musik Klasik DOI: http://dx.doi.org/10.22342/jpm.10.2.3636.87-92

  9. Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice.

    Science.gov (United States)

    Miao, Carol H; Ye, Peiqing; Thompson, Arthur R; Rawlings, David J; Ochs, Hans D

    2006-07-01

    A robust humoral immune response against human factor VIII (hFVIII) following naked DNA transfer into immunocompetent hemophilia A mice completely inhibits circulating FVIII activity despite initial high-level hFVIII gene expression. To prevent this undesirable response, we compared transient immunomodulation strategies. Eight groups of mice (n = 4-9 per group) were treated with naked DNA transfer of pBS-HCRHPI-hFVIIIA simultaneously with immunosuppressive reagents that included cyclosporine A (CSA), rapamycin (RAP), mycophenylate mofetil (MMF), a combination of CSA and MMF, a combination of RAP and MMF, a monoclonal antibody against murine CD40 ligand (MR1), recombinant murine Ctla4Ig, and a combination of MR1 and Ctla4Ig. All animals except those receiving only CSA exhibited delayed or absent immune responses against hFVIII. The most effective immunosuppressive regimen, the combination of Ctla4Ig and MR1, prevented inhibitor formation in 8 of 9 animals; the ninth had transient low-titer antibodies. All 9 mice of this group produced persistent, therapeutic levels of hFVIII for more than 6 months. When challenged with the T-dependent antigen bacteriophage Phix174, tolerized mice exhibited normal primary and secondary antibody responses, suggesting that transient immunomodulation to disrupt B/T-cell interaction at the time of plasmid injection effectively promoted long-term immune tolerance specific for hFVIII.

  10. Optimisation of the Factor VIII yield in mammalian cell cultures by reducing the membrane bound fraction

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Berchtold, Martin Werner

    2011-01-01

    of active membrane bound rFVIII to the culture medium. Moreover, the attachment of rFVIII to cell membranes of un-transfected HEK293 cells was studied in the presence of compounds that competes for interactions between rFVIII and PS. Competitive assays between iodinated rFVIII (¹²5I-rFVIII) and annexin V......In vivo, clotting Factor VIII (FVIII) circulates in plasma bound to von Willebrand factor (vWF), and the vWF:FVIII complex prevents binding of FVIII to phosphatidylserine (PS). Activation of FVIII by thrombin releases FVIII from vWF, and subsequently FVIII binds to PS exposed on activated platelets...... of the production cells. Recently, we showed that as much as 90% of secreted rFVIII is bound to transiently transfected production cells during serum free conditions. In this study, we investigated the effect of including vWF in the serum free medium, and demonstrate that addition of vWF results in release...

  11. Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy.

    Science.gov (United States)

    Finn, Jonathan D; Ozelo, Margareth C; Sabatino, Denise E; Franck, Helen W G; Merricks, Elizabeth P; Crudele, Julie M; Zhou, Shangzhen; Kazazian, Haig H; Lillicrap, David; Nichols, Timothy C; Arruda, Valder R

    2010-12-23

    Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients. Current treatment for inhibitors is based on long-term, daily injections of large amounts of FVIII protein. Liver-directed gene therapy has been used to induce antigen-specific tolerance, but there are no data in hemophilic animals with pre-existing inhibitors. To determine whether sustained endogenous expression of FVIII could eradicate inhibitors, we injected adeno-associated viral vectors encoding canine FVIII (cFVIII) in 2 strains of inhibitor hemophilia A dogs. In 3 dogs, a transient increase in inhibitor titers (up to 7 Bethesda Units [BU]) at 2 weeks was followed by continuous decline to complete disappearance within 4-5 weeks. Subsequently, an increase in cFVIII levels (1.5%-8%), a shortening of clotting times, and a reduction (> 90%) of bleeding episodes were observed. Immune tolerance was confirmed by lack of antibody formation after repeated challenges with cFVIII protein and normal protein half-life. A fourth dog exhibited a strong early anamnestic response (216 BU), with slow decline to 0.8 BU and cFVIII antigen detection by 18 months after vector delivery. These data suggest that liver gene therapy has the potential to eradicate inhibitors and could improve the outcomes of hemophilia A patients.

  12. Lithium ionophore VIII as an extraordinarily effective receptor for the strontium cation: Experimental and theoretical study

    Science.gov (United States)

    Makrlík, Emanuel; Novák, Vít; Vaňura, Petr; Bouř, Petr

    2014-03-01

    From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Sr2+(aq) + 2A-(aq) + 1(nb) ⇔ 1ṡSr2+(nb) + 2A-(nb) taking place in the two-phase water-nitrobenzene system (A- = picrate, 1 = lithium ionophore VIII; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log Kex (1ṡSr2+, 2A-) = 7.8 ± 0.1. Further, the extremely high stability constant of the 1ṡSr2+ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log βnb (1ṡSr2+) = 16.9 ± 0.1. Finally, by using DFT calculations, the most probable structure of the cationic complex species 1ṡSr2+ was derived. In the resulting complex, the "central" cation Sr2+ is bound by six very strong bond interactions to the corresponding six oxygen atoms of the parent ligand 1; the interaction energy of this complex was found to be -959.9 kJ/mol.

  13. Lithium ionophore VIII as an extraordinarily strong receptor for the trivalent europium cation

    Science.gov (United States)

    Makrlík, Emanuel; Novák, Vít; Vaňura, Petr

    2015-01-01

    On the basis of extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Eu3+(aq) + 3A-(aq) + 1(nb) ⇆ 1.Eu3+(nb) + 3A-(nb) occurring in the two-phase water-nitrobenzene system (A- = CF3SO-3; 1 = lithium ionophore VIII; aq = aqueous phase, nb = nitrobenzene phase) was determined as log Kex (1.Eu3+, 3A-) = 2.5 ± 0.1. Furthermore, the extremely high stability constant of the 1.Eu3+ complex in nitrobenzene saturated with water was calculated: log βnb (1.Eu3+) = 15.6 ± 0.1. Finally, by using DFT calculations, the most probable structure of the cationic complex species 1.Eu3+ was derived. In the resulting complex, the 'central' cation Eu3+ is bound by six very strong bond interactions to the corresponding six oxygen atoms of the parent ligand 1. It is evident that this exceptionally effective receptor 1 for the Eu3+ cation could be considered as a potential extraction agent for nuclear waste treatment.

  14. IMPLEMENTASI PENDEKATAN KONFLIK KOGNITIF DALAM PEMBELAJARAN FISIKA UNTUK MENUMBUHKAN KEMAMPUAN BERPIKIR KRITIS SISWA SMP KELAS VIII

    Directory of Open Access Journals (Sweden)

    A. Setyowati

    2012-01-01

    Full Text Available Tujuan dari penelitian ini adalah untuk mengetahui pengaruh implementasi pendekatan konflik kognitif dalam pembelajaran fisikapokok bahasan tekanan pada siswa kelas VIII terhadap kemampuan berpikir kritis, pemahaman konsep dan hasil belajar kognitifsiswa. Penelitian ini merupakan penelitian eksperimen. Setelah dilakukan pengambilan sampel secara random sampling,diperoleh kelas VIIIB sebagai kelas eksperimen dan kelas VIIIC sebagai kelas kontrol. Dari analisis uji rata-rata dua pihak atau uji tdiperoleh harga t tabel < t hitung yang berarti bahwa terdapat perbedaan yang signifikan terhadap rata-rata kemampuan berpikir kritis,pemahaman konsep dan hasil belajar kognitif kedua kelompok. Kesimpulan dari penelitian ini adalah implementasi pendekatankonflik kognitif pada pokok bahasan tekanan efektif digunakan dalam menumbuhkan kemampuan berpikir kritis, pemahamankonsep dan hasil belajar kognitif siswa kelas VIIISMP. This experiment research aims to examine the influence of cognitive conflict approach application to physics lesson with pressuretopic on critical thinking ability, concept understanding and cognitive learning achievement of the student. The random samplingused resulted class VIIIC as control group and VIIIB as experiment group. The t-test was performed to analyse the average ofcritical thinking ability, concept understanding and cognitive learning achievement of both groups. It was concluded thatimplementation of cognitive conflict approach to physics lesson with pressure topic can grow critical thinking ability, conceptunderstanding and cognitive learning achievement of the JHS student.Keyword: cognitive conflict approach, critical thinking ability, concept understanding, cognitive learning achievement

  15. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    Science.gov (United States)

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  16. Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII.

    Science.gov (United States)

    Choi, Qute; Kim, Ji-Eun; Kim, Seon Young; Han, Kyou Sup; Kim, Hyun Kyung

    2015-08-01

    As ABO blood type influences the plasma level of coagulation factor VIII (FVIII), it likely also affects activated partial thromboplastin time (aPTT) and thrombin generation assay (TGA) values. Here, we aimed to investigate the effect of ABO type on the normal values of three global coagulation assays: prothrombin time (PT), aPTT, and TGA. PT, aPTT, TGA [1 or 5 pmol/L tissue factor (TF)], coagulation factors, anticoagulation factors, and ABO type were measured in 200 healthy adults. aPTT was significantly prolonged in those with type O compared with those with type non-O, whereas PT was not significantly different between those with type O and type non-O. The time to peak induced by 5 pmol/L TF was significantly prolonged, and the peak thrombin level was decreased in those with type O compared with those with type non-O. FVIII was a major contributor to the ABO-specific reference range of aPTT, 5 pmol/L TF-induced time to peak, and peak thrombin level. The reference ranges of aPTT and TGA (time to peak and peak thrombin level) differed by ABO type. FVIII level is considered a major contributor to ABO type-specific differences with respect to aPTT and TGA.

  17. Penggunaan Media Software GeoGebra untuk Meningkatkan Kemampuan Representasi Matematis Siswa SMP Kelas VIII

    Directory of Open Access Journals (Sweden)

    Marini Oktaria

    2016-06-01

    Full Text Available Rendahnya kemampuan representasi matematis siswa menjadi salah satu penyebab rendahnya prestasi belajar matematika siswa. Hal ini diperkuat dengan hasil laporan TIMSS dan PISA yang menunjukkan rendahnya kemampuan matematika siswa Indonesia. Untuk membantu siswa meningkatkan kemampuan representasi matematis digunakan suatu media pembelajaran matematika. Salah satu media pembelajaran matematika yang dapat merepresentasikan model matematika adalah software GeoGebra. Maka dari itu, penelitian ini bertujuan untuk mengetahui apakah software GeoGebra dapat meningkatkan kemampuan representasi matematis siswa pada materi SPLDV. Sampel dalam penelitian ini adalah siswa kelas VIII.2 SMP Islamic Village tahun ajaran 2015/2016 semester II sebanyak 29 orang dengan purposive sampling. Instrumen penelitian berupa tes uraian untuk mengukur kemaampuan representasi matematis. Metode dalam penelitian ini adalah metode kuantitatif jenis pra eksperimen dengan one group pretest-posttest design. Analisis data penelitian ini menggunakan uji non-parametrik Wilcoxon Signed Ranks Test. Hasil penelitian menunjukkan bahwa penggunaan media software GeoGebra dapat meningkatkan kemampuan representasi matematis siswa pada materi sistem persamaan linier dua variabel (SPLDV. Peningkatan yang diperoleh berada pada kategori sedang sebesar 0,651

  18. Allometry of Factor VIII and informed scaling of next generation therapeutic proteins

    Science.gov (United States)

    Kosloski, Matthew P.; Pisal, Dipak S.; Mager, Donald E.; Balu-Iyer, Sathy V.

    2013-01-01

    Allometric scaling has been applied to the pharmacokinetics (PK) of factor VIII (FVIII), but published relationships are based on relatively small subsets of available data. Numerous next generation forms of FVIII are being developed (e.g. Fc fusion, PEGylated, and liposomal formulations) and traditional pharmacokinetic scaling of these products would not incorporate the wealth of existing knowledge for current FVIII therapy in humans. We conducted a meta-analysis and developed allometric relationships of FVIII from over 100 PK studies collected from literature. Normalized Wajima curves were used to relate mean FVIII profiles between species. An ‘informed scaling’ approach was derived for predicting first-in-human PK parameters and demonstrated with a case study for an Fc fusion FVIII. NCA values for FVIII PK were well described by the allometric equations CL=6.59·W0.85 and Vss=65.0·W0.97. A subset of studies characterized by two compartment modeling showed strong linearity in scaling of total clearance and central volume, but more variability in distributional clearance and peripheral volume. Wajima curves for FVIII superimposed across species and the disposition of Fc fusion FVIII in humans was well predicted by ‘informed scaling.’ This approach might be generally applicable for predicting human PK of next generational therapeutics. PMID:23620343

  19. Potential for cellular stress response to hepatic factor VIII expression from AAV vector

    Directory of Open Access Journals (Sweden)

    Irene Zolotukhin

    2016-01-01

    Full Text Available Hemophilia A and B are coagulation disorders resulting from the loss of functional coagulation factor VIII (FVIII or factor IX proteins, respectively. Gene therapy for hemophilia with adeno-associated virus vectors has shown efficacy in hemophilia B patients. Although hemophilia A patients are more prevalent, the development of therapeutic adeno-associated virus vectors has been impeded by the size of the F8 cDNA and impaired secretion of FVIII protein. Further, it has been reported that over-expression of the FVIII protein induces endoplasmic reticulum stress and activates the unfolded protein response pathway both in vitro and in hepatocytes in vivo, presumably due to retention of misfolded FVIII protein within the endoplasmic reticulum. Engineering of the F8 transgene, including removal of the B domain (BDD-FVIII and codon optimization, now allows for the generation of adeno-associated virus vectors capable of expressing therapeutic levels of FVIII. Here we sought to determine if the risks of inducing the unfolded protein response in murine hepatocytes extend to adeno-associated virus gene transfer. Although our data show a mild activation of unfolded protein response markers following F8 gene delivery at a certain vector dose in C57BL/6 mice, it was not augmented upon further elevated dosing, did not induce liver pathology or apoptosis, and did not impact FVIII immunogenicity.

  20. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII

    Science.gov (United States)

    Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C

    2016-01-01

    Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008

  1. The Effectiveness of Team's Game Tournament Seen From Communication and Problem Solveing Capabilities (Experimental Study of Class VIII students in SMP Negeri 1 Seyegan

    Directory of Open Access Journals (Sweden)

    Nuryadi Nuryadi

    2016-10-01

    Full Text Available Cooperative learning is the type of Team's Games Tournament (TGT which is a learning model in which there are stages such as games which can make the students communicate mathematically, more creative, have a positive attitude towards mathematics, and appropriate in solving mathematical problems. But in fact, communication skills and problem solving that should be owned by the students as a result of the learning process of mathematics meet the minimum completeness criteria (KKM. This study aims to describe the effectiveness of Cooperative learning of TGT type at mathematics learning in terms of communication skills and problem solving in class VIII SMP N 1 Seyegan the school year 2016/2017.  This research is a quasi ekspreriment research with pre-posttest nonequivalent control group design. This study uses two groups: the experimental group and the control group. The population study includes all students of class VIII which consists of four classes. From the existing population, it is drawn randomly two classes, namely VIII A and VIII C as samples. Mathematics Learning in class VIII A (experimental group uses TGT type Cooperative learning and mathematics learning in class VIII C (control group uses direct instruction. The instrument of this study is testing the communication and problem solving capability. To test the effectiveness of the study, it is used the analysis of one sample t-test. Whereas the T2 test hotteling is foolowed by univariate t-test which is used to determine more effective model. The result of research indicates that: (1 Cooperative learning of TGT-type and direct instruction in mathematics is effective in terms of communication skills and problem-solving; and (2 Cooperative learning of TGT type is more effective than direct instruction type in term of communication skill in class VIII SMPN 1 Seyegan.   Keywords: TGT, mathematical communication, problem solving

  2. Fault diagnosis in the steam generator of a thermoelectric power plant using Petri networks; Diagnostico de fallas en el generador de vapor de una termoelectrica usando redes de Petri

    Energy Technology Data Exchange (ETDEWEB)

    Suarez Cerda, Dionisio A; Sanchez Lopez, Alfredo [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Martinez Prieto, Jose E; Garcia Beltran, Carlos D. [Centro Nacional de Investigacion y Desarrollo Tecnologico, Cuernavaca, Morelos (Mexico)

    2007-07-01

    , disponibilidad, eficiencia, seguridad y continuidad de la operacion, las cuales afectan gravemente los indices de desempeno del sistema. En este articulo se presenta un esquema de diagnostico de fallas, aplicado al generador de vapor de una unidad termoelectrica, basado en tecnicas de modelado de sistemas dinamicos mediante redes de Petri. Frente a otros metodos, el esquema ofrece mayor facilidad para su implementacion, rapidez de adaptacion ante cambios de zona de operacion y buena robustez. Una manera de reducir el efecto de las fallas en un sistema de produccion, consiste de dos pasos. El primero es diagnosticar la falla tan pronto como ocurra y subsecuentemente poner en practica acciones correctivas. El concepto de diagnostico de fallas se relaciona con la primera etapa y comprende tanto la deteccion, como la localizacion de esta. Es decir, ademas de determinar que una falla esta presente, se sabe en que componente ha ocurrido. Con base en lo anterior, es claro que un sistema de diagnostico requiere supervisar las variables que caracterizan el comportamiento de las fallas, a fin de detectarlas en el momento en que se presenten e informarlo al operador. Con esta informacion, el operador podra realizar las acciones correctivas necesarias para que la planta siga operando en la medida de lo posible.

  3. STUDI KOMPARASI PEMBELAJARAN NOVICK DAN GROUP INVESTIGATION TERHADAP KEMAMPUAN SPASIAL SISWA KELAS VIII MATERI GEOMETRI

    Directory of Open Access Journals (Sweden)

    Dian Nailis Suroyya

    2015-03-01

    Full Text Available Tujuan penelitian ini adalah mengetahui apakah apakah rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Direct Instruction, mengetahui apakah rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Direct Instruction, mengetahui apakah rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation, dan mengetahui apakah peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick lebih baik dari peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation. Populasi dalam penelitian ini adalah seluruh siswa kelas VIII MTs N 1 Kudus tahun pelajaran 2013/2014. Pengambilan sampel menggunakan teknik random sampling. Data diperoleh melalui metode tes dan data dianalisis menggunakan uji t. Hasil penelitian menunjukkan bahwa rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick dan rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Direct Instruction, rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick kurang dari atau sama dengan kemampuan rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation, dan peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick kurang dari atau sama dengan peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group

  4. The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism.

    Science.gov (United States)

    Tirado, Isabel; Mateo, José; Soria, José Manuel; Oliver, Arturo; Martínez-Sánchez, Elisabeth; Vallvé, Cristina; Borrell, Monserrat; Urrutia, Teresa; Fontcuberta, Jordi

    2005-03-01

    Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have been associated with thrombosis. The ABO locus has functional effects on vWF and FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We carried out a case-control study to assess the role of FVIII, vWF and ABO types on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250 unrelated controls. FVIII, vWF and other factors related to thrombophilia were measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%; difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%; difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF disappeared after adjusting for the ABO group. Patients with FVIII above the 90th percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII levels and non-O blood groups, likely those with the A1 allele, are independent risk factors for venous thromboembolism and should be considered in evaluating of thrombophilia.

  5. Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

    Energy Technology Data Exchange (ETDEWEB)

    Fong, I.; Lai, P.S.; Ouah, T.C. [National Univ. of Singapore (Malaysia)] [and others

    1994-09-01

    The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1 = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.

  6. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A.

    Science.gov (United States)

    Cannavò, Antonino; Valsecchi, Carla; Garagiola, Isabella; Palla, Roberta; Mannucci, Pier Mannuccio; Rosendaal, Frits R; Peyvandi, Flora

    2017-03-09

    The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors. © 2017 by The American Society of Hematology.

  7. Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A.

    Science.gov (United States)

    Delignat, S; Repessé, Y; Navarrete, A-M; Meslier, Y; Gupta, N; Christophe, O D; Kaveri, S V; Lacroix-Desmazes, S

    2012-03-01

    The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen. © 2011 Blackwell Publishing Ltd.

  8. Expanding the Ortholog Approach for Hemophilia Treatment Complicated by Factor VIII Inhibitors

    Science.gov (United States)

    Zakas, P.M.; Vanijcharoenkarn, K.; Markovitz, R.C.; Meeks, S.L.; Doering, C.B.

    2014-01-01

    Summary Background The formation of neutralizing antibodies (inhibitors) directed against human coagulation factor VIII (hFVIII) is a life-threatening pathogenic response that occurs in 20–30% of severe congenital hemophilia A patients and 0.00015% of remaining population (i.e. acquired hemophilia A). Interspecies amino acid sequence disparity among FVIII orthologs represents a promising strategy to mask FVIII from existing inhibitors while retaining procoagulant function. Evidence for the effectiveness of this approach exists in clinical data obtained for porcine FVIII products, which have demonstrated efficacy in the setting of congenital and acquired hemophilia. Objectives In the current study, recombinant (r) ovine FVIII (oFVIII), was evaluated for antigenicity and procoagulant activity in the context of human patient-derived and murine model-generated FVIII inhibitors. Methods The antigenicity of roFVIII was assessed using i) inhibitor patient plasma samples, ii) murine anti-FVIII MAbs, iii) immunized murine hemophilia A plasmas, and iv) an in vivo model of acquired hemophilia A Results Overall, roFVIII demonstrated reduced reactivity to, and inhibition by, anti-hFVIII immunoglobulin in patient plasmas. Additionally, several hFVIII epitopes were predicted and empirically shown not to exist within roFVIII. In a murine hemophilia A model designed to mimic clinical inhibitor formation, it was demonstrated that inhibitor titers to roFVIII were significantly reduced compared to the orthologous immunogens, rhFVIII or rpFVIII. Furthermore in a murine model of acquired hemophilia A, roFVIII administration conferred protection from bleeding following tail transection. Conclusion These data support the investigation of FVIII orthologs as treatment modalities in both the congenital and acquired FVIII inhibitor settings. PMID:25315236

  9. Rancang Bangun Perangkat Eksperimen Hukum Archimedes untuk MTs LB/A Yaketunis Kelas VIII

    Directory of Open Access Journals (Sweden)

    Rofiqoh Utami

    2014-06-01

    Full Text Available Blind students find difficulties whenever they are involved in the experiment of Archimedes principle as it requests an active visual role. Thus, it is very important to design a special tool for blind students so their practice of Archimedes principle become easier. This paper discusses a research finding which is an innovation of adaptive tools for blind students, such as beaker glass with Braille number, dynamometer with modification and Braille number (Braille Spring Balance and recording lesson about Archimedes principle. This research done for students MTs LB / A Yaketunis Class VIII which aims at analyzing the quality of each tool by media experts, lesson experts, and physics teacher of MTs LB/A.This research is R & D with procedural models adapted from the development of the 4-D models, namely Define, Design, Develop, and Disseminate. According to media expert assessment, beaker glass with Braille number and Braille spring balance has a very good quality with percentage of their respective 100% of the ideal score, while the assessment by lesson experts for each tool have a good quality with percentage 80% and 73.33% of the ideal score, and physics teacher of MTs LB / A assessment for each tool have a very good quality with percentage 100%. According to the media and lesson experts, the recording lesson about Archimedes principle have a good quality with percentage 80% of the ideal score, according to physics teacher MTs LB / A, the recording tool has excellent quality either with percentage 91.82% of the ideal score. This research recommends the blinds students to utilize these innovative-adaptive tools which will enable them appropriately practice Archimedes principle as non-blind students.

  10. A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke.

    Science.gov (United States)

    Samai, Alyana A; Boehme, Amelia K; Shaban, Amir; George, Alexander J; Dowell, Lauren; Monlezun, Dominique J; Leissinger, Cindy; Schluter, Laurie; El Khoury, Ramy; Martin-Schild, Sheryl

    2016-02-01

    Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0-5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63-66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82-57.5, P = .0083) increased 10 times. Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Enhanced factor VIII heavy chain for gene therapy of hemophilia A.

    Science.gov (United States)

    Chen, Lingxia; Lu, Hui; Wang, Jinhui; Sarkar, Rita; Yang, Xiao; Wang, Hongli; High, Katherine A; Xiao, Weidong

    2009-03-01

    Hemophilia A gene therapy using recombinant adenovirus-associated virus (AAV) vectors has been hampered by the size of the factor VIII (FVIII) cDNA. Previously, splitting the FVIII coding sequence into a heavy-chain (HC) fragment and a light-chain (LC) fragment for dual recombinant AAV vector delivery has been successfully explored. However, the main disadvantage of this approach is a "chain imbalance" problem in which LC secretion is approximately 1-2 logs higher than that of HC, and therefore, the majority of protein synthesized is nonfunctional. To improve HC secretion, we constructed alternate FVIII HCs based on our observation that LC facilitates HC secretion. To our surprise, most of the new HC molecules exhibited enhanced expression over the traditional HC molecule (HC(745)). The optimized HC mutein, HC(HL), including additional acidic-region-3 (ar3) sequences, exhibited three- to fivefold higher activity in both enzyme-linked immunosorbent assay (ELISA) and activated partial thromboplastin time (aPTT) assay in in vitro testing. Further characterization suggested ar3 sequences increased HC secretion, rather than promoting HC synthesis. Intravenous delivery of AAV8-HC(HL)+AAV8-LC or AAV8-HC(745)+AAV8-LC achieved phenotypic correction in hemophilia A mice. Mice receiving AAV8-HC(HL)+AAV8-LC achieved three- to fourfold higher HC expression than AAV8-HC(745)+AAV8-LC, consistent with the FVIII functional assays. HC(HL) should be substituted for HC(745) in a dual AAV vector strategy due to its enhanced expression.

  12. Intraosseous delivery of lentiviral vectors targeting factor VIII expression in platelets corrects murine hemophilia A.

    Science.gov (United States)

    Wang, Xuefeng; Shin, Simon C; Chiang, Andy F J; Khan, Iram; Pan, Dao; Rawlings, David J; Miao, Carol H

    2015-04-01

    Intraosseous (IO) infusion of lentiviral vectors (LVs) for in situ gene transfer into bone marrow may avoid specific challenges posed by ex vivo gene delivery, including, in particular, the requirement of preconditioning. We utilized IO delivery of LVs encoding a GFP or factor VIII (FVIII) transgene directed by ubiquitous promoters (a MND or EF-1α-short element; M-GFP-LV, E-F8-LV) or a platelet-specific, glycoprotein-1bα promoter (G-GFP-LV, G-F8-LV). A single IO infusion of M-GFP-LV or G-GFP-LV achieved long-term and efficient GFP expression in Lineage(-)Sca1(+)c-Kit(+) hematopoietic stem cells and platelets, respectively. While E-F8-LV produced initially high-level FVIII expression, robust anti-FVIII immune responses eliminated functional FVIII in circulation. In contrast, IO delivery of G-F8-LV achieved long-term platelet-specific expression of FVIII, resulting in partial correction of hemophilia A. Furthermore, similar clinical benefit with G-F8-LV was achieved in animals with pre-existing anti-FVIII inhibitors. These findings further support platelets as an ideal FVIII delivery vehicle, as FVIII, stored in α-granules, is protected from neutralizing antibodies and, during bleeding, activated platelets locally excrete FVIII to promote clot formation. Overall, a single IO infusion of G-F8-LV was sufficient to correct hemophilia phenotype for long term, indicating that this approach may provide an effective means to permanently treat FVIII deficiency.

  13. Impact of being overweight on factor VIII dosing in children with haemophilia A.

    Science.gov (United States)

    Henrard, S; Hermans, C

    2016-05-01

    Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%. The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)-for-age, height), age and type of FVIII concentrate on FVIII recovery in children with HA. A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery. The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI-for-age percentile

  14. Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII.

    Science.gov (United States)

    O'Sullivan, Jamie M; Jenkins, P Vince; Rawley, Orla; Gegenbauer, Kristina; Chion, Alain; Lavin, Michelle; Byrne, Barry; O'Kennedy, Richard; Preston, Roger J S; Brophy, Teresa M; O'Donnell, James S

    2016-05-01

    Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor-dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVIII. Immunosorbant assays and surface plasmon resonance analysis confirmed that Gal-1 and Gal-3 bound purified FVIII with high affinity. Exoglycosidase removal of FVIII N-linked glycans significantly reduced binding to both Gal-1 and Gal-3. Moreover, combined removal of both the N- and O-glycans of FVIII further attenuated Gal-3 binding. Notably, specific digestion of FVIII high-mannose glycans at N239 and N2118 significantly impaired FVIII affinity for Gal-1. Importantly Gal-1, but not Gal-3, bound to free FVIII in the plasma milieu, and significantly inhibited FVIII functional activity. Interestingly, commercial recombinant FVIII (rFVIII) concentrates are manufactured in different cell lines and differ in their glycosylation profiles. Although the biological mechanism has not been defined, recent studies in previously untreated patients with severe hemophilia A reported significant differences in inhibitor development associated with different rFVIII products. Interestingly, Gal-1 and Gal-3 both displayed enhanced affinity for BHK-rFVIII compared with CHO-rFVIII. Furthermore, binding of Gal-1 and Gal-3 to BDD-FVIII was markedly reduced compared with full-length rFVIII. We have identified Gal-1 and Gal-3 as novel-binding partners for human FVIII and demonstrated that Gal-1 binding can influence the procoagulant activity of FVIII. © 2016 American Heart Association, Inc.

  15. Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII.

    Science.gov (United States)

    Shah, A; Delesen, H; Garger, S; Lalezari, S

    2015-11-01

    BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII (rFVIII-FS) but is produced with advanced manufacturing technologies. To analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing across different age and ethnic groups in the LEOPOLD clinical trial programme. The LEOPOLD trials enrolled patients with severe haemophilia A aged 12-65 years (LEOPOLD I and II) or ≤12 years (LEOPOLD Kids) with ≥150 (LEOPOLD I and II) or ≥50 (LEOPOLD Kids) exposure days to any FVIII product and no history of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY 81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing. Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6 to <12 and <6 years) and ethnicity (Asian and non-Asian). Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY 81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and multiple dosing. Age-based analysis in the three trials showed that plasma concentrations were slightly lower for children, but similar for adolescents compared with adults. Pharmacokinetic results were similar in the different ethnic groups. Results of the LEOPOLD trials show that the BAY 81-8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973 pharmacokinetic values were observed following single and repeated dosing and across ethnic groups. © 2015 John Wiley & Sons Ltd.

  16. Contribución a la histopatologia del distemper canino

    Directory of Open Access Journals (Sweden)

    E. Encinas

    1945-09-01

    Full Text Available En un caso de distemper canino el examen anatómico del sistema nervioso ofrece cambios elementales y estructurales sistematizados, no revelados hasta ahora. El hecho de que determinadas unidades estructurales, en evidente relación con los espacios sub-aracnoideos, hayan sido preferentemente comprometidas, en contraste con otras que se han mantenido indemnes por estar fuera de la influencia de aquellos y de su liquor circulante, hace sospechar que aparte de la vía sanguínea, sea el liquor uno de los vehículos del agente infectante. Pero lo que esta influencia no explica es el cambio parcial de las células nerviosas de ciertas zonas, de las formaciones ammónicas, Fig. Nº 44, ni la alteración de los componentes celulares de una unidad arquitectural, de lámina Vª de la corteza, por ejemplo. Para esta especie de variación no cabe al presente, mas que la sospecha, a menudo comprobada, de que determinadas unidades celulares o arquitecturales, poseen cierto grado de vulnerabilidad bis a bis de los agentes agresores. Y esta opinión tan a menudo verificada en la patología humana no tiene porqué no ser extendida a los cambios en los tejidos nerviosos de animales inferiores. El asta de Ammón humana ha sido con frecuencia estudiada en múltiples procesos patológicos, comprobándose la manera fácil con que agentes vulnerantes la modifican y lesionan, pero, que sepamos, no se han hecho estudios detenidos de ella en procesos sospechosos virulentos como en las encefalitis, ni en aquellos debidos a bacterias. En estos aspectos como en otros de las investigaciones biológicas parece que todos los recursos estuvieran dirigidos a verificar hallazgos ya realizados, o a comprobar sus variaciones, más nó a ir al encuentro de nuevos hechos de información mayor, y de provecho para el conocimiento, Asunto sería de investigar por ejemplo si en la encefalitis humanas ocurren alteraciones semejantes a las mencionadas en este trabajo (de distemper, y, si en efecto las unidades celulares o estructurales reaccionan en la medida y forma señaladas frente a cualquier otro agente alterativo. Posible es que en el caso particular de las lesiones aisladas de la lámina Vª juegue rol determinante la especial susceptibilidad de esta lámina a deficiencias en el aporte de oxígeno, ocasionadas por perturbaciones en el aprovisionamiento de sangre, portador de este gas cuestión que discutieron acertadamente BIELCHOWSKY y PALADINO, MARINESCO y otros; y como alteraciones pericapilares y endocapilares son hechos frecuentes en este proceso, no sería aventurado sostener que las lesiones aisladas de esta lámina se deban a aportes insuficientes de oxígeno por las anotadas alteraciones vasculares. Pero, y repitiendo lo que dijimos en líneas anteriores, factor este vascular, no explica el hecho anatómico del cambio celular aislado como el de las unidades mencionadas de la formación ammónica (Fig. 44. Alguna otra causal citoespecífica debe ser la sola causante de alteración tan particular. Y no es extraño que el virus del distemper, tan notable por la especificidad de las inclusiones citoplasmáticas y nucleares que provoca, sea ajeno a esta modificación. En lo fundamental, desearíamos que nuestros hallazgos sean verificados y que la autorizada opinión de los cultores del tema se pronuncien sobre ellos.

  17. Results on the application of the methodology for power diagnoses Iac-DOE to Mexican companies; Resultados de la aplicacion de la metodologia de diagnosticos energeticos Iac-DOE a empresas mexicanas

    Energy Technology Data Exchange (ETDEWEB)

    Ambriz Garcia, Juan Jose [Universidad Autonoma de Mexico, Mexico, D.F. (Mexico)

    2001-07-01

    This work presents an analysis of the results of eight industrial power audits made in Mexico by a team of professors and students of the Universidad Autonoma Metropolitana-Ixtapalapa (UAM), following the methodology of the Centers of Industrial Consultant's office and Analyses and Power Diagnoses sponsored by the Office of Industrial Technologies of the Department of Energy of the United Studies (IAC-DOE Program). In these diagnosis studies, that could be classified as of fast execution, it was possible to find and to evaluate from 6 to 13 actions by company to increase their energy efficiency. This represents at the moment between 6 and 29% of the currently used energy, being the average 18.4%. The equivalent economic saving ascends to a value between 7 and 31% of the total paid, with an average value of 13.8%. Finally, the simple period of return for the saving recommendations is of 0.87 years, with an average number of 0.51 years for the actions focused to the saving of thermal energy and 1.52 years for the actions that improve the use of the electric energy. [Spanish] Este trabajo se presenta un analisis de los resultados de ocho auditorias energeticas industriales realizadas en Mexico por un equipo de profesores y estudiantes de la Universidad Autonoma Metropolitana-Iztapalapa (UAM), siguiendo la metodologia de los Centros de Asesoria Industrial y de Analisis y Diagnosticos Energeticos patrocinados por la Oficina de Tecnologias Industriales del Departamento de Energia de los Estudios Unidos (Programa IAC-DOE). En estos estudios de diagnostico, que podrian ser clasificados como de rapida ejecucion, fue posible encontrar y evaluar de 6 a 13 acciones por empresa para incrementar su eficiencia energetica. Esto representa entre 6 y 29% de la energia empleada actualmente, siendo el promedio del 18.4%. El ahorro economico equivalente asciende a un valor entre 7 y 31% del total pagado, con un valor promedio de 13.8%. Finalmente, e periodo simple de retorno para

  18. MENINGKATKAN AKTIVITAS BELAJAR SISWA DENGAN MENGGUNAKAN METODE GROUP INVESTIGATION (GI PADA POKOK BAHASAN PASAR DI KELAS VIII SMP 5 KUDUS

    Directory of Open Access Journals (Sweden)

    Mutthofiyah Mutthofiyah

    2016-03-01

    Full Text Available Penelitian ini bertujuan untukmeningkatkan aktivitas belajar siswa dengan menggunakan metode group investigation (GI pada pokok bahasan pasar pada penelitian ini menggunakan penelitian tindakan kelas (PTK. Dalam penelitian ini dirancang menggunakan siklus, masing-masing siklus dengan tahapan perencanaan, pelaksanaan tindakan, observasi dan refleksi. Teknik pengumpulan data pada penelitian ini adalah dokumentasi, observasi dan tes.Hasil penelitian menunjukkan melalui meningkatkan metode group investigation (GI aktivitas siswa SMP 5 Kudus ada peningkatan yang sigifikan, dari siklus I kelas VIII F 15,8 (41,62% meningkat di siklus II menjadi 24,8 (72,9%, sedangkan di kelas VIII G siklus I 18,5 (47,04% meningkat menjadi 26,2 (74,7%; melalui penerapan metode group investigation hasil belajar siswa SMP 5 kudus meningkat sangat signifkan, ketuntasan belajar secara klasikal dari kelas VIII F pra siklus sebesar 17,64% terjadi peningkatan 47% ke siklus I dan meningkat menjadi 82,35% di siklus II. Sedangkan di kelas VII G pra siklus sebesar 22,85% meningkat 54,28% di siklus I dan meningkat menjadi 94,28% di siklus II. Saran yang peneliti berikan adalah sebagai berikut:1Kepada para guru diharapkan dapat menerapkan pembelajaran kooperatif khususnya pembelajaran kooperatif tipe Group Investigation (GI dalam proses pembelajaran ekonomi dan mata pelajaran lainya dan mengembangkannya; 2 Kepada para peneliti selanjutnya diharapkan dapat melakukan penelitian tentang penerapan model pembelajaran yang dapat membangkitkan keaktifan siswa untuk belajar ekonomi. This study aims to improve students' learning activities using group investigation (GI on the subject of markets in class VIII SMP 5 Kudus. In this study is designed to use cycles, with each cycle stages of planning, action, observation and reflection. Data collection techniques in this study is documentation, observation and tests. Results showed through improved methods of group investigation (GI junior 5 high

  19. Development of a reliable analytical method for the precise extractive spectrophotometric determination of osmium(VIII) with 2-nitrobenzaldehydethiocarbohydrazone: Analysis of alloys and real sample

    Science.gov (United States)

    Zanje, Sunil B.; Kokare, Arjun N.; Suryavanshi, Vishal J.; Waghmode, Duryodhan P.; Joshi, Sunil S.; Anuse, Mansing A.

    2016-12-01

    The proposed method demonstrates that the osmium(VIII) forms complex with 2-NBATCH from 0.8 mol L- 1 HCl at room temperature. The complex formed was extracted in 10 mL of chloroform with a 5 min equilibration time. The absorbance of the red colored complex was measured at 440 nm against the reagent blank. The Beer's law was obeyed in the range of 5-25 μg mL- 1, the optimum concentration range was 10-20 μg mL- 1 of osmium(VIII) as evaluated by Ringbom's plot. Molar absorptivity and Sandell's sensitivity of osmium(VIII)-2NBATCH complex in chloroform is 8.94 × 103 L mol- 1 cm- 1 and 0.021 μg cm- 2, respectively. The composition of osmium(VIII)-2NBATCH complex was 1:2 investigated from Job's method of continuous variation, Mole ratio method and slope ratio method. The interference of diverse ions was studied and masking agents were used wherever necessary. The present method was successfully applied for determination of osmium(VIII) from binary, ternary and synthetic mixtures corresponding to alloys and real samples. The validity of the method was confirmed by finding the relative standard deviation for five determinations which was 0.29%.

  20. Combined X-ray and neutron diffraction study of vacancies and disorder in the dimorphic clathrate Ba8Ga16Sn30 of type I and VIII.

    Science.gov (United States)

    Christensen, Sebastian; Avila, Marcos A; Suekuni, Koichiro; Piltz, Ross; Takabatake, Toshiro; Christensen, Mogens

    2013-10-01

    We report detailed structural investigations of the dimorphic clathrate Ba8Ga16Sn30 that crystallizes in both type I and VIII clathrate structures. Single crystals of type I and VIII have been examined using single crystal X-ray and Laue neutron diffraction in the temperature range T = 10 K-500 K. The utilization of both X-ray and neutron diffraction gives a unique ability to reveal the occurrence of minute vacancy occupancies in the host structure. The vacancies are shown to be located on the 6c (type I) and 24g (type VIII) framework sites. Largest vacancy densities are observed for type I p-Ba8Ga16Sn30, 1.3(4)%, and type VIII n-Ba8Ga16Sn30, 0.7(2)%. The relation between guest atom disorder and occurrence of glasslike thermal conductivity in intermetallic clathrates was also investigated. In type VIII Ba8Ga16Sn30 neither n-type (crystalline thermal conductivity) nor p-type (glasslike thermal conductivity) showed any significant disorder of the guest atoms; they do however show anharmonic motion. The glasslike thermal conductivity of p-type Ba8Ga16Sn30 is interpretable as a result of higher effective mass of p-type charge-carriers affecting phonon scattering. In type I Ba8Ga16Sn30 guest atoms are highly disordered for both carrier types and samples of both charge carrier types have glasslike thermal conductivity.

  1. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  2. The Effect of Growth Temperature and V/III Flux Ratio of MOCVD Antimony Based Semiconductors on Growth Rate and Surface Morphology

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    Ramelan Ari Handono

    2017-01-01

    Full Text Available Epitaxial Alx Ga1-x Sb layers on GaSb and GaAs substrates have been grown by atmospheric pressure metalorganic chemical vapor deposition using TMAl, TMGa and TMSb. Nomarski microscope and a profiler were employed to examine the surface morphology and growth rate of the samples. We report the effect of growth temperature and V/III flux ratio on growth rate and surface morphology. Growth temperatures in the range of 520°C and 680°C and V/III ratios from 1 to 5 have been investigated. A growth rate activation energy of 0.73 eV was found. At low growth temperatures between 520 and 540°C, the surface morphology is poor due to antimonide precipitates associated with incomplete decomposition of the TMSb. For layers grown on GaAs at 580°C and 600°C with a V/III ratio of 3 a high quality surface morphology is typical, with a mirror-like surface and good composition control. It was found that a suitable growth temperature and V/III flux ratio was beneficial for producing good AlGaSb layers. Undoped AlGaSb grown at 580°C with a V/III flux ratio of 3 at the rate of 3.5 μm/hour shows p-type conductivity with smooth surface morphology

  3. Effect of V/III ratio on the surface morphology and electrical properties of m-plane (10 1 bar 0) GaN homoepitaxial layers

    Science.gov (United States)

    Barry, Ousmane I.; Tanaka, Atsushi; Nagamatsu, Kentaro; Bae, Si-Young; Lekhal, Kaddour; Matsushita, Junya; Deki, Manato; Nitta, Shugo; Honda, Yoshio; Amano, Hiroshi

    2017-06-01

    We have investigated the effect of V/III ratio on the surface morphology, impurity concentration and electrical properties of m-plane (10 1 bar 0) Gallium Nitride (GaN) homoepitaxial layers. Four-sided pyramidal hillocks are observed on the nominally on-axis m-plane GaN films. Hillocks sizes relatively increase by increasing the V/III ratio. All facets of pyramidal hillocks exhibit well-defined step-terrace features. Secondary ion mass spectrometry depth profiles reveal that carbon impurities decrease by increasing the V/III ratio while the lowest oxygen content is found at an optimized V/III ratio of 900. Vertical Schottky barrier diodes fabricated on the m-GaN samples were characterized. Low leakage current densities of the order of 10-10 A/cm2 at -5 V are obtained at the optimum V/III ratio. Oxygen impurities and screw-component dislocations around hillocks are found to have more detrimental impact on the leakage current mechanism.

  4. EFFECT OF INFORMATION SERVICES USING THE MEDIA FILM TO SELF-CONFIDENCE STUDENT OF CLASS VIII SMP NEGERI 8 METRO

    Directory of Open Access Journals (Sweden)

    MUDAIM MUDAIM

    2015-06-01

    Full Text Available Abstract: Pessimism and attitudes that consider themselves weak and does not have the ability when facing a problem will make individual impediment in the task of development. Problems confidence that underlies the research are: a Students are less confident in the ability it has, b Students feel pessimistic when faced with an issue, c Student perception subjectively, d Students still do not do the work independently, and e negative minded students with a state-owned. The problems of this study are whether there is an influence of information services using the medium of film to the confidence of eighth-grade students of SMP Negeri 8 Metro. The purpose of this study was to determine whether there is an influence of information services using the medium of film to the self-confidence of students in class VIII SMP Negeri 8 Metro. Subject participant is graders VIII-E total 30 students. Data were collected by questionnaire self-confidence and analyzed the data used is the t-test. The results of this study, shown by the difference in change scores of confidence from the pre-test and post-test of 17.1. Testing the hypothesis obtained calculation results thitung6,036> table = 1.699. The conclusion is that the information services implemented using the film medium can be a positive influence on self-esteem, especially students of class VIII. The advice given is to use the medium of film should be done intensively and more creative by BK teachers in giving information service. Keywords: Confidence, Service Information Using Media Film.

  5. Joint bleeds increase the inhibitor response to human factor VIII in a rat model of severe haemophilia A

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    Introduction The most serious complication in haemophilia A (HA) replacement therapy with coagulation factor VIII (FVIII) is neutralizing antibodies, i.e. inhibitors. It has been hypothesized that danger signals generated during a bleed might have an adjuvant effect on the immune response to FVIII...... in on-demand treatment, increasing the inhibitor risk. Aim To compare the antibody response to treatment with recombinant human FVIII (rhFVIII) in relation to induced knee joint bleeds and treatment without concurrent bleeds in a HA rat model. Method HA rats were divided into two groups: one group (n...

  6. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.

    Science.gov (United States)

    Young, G; Mahlangu, J; Kulkarni, R; Nolan, B; Liesner, R; Pasi, J; Barnes, C; Neelakantan, S; Gambino, G; Cristiano, L M; Pierce, G F; Allen, G

    2015-06-01

    Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of hemophilia A. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  7. CONSTRAINING THE MILKY WAY'S HOT GAS HALO WITH O VII AND O VIII EMISSION LINES

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Matthew J.; Bregman, Joel N., E-mail: mjmil@umich.edu, E-mail: jbregman@umich.edu [Department of Astronomy, University of Michigan, Ann Arbor, MI 48104 (United States)

    2015-02-10

    The Milky Way hosts a hot (≈2 × 10{sup 6} K), diffuse, gaseous halo based on detections of z = 0 O VII and O VIII absorption lines in quasar spectra and emission lines in blank-sky spectra. Here we improve constraints on the structure of the hot gas halo by fitting a radial model to a much larger sample of O VII and O VIII emission line measurements from XMM-Newton/EPIC-MOS spectra compared to previous studies (≈650 sightlines). We assume a modified β-model for the halo density distribution and a constant-density Local Bubble from which we calculate emission to compare with the observations. We find an acceptable fit to the O VIII emission line observations with χ{sub red}{sup 2} (dof) = 1.08 (644) for best-fit parameters of n{sub o}r{sub c}{sup 3β}=1.35±0.24 cm{sup –3} kpc{sup 3β} and β = 0.50 ± 0.03 for the hot gas halo and negligible Local Bubble contribution. The O VII observations yield an unacceptable χ{sub red}{sup 2} (dof) = 4.69 (645) for similar best-fit parameters, which is likely due to temperature or density variations in the Local Bubble. The O VIII fitting results imply hot gas masses of M(<50 kpc) = 3.8{sub −0.3}{sup +0.3}×10{sup 9} M{sub ⊙} and M(<250 kpc) = 4.3{sub −0.8}{sup +0.9}×10{sup 10} M{sub ⊙}, accounting for ≲50% of the Milky Way's missing baryons. We also explore our results in the context of optical depth effects in the halo gas, the halo gas cooling properties, temperature and entropy gradients in the halo gas, and the gas metallicity distribution. The combination of absorption and emission line analyses implies a sub-solar gas metallicity that decreases with radius, but that also must be ≥0.3 Z {sub ☉} to be consistent with the pulsar dispersion measure toward the Large Magellanic Cloud.

  8. Conversaciones en el VIII Congreso Panamericano de Mecánica de Suelos e Ingeniería de Fundaciones

    OpenAIRE

    Ruiz Restrepo, Carlos Enrique

    1988-01-01

    En el mes de agosto de 1987 se cumplió, en Cartagena de Indias el "VIII Congreso Panamericano de Mecánica de Suelos", bajo la presidencia del geólogo colombiano Juan Montero Olarte, asistido por un Comité Organizador de todas las excelencias. Abrir canales para la comunicación permanente entre todos nuestros centros educativos, o entre los más representativos, es el método más simple para garantizar, como en simbólico vaso comunicante, que el nivel de enseñanza vibre en un clima de con...

  9. Seleucid, Demotic and Mediterranean mathematics versus Chapters VIII and IX of the Nine Chapters: accidental or significant similarities?

    DEFF Research Database (Denmark)

    Høyrup, Jens

    Similarities of geometrical diagrams and arithmetical structures of problems have often been taken as evidence of transmission of mathematical knowledge or techniques between China and “the West”. Confronting on one hand some problems from Chapter VIII of the Nine Chapters with comparable problems...... known from Ancient Greek sources, on the other a Seleucid collection of problems about rectangles with a subset of the triangle problems from Chapter IX, it is concluded, (1) that transmission of some arithmetical riddles without method – not “from Greece” but from a transnational community of traders...

  10. Love and/in psychoanalysis: a commentary on Lacan's reading of Plato's Symposium in Seminar VIII: Transference.

    Science.gov (United States)

    Fink, Bruce

    2015-02-01

    What is love and what part does it play in psychoanalysis? Where are the analyst and the analysand situated in relation to the roles defined as those of the "lover" and the "beloved"? Jacques Lacan explores these and other questions in his soon-to-be-published Seminar VIII: Transference by providing an extensive commentary on Plato's most famous dialogue on love, the Symposium. This paper outlines some of the major points about love that grow out of Lacan's reading of the dialogue and examines their relevance to the analytic setting. Can the analyst be characterized as a sort of modern-day Socrates?

  11. EK(b)P Keskkomitee VIII pleenumi stenogramm / tõlk. Mart Arold, tõlk. Jaan Isotamm

    Index Scriptorium Estoniae

    1999-01-01

    EK(b)P Keskkomitee VIII pleenum, 21.-23. märts 1950. Sõnavõtud: N. Karotamm, P. Ponomarenko, I. Käbin, V. Kuusik, A. Jaanus, V. Hiznjakov, E. Ristimägi, I. Suija, H. Ajo, A. Meri, G. Abels, M. Assin, G. Latõshov, Rumjantsev, Müürisepp. Kommenteerinud Viktor Niitsoo. Algus: Akadeemia (1998) nr. 12, lk. 2655-2683 ; Järg nr.2;3;4;5;6;7;8;9;10 lk.415-446;639-670;863-894;1087-1118;1310-1342;1534-1566;1759-1790;2017-2048;2220-2256

  12. Partial versus complete factor VIII inhibition in a mouse model of venous thrombosis.

    Science.gov (United States)

    Emmerechts, J; Vanassche, T; Loyen, S; Van Linthout, I; Cludts, K; Kauskot, A; Long, C; Jacquemin, M; Hoylaerts, M F; Verhamme, P

    2012-04-01

    Partial inhibition of Factor VIII (FVIII) may provide antithrombotic efficacy whilst avoiding excessive anticoagulation. We studied the anticoagulant effects of a partial (TB-402) and a complete (BO2C11) FVIII-inhibiting monoclonal antibody (MAb) on FVIII, aPTT, thrombin generation and fibrin deposition in a flow chamber model. The antithrombotic efficacy of TB-402 and BO2C11 was compared in a mouse model of venous thrombosis. Both in vitro and ex vivo, the maximally achievable FVIII inhibition by TB-402 was about 25 to 30%. The degree of inhibition reached a plateau in vitro at 0.316 μg/mL and ex vivo after administering 0.1mg/kg and higher doses. BO2C11 strongly inhibited FVIII:C, up to 91% at 100 μg/mL in vitro, and by 88% ex vivo 1 hour after administering 1mg/kg to the mice. Whereas BO2C11 also markedly prolonged the aPTT and completely inhibited thrombin generation in vitro and ex vivo, the effect of TB-402 on the aPTT and on thrombin generation was limited. Similarly, in a dynamic flow chamber model, TB-402 and BO2C11 inhibited tissue factor-induced human fibrin deposition by 40% and 76%, respectively. In a mouse model of FeCl(3)-induced venous thrombosis, TB-402 (1mg/kg) inhibited thrombus formation to the same extent as BO2C11 (2mg/kg) and enoxaparin (5mg/kg), with a mean (±SD) occlusion time of 51 ± 13 minutes for TB-402, compared to 28 ± 6 minutes for the controls, 51 ± 13 minutes for BO2C11 and 55 ± 11 minutes for enoxaparin. In this mouse model of venular thrombosis, partial FVIII inhibition yielded similar antithrombotic effects as nearly complete FVIII inhibition. These preclinical data are indicative of a therapeutic potential of partial FVIII inhibition in the management of venous thromboembolism. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Diagnosis on line and off line of induction motors of low, medium and high voltage; Diagnostico en linea y fuera de linea de motores de induccion de baja, mediana y alta tension

    Energy Technology Data Exchange (ETDEWEB)

    Carvajal, Francisco Antonio; Ramirez, Jose Manuel; Arcos, Luis Fernando [Instituto de Investigaciones Electricas, Temixco, Morelos (Mexico)

    1999-07-01

    The induction motors of low, medium and high voltage are the electrical equipment of greatest application in industry. The importance which they have in the different productive processes does necessary to assure its operative continuity. The anticipated detection of a possible cause of fault allows to plan, with maintenance aims, the programmed removal of the motor. In this article are presented the results of the activities nowadays performed by Management of Electrical Equipment of the Instituto de Investigaciones Electricas (IIE) for the development and application of online diagnosis techniques for induction motors up to 13.8 kV. [Spanish] Los motores de induccion de baja, mediana y alta tension son los equipos eletricos de mayor aplicacion en la industria. La importancia que tienen en los diferentes procesos productivos hace necesario asegurar su continuidad operativa. La deteccion anticipada de una posible causa de falla permite planear, con fines de mantenimiento, la remocion programada del motor. En este articulo se presentan los resultados de las actividades que realiza actualmente la Gerencia de equipos Electricos del Instituto de investigaciones Electricas (IIE) para el desarrollo y la aplicacion de tecnicas de diagnostico en linea para motores de induccion de hasta 13.8 kV.

  14. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

    Science.gov (United States)

    Dumont, Jennifer A.; Liu, Tongyao; Low, Susan C.; Zhang, Xin; Kamphaus, George; Sakorafas, Paul; Fraley, Cara; Drager, Douglas; Reidy, Thomas; McCue, Justin; Franck, Helen W. G.; Merricks, Elizabeth P.; Nichols, Timothy C.; Bitonti, Alan J.; Pierce, Glenn F.

    2012-01-01

    Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation. PMID:22246033

  15. PERSAMAAN DERAJAT TERHADAP PEMBAGIAN HAK WARIS ANAK DALAM PUTUSAN MAHKAMAH KONSTITUSI NOMOR 46/PUU-VIII/2010

    Directory of Open Access Journals (Sweden)

    Atik Abidah

    2014-12-01

    Full Text Available This research aims to analyze the equality rights of biological children in the decision of the Constitutional Court of the Republic of Indonesia number: 46/PUU-VIII/2010 and its legal consequence. This research included in the normative legal research that used a statue approach and case study approach. The research’s data analyzed using preskriptive-analytic methode and hermeneutic methode. The Research’s results showed that the  decision of  Constitutional Court of the Republic of Indonesia number: 46/PUU-VIII/2010 expand the interpretation of the concept of nasab from legal  children towards biological children to achieve the equality and the sense of fairness. This verdict also expand the interpretation of the evidence. The relationship between parents and their childrens can be proved with the aid of science and technology. The similarity of DNA / RNA betwen parents and their childern is the ratio legis ('illat al-hukm that into consideration the biological children acquire the civil rights, including inheritance rights.

  16. Il ruolo di El Escorial, V.III.6 e dei suoi discendenti nella tradizione manoscritta del Lucullus

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    Corinna Senore

    2017-05-01

    Full Text Available L’articolo riguarda un gruppo di sette codici che tramanda il testo del Lucullus di Cicerone e che appartiene al ramo della tradizione discendente dal manoscritto Wien, Österreichische Nationalbibliothek 189. I sette manoscritti costituiscono uno stadio della tradizione caratterizzato dalla presenza di tre lacune testuali. Sulla base di alcuni elementi paleografici e della presenza di una glossa riportata a margine del testo di uno di essi, El Escorial, V.III.6 (Scor4, e inglobata all’interno del testo degli altri sei, è possibile individuare in Scor4 il capostipite di questo gruppo della tradizione. Lo studio si occupa inoltre di fare chiarezza sui rapporti che intercorrono tra i sei discendenti di Scor4. The article focuses on a group of seven codices which carry the text of Cicero’s Lucullus. This group belongs to the branch of the tradition descending from the manuscript Wien, Österreichische Nationalbibliothek 189. The seven manuscripts represent a step of the tradition marked by the presence of some textual lacunas. I start from some paleographic elements and from the presence of a gloss on text’s margin of one of them, El Escorial, V.III.6 (Scor4. The gloss has been then incorporated in the text of the other six manuscripts and I assume that Scor4 is the founder of this group of tradition. Furthermore, this article aims to clarify the relations between the six descendants of Scor4.

  17. MENINGKATKAN KETRAMPILAN MEMBUAT DAN MEMBACA KURVE KESEIMBANGAN SERTA HASIL BELAJAR SISWA MENGGUNAKAN METODE DISCOVERY DENGAN MENGGUNAKAN MEDIA VISUAL PADA SISWA KELAS VIII C SMP MUHAMMADIYAH 1 KUDUS

    Directory of Open Access Journals (Sweden)

    Desi Riana Prihandika

    2014-11-01

    Full Text Available Dari observasi awal yang dilakukan di SMP Muhammadiyah 1 Kudus, Pada mata pelajaran IPS khususnya pada materi kurve keseimbangan kurang variatif yaitu hanya ceramah tanpa variasi. Sedangkan materi yang diajarkan adalah aplikatif yaitu menuntut adanya keterampilan dari siswa.Untuk meningkatkan keterampilan siswa membuatdanmembacakurvekeseimbangan maka dilakukan penelitian tindakan kelas dengan Metode Discovery. Subjek penelitian ini adalah siswa kelas VIII C SMP Muhammadiyah 1 Kudus. Prosedur penelitian ini merupakan proses pembelajaran yang terdiri dari 2 siklus, dimana setiap siklus meliputi perencanaan, pelaksanaan tindakan, observasi dan refleksi. Instrumen yang digunakan yaitu lembar observasi dan test keterampilan. Hasil penelitian ini diperoleh presentase keterampilan siswa pada pembelajaran siklus I dengan kategori baik dan pada siklus II meningkat menjadi dengan kategori amat baik, persentase aktivitas guru pada pembelajaran siklus I dengan kategori amat baik dan pada siklus II meningkat menjadi dengan kategori amat baik, Berdasarkan hasil penelitian di atas dapat diambil kesimpulan bahwa, adanya peningkatan keterampilan siswa membuatdanmembacakurvekeseimbangankelas VIII C. From the first observation done in Muhammadiyah 1 Junior High School Kudus, gained information based on the interview result with the teacher of Social Studies grade VIII. Indeed, learning method that usually used are still conventional on Social Studies especially in equilibrium curve lesson is less variativethat is only speech without variants. Whereas the lessons taught are applicative that is demand skill existence for the students. The lesson that felt hard to understand to students are generally the lesson on making equilibrium curve and on reading curve mostly students still don’t understand the meaning of that curve. This is strengthened by average value on equilibrium cost lesson especially equilibrium curve on the VIII grade classified to quite low if

  18. Mechanistic Aspects of Osmium(VIII Catalyzed Oxidation of L-Tryptophan by Diperiodatocuprate(III in Aqueous Alkaline Medium: A Kinetic Model

    Directory of Open Access Journals (Sweden)

    Nagaraj P. Shetti

    2008-01-01

    Full Text Available In presence of osmium(VIII, the reaction between L-tryptophan and diperiodatocuprate(III DPC in alkaline medium exhibits 1:4 stochiometry (L-tryptophan:DPC. The reaction shows first-order dependence on [DPC] and [osmium(VIII], less than unit order in both [L-tryptophan] and [alkali], and negative fractional order in [periodate]. The active species of catalyst and oxidant have been identified. The main products were identified by spectral studies and spot test. The probable mechanism was proposed and discussed.

  19. Angioma cavernoso do meato acústico interno envolvendo o complexo VII e VIII nervos cranianos: relato de caso Cavernous hemangioma of the internal auditory canal encasing the VII and VIII cranial nerve complex: case report

    Directory of Open Access Journals (Sweden)

    Roberto Leal Silveira

    2005-03-01

    Full Text Available Relata-se o caso de homem de 21 anos, leucoderma, portador de angioma cavernoso do meato acústico interno direito envolvendo o complexo VII e VIII nervos cranianos tratado cirurgicamente. Apenas 18 casos de angiomas cavernosos dessa localização foram relatados na literatura. São comentados os aspectos clínicos, o diagnóstico diferencial e o tratamento.We report the surgically treated case of a 21-year-old caucasian male harboring a cavernous hemangioma of the right internal auditory canal encasing the seventh and eighth cranial nerves complex. Only 18 cases of cavernous hemangiomas of this location have been previously reported. The clinical features, the differential diagnosis and the treatment are discussed.

  20. Recurrent myocardial infarctions in a young football player secondary to thrombophilia, associated with elevated factor VIII activity

    Directory of Open Access Journals (Sweden)

    Vacek TP

    2014-10-01

    Full Text Available Thomas P Vacek, Shipeng Yu, Shahnaz Rehman, Blair P Grubb, Daniel Kosinski, Cherian Verghese, Ehab A Eltahawy, Shafiq Qaiser Department of Medicine, University of Toledo Medical Center, Toledo, OH, USAAbstract: Myocardial infarction (MI due to coronary atherosclerosis in young adults is uncommon; rare causes such as cocaine abuse, arterial dissection, and thromboembolism should be considered. A 21-year-old football player, and otherwise healthy African American man, developed chest pain during exercise while bench-pressing 400 lbs. Acute MI was diagnosed based on physical examination, electrocardiography findings, and elevated cardiac enzymes. Coronary arteriography showed a thrombus occluding the proximal left anterior descending artery (LAD. Aggressive antiplatelet therapy with aspirin, clopidogrel, and eptifibatide was pursued, in addition to standard post-MI care. This led to the successful resolution of symptoms and dissolution of the thrombus, demonstrated by repeat coronary arteriography. Five months later, he presented with similar symptoms during exercise after lifting heavy weights, and was found to have another acute MI. Coronary arteriography again showed a thrombus occluding the LAD. No evidence of coronary artery dissection or vasospasm was found. Only mild atherosclerotic plaque burden was observed on both occasions by intravascular ultrasound. A bare metal stent was placed at the site as it was thought this site had acted as a nidus for small plaque rupture and thrombus formation. Elevated serum factor VIII activity at 205% (reference range 60%–140% was found, a rare cause of hypercoagulability. Further workup revealed a patent foramen ovale during a Valsalva maneuver by transesophageal echocardiography. Both events occurred during weight lifting, which can transiently increase right heart pressure in a similar way to the Valsalva maneuver. In light of all the findings, we concluded that an exercise-related increase in factor

  1. Analisis Deskriptif Soal Geometri dalam Buku Matematika Bilingual untuk Sekolah Menengah Pertama Kelas VIII Berdasarkan Kriteria International Assessment TIMSS 2007

    Directory of Open Access Journals (Sweden)

    Etik Rahayu

    2012-06-01

    Full Text Available Tujuan penelitian ini adalah untuk mendeskripsikan  domain kognitif dan aspek kognitif (required behavior soal matematika dalam Buku Matematika Bilingual untuk Sekolah Menengah Pertama (SMP Kelas VIII berdasarkan kriteria International Assessment TIMSS 2007 dan proporsinya. Metode penelitian yang digunakan adalah deskriptif kualitatif, dengan subjek penelitian adalah soal geometri dalam Buku Matematika Bilingual SMP. yang berjudul “Mathematics for Junior High School Grade VIII 1st Semester” dan “Mathematics for Junior High School Grade VIII 2nd Semester” karangan karangan M. Cholik Adinawan dan Sugijono. Pengumpulan data menggunakan metode observasi dan wawancara tentang penggunaan buku matematika bilingual yang paling banyak digunakan di kota semarang. Pedoman analisis soal berdasarkan kriteria International Assessment TIMSS 2007, dengan validasi hasil oleh ahli. Hasil penelitian menunjukkan bahwa soal yang dianalisis memuat satu hingga tujuh aspek kognitif. Sebagian besar soal memuat 4 aspek kognitif yaitu 44.04 %, diikuti soal dengan 3 aspek kognitif  yaitu 36, 42%,  soal dengan 2 aspek kognitif yaitu 14, 90%, kemudian 1,99% untuk soal dengan 1 atau 5 aspek kognitif, dan 0,33% untuk soal dengan 6 atau 7 aspek kognitif. Proporsi tinggi pada recall (28.26% dan compute (26.57%, diikuti dengan SRP (10.85%, implement (10.65%, retrieve (8.36%, recognize (6.17%, analyze (1.99%, measure (1.59%, generalize (1.09%, SNRP (1.00%, classify (0.80%, represent (0.80%, justify (0.80%, select (0.60%, model (0.30%, synthesis (0.20%. Secara keseluruhan berdasarkan International Assessment TIMSS 2007 soal yang termasuk domain knowing memiliki persentase paling tinggi (52.28%, domain knowing-applying (24.83%, domain knowing- reasoning (12.91%, dan hanya sedikit yang termasuk domain knowing-apllying-reasoning (3.97%. Serta terdapat 4 soal (1.32% yang mempunyai ketidaksesuaian penggunaan mathematics terms serta 1 soal (0

  2. [Abstracts of VIII Young Scientists Conference dedicated to 55th anniversary of Central Research Institute of Dentistry and Maxillofacial Surgery 'Modern scientific achievements in dentistry and maxillofacial surgery'].

    Science.gov (United States)

    2017-01-01

    Abstracts of VIII Young Scientists Conference dedicated to 55th anniversary of Central Research Institute of Dentistry and Maxillofacial Surgery 'Modern scientific achievements in dentistry and maxillofacial surgery'. Therapeutic stomatology. Surgical dentistry. Maxillofacial surgery. Orthopedic stomatology. Orthodontics. Organization of dental care.

  3. Factor VIII C1 domain spikes 2092-2093 and 2158-2159 comprise regions that modulate cofactor function and cellular uptake

    NARCIS (Netherlands)

    Bloem, Esther; van den Biggelaar, Maartje; Wroblewska, Aleksandra; Voorberg, Jan; Faber, Johan H.; Kjalke, Marianne; Stennicke, Henning R.; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    The C1 domain of factor VIII (FVIII) has been implicated in binding to multiple constituents, including phospholipids, von Willebrand factor, and low-density lipoprotein receptor-related protein (LRP). We have previously described a human monoclonal antibody called KM33 that blocks these

  4. Factor VIII interacts with the endocytic receptor low-density lipoprotein receptor-related protein 1 via an extended surface comprising "hot-spot" lysine residues

    NARCIS (Netherlands)

    Van Den Biggelaar, Maartje|info:eu-repo/dai/nl/304831433; Madsen, Jesper J.; Faber, Johan H.; Zuurveld, Marleen G.; Van Der Zwaan, Carmen; Olsen, Ole H.; Stennicke, Henning R.; Mertens, Koen|info:eu-repo/dai/nl/070940258; Meijer, Alexander B.

    2015-01-01

    Background: It is unclear how the LDL receptor family binds large protein ligands. Results: HDX and lysine scanning identified factor (F)VIII regions and specific lysine residues binding low-density lipoprotein receptor-related protein 1 (LRP1). Conclusion: FVIII-LRP1 interaction involves multiple

  5. PENGARUH STRATEGI PEMBELAJARAN THE POWER OF TWO BERBANTUAN CROSSWORD PUZZLE TERHADAP HASIL BELAJAR SISWA PADA MATERI GERAK PADA TUMBUHAN DI KELAS VIII SMP NEGERI 1 MINAS

    Directory of Open Access Journals (Sweden)

    Raudhah Awal

    2017-07-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui pengaruh strategi pembelajaran thepower of two berbantuan crossword puzzle terhadap hasil belajar siswa pada materi gerakpada tumbuhan di kelas VIII SMP Negeri 1 Minas. Penelitian ini dilaksanakan pada semesterganjil bulan November tahun ajaran 2015/2016. Desain penelitian yang digunakan adalahkuasi eksperimen dengan the matching only pretest-posttest group design. Sampel penelitianadalah siswa kelas VIII1 dan VIII2, yang diambil dengan teknik simple random sampling.Pengumpulan data dilakukan melalui pretest, posttest dan lembar observasi aktivitas guru dansiswa. Teknik analisis data menggunakan uji-t independen 2 sampel. Rerata N-Gain padakelas eksperimen adalah 0,75 kategori tinggi dan pada kelas kontrol 0,25 kategori rendah.Berdasarkan analisis hasil uji-t menunjukkan perbedaan yang signifikan antara kelas kontroldan kelas eksperimen, dengan demikian dapat disimpulkan bahwa strategi pembelajaran thepower of two berbantuan crossword puzzle memberikan pengaruh yang positif terhadap hasilbelajar siswa pada materi gerak pada tumbuhan di kelas VIII SMP Negeri 1 Minas TahunAjaran 2015/2016.Kata kunci : the power of two, crossword puzzle, hasil belajar, gerak pada tumbuhan

  6. Comparative analysis of activity of coagulation Factors V and VIII and level of fibrinogen in fresh frozen plasma and frozen plasma

    Directory of Open Access Journals (Sweden)

    Mitu Dogra

    2015-01-01

    Full Text Available Background: The aim of this study was to analyse and compare the activity of factor V, VIII and fibrinogen level in fresh frozen plasma and frozen plasma frozen after 8 hrs but within 24 hours after phlebotomy. Materials and Methods: Fresh frozen plasma separated from whole blood within 8 hours was compared with plasma separated within 24 hours after phlebotomy in terms of coagulation factors V and VIII and level of fibrinogen by standard methods using semi automated coagulometer sysmex CA50. Results: Longer storage of whole blood before processing resulted in significant decrease (18.4% in activity of factor VIII but the fall in activity of factor V (6.52% or level of fibrinogen (1.81% was not significant. Discussion: These data suggest that there is good retention of coagulation factors in both types of plasma. Although there is significant fall in activity of factor VIII, but it is an acute phase reactant and raised in most of the diseases so it is suggested that frozen plasma would be an acceptable product for most patients requiring fresh frozen plasma.

  7. Long-Term Expression of Human Coagulation Factor VIII in a Tolerant Mouse Model Using the phi C31 Integrase System

    NARCIS (Netherlands)

    Chavez, Christopher L.; Keravala, Annahita; Chu, Jacqueline N.; Farruggio, Alfonso P.; Cuéllar, Vanessa E.; Voorberg, Jan; Calos, Michele P.

    2012-01-01

    We generated a mouse model for hemophilia A that combines a homozygous knockout for murine factor VIII (FVIII) and a homozygous addition of a mutant human FVIII (hFVIII). The resulting mouse, having no detectable FVIII protein or activity and tolerant to hFVIII, is useful for evaluating FVIII

  8. Retsensioon : Riigikogu VII, VIII ja IX koosseis. Statistikat ja kommentaare. Peatoimetaja Aaro Mõttus. Tallinn : Riigikogu Kantselei, Eesti Rahvusraamatukogu, 2004. 326 lk. / Mart Nutt

    Index Scriptorium Estoniae

    Nutt, Mart, 1962-

    2004-01-01

    Arvustus: Riigikogu VII, VIII ja IX koosseis. Statistikat ja kommentaare / peatoim. Aaro Mõttus. Tallinn : Riigikogu Kantselei, Eesti Rahvusraamatukogu, 2004. - Lisatud: Ott Heinapuu tutvustav sõnum retsenseeritud väljaande kohta lk. 193. - Vt. ka: http://www.riigikogu.ee/rito/index.php?id=11357

  9. Understanding the first Neolithic occupation of Cova d'En Pardo (Planes, Alicante: Preliminary results of the multidisciplinary analysis of levels VIII and VIIIB

    Directory of Open Access Journals (Sweden)

    Jorge Agatángelo Soler Díaz

    2014-01-01

    Full Text Available We present the results of excavations carried out in the Cova d'En Pardo (Planes, Alicante, specifically the levels VIII and VIIIb. The development of a multidisciplinary project has allowed to us characterize the occupation of a small cavity by the first farming communities associated with the Neolithization process of the east of Iberian Peninsula.

  10. Report on corrections and future considerations for Appendices II–VIII of the International Code of Nomenclature for Algae, Fungi, and Plants

    Science.gov (United States)

    For the first time, the main text and Appendices II–VIII of the International Code of Nomenclature were separately published following decisions of the Melbourne Nomenclature Section, which contributed to subsequent development of an online resource capable of producing the Appendices in real time. ...

  11. 75 FR 33760 - Notice of a New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447...

    Science.gov (United States)

    2010-06-15

    ... Forest Service Notice of a New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L...: The Chequamegon-Nicolet National Forest is proposing to begin charging a $5.00 daily user fee or... Trailhead was posted for a one year comment period pertaining to the implementation of use fees on March 18...

  12. 75 FR 33761 - Notice of a New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447)

    Science.gov (United States)

    2010-06-15

    ... Forest Service Notice of a New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L... Register whenever new recreation fee areas are established. Once public involvement is complete, these new fees will be reviewed by a Recreation Resource Advisory Committee prior to a final decision and...

  13. Reticular Basement Membrane Vessels Are Increased in COPD Bronchial Mucosa by Both Factor VIII and Collagen IV Immunostaining and Are Hyperpermeable

    Directory of Open Access Journals (Sweden)

    Amir Soltani

    2012-01-01

    Full Text Available Background and Objective. Using Collagen IV staining, we have previously reported that the reticular basement membrane (Rbm is hypervascular and the lamina propria (LP is hypovascular in COPD airways. This study compared Collagen IV staining with vessels marked with anti-Factor VIII and examined vessel permeability in bronchial biopsies from COPD and normal subjects using albumin staining. Results. Anti-Collagen IV antibody detected more vessels in the Rbm (P=0.002 and larger vessels in both Rbm (P<0.001 and LP (P=0.003 compared to Factor VIII. COPD airways had more vessels (with greater permeability in the Rbm (P=0.01 and fewer vessels (with normal permeability in the LP compared to controls with both Collagen IV and Factor VIII antibodies (P=0.04 and P=0.01. Conclusion. Rbm vessels were increased in number and were hyperpermeable in COPD airways. Anti-Collagen IV and anti-Factor VIII antibodies did not uniformly detect the same vessel populations; the first is likely to reflect larger and older vessels with the latter reflecting smaller, younger vessels.

  14. Reticular Basement Membrane Vessels Are Increased in COPD Bronchial Mucosa by Both Factor VIII and Collagen IV Immunostaining and Are Hyperpermeable

    Science.gov (United States)

    Soltani, Amir; Wood-Baker, Richard; Sohal, Sukhwinder S.; Muller, H. Konrad; Reid, David; Walters, E. Haydn

    2012-01-01

    Background and Objective. Using Collagen IV staining, we have previously reported that the reticular basement membrane (Rbm) is hypervascular and the lamina propria (LP) is hypovascular in COPD airways. This study compared Collagen IV staining with vessels marked with anti-Factor VIII and examined vessel permeability in bronchial biopsies from COPD and normal subjects using albumin staining. Results. Anti-Collagen IV antibody detected more vessels in the Rbm (P = 0.002) and larger vessels in both Rbm (P < 0.001) and LP (P = 0.003) compared to Factor VIII. COPD airways had more vessels (with greater permeability) in the Rbm (P = 0.01) and fewer vessels (with normal permeability) in the LP compared to controls with both Collagen IV and Factor VIII antibodies (P = 0.04 and P = 0.01). Conclusion. Rbm vessels were increased in number and were hyperpermeable in COPD airways. Anti-Collagen IV and anti-Factor VIII antibodies did not uniformly detect the same vessel populations; the first is likely to reflect larger and older vessels with the latter reflecting smaller, younger vessels. PMID:22500190

  15. Late-Onset Invasive Group B Streptococcal Infection with Serotype VIII in a Neonate Having Congenital Biliary Atresia

    Directory of Open Access Journals (Sweden)

    Tomoaki Takei

    2013-02-01

    Full Text Available A female newborn was admitted to our department 15 days after birth for insufficient sucking and jaundice. The patient’s blood and urine cultures were both positive for group B streptococcal (GBS infection. A maternal vaginal sample at 35 weeks’ gestation was negative for GBS in culture-based microbiologic screening. The patient recovered shortly after receiving systemic antibiotic therapy. On the basis of clinical evidence of white stool and progressive jaundice, we suspected that the newborn had complications related to congenital biliary atresia (CBA; surgery was performed. Isolates from the mother’s vaginal sample obtained when the patient was 25 days old, along with neonatal blood, revealed identical patterns (serotype VIII and sequence type 1 of GBS capsular and multilocus sequence typing, suggestive of maternal transmission. Molecular epidemiologic examination may be useful to clarify the transmission route and etiology; culture-based microbiologic screening appears to have limitations for detecting the route of transmission.

  16. The B-domain of factor VIII reduces cell membrane attachement to host cells in serum free conditions

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Flintegaard, Thomas Veje

    2010-01-01

    % of rFVIII is attached to the cell membrane of the producing cell when the rFVIII variant contains a short B-domain (21 aa). By increasing the length of the B-domain the membrane attached fraction can be reduced to 50% of the total expressed rFVIII. Further, our studies show that the N-linked......Factor VIII (FVIII) is an important protein in the blood coagulation cascade and dysfunction or deficiency of FVIII causes haemophilia A. Replacement therapy with exogenous recombinant FVIII (rFVIII) works as a substitute for the missing or non-functioning FVIII. The rFVIII protein has been...... engineered extensively throughout the years to increase the low production yields that initially were obtained from mammalian cell cultures. The scope of this work was to investigate the interaction of rFVIII with the cell membrane surface of the producing cells in serum free medium. We wondered whether...

  17. Detailed Analysis of Configuration Interaction and Calculation of Radiative Transition Rates in Seven Times Ionized Tungsten (W VIII

    Directory of Open Access Journals (Sweden)

    Jérôme Deprince

    2015-06-01

    Full Text Available A new set of oscillator strengths and transition probabilities for EUV spectral lines of seven times ionized tungsten (W VIII is reported in the present paper. These results have been obtained using the pseudo-relativistic Hartree-Fock (HFR method combined with a semi-empirical optimization of the radial parameters minimizing the discrepancies between computed energy levels and available experimental data. The final physical model considered in the calculations has been chosen further to a detailed investigation of the configuration interaction in this atomic system characterized by complex configurations of the type 4f145s25p5, 4f145s25p4nl, 4f145s5p6, 4f135s25p6, 4f135s25p5nl and 4f125s25p6nl (nl = 5d, 6s.

  18. RELATO del VIII ENCUENTRO NACIONAL ACADÉMICO de ADMINISTRACIÓN de AGRONEGOCIOS-Febrero 23 y 24, 2007

    OpenAIRE

    José Mendoza Becerril

    2007-01-01

    Después de haber sido recibidos cortés y amablemente por el Dr. José Sergio Barrales Domínguez, Rector de la Universidad Autónoma Chapingo, se inicia el VIII Encuentro con la presentación del Proyecto de Doctorado, el Dr. Javier Ruiz Ledezma, señaló que por muchos años se mantuvo un área de estudios para formar licenciados en economía agrícola y con los retos que impuso la apertura comercial de México ante el mundo se impulsaron las carreras de licenciado en administración agro...

  19. PENGEMBANGAN MATERI LUAS PERMUKAAN DAN VOLUM LIMAS YANG SESUAI DENGAN KARAKTERISTIK PMRI DI KELAS VIII SMP NEGERI 4 PALEMBANG

    Directory of Open Access Journals (Sweden)

    Hariyati Hariyati

    2013-09-01

    Full Text Available Penelitian ini bertujuan mengembangkan materi luas permukaan dan volum limas dengan pendekatan PMRI. Subjek dalam penelitian ini adalah siswa kelas VIII SMP Negeri 4 Palembang. Dalam mengembangkan materi terdapat proses evaluasi formatif dan uji coba terhadap materi, yaitu expert review, one-to-one evaluation, small group, dan field test. Dari tiga tahap pertama, materi dinyatakan valid. Kemudian materi diujicobakan di lapangan (field test. Dari hasil uji coba diperoleh simpulan yaitu menghasilkan buku siswa untuk materi luas permukaan dan volum limas yang sesuai dengan karakteristik PMRI. Dan buku siswa ini baik karena dilihat dari aktivitas siswa yang menunjukkan kategori aktif, hasil belajar siswa yang menunjukkan kategori baik, dan sikap siswa yang cenderung positif terhadap proses pembelajaran matematika menggunakan buku siswa yang sesuai dengan karakteristik PMRI.

  20. Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Sørensen, Hanne Thykjær; Norengaard, Lisbeth

    2007-01-01

    BACKGROUND: Most patients with severe hemophilia A suffer from a profoundly compromised hemostatic response. In addition to both the delayed and slow development of a clot, previous studies have documented that severe hemophilia A is also associated with reduced clot stability. OBJECTIVES: We...... examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII). PATIENTS/METHODS: Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of r...... the elasticity curve increased 5-fold after rFVIII and 24-fold after addition of TXA. CONCLUSIONS: The study demonstrates that simultaneous treatment with TXA and rFVIII significantly improves the clot stability in patients with hemophilia A. Udgivelsesdato: December...

  1. The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right Hepatic Malignancy Therapy.

    Science.gov (United States)

    Hu, Min; Hu, Haoyu; Cai, Wei; Mo, Zhikang; Xiang, Nan; Yang, Jian; Fang, Chihua

    2017-11-27

    Hepatectomy is the optimal method for liver cancer; the virtual liver resection based on three-dimensional visualization technology (3-DVT) could provide better preoperative strategy for surgeon. We aim to introduce right posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as a promising treatment for massive or multiple right hepatic malignancies to retain maximum residual liver volume on the basis of R0 resection. Among 126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which provided better observation of spatial position relationship between tumor and vessels, and the more accurate estimation of the remnant liver volume. If remnant liver volume was right posterior lobe allied with part of V and VIII sectionectomy should be undergone. Then, the precut line ought to be planned on the basis of protecting the portal branch of subsegment 5 and 8. The postoperative outcome of patients was compared before and after propensity score matching. Nine patients meeting the eligibility criteria received right posterior lobe allied with part of V and VIII sectionectomy. The variables, including the overall mean operation time, blood transfusion, operation length, liver function, and postoperative complications, were similar between two groups before and after propensity matching. The postoperative first, third, fifth, and seventh days mean value of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant difference compared with preoperative value. One patient in each group had recurrence six months after surgery. Right posterior lobe allied with part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way, and can be a very promising method in massive or multiple right hepatic malignancy therapy.

  2. Recurrent myocardial infarctions in a young football player secondary to thrombophilia, associated with elevated factor VIII activity.

    Science.gov (United States)

    Vacek, Thomas P; Yu, Shipeng; Rehman, Shahnaz; Grubb, Blair P; Kosinski, Daniel; Verghese, Cherian; Eltahawy, Ehab A; Shafiq, Qaiser

    2014-01-01

    Myocardial infarction (MI) due to coronary atherosclerosis in young adults is uncommon; rare causes such as cocaine abuse, arterial dissection, and thromboembolism should be considered. A 21-year-old football player, and otherwise healthy African American man, developed chest pain during exercise while bench-pressing 400 lbs. Acute MI was diagnosed based on physical examination, electrocardiography findings, and elevated cardiac enzymes. Coronary arteriography showed a thrombus occluding the proximal left anterior descending artery (LAD). Aggressive antiplatelet therapy with aspirin, clopidogrel, and eptifibatide was pursued, in addition to standard post-MI care. This led to the successful resolution of symptoms and dissolution of the thrombus, demonstrated by repeat coronary arteriography. Five months later, he presented with similar symptoms during exercise after lifting heavy weights, and was found to have another acute MI. Coronary arteriography again showed a thrombus occluding the LAD. No evidence of coronary artery dissection or vasospasm was found. Only mild atherosclerotic plaque burden was observed on both occasions by intravascular ultrasound. A bare metal stent was placed at the site as it was thought this site had acted as a nidus for small plaque rupture and thrombus formation. Elevated serum factor VIII activity at 205% (reference range 60%-140%) was found, a rare cause of hypercoagulability. Further workup revealed a patent foramen ovale during a Valsalva maneuver by transesophageal echocardiography. Both events occurred during weight lifting, which can transiently increase right heart pressure in a similar way to the Valsalva maneuver. In light of all the findings, we concluded that an exercise-related increase in factor VIII activity led to coronary arterial thrombosis in the presence of a small ruptured plaque. Alternatively, venous clots may have traversed the patent foramen ovale and occluded the LAD. In addition to continuing aggressive risk

  3. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

    Directory of Open Access Journals (Sweden)

    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  4. Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study.

    Science.gov (United States)

    Bugnicourt, Jean-Marc; Roussel, Bertrand; Tramier, Blaise; Lamy, Chantal; Godefroy, Olivier

    2007-07-01

    High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study. The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty-four healthy subjects matched for age and sex formed the group control. Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009). Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.

  5. PENGARUH FAKTOR INTERNAL DAN EKSTERNAL SISWA TERHADAP HASIL BELAJAR MATA PELAJARAN IPS KELAS VIII DI MTS N 02 SEMARANG

    Directory of Open Access Journals (Sweden)

    Erlina Indriasari

    2014-08-01

    Full Text Available Hasil belajar mempunyai fungsi sebagai indikator untuk mengetahui sejauh manakompetensi yang telah dikuasai oleh siswa. Tujuan dari penelitian ini adalah untukmengetahui, menganalisis dan mengkaji pengaruh motivasi, sikap, lingkungankeluarga dan lingkungan sekolah secara parsial dan secara simultan terhadap hasilbelajar mata pelajaran IPS. Penelitian ini menggunakan metode kuantitatif. Sampelpenelitian ini berjumlah 161 siswa kelas VIII. pengumpulan data melalui angketdan dokumentasi. Analisis data dengan menggunakan analisis Regresi LinierSederhana dan Berganda. Hasil penelitian menunjukkan (1 ada pengaruh yangsignifikan antara motivasi dan hasil belajar sebesar 8,47%, (2 ada pengaruh yangsignifikan antara sikap dan hasil belajar sebesar 18,57%, (3 ada pengaruh yang signifikanantara lingkungan keluarga dan hasil belajar sebesar 10,62%, (4 ada pengaruhyang signifikan antara lingkungan sekolah dan hasil belajar sebesar4,28%, dan(5 ada pengaruh yang signifikan antara motivasi, sikap, lingkungan keluarga, danlingkungan sekolah dan hasil belajar IPS kelas VIII di MTs N 02 Semarang secarabersama-sama sebesar 49,3%. Learning outcomes has the function as an indicator to determine the extent of competencethat has been mastered by the student. The purpose of this study is to investigate, analyzeand assess the influence of motivation, attitude, family environment and school environmentpartially and simultaneously to the learning outcomes of the eye social studies. This study usesquantitative methods. The study sample totaled 161 eighth grade students. collection of datathrough questionnaires and documentation. Analysis of the data using the Simple LinearRegression analysis and Regression. The results showed (1 no significant relationship betweenmotivation and learning outcomes of 8.47%, (2 no significant relationship between attitudesand learning outcomes of 18.57%, (3 no significant relationship between family environmentand learning outcomes of 10

  6. Incidence of low-titre factor VIII inhibitors in patients with haemophilia A: meta-analysis of observational studies.

    Science.gov (United States)

    Messori, A; Peyvandi, F; Mengato, D; Mannucci, P M

    2017-03-01

    A few studies have been focused on low-titre inhibitors in patients with haemophilia A. Although several putative factors have been implicated in the development of these inhibitors, solid data are still lacking. The aim of this study was to perform a proportion meta-analysis on the incidence of low-titre inhibitors in haemophilia A. We surveyed the PubMed database to identify studies on de novo development of low-titre inhibitors in haemophilia A patients. On the basis of these data, we carried out a proportion meta-analysis to summarize information on incidence and between-study variability. Furthermore, the following three covariates were assessed by meta-regression: (i) mild disease vs. severe haemophilia; (ii) status of previously untreated patient (PUP) as opposed to multi-transfused and (iii) type of factor VIII. Our literature search on PubMed extracted 340 eligible articles. From these, we selected 33 patient cohorts that were included in our meta-analysis (19 cohorts for PUPs and 14 cohorts for multi-transfused or unselected patients). The pooled incidence of low-titre inhibitors was 10.3% (95%CI: 8.3-12.5%) for studies including PUPs and 5.8% (95%CI: 2.5-10.4%) for the other studies; the difference was statistically significant (P = 0.003). Meta-regression of 31 patient cohorts found that mild disease and type of factor VIII were not associated with an increased incidence of low-titre inhibitors. Our results confirmed that PUPs show a higher incidence of low-titre inhibitors than the other patients. Furthermore, our data showed that mild haemophilia was not associated with an increased incidence of low-titre inhibitors. © 2017 John Wiley & Sons Ltd.

  7. Alteration in lymphocyte responses, cytokine and chemokine profiles in chickens infected with genotype VII and VIII velogenic Newcastle disease virus.

    Science.gov (United States)

    Rasoli, Mehdi; Yeap, Swee Keong; Tan, Sheau Wei; Moeini, Hassan; Ideris, Aini; Bejo, Mohd Hair; Alitheen, Noorjahan Banu Mohamed; Kaiser, Pete; Omar, Abdul Rahman

    2014-01-01

    Newcastle disease (ND) is a highly contagious avian disease and one of the major causes of economic losses in the poultry industry. The emergence of virulent NDV genotypes and repeated outbreaks of NDV in vaccinated chickens have raised the need for fundamental studies on the virus-host interactions. In this study, the profiles of B and T lymphocytes and macrophages and differential expression of 26 immune-related genes in the spleen of specific-pathogen-free (SPF) chickens, infected with either the velogenic genotype VII NDV strain IBS002 or the genotype VIII NDV strain AF2240, were evaluated. A significant reduction in T lymphocyte population and an increase in the infiltration of IgM+ B cells and KUL01+ macrophages were detected in the infected spleens at 1, 3 and 4 days post-infection (dpi) (PTNFSF13B (P<0.05). However, these two genotypes showed different cytokine expression patterns and viral load. IBS002 showed higher viral load than AF2240 in spleen at 3 and 4dpi and caused a more rapid up-regulation of CXCLi2, IFN-γ, IL-12α, IL-18, IL-1β, iNOS and IL-10 at 3dpi. Meanwhile, the expression levels of CCLI3, CXCLi1, IFN-γ, IL-12α, IL-1β and iNOS genes were significantly higher in AF2240 at 4dpi. In addition, the expression levels of IL-10 were significantly higher in the IBS002-infected chickens at 3 and 4dpi. Hence, infection with velogenic genotype VII and VIII NDV induced different viral load and production of cytokines and chemokines associated with inflammatory reactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

    Science.gov (United States)

    Baumgartner, C K; Mattson, J G; Weiler, H; Shi, Q; Montgomery, R R

    2017-01-01

    Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of

  9. Recent developments in the techniques of IMAG processing and diagnostic imaging for the cultural heritage; Recenti sviluppi nelle metodologie di elaborazione di immagini e di imaging diagnostico per i beni culturali

    Energy Technology Data Exchange (ETDEWEB)

    Maino, G. [ENEA, Divisione Fisica Applicata, Centro Ricerche E. Clementel, Bologna (Italy); Bonifazzi, C. [Ferrara Univ., Ferrara (Italy). Dipt. di Scienze Biomediche; Sabia, E. [ENEA, Tecnologie Ingegneria e Servizi Ambientali, Centro Ricerche Portici, Naples (Italy)

    2000-07-01

    In this report, the contributions presented to the mini symposium on Recent developments in the techniques of image processing and diagnostic imaging for the cultural heritage are collected. The symposium has been organized within the framework of the V National Congress of SIMAI Italian Society for Applied and Industrial Mathematics (SIMAI 2000), held in Ischia from June 5 to 9, 2000, and shows the main scientific results obtained relevant to the research activities carried out in the frame of sub project 3 of research project GIANO (Advanced Graphics for the National cultural heritage and Employment), jointly funded by MURST (Ministry of University, Scientific and Technological Research) EC (law 488/92). The GIANO-ENEA project contributed, together with CRS4, GNIM-IndAM, Ministero degli Affari Esteri and ST-Microelectronics, to the organization of SIMAI 2000. [Italian] In questo rapporto sono raccolti i contributi presentati al minisimposio su Recenti sviluppi nelle metodologie di elaborazione di immagini e di imaging diagnostico per i beni culturali, organizzato nell'ambito del 5. Congresso Nazionale della SIMAI Societa' Italiana di Matematica Applicata e Industriale (SIMAI 2000), svoltosi a Ischia dal 5 al 9 giugno 2000. Il simposio illustra i principali risultati scientifici ottenuti nel quadro delle attivita' di ricerca del sottoprogetto 3 del piano nazionale GIANO (Grafica Innovativa per il patrimonio Artistico Nazionale e per l'Occupazione giovanile), finanziato dal MURST e dall'UE (legge 488/92). Il progetto GIANO-ENEA ha contribuito, insieme con CRS4, GNIM-IndAM, Ministero degli Affari Esteri e ST-Microelectronics, alla realizzazione di SIMAI 2000.

  10. Graphic proposal for multi thematic maps: the case of geoenvironmental diagnostic map of the Igarapava hydroelectric power plant; Proposta grafica para mapas politematicos: o caso do mapa diagnostico geoambiental da U.H.E. de Igarapava

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Valeria Amorim do [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Geociencias. Dept. de Geografia

    1995-12-31

    This article aims at developing a graphic proposal for multithematic diagnostic map. The research`s objective is the analysis of the legends of the maps entitled Mapa Diagnostico Geoambiental da Usina Hidreletrica de Igarapava (Geoenvironmental Diagnostic map of the Igarapava Hydroelectric Plant). The analysis emphases on identifying and solving problems resulting in non-respect of the graphic transcription laws which prejudice the map`s clarity. Upon analyzing both versions of the maps, it appeared that these problems were basically resulting from bad legibility and visualization and the inadequate use of retina`s variables in the translation of graphic density and both retinian and angular separation. Graphic density was reduced and retinian separation was improved through leading a better contrast between elements of cartographic base and the Geoenvironment Synthesis Map. The angular separation was increased by using simplified forms to better visualization of the spatial structure of the information. That aspect was laos improved by creating a series of small maps to accompany the legend. Point and line elements were represented on the same map so to not prejudice hierarchical relationship between elements. All these modifications were done without affecting information extraction of the various levels of the Geoenvironmental Synthesis (BASE MAP, VEGETATION and LAND USE, HUMAN ASPECTS, CULTURAL ASPECTS AND ENVIRONMENTAL DYNAMIC). The visualization of the document as a whole was greatly improved with respect to the original proposed format. This research is but one of the various steps to the preparation of an environmental map that aims at giving clear visibility to the thousands of words of an environmental study report. (author) 4 refs., 8 figs.

  11. Temperature, salinity and other measurements found in dataset CTD taken from the BARUNA JAYA VIII (FRV; call sign YFZQ; built 08.1998; IMO9155171) in the Coastal Equatorial Pacific, South Indian and other locations in 2005 (NODC Accession 0044407)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Temperature, salinity and other measurements found in dataset CTD taken from the BARUNA JAYA VIII (FRV; call sign YFZQ; built 08.1998; IMO9155171) in the Coastal...

  12. PENINGKATAN AKTIVITAS DAN HASIL BELAJAR TERBENTUKNYA HARGA PASAR DENGAN PENERAPAN MODEL CORE PADA SISWA KELAS VIII SMP N 2 UNGARAN

    Directory of Open Access Journals (Sweden)

    Lala Sakuntala

    2013-11-01

    Full Text Available Permasalahan yang muncul dalam pembelajaran di SMP N 2 Ungaran berawal dari penggunan metode dan model pembelajaran yang digunakan guru pada saat pembelajaran. Dalam pembalajaran guru cenderung masih menggunakan ceramah, sehingga menyebabkan kurangnya interaksi dan motivasi siswa pada saat pembelajaran berlangsung. Berdasarkan hasil observasi awal di SMP N 2 Ungaran, diperoleh data bahwa 53,12% siswa belum tuntas dalam pembelajaran materi harga keseimbangan. Tujuan dari penelitian ini yaitu untuk mengetahui apakah ada peningkatan menggunakan model pembelajaran CORE terhadap aktivitas dan hasil belajar pokok bahasan pembentukan harga pasar siswa kelas VIII di SMP Negeri 2 Ungaran. Subjek penelitian ini adalah siswa kelas VIII D SMP N 2 Ungaran dengan menerapkan model pembelajaran CORE. Rancangan penelitian ini merupakan penelitian tindakan kelas yang terdiri dari dua siklus, setiap siklus meliputi perencanaan, pelaksanaan, pengamatan, dan refleksi. Hasil penelitian siklus I menunjukkan rata-rata hasil belajar siswa sebesar 74,2 dengan ketuntasn klasikal 72%. Untuk hasil penelitian siklus II menunjukkan rata-rata hasil belajar siswa sebesar 78.9 dengan ketuntasan klasikal 88%. Hasil aktivitas siswa dan guru meningkat dengan diterapkannya model pembelajaran CORE. Terlihat pada hasil aktivitas siswa siklus I sebesar 70% meningkat menjadi 87.5% pad siklus II. Sedangkan aktivitas guru pada siklus II sebesar 75% meningkat menjadi 95% pada siklus II. Berdasarkan hasil penelitian diatas dapat disimpulkan bahwa terjadi peningkatan aktivitas dan hasil belajar siswa dengan menggunakan model pembelajaran CORE pada materi harga keseimbangan. Saran yang berkaitan dengan hasil penelitian adalah perlu adanya kesiapan guru sebelum memulai pelajaran, guru hendaknya mampu menguasai kelas dengan baik, dan memilih metode yang tepat untuk diterapkan dalam proses belajar mengajar. The problems that arise in learning in SMP 2 Ungaran originated from the use of learning

  13. Factors Associated with the Time of Admission among Notified Dengue Fever Cases in Region VIII Philippines from 2008 to 2014.

    Directory of Open Access Journals (Sweden)

    Jason Echavez Abello

    2016-10-01

    Full Text Available In cases of Dengue fever, late hospital admission can lead to treatment delay and even death. In order to improve early disease notification and management, it is essential to investigate the factors affecting the time of admission of Dengue cases. This study determined the factors associated with the time of admission among notified Dengue cases. The study covered the period between 2008 and 2014 in Region VIII, Philippines. The factors assessed were age, sex, hospital sector, hospital level, disease severity based on the 1997 WHO Dengue classification, and period of admission (distinguishing between the 2010 Dengue epidemic and non-epidemic time. We analysed secondary data from the surveillance of notified Dengue cases. We calculated the association through chi-square test, ordinal logistic regression and linear regression at p value < 0.05. The study included 16,357 admitted Dengue cases. The reported cases included a majority of children (70.09%, mild cases of the disease (64.00%, patients from the public sector (69.82%, and non-tertiary hospitals (62.76%. Only 1.40% of cases had a laboratory confirmation. The epidemic period in 2010 comprised 48.68% of all the admitted cases during this period. Late admission was more likely among adults than children (p<0.05. The severe type of the disease was more likely to be admitted late than the mild type (p<0.05. Late admission was also more likely in public hospitals than in private hospitals (p<0.05; and within tertiary level hospitals than non-tertiary hospitals (p<0.05. Late admission was more likely during the non-epidemic period than the 2010 epidemic period (p<0.05. A case fatality rate of 1 or greater was significantly associated with children, severe diseases, tertiary hospitals and public hospitals when admitted late (p<0.05. Data suggests that early admission among child cases was common in Region VIII. This behavior is encouraging, and should be continued. However, further study is needed

  14. Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A.

    Science.gov (United States)

    Nguyen, G N; George, L A; Siner, J I; Davidson, R J; Zander, C B; Zheng, X L; Arruda, V R; Camire, R M; Sabatino, D E

    2017-01-01

    Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy. Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function. Objective We hypothesized that deletion(s) of the furin site modulates FVIII biology and may enhance its function. Methods A series of recombinant hFVIII-furin deletion variants were introduced into hFVIII-BDD [Δ1645, 1645-46(Δ2), 1645-47(Δ3), 1645-48(Δ4), or Δ1648] and characterized. Results In vitro, recombinant purified Δ3 and Δ4 were primarily SC and, interestingly, had 2-fold higher procoagulant activity compared with FVIII-BDD. In vivo, the variants also have improved hemostatic function. After adeno-associated viral (AAV) vector delivery, the expression of these variants is 2-4-fold higher than hFVIII-BDD. Protein challenges of each variant in mice tolerant to hFVIII-BDD showed no anti-FVIII immune response. Conclusions These data suggest that the furin deletion hFVIII variants are superior to hFVIII-BDD without increased immunogenicity. In the setting of gene-based therapeutics, these novel variants provide a unique strategy to increase FVIII expression, thus lowering the vector dose, a

  15. Cyclic peptide analogs of 558-565 epitope of A2 subunit of Factor VIII prolong aPTT. Toward a novel synthesis of anticoagulants.

    Science.gov (United States)

    Anastasopoulos, C; Sarigiannis, Y; Stavropoulos, G

    2014-04-01

    Novel anticoagulant therapies target specific clotting factors in blood coagulation cascade. Inhibition of the blood coagulation through Factor VIII-Factor IX interaction represents an attractive approach for the treatment and prevention of diseases caused by thrombosis. Our research efforts are continued by the synthesis and biological evaluation of cyclic, head to tail peptides, analogs of the 558-565 sequence of the A2 subunit of FVIII, aiming at the efficient inhibition of Factor VIIIa-Factor IXa interaction. The analogs were synthesized on solid phase using the acid labile 2-chlorotrityl chloride resin, while their anticoagulant activities were examined in vitro by monitoring activated partial thromboplastin time and the inhibition of Factor VIII activity. The results reveal that these peptides provide bases for the development of new anticoagulant agents.

  16. Successful immunoadsorption of life-threatening bleeding in factor VIII inhibitor disease, but no long-term remission with anti-CD20 treatment.

    Science.gov (United States)

    Grahammer, Florian; Fischer, Karl-Georg

    2015-08-30

    A 62-year-old man and a 64-year-old woman presented to our institution with acquired haemophilia A. They both developed life-threatening bleeding. Immunoadsorption using protein A columns was used to rapidly lower factor VIII inhibitor levels. Immunosuppression with steroids and the anti-CD20 antibody, rituximab, was instituted. Yet their effects were either partial or complicated by an early relapse. Repetitive cyclophosphamide administration led to a sustained immunological response. While immunoadsorption appears effective and safe to lower factor VIII inhibitor levels, it seems that further preferably randomised controlled trials are needed to establish the value of rituximab versus the standard immunosuppressive regime comprising cyclophosphamide. 2015 BMJ Publishing Group Ltd.

  17. Alterations in hemostatic parameters during hemodialysis with dialyzers of different membrane composition and flow design. Platelet activation and factor VIII-related von Willebrand factor during hemodialysis.

    Science.gov (United States)

    Schmitt, G W; Moake, J L; Rudy, C K; Vicks, S L; Hamburger, R J

    1987-09-01

    The effect of dialyzer membrane and design on hemostatic parameters during hemodialysis were evaluated in a prospective controlled study. This study demonstrated that hemodialysis is associated with significant platelet activation and loss, which are influenced by both dialyzer configuration and membrane composition. In addition, use of the cuprophan membrane is associated with greater perturbations of the vascular endothelium, as reflected in changes in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha concentrations not seen with the polyacrylonitrile membrane. Of the dialyzers studied, the polyacrylonitrile membrane in a hollow-fiber configuration appears to minimize platelet loss and activation, and to minimize increases in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha.

  18. In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents anti-factor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy.

    Science.gov (United States)

    Liu, Chao-Lien; Ye, Peiqing; Yen, Benjamin C; Miao, Carol H

    2011-08-01

    Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4(+)CD25(+)Foxp3(+) Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7-14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII.

  19. Evaluation of the expression of VIII factor and VEGF in the regeneration of non-vital teeth in dogs using propolis

    Science.gov (United States)

    Zarei, Mina; Jafarian, Amir Hossein; Harandi, Azadeh; Javidi, Maryam; Gharechahi, Maryam

    2017-01-01

    Objective(s): The purpose of the present study was the immunohistochemical evaluation of VEGF and VII factors in dog’s teeth pulp revascularized with MTA and propolis. Materials and Methods: 144 mature and immature two rooted dog’s premolar canals were selected. Pulp necrosis and infection were established after 2 weeks and the disinfection of the canals was done with copious NaOCl irrigation and triantibiotic mixture (ciprofloxacin, metronidazole, and minocycline) for 3 weeks. Subsequently, the blood clot was evoked in the canal by periapical tissue irritation with a k-file. The samples were randomly divided into 6 experimental groups: propolis (groups 1, 2), MTA (groups 3, 4), and parafilm (groups 5, 6) in immature and mature teeth. The animals were sacrificed and samples were prepared for immunohistochemical evaluation of VEGF and the VIII factor. Results: Tissue regeneration was seen in 64.5% of MTA, 38% of propolis, and 0% of parafilm group samples. Expression of VEGF and VIII factor in the propolis group was more than the MTA group and it showed a reduction after 3 months in comparison to 1 month. VEGF and VIII factor were seen in stromal cells in addition to endothelial vessel cells. Overall, expression of angiogenic factors was more in the open apex teeth compared to close apex ones. Conclusion: According to the results of this study, propolis can induce the expression of VEGF and VIII factor in infected mature and immature dog’s teeth and is a suitable biomaterial for the revascularization technique. PMID:28293394

  20. Recombinant Factor VIIa (Eptacog Alfa): A Pharmacoeconomic Review of its Use in Haemophilia in Patients with Inhibitors to Clotting Factors VIII or IX

    OpenAIRE

    Katherine A. Lyseng-Williamson; Greg L. Plosker

    2007-01-01

    Recombinant factor VIIa (NovoSeven(R); also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of succe...

  1. Rate-limiting roles of the tenase complex of factors VIII and IX in platelet procoagulant activity and formation of platelet-fibrin thrombi under flow.

    Science.gov (United States)

    Swieringa, Frauke; Kuijpers, Marijke J E; Lamers, Moniek M E; van der Meijden, Paola E J; Heemskerk, Johan W M

    2015-06-01

    The importance of factor Xa generation in thrombus formation has not been studied extensively so far. Here, we used mice deficient in either factor VIII or factor IX to determine the role of platelet-stimulated tenase activity in the formation of platelet-fibrin thrombi on collagen. With tissue factor present, deficiency in factor VIII or IX markedly suppressed thrombus growth, fibrin formation and platelet procoagulant activity (phosphatidylserine exposure). In either case, residual fibrin formation was eliminated in the absence of tissue factor. Effects of factor deficiencies were antagonized by supplementation of the missing coagulation factor. In wild-type thrombi generated under flow, phosphatidylserine-exposing platelets bound (activated) factor IX and factor X, whereas factor VIII preferentially co-localized at sites of von Willebrand factor binding. Furthermore, proteolytic activity of the generated activated factor X and thrombin was confined to the sites of phosphatidylserine exposure. With blood from a hemophilia A or B patient, the formation of platelet-fibrin thrombi was greatly delayed and reduced, even in the presence of high concentrations of tissue factor. A direct activated factor X inhibitor, rivaroxaban, added to human blood, suppressed both thrombin and fibrin formation. Together, these data point to a potent enforcement loop in thrombus formation due to factor X activation, subsequent thrombin and fibrin generation, causing activated factor X-mediated stimulation of platelet phosphatidylserine exposure. This implies that the factor VIII/factor IX-dependent stimulation of platelet procoagulant activity is a limiting factor for fibrin formation under flow conditions, even at high tissue factor concentrations. Copyright© Ferrata Storti Foundation.

  2. Penerapan Model Pembelajaran Berbasis Masalah (Problem Based Learning) untuk Meningkatkan Hasil Belajar Matematika Siswa Kelas Viii.2 SMP Negeri 4 Pekanbaru

    OpenAIRE

    Pratiwi, Ratih Surya Pratiwi Surya; Solfitri, Titi Solfitri; ', Sakur

    2015-01-01

    This research is classroom action research that aims to improve learning process and to increase mathematics achievement with applied the learning model of Problem Based Learning. The subject of this research is student of class VIII.2 SMPN 4 Pekanbaru in the second semester academic years 2014/2015, which amounted to 34 students, consist of 13 boys and 21 girls. The research consisit of two cycles, each cycle has four stages, which are planning, implementation, observation, and reflection. A...

  3. Evaluation of the expression of VIII factor and VEGF in the regeneration of non-vital teeth in dogs using propolis

    Directory of Open Access Journals (Sweden)

    Mina Zarei

    2017-02-01

    Full Text Available Objective(s: The purpose of the present study was the immunohistochemical evaluation of VEGF and VII factors in dog’s teeth pulp revascularized with MTA and propolis. Materials and Methods: 144 mature and immature two rooted dog’s premolar canals were selected.  Pulp necrosis and infection were established after 2 weeks and the disinfection of the canals was done with copious NaOCl irrigation and triantibiotic mixture (ciprofloxacin, metronidazole, and minocycline for 3 weeks. Subsequently, the blood clot was evoked in the canal by periapical tissue irritation with a k-file. The samples were randomly divided into 6 experimental groups: propolis (groups 1, 2, MTA (groups 3, 4, and parafilm (groups 5, 6 in immature and mature teeth. The animals were sacrificed and samples were prepared for immunohistochemical evaluation of VEGF and the VIII factor. Results: Tissue regeneration was seen in 64.5% of MTA, 38% of propolis, and 0% of parafilm group samples. Expression of VEGF and VIII factor in the propolis group was more than the MTA group and it showed a reduction after 3 months in comparison to 1 month. VEGF and VIII factor were seen in stromal cells in addition to endothelial vessel cells. Overall, expression of angiogenic factors was more in the open apex teeth compared to close apex ones. Conclusion: According to the results of this study, propolis can induce the expression of VEGF and VIII factor in infected mature and immature dog’s teeth and is a suitable biomaterial for the revascularization technique.

  4. Pengaruh Manajemen Kesiswaan Terhadap Hasil Belajar Mata Pelajaran SKI Siswa Kelas VIII E MTsN Sambirejo Banyuwangi Tahun Pelajaran 2016/2017

    Directory of Open Access Journals (Sweden)

    Ribut Suprapto

    2017-10-01

    Full Text Available Manajemen Kesiswaan adalah suatu proses pengurusan segala hal yang berkaitan dengan siswa di suatu sekolah mulai dari perencanaan, penerimaan siswa pembinaan yang dilakukan selama siswa berada di sekolah, sampai dengan siswa menyelesaikan pendidikannya di sekolah melalui penciptaan suasana pembelajaran yang kondusif terhadap berlangsungnya  proses belajar mengajar atau pembelajaran yang efektif. Penelitian ini diarahkan pada 3 hal pokok, yaitu (1 Bagaimana penerapan manajemen kesiswaan  siswa kelas VIIIE di MTsN Sambirejo tahun pelajaran 2016/2017? (2 Bagaimana hasil belajar siswa kelas  VIIIE MTsN Sambirejo tahun pelajaran 2016/2017? (3 Adakah pengaruh penerapan manajemen kesiswaan terhadap hasil belajar siswa kelas VIIIE MTsN Sambirejo tahun pelajaran 2016/2017? (4 Seberapa besar pengaruh penerapan manajemen kesiswaan terhadap hasil belajar siswa kelas VIIIE MTsN Sambirejo tahun pelajaran 2016/2017?. Penelitian ini menggunakan metode deskriptif kuantitatif dengan teknik product moment pada uji validitas data dan untuk mencari reliabilitas data menggunakan rumus alpha, sedangkan pada uji hipotesis menggunakan uji F dan uji T kemudian untuk teknik analisis data menggunakan uji normalitas dengan menggunakan model regresi. Popoulasi penelitian ini adalah siswa kelas VIII E MTsN Sambirejo yang berjumlah 33. Untuk mengukur variabel, peneliti menggunakan kuesioner untuk manajemen kesiswaan sedangkan Hasil Belajar menggunakan data nilai semester ganjil. Setelah melakukan analisis data yang dikumpulkan, ditemukan bahwa (1 Pengaruh Penerapan manajemen kesiswaan di MTsN Sambirejo baik. (2 Hasil pengaruh  penerapan manajemen kesiswaan di kelas VIII E MTsN Sambirejo baik. (3 Pengaruh penerapan manajemen kesiswaan terhadap hasil belajar VIII E di MTsN Sambirejo ada. (4 pengaruh penerapan manajemen kesiswaan terhadap hasil belajar siswa kelas  VIII E di MTsN Sambirejo sebesar 19,1%

  5. Design local exhaust ventilation on sieve machine at PT.Perkebunan Nusantara VIII Ciater using design for assembly (DFA) approach with Boothroyd and Dewhurst method

    Science.gov (United States)

    Khalqihi, K. I.; Rahayu, M.; Rendra, M.

    2017-12-01

    PT Perkebunan Nusantara VIII Ciater is a company produced black tea orthodox more or less 4 tons every day. At the production section, PT Perkebunan Nusantara VIII will use local exhaust ventilation specially at sortation area on sieve machine. To maintain the quality of the black tea orthodox, all machine must be scheduled for maintenance every once a month and takes time 2 hours in workhours, with additional local exhaust ventilation, it will increase time for maintenance process, if maintenance takes time more than 2 hours it will caused production process delayed. To support maintenance process in PT Perkebunan Nusantara VIII Ciater, designing local exhaust ventilation using design for assembly approach with Boothroyd and Dewhurst method, design for assembly approach is choosen to simplify maintenance process which required assembly process. There are 2 LEV designs for this research. Design 1 with 94 components, assembly time 647.88 seconds and assembly efficiency level 23.62%. Design 2 with 82 components, assembly time 567.84 seconds and assembly efficiency level 24.83%. Design 2 is choosen for this research based on DFA goals, minimum total part that use, optimization assembly time, and assembly efficiency level.

  6. PENGARUH MODEL PEMBELAJARAN KOOPERATIF TIPE STAD BERBANTUAN PEMETAAN PIKIRAN (MIND MAPPING TERHADAP KEMAMPUAN MENULIS TEKS BERITA SISWA KELAS VIII SMP NEGERI 1 PANTI

    Directory of Open Access Journals (Sweden)

    Ricci Gemarni Tatalia, M.Pd

    2017-05-01

    Full Text Available This study was generated from the problem of students’ ability in writing news texts ini class VIII, SMPN 1 Panti. Some of the problem were (1 lack of the students’ response towards news writing teaching and learning process, (2 lack of teacher’s creativity in designing interesting news sriting learning model, (3 no appropriate creative techniques applied by the teacher which could train the students to develop their skill in writing news texts and (4 lack of the students’ motivation in participating in teaching and learning process because of their lack of understanding in the elements of news. Thus, this study was aimed at escribing the effect of the students’ ability ini writing news texts in class VIII SMP N 1 Panti. This was a quantitative research with factorial 2x2 experimental design. The population was the students in class VIII SMPN 1 Panti. Sampling technique was done by using random sampling and the data was collected through test. The result of the study revealed that cooperative learning model with STAD mind mapping type affected the students’ ability in writing news texts

  7. Enhancement of pig embryonic implants in factor VIII KO mice: a novel role for the coagulation cascade in organ size control.

    Directory of Open Access Journals (Sweden)

    Anna Aronovich

    Full Text Available Very little is known about the mechanisms that contribute to organ size differences between species. In the present study, we used a mouse model of embryonic pig tissue implantation to define the role of host Factor VIII in controlling the final size attained by the implant. We show here that pig embryonic spleen, pancreas, and liver all grow to an increased size in mice that are deficient in the Factor VIII clotting cascade. Similar results were obtained using the transplantation model after treatment with the low molecular weight heparin derivative Clexane which markedly enhanced transplant size. Likewise, enhanced size was found upon treatment with the direct thrombin inhibitor Dabigatran, suggesting that organ size regulation might be mediated by thrombin, downstream of Factor VIII. Considering that thrombin was shown to mediate various functions unrelated to blood clotting, either directly by cleavage of protease-activated receptors (PARs or indirectly by cleaving osteopontin (OPN on stroma cells, the role of PAR1 and PAR4 antagonists as well as treatment with cleaved form of OPN (tcOPN were tested. While the former was not found to have an impact on overgrowth of embryonic pig spleen implants, marked reduction of size was noted upon treatment with the (tcOPN. Collectively, our surprising set of observations suggests that factors of the coagulation cascade have a novel role in organ size control.

  8. Plasma homocysteine, methylene tetrahydrofolate reductase C677T and factor II G20210A polymorphisms, factor VIII, and VWF in central retinal vein occlusion.

    Science.gov (United States)

    Boyd, S; Owens, D; Gin, T; Bunce, K; Sherafat, H; Perry, D; Hykin, P G

    2001-11-01

    To determine whether plasma homocysteine, methylene tetrahydrofolate reductase (MTHFR) C677T and factor II G20210A polymorphisms, factor VIII, and vWF are risk factors for central retinal vein occlusion (CRVO). Prospective comparison of 63 consecutive patients with central retinal vein occlusion and 63 age matched controls. Plasma homocysteine and vWF were estimated by ELISA, the MTFHR and factor II G20210A polymorphisms determined by polymerase chain reaction with restriction enzyme product digestion and factor VIII by one stage automated clotting assay. Plasma homocysteine (patients: median 12.4 micromol/l, controls: median 11.6 micromol OR = 1.05, p=0.20), factor VIII (patients: median = 115 U/dl, controls: median = 113 U/dl), and vWF (patients: median = 115 U/dl, controls: median = 108 U/dl) were not statistically higher in patients than in controls. Five CRVO patients and seven controls were homozygous for the MTHFR C677T mutation. One control was heterozygous for the factor II G20210A mutation. This study has not identified new risk factors for CRVO.

  9. On-line diagnosis of high power motors based on ultra wide band partial discharge detection; Diagnostico en linea de motores de gran capacidad mediante la deteccion de descargas parciales utilizando tecnicas de banda ultra ancha

    Energy Technology Data Exchange (ETDEWEB)

    Carvajal M, F. Antonio; Garcia Colon H, Vicente R. [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Asiain, Tomas [Instituto Politecnico Nacional, Escuela Superior de Ingenieria Mecanica y Electrica (Mexico)

    2009-07-01

    In this work a non-standardized method for on-line diagnostic of high capacity motors based on Ultra Wide Band (UWB) Partial Discharge (PD) measuring techniques is theoretically supported, implemented and applied. The method developed is non invasive and consist in the measurement of PD in the main motor power supply cables and its ground shields connection using a near field sensor (Rogowski coil, clamp-on type) with a bandwidth of 2 to 40 MHz. The measured signals by the sensor, are stretched electronically, digitized and fed to a conventional Partial Discharge digital detector. The UWB PD detection system used displays the output in a Pulse repetition frequency-Charge-Phase angle (N-Q-?) PD pattern. The results obtained in thirteen 2500 H.P., 13.8 kV motors performed during operating in an Oil Pumping facility are presented, including its analysis and comparison with values and PD patterns reported in literature. [Spanish] En este trabajo se presentan los fundamentos teoricos, la implementacion y aplicacion de un metodo no normalizado, para el diagnostico en linea de motores de gran capacidad, basado en la deteccion de Descargas Parciales (DP) utilizando tecnicas de medicion de Banda Ultra Ancha. El metodo desarrollado es no invasivo y consiste en la medicion de las DP en los conductores y conexiones a tierra de la pantalla de los cables principales de suministro de energia al motor, utilizando un sensor de campo cercano (bobina Rogowski, tipo gancho) cuyo ancho de banda de medicion es de 2 a 40 MHz. Las senales medidas por el sensor son electronicamente procesadas para ampliar su duracion, digitalizadas y enviadas a un detector digital de Descargas Parciales convencional. El sistema de deteccion de DP en Banda Ultra Ancha despliega la medicion en un patron de DP tipo frecuencia de repeticion de Pulso-Carga-Angulo de fase (N-Q-?). Se presentan los resultados obtenidos de la evaluacion en linea de trece motores de 2500 C.P. a 13.8 kV, instalados y operando en una

  10. Direct Observation of the M1 Transition between the Ground Term Fine Structure Levels of W VIII

    Directory of Open Access Journals (Sweden)

    Momoe Mita

    2017-03-01

    Full Text Available We present a direct observation of the M1 transition between the fine structure splitting in the 4 f 13 5 s 2 5 p 6 2 F ground term of W VIII. The spectroscopic data of few-times ionized tungsten ions are important for the future ITER diagnostics, but there is a serious lack of data. The present study is part of an ongoing effort to solve this problem. Emission from the tungsten ions produced and trapped in a compact electron beam ion trap is observed with a Czerny–Turner visible spectrometer. Spectra in the EUV range are also observed at the same time to help identify the previously-unreported visible lines. The observed wavelength 574.47 ± 0.03 nm (air, which corresponds to the fine structure splitting of 17,402.5 ± 0.9 cm − 1 , shows reasonable agreement with the previously reported value 17,410 ± 5 cm − 1 obtained indirectly through the analysis of EUV spectra [Ryabtsev et al., Atoms 3 (2015 273].

  11. Baby hamster kidney cell-derived recombinant factor VIII: a quarter century of learning and clinical experience.

    Science.gov (United States)

    Afonja, Olubunmi; Kozak, Robert; Petraro, Paul; Michaels, Lisa A; Mathew, Prasad; Lemm, Georg; Kessler, Craig

    2016-12-01

    Management and care of individuals with hemophilia A advanced immensely with the introduction of recombinant factor VIII (rFVIII) replacement products. This review provides a historical overview of rFVIII development with a focus on Bayer's rFVIII (with albumin) and sucrose-formulated rFVIII (rFVIII-FS), the only rFVIII products cloned in baby hamster kidney (BHK) cells with >25 years of proven safety and efficacy. Areas covered: We review the advances in rFVIII technology and the efficacy and safety data for BHK-derived rFVIII/rFVIII-FS from clinical trials, investigator-initiated studies, and observational studies. Innovative products with new treatment potentials (eg, BAY 81-8973 and BAY 94-9027) built on this established safety and efficacy profile are also briefly discussed. The literature search strategy included targeted searches (PubMed) with manual article selection and other product-specific searches. Expert commentary: Development of rFVIII products and related improvements in viral safety and manufacturing efficiency have guaranteed an adequate supply of factor products worldwide and increased prophylaxis use. The net effects have been joint health preservation, reduction in morbidity and mortality, and quality-of-life enhancements. Current treatment challenges include lack of adherence to prophylaxis and inhibitor development; extended-half-life rFVIII products and non-FVIII replacement therapies in development may help overcome these challenges.

  12. Direct observation of the M1 transition between the ground state fine structure splitting of W VIII

    CERN Document Server

    Mita, Momoe; Kato, Daiji; Murakami, Izumi; Nakamura, Nobuyuki

    2016-01-01

    We present direct observation of the M1 transition between the fine structure splitting in the 4f13 5s2 5p6 2F ground state of W VIII. The spectroscopic data of few-times ionized tungsten ions are important for the future ITER diagnostics, but there is a serious lack of data. The present study is part of an ongoing effort to solve this lack. Emission from the tungsten ions produced and trapped in a compact electron beam ion trap is observed with a Czerny-Turner visible spectrometer. Spectra in the EUV range are also observed at the same time to help the identification of the previously-unreported visible lines. The observed wavelength 574.47 pm 0.03 nm (air), which corresponds to the fine structure splitting of 17402.5 pm 0.9 cm-1, shows reasonable agreement with the previously reported value 17410 pm 5 cm-1 obtained indirectly through the analysis of EUV spectra [Ryabtsev et al., Atoms 3 (2015) 273].

  13. The Abdication of King Edward VIII: a study of estrangement between an adult son and elderly mother.

    Science.gov (United States)

    Abrams, Robert C

    2017-09-08

    In this article the Abdication of King Edward VIII of Great Britain and his estrangement from the dowager Queen Mary are reconsidered as prototypes of intergenerational conflict arising from a collision of values between an adult child and an elderly mother. Historical materials on the Abdication and other respected secondary sources, including biographies of key individuals, were consulted, and the limited sociological and clinical literature on estrangement between elderly parents and adult children was referenced. Although estrangement was perpetuated by the rigid and incompatible positions taken up by both the former king and his widowed mother, the elderly Queen Mary, it was the latter who suffered the greater emotional consequences of the permanent separation that followed the Abdication. Most accounts of the Abdication have put forward views of the conflict of values at its centre that emphasise the vulnerability of the elderly mother. The clinical narrative supports a characterisation of estrangement as a subtype of bereavement with particular relevance to the geriatric population. © 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.

  14. Overexpression of factor VIII after AAV delivery is transiently associated with cellular stress in hemophilia A mice

    Directory of Open Access Journals (Sweden)

    Amy M Lange

    2016-01-01

    Full Text Available Factor VIII (FVIII is a large glycoprotein that is challenging to express both in vitro and in vivo. Several studies suggest that high levels of FVIII expression can lead to cellular stress. After gene transfer, transgene expression is restricted to a subset of cells and the increased FVIII load per cell may impact activation of the unfolded protein response. We sought to determine whether increased FVIII expression in mice after adeno-associated viral liver gene transfer would affect the unfolded protein response and/or immune response to the transgene. The FVIII gene was delivered as B-domain deleted single chain or two chain (light and heavy chains at a range of doses in hemophilia A mice. A correlation between FVIII expression and anti-FVIII antibody titers was observed. Analysis of key components of the unfolded protein response, binding immunoglobulin protein (BiP, and C/EBP homologous protein (CHOP, showed transient unfolded protein response activation in the single chain treated group expressing >200% of FVIII but not after two chain delivery. These studies suggest that supraphysiological single chain FVIII expression may increase the likelihood of a cellular stress response but does not alter liver function. These data are in agreement with the observed long-term expression of FVIII at therapeutic levels after adeno-associated viral delivery in hemophilia A dogs without evidence of cellular toxicity.

  15. Body weight and fat mass index as strong predictors of factor VIII in vivo recovery in adults with hemophilia A.

    Science.gov (United States)

    Henrard, S; Speybroeck, N; Hermans, C

    2011-09-01

    The treatment of hemophilia A requires infusions of factor VIII (FVIII) concentrates. The number of units to be given in order to obtain the target level is calculated using the formula: [body weight (BW) × desired FVIII increase]/2, which assumes that each unit infused per kg of BW increases the FVIII level by 2%. The present observational study evaluated the dependence of FVIII recovery on different morphometrical variables: BW, fat mass index (FMI), body mass index, and the difference between actual and ideal BW. FVIII recovery was measured in 46 non-actively bleeding hemophilia A patients, being treated with a recombinant FVIII concentrate. Regression trees were used to identify morphometrical predictors of recovery. The median recovery was 2.08 for all patients, 2.63 for those with a BW ≥ 81.0 kg and 1.87 for others (P recovery was significantly higher when FMI was ≥ 20% compared with FMI recovery: 2.35 vs. 1.74; P = 0.007). Using regression trees, three groups were created: BW recovery in these groups was 1.80, 2.16 and 2.63, respectively (P recovery after different FVIII concentrates should keep in mind morphometrical patient characteristics. © 2011 International Society on Thrombosis and Haemostasis.

  16. Evolution of the European guidelines for the clinical development of factor VIII products: little progress towards improved patient management.

    Science.gov (United States)

    Mannucci, P M

    2013-05-01

    In the process of clinical development and licensing of factor VIII (FVIII) products for treatment of haemophilia A, the safety concerns generated in the 1980s by the risk of pathogen transmission were tremendously reduced by the implementation of an array of methods for inactivation/removal of blood borne pathogens. The current focus on the risk of FVIII inhibitors does not stem from a new awareness, because this multifactorial complication has long been recognized. With this background, I believe that the current European regulatory guidelines for the clinical development and licensing of FVIII products fail to reflect the tremendous progress made in terms of clinical efficacy and safety, because they are witnessing a continuous increase in the demands from health agencies to the point that clinical studies have become more and more difficult to carry out. This article reviews the evolution of the European regulations on new FVIII products, lists a number of regulatory requirements whose scientific and/or clinical rationale is perhaps questionable and recommends keeping such requirements in reasonable limits of feasibility, without jeopardizing current high standards of efficacy and safety. © 2012 Blackwell Publishing Ltd.

  17. Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A.

    Science.gov (United States)

    Kruse-Jarres, R; St-Louis, J; Greist, A; Shapiro, A; Smith, H; Chowdary, P; Drebes, A; Gomperts, E; Bourgeois, C; Mo, M; Novack, A; Farin, H; Ewenstein, B

    2015-03-01

    Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI-1 is an investigational, B-domain deleted, recombinant FVIII, porcine sequence, with low cross-reactivity to anti-hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI-1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg(-1) , OBI-1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI-1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti-porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI-1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI-1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients. © 2015 John Wiley & Sons Ltd.

  18. A novel cell-sheet technology that achieves durable factor VIII delivery in a mouse model of hemophilia A.

    Directory of Open Access Journals (Sweden)

    Kohei Tatsumi

    Full Text Available Gene- or cell-based therapies aimed at creating delivery systems for coagulation factor VIII (FVIII protein have emerged as promising options for hemophilia A treatment. However, several issues remain to be addressed regarding the efficacies and adverse events of these new classes of therapies. To improve an existing cell-based therapy involving the subcutaneous transplantation of FVIII-transduced blood outgrowth endothelial cells (BOECs, we employed a novel cell-sheet technology that allows individual dispersed cells to form a thin and contiguous monolayer without traditional bioabsorbable scaffold matrices. Compared to the traditional methodology, our cell-sheet approach resulted in longer-term and 3-5-fold higher expression of FVIII (up to 11% of normal in recipient hemophilia A mice that lacked a FVIII humoral immune response due to transient immunosuppression with cyclophosphamide. Histological studies revealed that the transplanted BOEC sheets were structured as flat clusters, supporting the long-term expression of therapeutic FVIII in plasma from an ectopic subcutaneous space. Our novel tissue-engineering approach using genetically modified BOEC sheets could aid in development of cell-based therapy that will allow safe and effective in vivo delivery of functional FVIII protein in patients with hemophilia A.

  19. Phenotypic correction and stable expression of factor VIII in hemophilia A mice by embryonic stem cell therapy.

    Science.gov (United States)

    Wang, J J; Kuang, Y; Zhang, L L; Shen, C L; Wang, L; Lu, S Y; Lu, X B; Fei, J; Gu, M M; Wang, Z G

    2013-05-13

    Hereditary deficiency of factor VIII (FVIII) leads to hemophilia A, a severe X-linked bleeding disorder. Current therapies include fixed-dose FVIII prophylaxis, factor replacement therapy, and most recently, gene therapy. Prophylaxis and FVIII replacement therapies are limited by incomplete efficacy, high cost, restricted availability, and development of neutralizing antibodies in chronically treated individuals. Limited success has been obtained in preclinical trials using gene therapy for the treatment of hemophilia. Therefore, new options for therapy for hemophilia A are needed. We evaluated the potential of embryonic stem cells for correcting hemophilia A in mice. FVIII-deficient mouse blastocysts were collected and injected with mouse embryonic stem cells stably expressing green-fluorescent protein (GFP) and transferred to pseudopregnant recipient mice. Expression of FVIII was measured in the liver and plasma of the 5 chimeric mice that were produced. Three of these mice were GFP-positive at the age of 6 months. The plasma FVIII activity levels were equal to those of wild-type mice. These data demonstrate that embryonic stem cell transplantation at an early embryonic stage has potential as therapy for this progressively debilitating, life-threatening bleeding disorder.

  20. Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice.

    Science.gov (United States)

    Kren, Betsy T; Unger, Gretchen M; Sjeklocha, Lucas; Trossen, Alycia A; Korman, Vicci; Diethelm-Okita, Brenda M; Reding, Mark T; Steer, Clifford J

    2009-07-01

    Liver sinusoidal endothelial cells are a major endogenous source of Factor VIII (FVIII), lack of which causes the human congenital bleeding disorder hemophilia A. Despite extensive efforts, gene therapy using viral vectors has shown little success in clinical hemophilia trials. Here we achieved cell type-specific gene targeting using hyaluronan- and asialoorosomucoid-coated nanocapsules, generated using dispersion atomization, to direct genes to liver sinusoidal endothelial cells and hepatocytes, respectively. To highlight the therapeutic potential of this approach, we encapsulated Sleeping Beauty transposon expressing the B domain-deleted canine FVIII in cis with Sleeping Beauty transposase in hyaluronan nanocapsules and injected them intravenously into hemophilia A mice. The treated mice exhibited activated partial thromboplastin times that were comparable to those of wild-type mice at 5 and 50 weeks and substantially shorter than those of untreated controls at the same time points. Further, plasma FVIII activity in the treated hemophilia A mice was nearly identical to that in wild-type mice through 50 weeks, while untreated hemophilia A mice exhibited no detectable FVIII activity. Thus, Sleeping Beauty transposon targeted to liver sinusoidal endothelial cells provided long-term expression of FVIII, without apparent antibody formation, and improved the phenotype of hemophilia A mice.

  1. A novel cell-sheet technology that achieves durable factor VIII delivery in a mouse model of hemophilia A.

    Science.gov (United States)

    Tatsumi, Kohei; Sugimoto, Mitsuhiko; Lillicrap, David; Shima, Midori; Ohashi, Kazuo; Okano, Teruo; Matsui, Hideto

    2013-01-01

    Gene- or cell-based therapies aimed at creating delivery systems for coagulation factor VIII (FVIII) protein have emerged as promising options for hemophilia A treatment. However, several issues remain to be addressed regarding the efficacies and adverse events of these new classes of therapies. To improve an existing cell-based therapy involving the subcutaneous transplantation of FVIII-transduced blood outgrowth endothelial cells (BOECs), we employed a novel cell-sheet technology that allows individual dispersed cells to form a thin and contiguous monolayer without traditional bioabsorbable scaffold matrices. Compared to the traditional methodology, our cell-sheet approach resulted in longer-term and 3-5-fold higher expression of FVIII (up to 11% of normal) in recipient hemophilia A mice that lacked a FVIII humoral immune response due to transient immunosuppression with cyclophosphamide. Histological studies revealed that the transplanted BOEC sheets were structured as flat clusters, supporting the long-term expression of therapeutic FVIII in plasma from an ectopic subcutaneous space. Our novel tissue-engineering approach using genetically modified BOEC sheets could aid in development of cell-based therapy that will allow safe and effective in vivo delivery of functional FVIII protein in patients with hemophilia A.

  2. Application of near infrared spectroscopy in monitoring the moisture content in freeze-drying process of human coagulation factor VIII

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2015-11-01

    Full Text Available As an important process analysis tool, near infrared spectroscopy (NIRS has been widely used in process monitoring. In the present work, the feasibility of NIRS for monitoring the moisture content of human coagulation factor VIII (FVIII in freeze-drying process was investigated. A partial least squares regression (PLS-R model for moisture content determination was built with 88 samples. Different pre-processing methods were explored, and the best method found was standard normal variate (SNV transformation combined with 1st derivation with Savitzky–Golay (SG 15 point smoothing. Then, four different variable selection methods, including uninformative variable elimination (UVE, interval partial least squares regression (iPLS, competitive adaptive reweighted sampling (CARS and manual method, were compared for eliminating irrelevant variables, and iPLS was chosen as the best variable selection method. The correlation coefficient (R, correlation coefficient of calibration set (Rcal, correlation coefficient of validation set (Rval, root mean square errors of cross-validation (RMSECV and root mean square errors of prediction (RMSEP of PLS model were 0.9284, 0.9463, 0.8890, 0.4986% and 0.4514%, respectively. The results showed that the model for moisture content determination has a wide range, good linearity, accuracy and precision. The developed approach was demonstrated to be a potential for monitoring the moisture content of FVIII in freeze-drying process.

  3. Kinerja Katalis Paduan ZnO dengan Tembaga dan Logam-Logam Golongan VIII pada Steam Reforming Etanol menjadi Hidrogen

    Directory of Open Access Journals (Sweden)

    Marwan Marwan

    2009-12-01

    Full Text Available Steam reforming of ethanol to H2 using ZnO catalyst with promotor metal, i.e. copper or metal group VIII (Pd, Pt and Ni has been investigated. Catalyst’s performances are tested further at micro reactor operating at atmosphere pressure. Ethanol solution 20% is injected to reactor at rate of 2 ml/jam and is mixed with nitrogen flow at 25 ml/menit. XRD analysis shows active phases existence of each promotor for produced catalyst. Reaction product includes H2, CO2, and a nonidentified component. Selectivity of H2 fromation depends on chosen promotor metal types, where the selectifity decreases as follows: Pt > Pd > Cu ≈ Ni. Reaction temperature and promotor concentration also influence selectifity H2. For catalyst 1% Pd/ZnO and 1% Pt/ZnO, selectivity H2 was optimum at temperature reaction 450oC. Whereas Pd promotor concentration’s increasing from 1% to 5% improves H2 selectivity. Keywords: ethanol, hidrogen, steam reforming, ZnO

  4. [Detection of carriers of hemophilia A by testing for HindIII polymorphism in the factor VIII gene by PCR].

    Science.gov (United States)

    Surin, V L; Aseev, M V; Zhukova, E L; Baranov, V S; Solov'ev, G Ia; Grineva, N I; Andreeva, T A; Izhevskaia, V L; Likhacheva, E A; Pliushch, O P

    1990-10-01

    Representatives of 62 families from Moscow and Leningrad with haemophilia A observed in the pedigree were tested for HindIII polymorphism in the factor VIII gene. The proposed scheme of investigation was based on intron 19 of the FVIII gene amplification by the PCR technique followed by restriction analysis with the inner control of hydrolysis. 207 unrelated X-chromosomes were analysed, the frequency of the incidence of the polymorphic HindIII site in the given population found to be 0.29. The frequency of incidence of the HindIII heterozygotes calculated according to Hardy-Weinberg equation was 0.41. This value evidences for relatively high informativity of this polymorphism for carrier detection and prenatal diagnosis of haemophilia A. 23 families (37%) out of 62 examined in the study were informative for this criteria. The new scheme proved to be effective in testing HindIII polymorphism for haemophilia A carrier detection and prenatal diagnosis. The whole procedure takes one day, the radiolabelled probes are not used. The scheme described was inculcated in the All-Union Research Center for Haematology, Ministry of Health, USSR, Moscow, Research Institute for Obstetrics and Gynecology, Leningrad, Institute of Medical Genetics, Greifswald, DDR.

  5. Effect of manufacturing process parameters on virus inactivation by dry heat treatment at 80 degrees C in factor VIII.

    Science.gov (United States)

    Roberts, P L; Dunkerley, C; McAuley, A; Winkelman, L

    2007-01-01

    Dry heat treatment at 80 degrees C for 72 h is used as a virus inactivation step for some coagulation factor concentrates such as Bio Products Laboratory's (BPL) factor VIII 8Y. In the current study, the effect of this process has been tested on a range of viruses. In addition the effect of various manufacturing process parameters on virus inactivation has been investigated. Samples of product intermediate were obtained from manufacturing, spiked with virus and subjected to freeze drying and dry heat treatment. Virus inactivation was determined by infectivity assay. Freeze drying followed by dry heat treatment was effective for inactivating a wide range of enveloped and nonenveloped viruses. Sucrose or protein concentration had no effect on virus inactivation. Product presentation or the interruption of heat treatment also had no effect. The inactivation of some of the viruses was greater at higher residual water content but under such conditions the stability of the product was reduced. This virus inactivation step was effective for a wide range of viruses and over the range of process conditions encountered in manufacturing. This demonstrates the robustness of this process step.

  6. The 1.7 Å X-ray crystal structure of the porcine factor VIII C2 domain and binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.

    Directory of Open Access Journals (Sweden)

    Caileen M Brison

    Full Text Available The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the "non-classical" antibody epitopes. Furthermore, antibody-binding results illustrate that the "classical" 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.

  7. Fault diagnosis in the steam turbo-generator of a Combined Cycle Power Plant; Diagnostico de fallas en el turbogenerador a vapor de una central de generacion de ciclo combinado

    Energy Technology Data Exchange (ETDEWEB)

    Flores Abad, Angel

    2006-12-15

    sensores y actuadores. En la actualidad este tipo de centrales tiende a dominar el mercado de generacion electrica por medio de combustibles fosiles, debido a que son las mas eficientes, rentables, de operacion flexible y con menor impacto ambiental. En la CGCC, la turbina de vapor (TV) es una componente fundamental, ya que representa la ganancia del proceso en el sentido de que permite la generacion de energia electrica adicional al aprovechar los gases de escape de la turbina de gas. En caso de que la TV falle, la eficiencia global del proceso se reduce hasta en un 40%. Por lo anterior, en este trabajo se desarrollo un sistema de diagnostico de fallas basado en modelos, de acuerdo a la metodologia FDI (Fault Detection and Isolation) de la teoria de control, con capacidad para detectar y localizar fallas en los sensores y actuadores del turbogenerador a vapor de una CGCC. El enfoque que se utilizo emplea la redundancia analitica con el objetivo de optimizar la redundancia fisica, de manera que sea posible disminuir el costo y espacio extra que implica el utilizar dispositivos repetidos. El diseno del sistema se llevo a cabo usando el analisis estructural AE) que es una herramienta basada en la teoria de grafos y ciencias de la computacion. El AE permitio realizar: analisis de monitoreabilidad, detectabilidad y aislabilidad del proceso; y proporciono la secuencia de computo de las variables no monitoreadas (desconocidas) para obtener las relaciones de redundancia analitica. Para validar el sistema de diagnostico de fallas de la TV, se programaron los algoritmos de deteccion y localizacion de fallas en LabWindows, CVI y se integraron al simulador de la CGCC. Ademas para facilitar al usuario la visualizacion de la presencia de una falla se desarrollo una interfase grafica que indica el elemento con comportamientos anormales, ya sea sensor o actuador.

  8. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

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    Maartje van den Biggelaar

    Full Text Available BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII binding to von Willebrand factor (VWF are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

  9. Effects of carbonic anhydrase-related protein VIII on human cells harbouring an A8344G mitochondrial DNA mutation.

    Science.gov (United States)

    Wang, Tze-Kai; Cheng, Che-Kun; Chi, Tang-Hao; Ma, Yi-Shing; Wu, Shi-Bei; Wei, Yau-Huei; Hsieh, Mingli

    2014-04-01

    MERRF (myoclonus epilepsy associated with ragged-red fibres) is a maternally inherited mitochondrial encephalomyopathy with various syndromes involving both muscular and nervous systems. The most common mutation in MERRF syndrome, the A8344G mutation in mtDNA, has been associated with severe defects in the respiratory function of mitochondria. In the present study, we show that there is a significant decrease in CA8 (carbonic anhydrase-related protein VIII) in cybrids harbouring the MERRF A8344G mutation. CA8 deficiency and mutations were found to be associated with a distinctive lifelong gait disorder in wdl (Waddles) mice and novel syndromes characterized by cerebellar ataxia and mental retardation in humans. The results of the present study showed that overexpression of CA8 in MERRF cybrids significantly decreased cell death induced by STS (staurosporine) treatment, suggesting a protective function of CA8 in cells harbouring the A8344G mutation of mtDNA. Interestingly, an increase in the formation of LC3-II (microtubule-associated protein 1 light chain 3-II) was found in the cybrids with down-regulated CA8 expression, suggesting that reduced expression of CA8 leads to autophagy activation. Furthermore, cybrids exhibiting down-regulated CA8 showed increased cytosolic Ca2+ signals and reduced levels of phospho-Akt compared with those in the cybrids with overexpressed CA8, indicating that phospho-Akt is involved in the protection of cells by CA8. Our findings suggest that CA8 is involved in the autophagic pathway and may have a protective role in cultured cells from patients with MERRF. Targeting CA8 and the downstream autophagic pathway might help develop therapeutic agents for treatment of MERRF syndrome in the future.

  10. Factor VIII (F8) inversions in severe hemophilia A: Male germ cell origin and diagnosis with RT-PCR

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E. [Geneva Medical School (Switzerland)]|[Johns Hopkins School of Medicine, Baltimore, MD (United States); Rossiter, J.P. [Johns Hopkins School of Medicine, Baltimore, MD (United States); Young, M. [Geneva Medical School (Switzerland)] [and others

    1994-09-01

    The Factor VIII (F8) gene, which is defective in hemophilia A, is located in the most telomeric megabase of Xq. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of the cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that therefore the event originates predominantly in male germ cells. In all 21 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis using markers within or very closely linked to F8, determined that it occurred in the male germline. In addition, all but one of 56 mothers of sporadic cases due to inversions were carriers. The data indicate that the F8 gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells. The mean age of maternal grandfathers at the birth of their carrier daughters was 29.9 years (13 cases), i.e. not different from the mean paternal age in the general population, supporting the hypothesis that the inversions occur in meiosis. The inversions can be diagnosed by Southern blot analysis. For more rapid diagnosis we have used RT-PCR of RNA ectopically expressed in blood. Oligonucleotides were used to PCR amplify, after the initial RT reaction of RNA samples using random hexamers, either the normal transcript (F8 exons 21 to 24;312 bp product) or the novel abnormal transcript that is generated after the inversion. Both type 1 and 2 inversions can be recognized in affecteds and carriers by the presence of the diagnostic PcR product of 248 bp. Correct diagnoses were made in samples from 6 patients and 2 carriers with type 1 inversions, 2 patients and 2 carriers with type 2 inversions and 5 normal controls.

  11. Most Factor VIII B Domain Missense Mutations Are Unlikely to Be Causative Mutations for Severe Hemophilia A: Implications for Genotyping

    Science.gov (United States)

    Ogata, Kyoichi; Selvaraj, Sundar R; Miao, Hongzhi Z; Pipe, Steven W

    2011-01-01

    Summary Background & Objective The factor VIII (FVIII) B domain shares very little amino acid homology to other known proteins and is not directly necessary for procoagulant activity. Despite this, missense mutations within the B domain have been reported in patients with hemophilia A. Given that the B domain is dispensable for secretion and function of FVIII, we hypothesized that these mutations should not be causative of hemophilia A in these patients. Methods Plasmid vectors containing B domain missense mutations that were reported to be associated with moderate/severe hemophilia A (T751S, D826E, V993L, H1047Y, T1353A, N1441K, L1462P, E1579D, A1591S, P1641L and S1669L) were analyzed for their effect on synthesis and secretion compared to FVIII wild-type (WT) following transient transfection into COS-1 and CHO cells in vitro. Further, H1047Y, N1441K and E1579D mutants were expressed in vivo in a hemophilia A mouse model by hydrodynamic tail-vein injection. Results FVIII activity and antigen levels for all mutants expressed into the conditioned media of COS-1 and CHO cells were similar to FVIII WT. Also, plasma expression of these mutants was similar to FVIII WT in hemophilia A mice. An in vivo tail clip bleeding assay also demonstrated that blood loss from hemophilia A mice expressing FVIII WT, H1047Y, N1441K and E1579D were similar. Conclusion We conclude that most missense mutations within the FVIII B domain would be unlikely to lead to severe hemophilia A and that the majority of such missense mutations represent polymorphisms or non-pathologic mutations. PMID:21645226

  12. Severe hemophilia A in a female by cryptic translocation: Order and orientation of factor VIII within Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; McGinniss, M.J.; Antonarakis, S.E.; Axelman, J.; Stasiowski, B.A.; Youssoufian, H.; Kearns, W.G.; Chung, A.; Pearson, P.L.; Kazazian, H.H. Jr. (Johns Hopkins Univ., Baltimore, MD (United States)); Muneer, R.S. (Univ. of Oklahoma, Norman (United States))

    1993-04-01

    The authors report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X; 17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24-Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1--15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5[prime] end of F8C, but left the more proximal G6PD locus intact on the der(17)chromosome. As the deleted segment includes the 5[prime] half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5[prime] region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD-3[prime]F8C-5[prime]F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the pro-band, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. 27 refs., 5 figs., 1 tab.

  13. Research and Evaluations of the Health Aspects of Disasters, Part VIII: Risk, Risk Reduction, Risk Management, and Capacity Building.

    Science.gov (United States)

    Birnbaum, Marvin L; Loretti, Alessandro; Daily, Elaine K; O'Rourke, Ann P

    2016-06-01

    There is a cascade of risks associated with a hazard evolving into a disaster that consists of the risk that: (1) a hazard will produce an event; (2) an event will cause structural damage; (3) structural damage will create functional damages and needs; (4) needs will create an emergency (require use of the local response capacity); and (5) the needs will overwhelm the local response capacity and result in a disaster (ie, the need for outside assistance). Each step along the continuum/cascade can be characterized by its probability of occurrence and the probability of possible consequences of its occurrence, and each risk is dependent upon the preceding occurrence in the progression from a hazard to a disaster. Risk-reduction measures are interventions (actions) that can be implemented to: (1) decrease the risk that a hazard will manifest as an event; (2) decrease the amounts of structural and functional damages that will result from the event; and/or (3) increase the ability to cope with the damage and respond to the needs that result from an event. Capacity building increases the level of resilience by augmenting the absorbing and/or buffering and/or response capacities of a community-at-risk. Risks for some hazards vary by the context in which they exist and by the Societal System(s) involved. Birnbaum ML , Loretti A , Daily EK , O'Rourke AP . Research and evaluations of the health aspects of disasters, part VIII: risk, risk reduction, risk management, and capacity building. Prehosp Disaster Med. 2016;31(3):300-308.

  14. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    Full Text Available The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors against factor VIII (FVIII. The current method for eradicating inhibitors, termed immune tolerance induction (ITI, is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8 gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance.

  15. The mesenchymal stem cells derived from transgenic mice carrying human coagulation factor VIII can correct phenotype in hemophilia A mice.

    Science.gov (United States)

    Wang, Qing; Gong, Xiuli; Gong, Zhijuan; Ren, Xiaoyie; Ren, Zhaorui; Huang, Shuzhen; Zeng, Yitao

    2013-12-20

    Hemophilia A (HA) is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. Previous studies showed that introduction of mesenchymal stem cells (MSCs) modified by FVIII-expressing retrovirus may result in phenotypic correction of HA animals. This study aimed at the investigation of an alternative gene therapy strategy that may lead to sustained FVIII transgene expression in HA mice. B-domain-deleted human FVIII (hFVIIIBD) vector was microinjected into single-cell embryos of wild-type mice to generate a transgenic mouse line, from which hFVIIIBD-MSCs were isolated, followed by transplantation into HA mice. RT-PCR and real-time PCR analysis demonstrated the expression of hFVIIIBD in multi-organs of recipient HA mice. Immunohistochemistry showed the presence of hFVIIIBD positive staining in multi-organs of recipient HA mice. ELISA indicated that plasma hFVIIIBD level in recipient mice reached its peak (77 ng/mL) at the 3rd week after implantation, and achieved sustained expression during the 5-week observation period. Plasma FVIII activities of recipient HA mice increased from 0% to 32% after hFVIIIBD-MSCs transplantation. APTT (activated partial thromboplastin time) value decreased in hFVIIIBD-MSCs transplanted HA mice compared with untreated HA mice (45.5 s vs. 91.3 s). Our study demonstrated an effective phenotypic correction in HA mice using genetically modified MSCs from hFVIIIBD transgenic mice. Copyright © 2013. Published by Elsevier Ltd.

  16. Characterization of Adeno-Associated Viral Vector-Mediated Human Factor VIII Gene Therapy in Hemophilia A Mice.

    Science.gov (United States)

    Greig, Jenny A; Wang, Qiang; Reicherter, Amanda L; Chen, Shu-Jen; Hanlon, Alexandra L; Tipper, Christopher H; Clark, K Reed; Wadsworth, Samuel; Wang, Lili; Wilson, James M

    2017-05-01

    Adeno-associated viral (AAV) vectors are promising vehicles for hemophilia gene therapy, with favorable clinical trial data seen in the treatment of hemophilia B. In an effort to optimize the expression of human coagulation factor VIII (hFVIII) for the treatment of hemophilia A, an extensive study was performed with numerous combinations of liver-specific promoter and enhancer elements with a codon-optimized hFVIII transgene. After generating 42 variants of three reduced-size promoters and three small enhancers, transgene cassettes were packaged within a single AAV capsid, AAVrh10, to eliminate performance differences due to the capsid type. Each hFVIII vector was administered to FVIII knockout (KO) mice at a dose of 10(10) genome copies (GC) per mouse. Criteria for distinguishing the performance of the different enhancer/promoter combinations were established prior to the initiation of the studies. These criteria included prominently the level of hFVIII activity (0.12-2.12 IU/mL) and the pattern of development of anti-hFVIII antibodies. In order to evaluate the impact of capsid on hFVIII expression and antibody formation, one of the enhancer and promoter combinations that exhibited high hFVIII immunogenicity was evaluated using AAV8, AAV9, AAVrh10, AAVhu37, and AAVrh64R1 capsids. The capsids subdivided into two groups: those that generated anti-hFVIII antibodies in ≤20% of mice (AAV8 and AAV9), and those that generated anti-hFVIII antibodies in >20% of mice (AAVrh10, AAVhu37, and AAVrh64R1). The results of this study, which entailed extensive vector optimization and in vivo testing, demonstrate the significant impact that transcriptional control elements and capsid can have on vector performance.

  17. Desmopressin acetate as a haemostatic elevator in individuals with combined deficiency of factors V and VIII: a clinical trial.

    Science.gov (United States)

    Mansouritorghabeh, H; Shirdel, A

    2016-02-01

    ESSENTIALS: Combined factor V (FV) and factor VIII (FVIII) deficiency (CF5F8D) is an autosomal recessive coagulation disorder. Desmopressin acetate (DDAVP) was intravenously infused in 20 adult patients with CF5F8D. DDAVP can enhance FVIII levels but has no effect on FV levels in patients with CF5F8D. DDAVP can be substituted for FVIII concentrates in patients with CF5F8D. Combined factor V (FV) and FVIII deficiency (CF5F8D) is a rare inherited autosomal recessive double-gene disorder most frequently seen in the Middle East. Although affected individuals have deficiency of two coagulation factors (range 5-30%), their bleeding tendencies are similar to patients who have deficiency of a single coagulation factor at the same level. The mainstay of their treatment is infusion of FVIII concentrate and fresh frozen plasma. Here, the effect of intravenous infusion of desmopressin acetate (DDAVP) on elevation of coagulation FV and FVIII was investigated through a clinical trial in May 2015. In a registered controlled trial, DDAVP (dosage 0.3 μg kg(-1) ) was intravenously infused into 20 adult patients with CF5F8D over 20 min. After an hour, blood samples were collected and plasma levels of FV and FVIII were measured. This study revealed that DDAVP can enhance FVIII levels but has no effect on FV plasma concentration in patients with CF5F8D. Based on these findings, FVIII concentrates may be substituted for DDAVP in patients with CF5F8D. © 2015 International Society on Thrombosis and Haemostasis.

  18. DAMPAK POSITIF DAN NEGATIF SOSIAL MEDIA TERHADAP PENDIDIKAN AKHLAK ANAK (Studi Kasus di SMP Negeri 2 Kelas VIII Banda Aceh

    Directory of Open Access Journals (Sweden)

    NISA KHAIRUNI

    2016-01-01

    Full Text Available The author examines the positive and negative effects of social media on the moral education of children in school SMPN 2 class VIII Banda Aceh, it is very interesting because of the many children who abuse social media. This work analyzes about the use of social media that have an impact on the moral education of children. The data collected in this study through the work of other literature, researchers also interviewed principals and students as many as 16 students as well as the observation at the school. Based on the analysis that has been done it can be seen the positive and negative impacts of the use of social media to the moral education of children. The positive impact on the social development of the media on moral education of children among children can adapt, socialize with the public and manage a network of friends, and make children easier to accomplish these tasks, while the negative impact of the development of social media to the moral education of children very much of them can make the omission in children so that children are less disciplined and be lazy, makes children easy to cheat the works of others, disrespectful both in dress and speech, often quarrel due to scenes that are as dangerous as scenes of pornography, violence, wars and so forth , as well as making children miss school because they feel more comfortable in the cafe of the study at the school, not only that social media also makes children spend pocket money a child so that the child took the money her parents secretly to access the internet cafe. Therefore, social media can lead education of children.

  19. A novel missense mutation in the FGB g. 3354 T>A (p. Y41N), Fibrinogen Caracas VIII

    Science.gov (United States)

    Marchi, Rita; Rojas, Héctor; Meyer, Michael; Castillo, Oscar; De Sáez Ruiz, Arlette; Weisel, John W.

    2012-01-01

    Summary A novel dysfibrinogenemia with a replacement of Tyr by Asn at Bβ41 has been discovered (fibrinogen Caracas VIII). An asymptomatic 39 year-old male was diagnosed as having dysfibrinogenemia due to a mildly prolonged thrombin time (+ 5.8 sec); his fibrinogen concentration was in the low normal range, both by Clauss and gravimetric determination, 1.9 g/l and 2.1 g/l, respectively. The plasma polymerization process was slightly impaired, characterized by a mildly prolonged lag time and a slightly increased final turbidity. Permeation through the patients’ clots was dramatically increased, with the Darcy constant around 4 times greater than that of the control (22 ± 2 ×10−9 cm2 compared to 6 ± 0.5 ×10−9 cm2 in controls). The plasma fibrin structure of the patient, by scanning electron microscopy, featured a mesh composed of thick fibers (148 ± 50 nm vs. 120 ± 31 nm in controls, p<0.05) and larger pores than those of the control fibrin clot. The viscoelastic properties of the clot from the patient were also altered, as the storage modulus (G′, 310 ± 30) was much lower than in the control (831 ± 111) (p ≤ 0.005). The interaction of the fibrin clot with a monolayer of human microvascular endothelial cells, by confocal laser microscopy, revealed that the patients’ fibrin network had less interaction with the cells. These results demonstrate the significance of the amino terminal end of the β chain of fibrin in the polymerization process and its consequences on the clot organization on the surface of endothelial cells. PMID:21301788

  20. Plasmid pEC156, a Naturally Occurring Escherichia coli Genetic Element That Carries Genes of the EcoVIII Restriction-Modification System, Is Mobilizable among Enterobacteria.

    Science.gov (United States)

    Werbowy, Olesia; Kaczorowski, Tadeusz

    2016-01-01

    Type II restriction-modification systems are ubiquitous in prokaryotes. Some of them are present in naturally occurring plasmids, which may facilitate the spread of these systems in bacterial populations by horizontal gene transfer. However, little is known about the routes of their dissemination. As a model to study this, we have chosen an Escherichia coli natural plasmid pEC156 that carries the EcoVIII restriction modification system. The presence of this system as well as the cis-acting cer site involved in resolution of plasmid multimers determines the stable maintenance of pEC156 not only in Escherichia coli but also in other enterobacteria. We have shown that due to the presence of oriT-type F and oriT-type R64 loci it is possible to mobilize pEC156 by conjugative plasmids (F and R64, respectively). The highest mobilization frequency was observed when pEC156-derivatives were transferred between Escherichia coli strains, Enterobacter cloacae and Citrobacter freundii representing coliform bacteria. We found that a pEC156-derivative with a functional EcoVIII restriction-modification system was mobilized in enterobacteria at a frequency lower than a plasmid lacking this system. In addition, we found that bacteria that possess the EcoVIII restriction-modification system can efficiently release plasmid content to the environment. We have shown that E. coli cells can be naturally transformed with pEC156-derivatives, however, with low efficiency. The transformation protocol employed neither involved chemical agents (e.g. CaCl2) nor temperature shift which could induce plasmid DNA uptake.

  1. Plasmid pEC156, a Naturally Occurring Escherichia coli Genetic Element That Carries Genes of the EcoVIII Restriction-Modification System, Is Mobilizable among Enterobacteria.

    Directory of Open Access Journals (Sweden)

    Olesia Werbowy

    Full Text Available Type II restriction-modification systems are ubiquitous in prokaryotes. Some of them are present in naturally occurring plasmids, which may facilitate the spread of these systems in bacterial populations by horizontal gene transfer. However, little is known about the routes of their dissemination. As a model to study this, we have chosen an Escherichia coli natural plasmid pEC156 that carries the EcoVIII restriction modification system. The presence of this system as well as the cis-acting cer site involved in resolution of plasmid multimers determines the stable maintenance of pEC156 not only in Escherichia coli but also in other enterobacteria. We have shown that due to the presence of oriT-type F and oriT-type R64 loci it is possible to mobilize pEC156 by conjugative plasmids (F and R64, respectively. The highest mobilization frequency was observed when pEC156-derivatives were transferred between Escherichia coli strains, Enterobacter cloacae and Citrobacter freundii representing coliform bacteria. We found that a pEC156-derivative with a functional EcoVIII restriction-modification system was mobilized in enterobacteria at a frequency lower than a plasmid lacking this system. In addition, we found that bacteria that possess the EcoVIII restriction-modification system can efficiently release plasmid content to the environment. We have shown that E. coli cells can be naturally transformed with pEC156-derivatives, however, with low efficiency. The transformation protocol employed neither involved chemical agents (e.g. CaCl2 nor temperature shift which could induce plasmid DNA uptake.

  2. Plasmid pEC156, a Naturally Occurring Escherichia coli Genetic Element That Carries Genes of the EcoVIII Restriction-Modification System, Is Mobilizable among Enterobacteria

    Science.gov (United States)

    Werbowy, Olesia; Kaczorowski, Tadeusz

    2016-01-01

    Type II restriction-modification systems are ubiquitous in prokaryotes. Some of them are present in naturally occurring plasmids, which may facilitate the spread of these systems in bacterial populations by horizontal gene transfer. However, little is known about the routes of their dissemination. As a model to study this, we have chosen an Escherichia coli natural plasmid pEC156 that carries the EcoVIII restriction modification system. The presence of this system as well as the cis-acting cer site involved in resolution of plasmid multimers determines the stable maintenance of pEC156 not only in Escherichia coli but also in other enterobacteria. We have shown that due to the presence of oriT-type F and oriT-type R64 loci it is possible to mobilize pEC156 by conjugative plasmids (F and R64, respectively). The highest mobilization frequency was observed when pEC156-derivatives were transferred between Escherichia coli strains, Enterobacter cloacae and Citrobacter freundii representing coliform bacteria. We found that a pEC156-derivative with a functional EcoVIII restriction-modification system was mobilized in enterobacteria at a frequency lower than a plasmid lacking this system. In addition, we found that bacteria that possess the EcoVIII restriction-modification system can efficiently release plasmid content to the environment. We have shown that E. coli cells can be naturally transformed with pEC156-derivatives, however, with low efficiency. The transformation protocol employed neither involved chemical agents (e.g. CaCl2) nor temperature shift which could induce plasmid DNA uptake. PMID:26848973

  3. Estudo citofotométrico da expressão do marcador tumoral Fator VIII e fatores prognósticos no adenocarcinoma gástrico Cytophotometric study of the expression of the tumoral marker Factor VIII and prognostic factors in gastrci adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Mary Tossa Nakamura

    2007-12-01

    Full Text Available RACIONAL: No câncer gástrico, a incidência, o diagnóstico e as opções terapêuticas apresentaram melhorias nas últimas décadas, porém o prognóstico permanece reservado, especialmente devido à maioria dos pacientes procurarem recurso médico com tumores avançados, metastáticos ou cirurgicamente irressecáveis já no diagnóstico. Biologia molecular é área de conhecimento recente com grandes questionamentos a serem respondidos e a atualidade dos fatos científicos mostra que o caminho deverá ser através da identificação de marcadores tumorais. Os grandes avanços na área da informática aprimoraram a análise da imagem celular através da citofotometria de imagem que possibilita através da imunoistoquímica estudar a proliferação celular e a angiogênese que participa em diversos processos tumorais, sendo pesquisadas por vários marcadores. Atualmente estudos são realizados para demonstrar o valor prognóstico de suas expressões, contudo, no adenocarcinoma gástrico resultados têm sido divergentes e estudos escassos. OBJETIVOS: Identificar e quantificar citofotometricamente a expressão dos marcadores da angiogênese através do fator VIII no adenocarcinoma e comparar suas expressões com fa classificação de Bormann, profundidade de invasão tumoral, grau de diferenciação, envolvimento nodal, padrão histológico e idade. MÉTODOS: Foram estudados 21 pacientes com adenocarcinoma gástrico, identificados de 1998 a 2006. Para a detecção do Fator VIII foi realizada imunoistoquímica, com anticorpo policlonal para Fator VIII. Foi realizada análise citofotométrica informatizada pelo sistema SAMBA 4000. RESULTADOS: Dos 21 pacientes 61,90% eram do sexo masculino e 38,10% do feminino, com idade mediana de 65 anos e apenas um não marcou para o Fator VIII (95,24% de marcação. As médias dos índices de marcagem para o Fator VIII foram de 61,14% (desvio-padrão de 15,06, variando de 29,16 a 73,91. Tumores com classifica

  4. Plasma homocysteine, methylene tetrahydrofolate reductase C677T and factor II G20210A polymorphisms, factor VIII, and VWF in central retinal vein occlusion

    OpenAIRE

    Boyd, S.; Owens, D.; Gin, T; Bunce, K.; Sherafat, H; Perry, D; Hykin, P

    2001-01-01

    AIMS—To determine whether plasma homocysteine, methylene tetrahydrofolate reductase (MTHFR) C677T and factor II G20210A polymorphisms, factor VIII, and vWF are risk factors for central retinal vein occlusion (CRVO).
METHOD—Prospective comparison of 63 consecutive patients with central retinal vein occlusion and 63 age matched controls. Plasma homocysteine and vWF were estimated by ELISA, the MTFHR and factor II G20210A polymorphisms determined by polymerase chain reaction with restriction enz...

  5. Komparasi Pembelajaran SAVI dan REACT Pada Kemampuan Pemecahan Masalah Siswa Kelas-VIII Materi Kubus dan Balok

    Directory of Open Access Journals (Sweden)

    Andriawan Meka Siswoyuono

    2016-10-01

    Full Text Available [Bahasa]: Penelitian ini bertujuan untuk mengetahui hasil komparasi antara model pembelajaran SAVI dan REACT terhadap kemampuan pemecahan masalah siswa. Penelitian ini merupakan penelitian eksperimen dengan post test-only control group design. Populasi penelitian ini adalah siswa kelas VIII SMP Negeri 1 Ungaran tahun ajaran 2013/2014 dengan sampel diambil secara cluster random sampling, terpilih tiga kelas sampel dimana setiap kelas terdiri dari 24 siswa. Kelas eksperimen 1 diberi perlakuan dengan model pembelajaran SAVI, kelas eksperimen 2 diberi perlakuan dengan model pembelajaran REACT, dan kelas kontrol dengan model pembelajaran Direct Instruction. Pengambilan data dilakukan dengan metode observasi untuk mengetahui aktivitas siswa dan guru, dan metode tes untuk mengetahui kemampuan pemecahan masalah siswa yang kemudian dianalisis dengan uji proporsi, uji perbedaan rata-rata, dan uji lanjut Tukey. Hasil penelitian ini menunjukkan bahwa tidak terdapat perbedaan signifikan kemampuan pemecahan masalah antara kelas eksperimen 1 dan 2. Jadi, baik model pembelajaran SAVI maupun REACT sama-sama efektif dalam mengembangkan kemampuan pemecahan masalah siswa. [English]: This study aims to evaluate the result of comparison between SAVI and REACT learning model toward problem-solving ability of students. This research is an experimental research with a post test-only control group design. The population of this research is the eight grade students of Junior High School 1 Ungaran 2013/2014 academic year. The sample is taken by random cluster sampling technique which select three sample classes where each class consists of 24 students. The experimental class 1 was treated with SAVI learning model, the experimental class 2 was treated with REACT learning model, and a control class was taught with the Direct Instruction learning model. Data is collected by observation method to determine the activity of students and teacher, and test method to determine the

  6. Milk fat globule-epidermal growth factor-factor VIII attenuates sepsis-induced acute kidney injury.

    Science.gov (United States)

    Cen, Cindy; Aziz, Monowar; Yang, Weng-Lang; Zhou, Mian; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

    2017-06-01

    Acute kidney injury (AKI) is most commonly caused by sepsis in critically ill patients, and it is associated with high morbidity and mortality. The pathophysiology of sepsis-induced AKI is generally accepted to include direct inflammatory injury, endothelial cell dysfunction, and apoptosis. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in the enhancement of apoptotic cell clearance and regulation of inflammation. We hypothesize that administration of recombinant mouse MFG-E8 (rmMFG-E8) can protect mice from kidney injuries caused by sepsis. Sepsis was induced in 8-wk-old male C57BL/6 mice by cecal ligation and puncture (CLP). rmMFG-E8 or phosphate-buffered saline (vehicle) was injected intravenously at a dosage of 20 μg/kg body weight at time of CLP (n = 5-8 mice per group). After 20 h, serum and renal tissue were harvested for various analyses. The renal injury markers blood urea nitrogen (BUN) and creatinine were determined by enzymatic and chemical reactions, respectively. The gene expression analysis was carried out by real-time quantitative polymerase chain reaction. At 20 h after CLP, serum levels of BUN and creatinine were both significantly increased in the vehicle group compared with the sham group, whereas the mice treated with rmMFG-E8 had a significant reduction in BUN and creatinine levels by 28% and 24.1%, respectively (BUN: 197.7 ± 23.6 versus 142.3 ± 20.7 mg/dL; creatinine: 0.83 ± 0.12 versus 0.63 ± 0.06 mg/dL; P sepsis through inhibiting the production of proinflammatory cytokines and chemokine, as well as through the activation of endothelial cells. Thus, MFG-E8 may have a therapeutic potential for treating AKI induced by sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Pathogen inactivation in fresh frozen plasma using riboflavin and ultraviolet light: Effects on plasma proteins and coagulation factor VIII

    Directory of Open Access Journals (Sweden)

    Stanojković Zoran

    2011-01-01

    Full Text Available Background/Aim. Riboflavin (vitamin B2 activated by ultraviolet (UV light, produces active oxygen which damages cell membrane and prevents replication of the carrier of diseases (viruses, bacteria, protozoa in all blood products. The aim of this study was to establish the influence of the process of photo inactivation in pathogens using riboflavin and UV rays on the concentration of coagulation factor VIII:C (FVIII:C and proteins in plasma that were treated before freezing. Methods. The examination included 20 units of plasma, separated from whole blood donated by voluntary blood donors around 6 hours from the moment of collection. The units were pooled and separated in to two groups: one consisted of 10 control units and the other of 10 experimental units. Experimental units of the plasma were treated by riboflavin (35 mL and UV rays (6.24 J/mL, 265-370 nm on Mirasol aparature (Caridian BCT Biotechnologies, USA in approximate duration of 6 minutes. Furthermore, 35 mL of saline solution was added to the control plasma. One sample for examining was taken from the control plasma (KG and two residual were taken from experimental plasma after the addition of riboflavin either before (EG1 or post illumination (EG2. Results. Comparing the mean values of FVIII:C (% we noticed statistically significantly higher level in the EG1 group than in the EG2 group (65.00 ± 4.52 vs 63.20 ± 4.73; t = 4.323, p = 0.002, while between the KG and experimental groups (EG1 and EG2 there was no statistically significant difference in the concentration of FVIII:C. There was a statistically significant decrease of albumin concentration (g/L in the EG2 group comparing to the KG (33.35 ± 0.94 vs 31.94 ± 0.84; t = 3.534, p = 0.002, but there was no mentioned difference in albumin concentration between the KG and the EG1, so as between the EG1 and the EG2. Conclusion. Plasma inactivated by riboflavin and UV rays (Mirasol PRT sistem, Caridian BCT, USA keeps all the

  8. BAY 81-8973, a full-length recombinant factor VIII: results from an International comparative laboratory field study.

    Science.gov (United States)

    Kitchen, S; Beckmann, H; Katterle, Y; Bruns, S; Tseneklidou-Stoeter, D; Maas Enriquez, M

    2016-05-01

    BAY 81-8973 is a full-length, unmodified, recombinant human factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII but produced with certain more advanced manufacturing technologies. This global laboratory study evaluated variability in measurement of BAY 81-8973 using one-stage and chromogenic assays compared with antihaemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM; Advate(®) ) under assay conditions routinely used in clinical laboratories. BAY 81-8973 or rAHF-PFM was spiked into FVIII-deficient plasma at 0.043 (low), 0.375 (medium) and 0.865 (normal) IU mL(-1) . Participating laboratories analysed blinded samples and normal plasma in triplicate using their routine assay, reagents and standards. Results were analysed for intra- and interlaboratory variability. Forty-one laboratories in 11 countries participated in the study. One-stage assay and chromogenic assays were used by 40 and 10 laboratories, respectively; 9 laboratories used both assays. Intralaboratory variability was <11% for both assays and both products at all concentrations. Interlaboratory variability was highest at the low concentration in the chromogenic and one-stage assay for BAY 81-8973 (60.0% and 33.7%, respectively) and rAHF-PFM (51.0% and 30.8%) and was lowest at the normal concentration (BAY 81-8973, 5.4% and 14.0%; rAHF-PFM, 5.8% and 12.4%), which was similar to the plasma control (6.6% and 10.3%). The chromogenic:one-stage assay ratio ranged from 0.95 (low concentration) to 1.10 (normal concentration) for BAY 81-8973 and 0.96-1.18 for rAHF-PFM. BAY 81-8973 can be accurately measured in plasma using the one-stage and chromogenic assays routinely used in clinical laboratories without a product-specific standard. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  9. Essays on Strategy VIII

    Science.gov (United States)

    1991-01-01

    a simplistic view belittles Panamanian nationalism, which existed long before Teddy Roosevelt, and attaches an artificial label to the country. As a...announced an offer to host some of the US forces currently based in the Philippines. His offer reduced left-wing pressure on President Corazon Aquino

  10. MENINGKATKAN KEMAMPUAN PEMECAHAN MASALAH MELALUI PEMBELAJARAN KOOPERATIF THINK-TALK-WRITE PADA PESERTA DIDIK KELAS VIII1 MTsN MODEL MAKASSAR

    Directory of Open Access Journals (Sweden)

    Andi Dian Angriani

    2016-06-01

    Full Text Available Penelitian ini bertujuan untuk: (1 Mendeskripsikan penerapan pembelajaran kooperatif Think-Talk-Write (TTW yang dapat meningkatkan kemampuan pemecahan masalah matematika pada peserta didik kelas VIII1 MTsN Model Makassar, (2 Mendeskripsikan peningkatan kemampuan pemecahan masalah matematika melalui penerapan pembelajaran kooperatif Think-Talk-Write pada peserta didik kelas VIII1 MTsN Model Makassar. Penelitian ini dilaksanakan dalam dua siklus, masing-masing siklus terdiri dari 4 tahap, yaitu tahap perencanaan (planning, pelaksanaan tindakan (acting, observasi (observing/evaluasi (evaluating dan refleksi (reflecting. Hasil penelitian menunjukkan bahwa: (1 Pembelajaran kooperatif Think-Talk-Write dapat meningkatkan kemampuan pemecahan masalah matematika, meliputi: (a Pada tahap berpikir (think, peserta didik membaca dan mamahami LKPD yang dibagikan secara individu dan diberi kesempatan untuk bertanya jika ada hal yang kurang dipahami. (b Pada tahap berdiskusi (talk, peserta didik terdiri dari 4 orang, berdiskusi secara berpasangan kemudian dipertukarkan dengan pasangan lain dalam kelompoknya, dan diberikan kesempatan untuk bertanya. (c Pada tahap menulis (write, setelah berdiskusi menyatukan pendapat, peserta didik menuliskan hasil diskusinya secara individual, (2 Peningkatan kemampuan pemecahan masalah tersebut sebagai berikut: pada siklus I, rata-rata hasil belajar peserta didik 72,85 meningkat menjadi 89,63 pada siklus II. Pada siklus I, terdapat 18 siawa (45% yang telah mencapai nilai KKM namun ketuntasan belajar secara klasikal belum tercapai. Sedangkan dari hasil tes siklus II, terdapat 33 peserta didik (82,5% yang telah mencapai nilai KKM dan ketuntasan belajar secara klasikal sudah tercapai.

  11. A comparison of the 12s rule and Bayesian approach for quality control: application to one-stage clotting factor VIII assay.

    Science.gov (United States)

    Sobas, Frédéric; Tsiamyrtzis, Panagiotis; Benattar, Norbert; Lienhart, Anne; Négrier, Claude

    2014-09-01

    An ideal medical biology internal quality control (IQC) plan should both monitor the laboratory methods efficiently and implement the relevant clinical-biological specifications. However, many laboratories continue to use the 12s quality control rule without considering the high risk of false rejection and without considering the relationship of analytical performance to quality requirements. Alternatively, one can move to the Bayesian arena, enabling probabilistic quantification of the information coming in, on a daily basis from the laboratory's IQC tests, and taking into account the laboratory's medical and economic contexts. Using the example of one-stage clotting factor VIII assay, the present study compares frequentist (12s quality control rule) and Bayesian IQC management with respect to prescriber requirements, process start-up phase issues, and abnormal scenarios in IQC results. To achieve comparable confidence, the traditional 12s quality control rule requires more data than the Bayesian approach in order to detect an increase in the random or systematic error of the method. Moreover, the Bayesian IQC management approach explicitly implements respect of prescriber requirements in terms of calculating the probability that the variable in question lies in a given predefined interval: for example, the factor VIII concentration required after knee surgery in a hemophilia patient.

  12. PENGARUH PENGGUNAAN VARIASI METODE DAN MODEL PEMBELAJARAN TERHADAP HASIL BELAJAR FISIKA SISWA KELAS VIII SMPN2 MARGATIGA SEMESTER GENAP TP 2013/2014

    Directory of Open Access Journals (Sweden)

    Eni Fitriani

    2015-03-01

    Full Text Available The purpose of this study was to investigate the effect of variations in the methods and models of teaching to student learning outcomes VIII SMPN2 MARGA TIGA.This research is experimental research which ofdesign completely randomized or completely randomized experimental design.The population in thisresearch is all of student VIII class in SMPN 2 MARGA TIGA2013/2014. The sample in this research is VIIIth class which totaling 34 students.In this research, conducted with three treatments of learning in a classroom.Data collection techniques in this research use the technique of the test, which tests the end (posttest were then analyzed with the test results hipotesis. From posttest analysis results of hypothesis testing using one-way ANOVA test (Completely Randomized Design at the 5% significance level value obtained results Fobs = 1.5244 and Ftab = 3.10 this shows that H0 is accepted and means variety of methods and learning models provide a similar impact on student learning outcomes.It can be concluded that all three treatments had similar quality if tailored to the needs of all three materials. 

  13. Enfermedad de Kawasaki: diagnostico y tratamiento

    National Research Council Canada - National Science Library

    Cardozo-Lopez, Margarita; Escobar-Berrio, Alejandra; Londono-Restrepo, Juan David; Alvaran-Mejia, Melissa

    2012-01-01

    ... cardiologica por ecocardiografia. En la actualidad no se cuenta con estadisticas nacionales ni locales, lo cual puede favorecer que muchos de los casos no sean diagnosticados oportunamente, pues se confunde con facilidad con enfermedades exantematicas...

  14. DIAGNOSTICO Y MANEJO PERINATAL DE TRISOMIA 9

    National Research Council Canada - National Science Library

    Inostroza C, Alexis; Navarro M, Héctor; Paublo M, Mario; Muñoz, Hernán; Hernández, Américo; Catalán, Jorge; Sanz, Patricia; Puig, Paula

    2002-01-01

    Presentamos dos casos clínicos de diagnóstico antenatal de trisomía 9. Esta aneuploidía se sospechó en la evaluación ultrasonográfica durante la segunda mitad del embarazo, siendo confirmada por cordocentesis...

  15. Haga su diagnostico Case for diagnosis

    Directory of Open Access Journals (Sweden)

    Victoria Rivelli

    2008-08-01

    Full Text Available Comunicamos un paciente joven, que presentaba una inmunodepresión atribuida al alcohol y la desnutrición, que consultó por numerosas lesiones. Luego de los estudios auxiliares se llegó al diagnóstico y mostró buena respuesta al tratamiento convencional para esta leishmaniasis. Las lesiones polimorfas obligaron a varios diagnósticos diferenciales, entre ellos histoplasmosis, paracoccidioidomicosis, ectima, linfoma.We report the case of a patient with alcohol intake and malnutrition-related immunosuppression who sought medical attention for multiple ulcerated lesions. Laboratory tests revealed the diagnosis and the patient responded well to conventional anti-leishmaniasis therapy. Polymorphous lesions prompted differential diagnoses such as histoplasmosis, paracoccidioidomycosis, ecthyma and lymphoma.

  16. Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

    Directory of Open Access Journals (Sweden)

    Cimino E

    2014-12-01

    Full Text Available Ernesto Cimino,1 Silvia Linari,2 Mara Malerba,3 Susan Halimeh,4 Francesca Biondo,5 Martina Westfeld5 1Dipartimento Medicina Clinica e Sperimentale, Universita’ degli Studi di Napoli Federico II, Naples, Italy; 2Agenzia per l’ Emofilia, AOU Careggi di Firenze, Florence, Italy; 3Fondazione Cà Granda Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi “A Bianchi Bonomi”, Milan, Italy; 4CRC Coagulation Research Centre GmbH, Duisburg, Germany; 5Pfizer Italia, Rome, Italy Introduction: Hemophilia A treatment involves replacing the deficient coagulation factor VIII. This process may involve multiple steps that might create a barrier to adherence. A new dual-chamber syringe (DCS; FuseNGo® was recently introduced with the aim of simplifying reconstitution. Aim: This study aimed to identify factors associated with adult patients’ preferences for different coagulation factor VIII reconstitution systems and to test ease of use and patient preference for the DCS. Methods: A cross-sectional survey of adults with hemophilia A in five European countries was conducted; a subset of subjects also participated in a practical testing session of the DCS. Results: Among the 299 survey participants, the device scenario requiring the least equipment and reconstitution steps (the DCS received a median preference rating of 71 out of 100 (0 being “the least desirable” and 100 “the most desirable” rating. This was significantly higher than the other scenarios (the next highest achieved a median of 50 points; P<0.001. Participants would be more likely to use this device prophylactically (P<0.001. Among the 98 participants who tested the DCS, 57% preferred this device over their current device, 26% preferred their current device, and 17% had no preference. The DCS was rated as easier to use than current treatment devices (median score 9/10 versus 7/10 for current treatment, P=0.001. Conclusion: The survey indicates that the prefilled DCS, Fuse

  17. Influence Model Assisted Learning Cycle Mind Map to Achievement Physics Laboratory Judging from the performance Grade VIII SMPN 1 Rejoso Pasuruan

    Directory of Open Access Journals (Sweden)

    Ary Analisa Rahma

    2014-06-01

    Full Text Available Pengaruh Model Siklus Belajar Berbantuan Mind Map terhadap Prestasi Belajar Fisika Ditinjau dari Kinerja Laboratorium Siswa Kelas VIII SMPN 1 Rejoso Kabupaten Pasuruan Abstract: This study aimed to examine the effect of the learning cycle models aided the mind map on the learning achievement in terms of the performance of laboratory physics class VIII student on light material in SMP Negeri 1 Rejoso Pasuruan. This study is a quasi-experimental research. The research design used is a 2 x 2 factorial design subject of this study consisted of 204 students. The research instrument consisted of a treatment instrument which includes syllabi, lesson plans and worksheets, as well as measuring instruments including by means of laboratory performance and achievement test. The results showed that the learning achievement of students studying physics model of mind mapping aided learning cycle is higher than that of learning by inquiry learning, there is an interaction between learning and performance laboratory models for studying physics student achievement, as well as physics learning achievement of students who have a high-performance laboratory and studying low-aided learning cycle model mind map is higher than that of learning by inquiry learning. Based on these results it can be concluded that learning with the learning cycle model aided mind map is more effective than inquiry learning on learning achievement physics. Key Words: model of learning cycle, mind map, the performance of the lab, physics learning achievement Abstrak: Penelitian ini bertujuan untuk menguji pengaruh model siklus belajar berbantuan mind map terhadap prestasi belajar fisika ditinjau dari kinerja laboratorium siswa kelas VIII pada materi cahaya di SMP Negeri 1 Rejoso Kabupaten Pasuruan. Penelitian ini merupakan penelitian eksperimen semu. Rancangan penelitian yang digunakan adalah factorial design 2 x 2. Subjek penelitian ini terdiri atas 204 siswa. Instrumen penelitian terdiri

  18. La cisma de Enrique VIII: ambición y dignidad. Catalina de Aragón y Ana Bolena en el imaginario de Calderón y Shakespeare

    OpenAIRE

    Vallejo Mateo, María Luisa

    2015-01-01

    El artículo tiene como finalidad comparar el tratamiento que dan Calderón y Shakespeare a sus personajes femeninos principales en La cisma de Ingalaterra y Enrique VIII, en torno a los conceptos de dignidad y ambición, que marcan su manera de ser y est

  19. PENGARUH METODE PEMBELAJARAN MAKE A MATCH BERBANTUAN READING GUIDE TERHADAP PENGUASAAN KONSEP PADA MATERI SISTEM PENCERNAAN MAKANAN PADA MANUSIA KELAS VIII SMPN 30 PEKANBARU TAHUN AJARAN 2014/2015

    Directory of Open Access Journals (Sweden)

    Raudhah Awal

    2017-07-01

    Full Text Available The purpose of this research is to know the effect of learning make a matchmethod assisted reading guide on students concept comprehension of the subjectmaters human digestive system in class VIII SMPN 30 Pekanbaru. This researchconducted on November 2014. The method of this research used was quasiexperiment with the nonequivalent pretest-posttest control group design. Thesampel of this research were students of VIII1 and VIII3 with using simple totalsampling technique. The data was analyzed in the from of t-test. The data wherecollected by pretest, posttest and observations. The mean of N-gain at experimentclass was 0,77 categorized at hight level, while at control class was 0,36Categorized at medium level. So it can be conduded that there was a significanteffect teacher learning and student’s activity of the subject matters humandigestive system in class VIII SMPN 30 Pekanbaru academic Year 2014/2015.Key words: make a match, reading guide, concept comprehension, digestivesystem.PendahuluanSalah satu usaha untukmeningkatkan mutu pendidikanadalah dengan cara memperbaikiproses belajar mengajar. Belajarmengajar pada dasarnya adalahinteraksi atau hubungan timbal balikantara pendidik dan peserta didik.Oleh karena itu, guru dalammengajar dituntut kesabaran,keuletan

  20. The Development of Geometri Teaching Materials Based on Constructivism to Improve the Students' Mathematic Reasoning Ability through Cooperative Learing Jigsaw at the Class VIII of SMP Negeri 3 Padangsidimpuan

    Science.gov (United States)

    Dewi, Izwita; Harahap, Muhammad Syahri

    2016-01-01

    The purposes of this research were to know the validity, practicality, and effectivity of geometrical learning material based on the constructivism to Increase students' mathematic reasoning ability and increasing students' mathematic reasoning ability by using learning material at the grade VIII of SMP Negeri 3 Padangsidimpuan. Type of the…

  1. Diagnóstico de brucelosis bovina en leche por el Ring Test y ELISA en lecherías de la provincia de Ñuble (VIII Región) Bovine brucellosis diagnosis in milk by Ring Test and ELISA in dairy farms of Ñuble (VIII Region, Chile)

    OpenAIRE

    Lopez, J; Best, A.

    1998-01-01

    Se utilizaron los métodos de ELISA y Ring Test en leche para diagnosticar brucelosis bovina en estanques de recolección en frío a 60 predios lecheros de la provincia de Ñuble, VIII Región de Chile, durante los meses de noviembre y diciembre de 1995. Estos fueron estratificados en relación al número de vacas en producción de leche. Los resultados obtenidos por ambos métodos fueron similares,18 muestras positivas y 42 negativas. La diferencia se estableció en 5 muestras (8.3%) que fueron clasif...

  2. Fundamentos geométricos, metrológicos y sistemas de proporción en la arquitectura altomedieval asturiana (siglos VIII y X

    Directory of Open Access Journals (Sweden)

    Arias Páramo, Lorenzo

    2001-12-01

    Full Text Available This paper aims to establish the criteria that ruled the proportions and order in early mediaeval Asturian architecture ( 8th-10th centuries. It includes the study of the metrological system and the module of proportions used in these buildings. As a result, these principles are used as a basis for establishing the forms and principles of proportion common to all Asturian architecture.Estudiamos los criterios de orden y proporción presentes en la arquitectura altomedieval asturiana (siglos VIII-X. El estudio abarca igualmente el sistema metrologico aplicado, estudiando asimismo el módulo de proporción presente en sus edificios. A partir de estos principios se establecen las formas tipológicas y los cánones de proporción comunes al conjunto de la arquitectura asturiana.

  3. Temperature dependence of the minimum V/III ratio for the growth of In[sub x]Ga[sub 1-x]As

    Energy Technology Data Exchange (ETDEWEB)

    Riechert, H. (Siemens Corporate Research and Development, Muenchen (Germany)); Averbeck, R. (Siemens Corporate Research and Development, Muenchen (Germany)); Bernklau, D. (Siemens Corporate Research and Development, Muenchen (Germany))

    1993-02-01

    We have quantitatively determined the minimum V/III ratios for the growth of In[sub x]Ga[sub 1-x]As(x=0, 0.1, 0.2 and 0.53) on GaAs and InP. Minimum As[sub 4] fluxes were measured for a wide range of growth temperatures using a transition of the surface reconstruction. Their temperature dependence can be fitted very well by the typical curve for thermally activated behavior. We find In[sub x]Ga[sub 1-x]As and GaAs are found to be similar (1.9 and 2.1 eV, respectively) but the rates of As-desorption are much higher for In[sub x]Ga[sub 1-x]As. This may be seen as evidence for a less effective dissociative reaction of As[sub 4] with In than with Ga. (orig.)

  4. Long-lasting remission and successful treatment of acquired factor VIII inhibitors using cyclophosphamide in a patient with systemic lupus erythematosus.

    Science.gov (United States)

    Trotta, F; Bajocchi, G; La Corte, R; Moratelli, S; Sun, L Y

    1999-10-01

    Acquired deficiency of clotting factor VIII (FVIII) is a rare bleeding diathesis seldom encountered in systemic lupus erythematosus (SLE). Reduction of FVIII activity by autoantibodies can cause potentially life-threatening situations. Herein, an SLE patient with a positive lupus anticoagulant (LAC) test who abruptly developed metrorrhagia 4 yr after diagnosis is reported. Coagulation tests revealed FVIII activity reduced to 3% and a prolonged aPTT. FVIII inhibitor(s) were found to be as high as 3.0 Bethesda Units. Plasmapheresis, immunoglobulins, prednisolone and FVIII plasma concentrates induced the cessation of metrorrhagia, but the clotting tests were barely improved. One month later, extensive ecchymosis appeared and worsened, despite re-administration of the previous therapy. Pulse cyclophosphamide followed by oral administration was then started with normalization of coagulation parameters and long-lasting disease remission.

  5. PENGARUH PERSEPSI SIWA TENTANG KETERAMPILAN MENGAJAR GURU DAN FASILITAS BELAJAR SISWA TERHADAP MINAT BELAJAR IPS KELAS VIII SMP N 3 PURBALINGGA

    Directory of Open Access Journals (Sweden)

    Muhammad Feriady,

    2012-10-01

    Full Text Available Tujuan dari penelitian ini adalah ada tidaknya pengaruh persepsi siswa tentang� keterampilan mengajar guru dan fasilitas belajar siswa terhadap minat belajar IPS kelas VIII SMP N 3 Purbalingga. Berdasarkan hasil analisis regresi diperoleh persamaan regresi Y = 12,347 + 0,206 X1 + 0,179 X2 dengan uji simultan diperoleh F hitung=13,4 dan signifikansi 0,000<0,05 menolak H0 dan menerima H1 yang menyatakan ada pengaruh persepsi siswa mengenai ketrampilan mengajar guru dan fasilitas belajar siswa terhadap minat belajar. Besarnya R square sebesar 26,5%. Uji partial diperoleh persepsi siswa mengenai keterampilan mengajar dengan t hitung=2,381 dan signifikansi 0,02<0,05 menerima H2 yang menyatakan ada pengaruh persepsi siswa mengenai keterampilan mengajar guru terhadap minat belajar. Fasilitas belajar siswa dengan t hitung=2,115 dengan signifikansi 0,032VIII SMP N 3 Purbalingga. Saran yang bisa diberikan dalam penelitian ini adalah kepada guru agar dapat meningkatkan ketertarikan siswa pada pelajaran IPS dan kepada sekolah diharapkan untuk meningkatkan ketergunaan peralatan pembelajaran dengan sebaik-baiknya. The purpose of this research is to know whether there is effect of students perception of teachers� skill and learning fasilitise related to students� interest in IPS clas VIII SMP N 3 Purbalingga. From regression analytic result, we get regression Y equality = 12,347+0,206X1+0,179X2. By simultaneous test, we get F count= 13,4 and signification 0,000<0,05 regret H0 and accept H1that said there effect of student perception about teachers� teaching skill and facilities of students� learning. The amount of R squere is 26,5%. Partial test obtained about teachers� teaching skill with t count=2

  6. Tartaglia’s science of weights and mechanics in the sixteenth century selections from quesiti et inventioni diverse books VII–VIII

    CERN Document Server

    Pisano, Raffaele

    2016-01-01

    This book presents a historical and scientific analysis as historical epistemology of the science of weights and mechanics in the sixteenth century, particularly as developed by Tartaglia in his Quesiti et inventioni diverse, Book VII and Book VIII (1546; 1554). In the early 16th century mechanics was concerned mainly with what is now called statics and was referred to as the Scientia de ponderibus, generally pursued by two very different approaches. The first was usually referred to as Aristotelian, where the equilibrium of bodies was set as a balance of opposite tendencies to motion. The second, usually referred to as Archimedean, identified statics with centrobarica, the theory of centres of gravity based on symmetry considerations. In between the two traditions the Italian scholar Niccolò Fontana, better known as Tartaglia (1500?–1557), wrote the treatise Quesiti et inventioni diverse (1546). This volume consists of three main parts. In the first, a historical excursus regarding Tartaglia’s lifetime,...

  7. Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

    2018-01-01

    Various experimental animal models are used in haemophilia research, however, little is known about how well the different species predict pharmacokinetic (PK) profiles in haemophilia patients. The aim of the current study was to describe the plasma concentration-time profile of recombinant...... activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...... for nonlinear kinetics and gender-specific difference in clearance for rFVIII. The predictive performance of the animal population PK models of rFVIIa and rFVIII revealed significant species-variation. The developed PK models of rFVIIa and rFVIII in monkeys and dogs along with allometric interspecies scaling...

  8. Pandangan Hakim Pengadilan Agama Palembang Terhadap Putusan Mahkamah Konstitusi Nomor 46/PUU-VIII/2010 Tentang Status Anak di Luar Nikah

    Directory of Open Access Journals (Sweden)

    Arne Huzaimah

    2016-03-01

    Full Text Available Penelitian ini mengkaji tentang status anak di luar nikah perpektif hukum Islam. Pertimbangan Hukum Majelis Hakim Mahkamah Konstitusi Nomor: 46/PUU-VIII/201. Pandangan Hakim Pengadilan Agama Kelas 1A Palembang terhadap Putusan Mahkamah Konstitusi Nomor: 46/PUU-VIII/2010 adalah: Putusan uji materi pasal 43 ayat 1 UUP, sesungguhnya ditujukan untuk anak yang lahir di luar perkawinan akibat nikah sirri atau kumpul kebo. Berdasarkan penetapan pengadilan agama yang berkaitan dengan pengesahan perkawinan/itsbat nikah dan penetapan asal usul anak, maka anak yang dilahirkan dari perkawinan sirri dapat dinyatakan sebagai anak yang sah. Dengan status anak sah, maka anak tersebut mempunyai hubungan perdata dengan ayah biologisnya. Hubungan perdata yang timbul akibat dari adanya hubungan darah ini meliputi hubungan hukum, hak dan kewajiban antara anak dengan ayah dan ibunya yang dapat berupa:  (1  hubungan  nasab;  (2  hubungan mahram; (3 hubungan hak dan kewajiban; (4 hubungan pewarisan (saling mewarisi  yang  merupakan  pelanjutan  hubungan  hak  dan  kewajiban karena  nasab  ketika mereka  sama-sama masih  hidup;  dan  (5  hubungan wali nikah antara ayah dengan anak perempuannya. This paper examined the status of children outside wedlock in perspective of Islamic law. Consideration of the judges of the Constitutional Court Law No. 46 / PUU-VIII / 2010: included: the right to obtain legal status of the child; registration of marriage was not a factor in determining the legal of the marriage and registration of marriages was an administrative obligations required by legislation. The factors that determined the legal of a marriage was the conditions prescribed by the religion of each pair bride; problems concerned children born out of wedlock should receive law protection and law certainty to the status of a child born and rights available to him, including toward children born though the legal of the marriage still disputed. While the

  9. Influence of the V/III ratio in the gas phase on thin epitaxial AlN layers grown on (0001) sapphire by high temperature hydride vapor phase epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Claudel, A., E-mail: arnaud.claudel@grenoble-inp.org [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Fellmann, V. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Science et Ingénierie des Matériaux et des Procédés, Grenoble INP-CNRS-UJF, BP 75, 38402 Saint Martin d' Hères (France); Gélard, I. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Coudurier, N. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Science et Ingénierie des Matériaux et des Procédés, Grenoble INP-CNRS-UJF, BP 75, 38402 Saint Martin d' Hères (France); Sauvage, D. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Balaji, M. [ACERDE, 354 Voie Magellan — Alpespace, 73800 Ste Hélène du Lac (France); Science et Ingénierie des Matériaux et des Procédés, Grenoble INP-CNRS-UJF, BP 75, 38402 Saint Martin d' Hères (France); Crystal Growth Center, Anna University, Chennai 600025 (India); and others

    2014-12-31

    Thin (0001) epitaxial aluminum nitride (AlN) layers were grown on c-plane sapphire using high temperature hydride vapor phase epitaxy. The experimental set-up consists of a vertical cold-wall quartz reactor working at low pressure in which the reactions take place on a susceptor heated by induction. The reactants used are ammonia and aluminum chlorides in situ formed via hydrogen chloride reaction with high purity aluminum pellets. As-grown AlN layers have been characterized by scanning electron microscopy, atomic force microscopy, X-ray diffraction, transmission electron microscopy, photoluminescence and Raman spectroscopies. The influence of the V/III ratio in the gas phase, from 1.5 to 15, on growth rate, surface morphology, roughness and crystalline quality is investigated in order to increase the quality of thin epitaxial AlN layers grown at high temperature. Typical growth rates of around 0.45 μm/h were obtained for such thin epitaxial AlN layers. The growth rate was unaffected by the V/III ratio. An optimum for roughness, crystalline quality and optical properties seems to exist at V/III = 7.5. As a matter of fact, for a V/III ratio of 7.5, best root mean square roughness and crystalline quality — measured on 0002 symmetric reflection — as low as 6.9 nm and 898 arcsec were obtained, respectively. - Highlights: • Growth of thin epitaxial AlN layers by high temperature hydride vapor phase epitaxy • Influence of V/III ratio on growth rate, morphology and crystalline quality • The effect of surface morphology on strain state and crystal quality is established.

  10. Driven equilibrium (drive) MR imaging of the cranial nerves V-VIII: comparison with the T2-weighted 3D TSE sequence

    Energy Technology Data Exchange (ETDEWEB)

    Ciftci, E. E-mail: eciftcis7@hotmail.com; Anik, Yonca; Arslan, Arzu; Akansel, Gur; Sarisoy, Tahsin; Demirci, Ali

    2004-09-01

    Purpose: The aim of this study is to evaluate the efficacy of the driven equilibrium radio frequency reset pulse (DRIVE) on image quality and nerve detection when used in adjunction with T2-weighted 3D turbo spin-echo (TSE) sequence. Materials and methods: Forty-five patients with cranial nerve symptoms referable to the cerebellopontine angle (CPA) were examined using a T2-weighted 3D TSE pulse sequence with and without DRIVE. MR imaging was performed on a 1.5-T MRI scanner. In addition to the axial resource images, reformatted oblique sagittal, oblique coronal and maximum intensity projection (MIP) images of the inner ear were evaluated. The nerve identification and image quality were graded for the cranial nerves V-VIII as well as inner ear structures. These structures were chosen because fluid-solid interfaces existed due to the CSF around (the cranial nerves V-VIII) or the endolymph within (the inner ear structures). Statistical analysis was performed using the Wilcoxon test. P<0.05 was considered significant. Results: The addition of the DRIVE pulse shortens the scan time by 25%. T2-weighted 3D TSE sequence with DRIVE performed slightly better than the T2-weighted 3D TSE sequence without DRIVE in identifying the individual nerves. The image quality was also slightly better with DRIVE. Conclusion: The addition of the DRIVE pulse to the T2-weighted 3D TSE sequence is preferable when imaging the cranial nerves surrounded by the CSF, or fluid-filled structures because of shorter scan time and better image quality due to reduced flow artifacts.

  11. Murine leukemia virus-derived retroviral vector has differential integration patterns in human cell lines used to produce recombinant factor VIII

    Directory of Open Access Journals (Sweden)

    Marcela Cristina Correa de Freitas

    2014-06-01

    Full Text Available OBJECTIVE: Nowadays recombinant factor VIII is produced in murine cells including in Chinese hamster ovary (CHO and baby hamster kidney cells (BHK. Previous studies, using the murine leukemia virus-derived retroviral vector pMFG-FVIII-P140K, modified two recombinant human cell lines, HepG2 and Hek293 to produce recombinant factor VIII. In order to characterize these cells, the present study aimed to analyze the integration pattern of retroviral vector pMFG-FVIII-P140K.METHODS: This study used ligation-mediated polymerase chain reaction to locate the site of viral vector integration by sequencing polymerase chain reaction products. The sequences were compared to genomic databases to characterize respective clones.RESULTS: The retroviral vector presented different and non-random profiles of integration between cells lines. A preference of integration for chromosomes 19, 17 and 11 was observed for HepG2FVIIIdB/P140K and chromosome 9 for Hek293FVIIIdB/P140K. In genomic regions such as CpG islands and transcription factor binding sites, there was no difference in the integration profiles for both cell lines. Integration in intronic regions of encoding protein genes (RefSeq genes was also observed in both cell lines. Twenty percent of integrations occurred at fragile sites in the genome of the HepG2 cell line and 17% in Hek293.CONCLUSION: The results suggest that the cell type can affect the profile of chromosomal integration of the retroviral vector used; these differences may interfere in the level of expression of recombinant proteins.

  12. Invención y tradición en la cancillería real de Alfonso VIII de Castilla (1158-1214

    Directory of Open Access Journals (Sweden)

    Pablo Martín Prieto

    2013-11-01

    Full Text Available El estudio de la evolución de la cancillería real de Castilla bajo Alfonso VIII permite derivar ciertas conclusiones sobre el papel individual de los miembros de su personal en la redacción de los diplomas regios, concretamente por medio de un análisis detenido de los preámbulos, su formación y alteraciones a lo largo del tiempo en la mano de los distintos scriptores. Asimismo, esta base permite medir el equilibrio entre tradición e innovación en el trabajo de cancillería. La consideración de la imagen del monarca ideal, tal como se propone tanto en fuentes literarias como en los mismos documentos de la cancillería, conduce a una comprensión más clara del alcance de la propaganda política de la época en el más amplio contexto cultural de la corte castellana.The study of the Castilian royal Chancery’s evolution under King Alfonso VIII allows us to draw certain conclusions on the role of individual members of that office in the process of drafting royal documents. We will present a detailed description of preambles, their elaboration and evolution in time and by the hands of different scriptores. This will also allow us to gauge the balance between tradition and innovation within the Chancery. A more thorough grasp of the scope of political propaganda at the time can be determined through the image of the ideal king as depicted both in literary sources and in Chancery documents within the wider context of cultural developments in the Castilian court.

  13. ANALISIS MAQÂṢID ASY-SYARÎ’AH TERHADAP PUTUSAN MK NOMOR 46/PUU-VIII/2010 DAN IMPLIKASINYA TERHADAP HUKUM KELUARGA ISLAM DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Muhammad Ubayyu Rikza

    2017-12-01

    Full Text Available The Constitutional Court made a revolutionary decision through the decision of Constitutional Court Number 46/PUU-VIII/2010 about the status of children outside of marriage. The decision stated that childrens born outside of marriage not only had a civil relationship with their mother and mother's family but also had a civil relationship with their biological father. Its implicates that children outside of marriage have the same rights with legal children, such as  earning a living, inheritance and equality before the law. Seen from the concept of maqâṣid asy-syarî'ah, the decision does not violate the Islamic law, otherwhise it is in the line with the principles of maqâṣid asy-syarî'ah especially the principles of ḥifẓ an-nasl and ḥifẓ an-nafs.   [Mahkamah Konstitusi telah membuat putusan revolusioner dalam putusan MK Nomor 46/PUU-VIII/2010 tentang status anak di luar perkawinan. Putusan tersebut menyatakan bahwa anak yang dilahirkan di luar perkawinan mempunyai hubungan perdata dengan ibu dan keluarga ibunya dan mempunyai hubungan perdata dengan ayah biologisnya yang dibuktikan berdasarkan ilmu pengetahuan dan teknologi. Implikasinya adalah anak di luar perkawinan mendapat hak sama dengan anak sah, mendapatkan nafkah, waris dan persamaan di hadapan hukum. Dilihat dari konsep maqâṣid asy-syarî’ah, putusan tersebut tidak melanggar hukum Islam, sebaliknya, ia sejalan dengan prinsip-prinsip maqâṣid asy-syarî’ah terutama prinsip ḥifẓ an-nasl dan ḥifẓ an-nafs.

  14. Iconoclasmo e iconodulia entre oriente y occidente (siglos VIII-IX Iconoclasm and iconoduly between east and west (8th-9th centuries

    Directory of Open Access Journals (Sweden)

    Alfonso Hernández Rodríguez

    2011-10-01

    Full Text Available El siguiente artículo trata acerca de la recepción en el occidente carolingio de la crisis iconoclasta. Reflexiona sobre la forma en que ambas cristiandades trataron el problema que las imágenes representan para las prácticas religiosas y las consecuencias políticas del culto de los iconos. El escrito afirma también que durante los siglos VIII y IX la crisis iconoclasta permitió la aparición de una tradición cristiana latina consciente de sí misma. Por lo tanto, se trató del momento que puso en evidencia el nacimiento de dos formas divergentes de piedad cristiana y la alienación de una respecto de la otra. La cristiandad occidental centrada en el edificio eclesiástico y que privilegiaba la ubicación de lo sagrado en el rito eucarístico, y la oriental cuyo centro era la adoración de las imágenes, con la consecuente multiplicación de los espacios sagrados.The following paper deals with the reception in the Carolingian west of the Byzantine Iconoclast Crisis. It considers the way both Christianities dealed with the problem that images presented to religious practices and the political consequences of iconic worship. The paper also states that during the VIII and IX centuries the iconoclast crisis allowed the emergence of a self conscious Latin Christian tradition. Consequently it was the moment that showed the beginning of two differing ways of Christian piety and the alienation of one towards the other. Western Christianity focused its religion practice in church building and the idea of Sacrality in the Eucharistic Rite. The oriental church, moreovers, centered its practices and theology on icon worship.

  15. Experiences in the instrumentation of power generators with the on-line analysis of generators AnGel system, for the internal insulation condition diagnosis; Experiencias en la instrumentacion de generadores de potencia con el sistema de analisis de generadores en linea AnGeL, para el diagnostico del estado del aislamiento interno

    Energy Technology Data Exchange (ETDEWEB)

    Carrillo C, Jaime; Ramirez N, Jose T. [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2009-07-01

    The instrumentation of power generators with monitoring systems on-line, allows the personnel responsible for its operation to determine the stator and rotor windings insulation condition, as well as to emit an opportune diagnosis of possible anomalies, to implant programs of predictive maintenance, to reduce costs and to increase its reliability. The experiences of the last five years in the commissioning of the AnGel System; the problematic to which these equipment is subjected to, is described within the intrinsic atmosphere of the area where they are installed in the turbo-generators and hydro-generators, and finally, the experiences in the commissioning of the monitoring systems are revised and analyzed. [Spanish] La instrumentacion de los generadores de potencia con sistemas de monitoreo en linea, permite al personal responsable de su operacion determinar el estado del aislamiento de los devanados del estator y rotor, asi como emitir un diagnostico oportuno de posibles anomalias, implantar programas de mantenimiento predictivo, reducir costos e incrementar su confiabilidad. Se presentan las experiencias de los ultimos cinco anos en la puesta en operacion del Sistema AnGeL; se describe la problematica a la que son sometidos estos equipos dentro del ambiente intrinseco del area donde se instalan en los turbogeneradores e hidrogeneradores, y por ultimo, se analizan y discuten las experiencias en la puesta en servicio de los sistemas de monitoreo.

  16. Obtenção e caracterização de anticorpo monoclonal murino anti-fator VIII da coagulação sangüínea Attainment and characterization of murine monoclonal anti-factor VIII antibodies

    Directory of Open Access Journals (Sweden)

    Rosana Rossi-Ferreira

    2006-06-01

    Full Text Available Entre os avanços da engenharia celular e biotecnologia nas últimas décadas, destaca-se a produção de anticorpos monoclonais murinos (AcMm utilizados no aprimoramento diagnóstico nas rotinas laboratoriais. A produção de fator VIII de alta pureza sempre foi o desejo e a preocupação das indústrias de hemoderivados para tratamento de pacientes portadores de hemofilia A, porém este produto inexiste no Brasil, sendo necessária sua obtenção no mercado internacional a custos elevados. O trabalho tem por objetivo a produção de AcMm anti-fator VIII humano (FVIII H através da expansão dos clones e caracterização imunoquímica do anticorpo. Camundongos Balb/c foram imunizados com FVIII H purificado como também proveniente de crioprecipitado e as células esplênicas dos animais foram fusionadas com células mielomatosas murinas segundo o método descrito por Kohler e Milstein para produção de híbridos em cultura. Foram testados 1.983 híbridos dos quais 105 foram submetidos à clonagem. Destes, 39 obtiveram monoclonalidade e 7 destes clones foram caracterizados através de técnicas de immunoblotting. Foram submetidas à purificação por cromatografia três imunoglobulinas de diferentes classes pertencentes aos clones LAMB1-10A1A4, LAMB1-17A1A1 e LAMB1-24A2A1. A imunoglobulina purificada pertencente ao clone LAMB1-10A1A4 foi adsorvida em coluna de imunoafinidade para purificação de concentrado de FVIII proveniente de crioprecipitado plasmático.Among the advances in cellular engineering and biotechnology over the last decades, the production of murine monoclonal antibodies (AcMm, used to improve laboratory diagnoses, stands out. The production of very pure factor VIII has always been a concern of suppliers of blood products to treat patients with hemophilia A and this product is still not produced in Brazil. Hence, it can only be attained on the international market at a high cost. The aim of this work was to produce AcMm anti

  17. Diagnostic and prognostic value of factor VIII binding antibodies in acquired hemophilia A: data from the GTH-AH 01/2010 study.

    Science.gov (United States)

    Werwitzke, S; Geisen, U; Nowak-Göttl, U; Eichler, H; Stephan, B; Scholz, U; Holstein, K; Klamroth, R; Knöbl, P; Huth-Kühne, A; Bomke, B; Tiede, A

    2016-05-01

    Essentials Factor VIII (FVIII) binding IgG detected by ELISA could be an alternative to the Bethesda assay. We studied the performance of anti-FVIII IgG ELISA in patients with acquired hemophilia and controls. Anti-FVIII IgG > 99th percentile of controls was highly sensitive and specific. Patients with high anti-FVIII IgG have a lower chance of achieving remission. Background Acquired hemophilia A is a severe bleeding disorder that requires fast and accurate diagnosis as it occurs often unexpectedly in previously healthy men and women of every age. The Nijmegen-modified Bethesda assay is the diagnostic reference standard for detecting neutralizing autoantibodies against factor VIII (FVIII), but is not widely available, not ideal for quantifying the complex type 2 inhibitors seen in acquired hemophilia, and suffers from high inter-laboratory variability. Objectives To assess the diagnostic and prognostic value of FVIII-binding antibodies as detected by ELISA compared with the Nijmegen Bethesda assay. Methods Samples from the time of first diagnosis and clinical data were available from 102 patients with acquired hemophilia enrolled in the prospective GTH-AH 01/2010 study. Controls (n = 102) were matched for gender and age. Diagnostic cut-offs were determined by receiver-operator curve analysis. The prognostic value was assessed in 92 of the 102 patients by Cox regression analysis of time to partial remission. Results Anti-FVIII IgG above the 99th percentile (> 15 arbitrary units per mL) revealed high sensitivity and specificity (both 0.99; 95% confidence interval, 0.95-1.0) for diagnosing acquired hemophilia. The likelihood of achieving partial remission was related to anti-FVIII IgG concentration ( 1050, 0.39). The Bethesda titer was only associated with the likelihood of partial remission when analyzed in the central laboratory, but not when data from local GTH study sites were used. Conclusion Although the Nijmegen-modified Bethesda assay is the reference

  18. A representação do espaço na "Odisseia":definindo isotopias, heterotopias e utopias na Grécia antiga (séc. X-VIII a.c.)

    OpenAIRE

    GABRECHT, A. P.

    2014-01-01

    A Idade do Ferro antiga (XII-VIII a.C.), na Grécia continental, configurou-se como um momento em que as comunidades estão saindo de um processo de isolamento. Após a destruição dos palácios micênicos uma série de eventos simultâneos ocorridos na virada do século XIII para o XII a.C., o mundo grego mergulha num período de aproximadamente quatro séculos entre o XII e o VIII a.C. , em que ocorre uma acentuada redução da produção material e do crescimento demográfico. Nesse momento, há tamb...

  19. Eksperimentasi Model Pembelajaran Kooperatif Tipe Pairs Check (Pc), Think Pair Share (Tps), dan Problem Based Learning (Pbl) pada Materi Kubus dan Balok Ditinjau dari Gaya Belajar Siswa Kelas VIII SMP Negeri Se-kota Surakarta

    OpenAIRE

    Irawati, Suci; Budiyono, Budiyono; Slamet, Isnandar

    2015-01-01

    This study aimed at determining the effect of learning models on the learning achievement in Mathematics viewed from the students' Learning Style. The learning models compared were learning model Pairs Check (PC), Think Pair Share (TPS) and Problem Based Learning (PBL). This research was a quasi-experimental research with 3×3 factorial design. The population of research was all grade VIII students of Junior High School (SMP) in Surakarta. The samples were chosen by using stratified cluster ra...

  20. Eksperimentasi Model Pembelajaran Problem Based Learning (Pbl) dengan Mind Mapping Ditinjau dari Gaya Belajar pada Materi Operasi Aljabar Siswa Kelas VIII SMP Negeri di Kabupaten Sragen Tahun Pelajaran 2014/2015

    OpenAIRE

    Primasari, Dessy Marlinda; Mardiyana, Mardiyana; Sari Saputro, Dewi Retno

    2016-01-01

    The aim of this research was to know the effect of learning models on mathematics achievement viewed from the student learning style. The learning models compared were PBL with Mind Mapping, PBL and Classical learning. This research was a quasi experimental with the factorial design of 3 x 3. The population of this research was all students of class VIII of the State Junior High School in the region of Sragen Regency. The sampling technique used was stratified cluster random sampling. The si...

  1. Mapping Henry: Synchrotron-sourced X-ray fluorescence mapping and ultra-high-definition scanning of an early Tudor portrait of Henry VIII

    Science.gov (United States)

    Dredge, Paula; Ives, Simon; Howard, Daryl L.; Spiers, Kathryn M.; Yip, Andrew; Kenderdine, Sarah

    2015-11-01

    A portrait of Henry VIII on oak panel c. 1535 has recently undergone technical examination to inform questions regarding authorship and the painting's relationship to a group of similar works in the collections of the National Portrait Gallery, London, and the Society of Antiquaries. Due to previous conservation treatments of the painting, the conventional transmission X-radiograph image was difficult to interpret. As a result, the painting underwent high-definition X-ray fluorescence (XRF) elemental mapping on the X-ray fluorescence microscopy beamline of the Australian Synchrotron. Scans were conducted at 12.6 and 18.5 keV, below and above the lead (Pb) L edges, respectively. Typical scan parameters were 120 μm pixel size at 7 ms dwell time, with the largest scan covering an area 545 × 287 mm2 collected in 23 h (10.8 MP). XRF mapping of the panel has guided the conservation treatment of the painting and the revelation of previously obscured features. It has also provided insight into the process of making of the painting. The informative and detailed elemental maps, alongside ultra-high-definition scans of the painting undertaken before and after varnish and over-paint removal, have assisted in comparison of the finely painted details with the London paintings. The resolution offered by the combination of imaging techniques identifies pigment distribution at an extremely fine scale, enabling a new understanding of the artist's paint application.

  2. Study on coordination numbers six and seven in V(III) complexes with aquo, cyanide and aminopolycarboxylic ligands by means of the angular overlap model

    Science.gov (United States)

    Schönherr, Thomas; Schmid, Volker; Meier, Roland

    1998-09-01

    Peculiarities due to six- and seven-coordination in V(III) complexes are investigated within the framework of the angular overlap model (AOM). Calculations of orbital schemes and d- d transitions are performed for complexes with aquo, cyanide and aminopolycarboxylic ligands. The competing influence of electronic and geometric effects on the energy level pattern is discussed in view of the derived AOM parameters. A characteristic feature of seven-coordination is the large splitting of the 3T 1g ground state (in O h notation) that leads to typical absorptions in the near-infrared ([V(edta)H 2O)] -), (edta, ethylenediaminetetraacetate) or visible ([V(CN) 7] 4-) spectral region which can be used in particular to distinguish between both coordination numbers in solution spectra. In the pentagonal-bipyramidal [V(CN) 7] 4- complex there is an unexpectedly high covalency in the σ-interactions with the axial ligands that conflicts a meaningful parametrization within the ligand field approach.

  3. Temperature dependence of the minimum V/III ratio for the growth of In xGa 1-xAs

    Science.gov (United States)

    Riechert, H.; Averbeck, R.; Bernklau, D.

    1993-02-01

    We have quantitatively determined the minimum V/III ratios for the growth of In xGa 1- xAs ( x = 0, 0.1, 0.2 and 0.53) on GaAs and InP. Minimum As 4 fluxes were measured for a wide range of growth temperatures using a transition of the surface reconstruction. Their temperature dependence can be fitted very well by thetypical curve for thermally activated behavior. We find that the basic reaction kinetics of As 4 with In xGa 1- xAs are the same as with GaAs. The activation energies for As desorption from In xGa 1- xAs and GaAs are found to be similar (1.9 and 2.1 eV, respectively) but the rates of As- In xGa 1- xAs. This may be seen as evidence for a less effective dissociative reaction of As 4 with In than with Ga.

  4. LEGISLASI MAHKAMAH KONSTITUSI DALAM PUTUSAN MAHKAMAH KONSTITUSI NOMOR: 46/PUU-VIII/2010 DITINJAU DARI TEORI HUKUM HANS KELSEN TENTANG KONSTITUSI

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    Subroto Subroto

    2014-12-01

    Full Text Available ABSTRAK: Legeslasi kewenangan Mahkamah Konstitusi (disingkat MK adalah sebagai berikut : (1 menguji undang-undang terhadap UUD NRI Th.1945; (2 memutus sengketa kewenangan lembaga Negara yang kewenangannya diberikan oleh UUD NRI Th.1945; (3 memutus pembubaran partai politik; dan (4 memutus perselisihan tentang hasil pemilihan umum. Dari legislasi MK tersebut, penulis tertarik untuk melihat sejauh mana legislasi MK dalam membuat suatu putusan berdasarkan teori hukum yang dikemukakan oleh Hans Kelsen, mengenai konstitusi. Pemikiran Kelsen, mendorong dibentuknya suatu lembaga yang diberi nama Verfassungsgerichtshoft atau MK (Constitutional Court yang berdiri sendiri di luar Mahkamah Agung, sering disebut The Kelsenian Model. Adanya putusan MK No. 46/PUU-VIII/2010, merupakan suatu produk hukum yang dikeluarkan oleh Mahkamah Konstitusi. Dari putusan tersebut, akan dianalisis berkaitan dengan dasar hukum dan pertimbangan hukum yang digunakan MK dalam memutus perkara telah sesuai dengan teori hukum yang dikemukakan oleh Hans Kelsen dalam teori konstitusinya atau belum dan tentang legislasi MK dalam membuat putusan tersebut berdasarkan teori hukum Hans Kelsan. Kata kunci : konstitusi, Hans Kelsen,

  5. Mapping Henry: Synchrotron-sourced X-ray fluorescence mapping and ultra-high-definition scanning of an early Tudor portrait of Henry VIII

    Energy Technology Data Exchange (ETDEWEB)

    Dredge, Paula; Ives, Simon [Art Gallery of New South Wales (AGNSW), Sydney, NSW (Australia); Howard, Daryl L.; Spiers, Kathryn M. [Australian Synchrotron, Clayton, VIC (Australia); Yip, Andrew [Art Gallery of New South Wales (AGNSW), Sydney, NSW (Australia); University of New South Wales, Laboratory for Innovation in Galleries, Libraries, Archives and Museums (iGLAM), National Institute for Experimental Arts, Sydney, NSW (Australia); Kenderdine, Sarah [University of New South Wales, Laboratory for Innovation in Galleries, Libraries, Archives and Museums (iGLAM), National Institute for Experimental Arts, Sydney, NSW (Australia)

    2015-11-15

    A portrait of Henry VIII on oak panel c. 1535 has recently undergone technical examination to inform questions regarding authorship and the painting's relationship to a group of similar works in the collections of the National Portrait Gallery, London, and the Society of Antiquaries. Due to previous conservation treatments of the painting, the conventional transmission X-radiograph image was difficult to interpret. As a result, the painting underwent high-definition X-ray fluorescence (XRF) elemental mapping on the X-ray fluorescence microscopy beamline of the Australian Synchrotron. Scans were conducted at 12.6 and 18.5 keV, below and above the lead (Pb) L edges, respectively. Typical scan parameters were 120 μm pixel size at 7 ms dwell time, with the largest scan covering an area 545 x 287 mm{sup 2} collected in 23 h (10.8 MP). XRF mapping of the panel has guided the conservation treatment of the painting and the revelation of previously obscured features. It has also provided insight into the process of making of the painting. The informative and detailed elemental maps, alongside ultra-high-definition scans of the painting undertaken before and after varnish and over-paint removal, have assisted in comparison of the finely painted details with the London paintings. The resolution offered by the combination of imaging techniques identifies pigment distribution at an extremely fine scale, enabling a new understanding of the artist's paint application. (orig.)

  6. PENGGUNAAN METODE PROBLEM SOLVING UNTUK MENINGKATKAN PRESTASI BELAJAR SISWA PADA PELAJARAN MATEMATIKA TENTANG LINGKARAN DI KELAS VIII A SMPN 11 MADIUN TAHUN PELAJARAN 2015/2016

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    Dwi Ratnasari Dewi

    2016-09-01

    Full Text Available Research carried out by two cycles, in which the first cycle of students working on quiz questions given by the teacher. Students noted the difficulties experienced while working on quiz questions received. Teachers and students discuss the material they are having trouble students. While in the second cycle, there is an additional action, the students were asked to present the quiz questions that come in front of the class. Students expressed difficulty verbally, another friend who helped work on the class. The results of the study before the first cycle, the first cycle and the second cycle increased. From the test results obtained by the average value of the first cycle = 68,75. Cycle II, = 87,75. Level classical completeness of each cycle rises of 48% and in the second cycle be 90,625%. Observation of learning activities more alive with many questions asked by the students.The conclusion of this study is the use of problem solving methods can increase student achievement in math on the circle A class VIII SMPN 11 Madiun in academic year 2015/2016.

  7. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  8. [Molecular identification of aminoglycoside-modifying enzymes among strains of Enterococcus spp. isolated in hospitals of the VIII Region of Chile].

    Science.gov (United States)

    Sepúlveda, Marcela A; Bello, Helia T; Domínguez, Mariana Y; Mella, Sergio M; Zemelman, Raúl Z; González, Gerardo R

    2007-05-01

    Infectious diseases produced by Enterococcus spp, must be treated with a synergistic combination between a penicillin and an aminoglycoside. High level resistance to aminoglycosides is a serious therapeutic problem, since it predicts the loss of synergistic activity of this antimicrobial combination. To investigate the presence of genes encoding aminoglycoside-modifying enzymes (AMEs) among strains of Enterococcus spp with high level of resistance to aminoglycosides. The genes encoding some of the AMEs were investigated among 305 aminoglycoside-resistant strains of Enterococcus spp isolated in hospitals of the VIII region of Chile, by dot blot hybridization and Polymerase Chain Reaction (PCS). High level resistance to some aminoglycosides was observed in 104 strains (34.1 %) and 93 of these harbored at least one of the genes encoding the investigated AMEs. Three genes were detected: aac(6)Ie-aph(2")Ia (14.8%) encoding for the enzyme AAC(6)Ie-APH(2")Ia (resistance to all aminoglycosides, except streptomycin); aph(3)IIIa (26%), and ant(6)la (28.5%) encoding for the phosphorylating enzymes APH(3)Ilia (resistance to kanamycin, amikacin and neomycin), and ANT(6)-la (resistance only to streptomycin), respectively. None of the strains harbored the gene ant (4) which encode for the enzyme ANT (4). The low frequency of strains harbouring the bifunctional enzyme (<15%), conferring an extended resistance profile to aminoglycosides, allows us to propose the empirical use of aminoglycoside-aminocyclitols, associated to a penicillin, in the treatment of serious infections produced by species of enterococci.

  9. Terminations VI and VIII (∼ 530 and ∼ 720 kyr BP tell us the importance of obliquity and precession in the triggering of deglaciations

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    D. Paillard

    2012-12-01

    Full Text Available The main variations of ice volume of the last million years can be explained from orbital parameters by assuming climate oscillates between two states: glaciations and deglaciations (Parrenin and Paillard, 2003; Imbrie et al., 2011 (or terminations. An additional combination of ice volume and orbital parameters seems to form the trigger of a deglaciation, while only orbital parameters seem to play a role in the triggering of glaciations. Here we present an optimized conceptual model which realistically reproduce ice volume variations during the past million years and in particular the timing of the 11 canonical terminations. We show that our model looses sensitivity to initial conditions only after ∼200 kyr at maximum: the ice volume observations form a strong attractor. Both obliquity and precession seem necessary to reproduce all 11 terminations and both seem to play approximately the same role. More precisely, obliquity plays a fundamental role in the triggering of termination VI (~530 kyr BP, while precession plays a fundamental role in the triggering of termination VIII (~720 kyr ago.

  10. Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A mice.

    Science.gov (United States)

    Peng, Baowei; Ye, Peiqing; Blazar, Bruce R; Freeman, Gordon J; Rawlings, David J; Ochs, Hans D; Miao, Carol H

    2008-09-01

    Formation of inhibitory antibodies is a common problem encountered in clinical treatment for hemophilia. Human factor VIII (hFVIII) plasmid gene therapy in hemophilia A mice also leads to strong humoral responses. We demonstrate that short-term therapy with an anti-ICOS monoclonal antibody to transiently block the inducible costimulator/inducible costimulator ligand (ICOS/ICOSL) signaling pathway led to sustained tolerance to hFVIII in hFVIII plasmid-treated hemophilia A mice and allowed persistent, high-level FVIII functional activity (100%-300% of normal). Anti-ICOS treatment resulted in depletion of ICOS(+)CD4(+) T cells and activation of CD25(+)Foxp3(+) Tregs in the peripheral blood, spleen, and lymph nodes. CD4(+) T cells from anti-ICOS-treated mice did not proliferate in response to hFVIII stimulation and produced high levels of regulatory cytokines, including interleukin-10 and transforming growth factor-beta. Moreover, CD4(+)CD25(+) Tregs from tolerized mice adoptively transferred dominant tolerance in syngeneic hFVIII plasmid-treated hemophilia A mice and reduced the production of antibodies against FVIII. Anti-ICOS-treated mice tolerized to hFVIII generated normal primary and secondary antibody responses after immunization with the T-dependent antigen, bacteriophage Phix 174, indicating maintenance of immune competency. Our data indicate that transient anti-ICOS monoclonal antibody treatment represents a novel single-agent immunomodulatory strategy to overcome the immune responses against transgene product after gene therapy.

  11. Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A.

    Science.gov (United States)

    Matsui, Hideto; Fujimoto, Naoko; Sasakawa, Noriko; Ohinata, Yasuhide; Shima, Midori; Yamanaka, Shinya; Sugimoto, Mitsuhiko; Hotta, Akitsu

    2014-01-01

    Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII) cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.

  12. Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A.

    Directory of Open Access Journals (Sweden)

    Hideto Matsui

    Full Text Available Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.

  13. Endogenous factor VIII synthesis from the intron 22-inverted F8 locus may modulate the immunogenicity of replacement therapy for hemophilia A.

    Science.gov (United States)

    Pandey, Gouri Shankar; Yanover, Chen; Miller-Jenkins, Lisa M; Garfield, Susan; Cole, Shelley A; Curran, Joanne E; Moses, Eric K; Rydz, Natalia; Simhadri, Vijaya; Kimchi-Sarfaty, Chava; Lillicrap, David; Viel, Kevin R; Przytycka, Teresa M; Pierce, Glenn F; Howard, Tom E; Sauna, Zuben E

    2013-10-01

    Neutralizing antibodies (inhibitors) to replacement factor VIII (FVIII, either plasma derived or recombinant) impair the effective management of hemophilia A. Individuals with hemophilia A due to major deletions of the FVIII gene (F8) lack antigenically cross-reactive material in their plasma ("CRM-negative"), and the prevalence of inhibitors in these individuals may be as high as 90%. Conversely, individuals with hemophilia A caused by F8 missense mutations are CRM-positive, and their overall prevalence of inhibitors is hemophilia A) have been grouped with the former on the basis of their genetic defect and CRM-negative status. However, only ∼20% of these individuals develop inhibitors. Here we demonstrate that the levels of F8 mRNA and intracellular FVIII protein in B lymphoblastoid cells and liver biopsies from individuals with the intron 22 inversion are comparable to those in healthy controls. These results support the hypothesis that most individuals with the intron 22 inversion are tolerized to FVIII and thus do not develop inhibitors. Furthermore, we developed a new pharmacogenetic algorithm that permits the stratification of inhibitor risk for individuals and subpopulations by predicting the immunogenicity of replacement FVIII using, as input, the number of putative T cell epitopes in the infused protein and the competence of major histocompatibility complex class II molecules to present such epitopes. This algorithm showed statistically significant accuracy in predicting the presence of inhibitors in 25 unrelated individuals with the intron 22 inversion.

  14. Use of affinity-directed liquid chromatography-mass spectrometry to map the epitopes of a factor VIII inhibitor antibody fraction.

    Science.gov (United States)

    Griffiths, A E; Wang, W; Hagen, F K; Fay, P J

    2011-08-01

    Neutralizing factor (F) VIII antibodies develop in approximately 30% of individuals with hemophilia A and show specificity to multiple sites in the FVIII protein. Reactive epitopes to an immobilized IgG fraction prepared from a high-titer, FVIII inhibitor plasma were determined after immuno-precipitation (IP) of tryptic and chymotryptic peptides derived from digests of the A1 and A2 subunits of FVIIIa and FVIII light chain. Peptides were detected and identified using highly sensitive liquid chromatography-mass spectrometry (LC-MS). Coverage maps of the A1 subunit, A2 subunit and light chain represented 79%, 69% and 90%, respectively, of the protein sequences. Dot blots indicated that the inhibitor IgG reacted with epitopes contained within each subunit of FVIIIa. IP coupled with LC-MS identified 19 peptides representing epitopes from all FVIII A and C domains. The majority of peptides (10) were derived from the A2 domain. Three peptides mapped to the C2 domain, while two mapped to the A1 and A3 domains, and single peptides mapped to the a1 segment and C1 domain. Epitopes were typically defined by peptide sequences of < 12 residues. IP coupled with LC-MS identified extensive antibody reactivity at high resolution over the entire functional FVIII molecule and yielded sequence lengths of < 15 residues. A number of the peptides identified mapped to known sequences involved in functionally important protein-protein and protein-membrane interactions. © 2011 International Society on Thrombosis and Haemostasis.

  15. ASME Section VIII Recertification of a 33,000 Gallon Vacuum-jacketed LH2 Storage Vessel for Densified Hydrogen Testing at NASA Kennedy Space Center

    Science.gov (United States)

    Swanger, Adam M.; Notardonato, William U.; Jumper, Kevin M.

    2015-01-01

    The Ground Operations Demonstration Unit for Liquid Hydrogen (GODU-LH2) has been developed at NASA Kennedy Space Center in Florida. GODU-LH2 has three main objectives: zero-loss storage and transfer, liquefaction, and densification of liquid hydrogen. A cryogenic refrigerator has been integrated into an existing, previously certified, 33,000 gallon vacuum-jacketed storage vessel built by Minnesota Valley Engineering in 1991 for the Titan program. The dewar has an inner diameter of 9.5 and a length of 71.5; original design temperature and pressure ranges are -423 F to 100 F and 0 to 95 psig respectively. During densification operations the liquid temperature will be decreased below the normal boiling point by the refrigerator, and consequently the pressure inside the inner vessel will be sub-atmospheric. These new operational conditions rendered the original certification invalid, so an effort was undertaken to recertify the tank to the new pressure and temperature requirements (-12.7 to 95 psig and -433 F to 100 F respectively) per ASME Boiler and Pressure Vessel Code, Section VIII, Division 1. This paper will discuss the unique design, analysis and implementation issues encountered during the vessel recertification process.

  16. Quality assessment of the mammographic screening programme in the 'Azienda Sanitaria Locale Provincia Milano' 1 - Analysis of interval cancers and discussion of possible causes of diagnostic error; Controllo di qualita' del programma screening mammografico nella Azienda Sanitaria Locale Provincia Milano 1 - Analisi dei carcinomi di intervallo e discussione delle possibili cause di errore diagnostico

    Energy Technology Data Exchange (ETDEWEB)

    Burani, Rossella; Maggioni, Carlo; Pirola, Maria Elena [Azienda Sanitaria Locale Provincia Milano 1, Milano, (Italy); Caimi, Francesco; Marinoni, Guia [Azienda Ospedaliera Ospedali Civili, Legnano (Italy); Pellizzoni, Romana; Villa, Roberto [Azienda Ospedaliera Salvini, Garbignate Milanese (Italy); Ciatto, Stefano [Centro per lo Studio e la Prevenzione Oncologica, Firenze (Italy)

    2005-03-01

    classificato 20 carcinomi come occulti (52,6%) mentre la presenza di segni minimi o errore di screening e' stata segnalata rispettivamente in 2 (5,2%) e 16 (42,1%) casi: un sospetto diagnostico era stato effettivamente originariamente formulato in 7 su 16 casi classificati come errori di screening, ma l'approfondimento diagnostico successivo non era stato in grado di diagnosticare il CI. Conclusioni: Il tasso proporzionale di CI risulta piu' elevato di quanto riscontrato in letteratura e comunemente raccomandato (<30% nel primo, <50% nel secondo anno dell'intervallo). L'analisi delle cause di errore rivela un eccesso di errori diagnostici rispetto a quanto raccomandato (<20% dei CI rivalutati come errori di screening), ma anche una certa frequenza di CI (7/38=18,4%) effettivamente positivi allo screening, ma misconosciuti all'approfondimento diagnostico. Complessivamente l'analisi rivela una ridotta sensibilita' del programma di screening, analogamente a quanto riscontrato in altri programmi di screening territoriali, che mostrano una performance inferiore ai centri di eccellenza, e suggerisce comunque l'introduzione di correttivi per migliorare l'accuratezza diagnostica. L'analisi e la revisione critica dei CI e' un indicatore precoce di efficacia dello screening mammografico ancora poco utilizzato nei programmi di screening in Italia. L'uso delle SDO, ancorche' affetto da limitate possibilita' di errore, e' vantaggioso perche' fornisce dati piu' precocemente rispetto ai registri tumori ed e' la fonte di informazione piu' attendibile ove questi ultimi non esistono: questa metodologia potrebbe essere applicata nei programmi di screening.

  17. Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 2. Resposta humoral tissular

    Directory of Open Access Journals (Sweden)

    Albino Verçosa de Magalhães

    1986-10-01

    Full Text Available Os A.A. analisaram a resposta humoral nas lesões de 90 pacientes de Leishmaniose Tegumentar — causada por Leishmania braziliensis brasiliensis —, utilizando o método da imunoperoxidase para identificar nos tecidos a presença de IgA, IgG, IgM, fração C3 do complemento e fibrina. Constataram a presença de IgA, IgC e IgM nos plasmócitos tissulares, com predomínio de IgG. Admitiram aue a passagem dessas imunoglobulinas para os tecidos possibilitando a opsonização do parasites e/ou de seus antígenos, permitiria a ocorrência de fenômenos necróticos que representam um dos mecanismos eficazes de redução da carga parasitária. Efetivamente, nas áreas de necrose e nas paredes dos vasos inflamados identificaram depósito de imunoglobulinas, fração C3 do complemento e fibrina — elementos do hospedeiro que fazem parte dos imunocomplexos. Interpretaram essa necrose tissular como o resultado da ação de imunocomplexos na região de equivalência ou com discreto excesso de antígenos ítipos ABTHTJS. A presença de antígenos parasitários, expressos nas membranas dos macrófagos quando em contato com imunoglobulinas tissulares, na fase inicial da lesão, possibilitaria a instalação de uma reação antígeno-anticorpo, a qual explicaria o aparecimento da necrose na Leishmaniose Tegumentar.

  18. HISTOPATOLOGIA DE LA INFECCIÓN EXPERIMENTAL DE OVEJAS SIN LANA Ovis aries POR Neospora caninum

    Directory of Open Access Journals (Sweden)

    Teresa Oviedo

    2003-01-01

    Full Text Available Ovejas sin lana en diferentes estados reproductivos fueron inoculadas por vía intravenosa con taquizoítos deN. caninum muestra «NC-beef» con el fin de estudiar la patofisiología de la enfermedad en estos animales yverificar la posibilidad de ser usados como modelo experimental de neosporosis bovina. Se utilizaron cincoovejas gestantes (una con 15 días, dos con 30 días, dos con 90 días, tres no gestantes y dos con 10 díasposparto. Los animales eran serologicamente negativos para N.caninum y T. gondii. Dos ovejas gestantes, noinoculadas, fueron utilizadas como control negativo. Los corderos necropsiados, nacidos de ovejas inoculadasantes o durante la gestación presentaron alteraciones histopatológicas en diferentes tejidos, siendo las masseveras observadas en el sistema nervioso central, caracterizadas por la presencia de formas quísticas delparásito asociadas con infiltrado inflamatorio predominantemente mononuclear, áreas de necrosis y en algunoscasos presencia de calcificación. Los corderos nacidos de ovejas inoculadas 10 días después del parto nopresentaron signos clínicos de la enfermedad ni anticuerpos contra o parásito y a la necropsia no presentaronlesiones en ninguno de los tejidos analizados. Un cordero nacido de oveja no inoculada no presentó alteracionesmicroscópicas en ninguno de los tejidos analizados

  19. Lesões pouco usuais na histopatologia experimental de arbovirus amazônicos

    Directory of Open Access Journals (Sweden)

    Leonidas Braga Dias

    1972-06-01

    Full Text Available São descritas as alterações histopatológicas observadas em camundongos infectados experimentalmente com os arbovirus Mucambo, EEE e Cocal. O virus Mucambo determinou lesões renais; o EEE demonstrou especial mesenquimotropismo; o virus Cocal lesões de topografia seletiva subependimária.

  20. Matching-adjusted indirect comparisons of efficacy of BAY 81-8973 vs two recombinant factor VIII for the prophylactic treatment of severe hemophilia A

    Directory of Open Access Journals (Sweden)

    Pocoski J

    2016-07-01

    Full Text Available Jennifer Pocoski,1 Nanxin Li,2 Rajeev Ayyagari,2 Nikki Church,1 Monika Maas Enriquez,1 Quer Xiang,2 Sneha Kelkar,3 Ella X Du,2 Eric Q Wu,2 Jipan Xie3 1Bayer HealthCare Pharmaceuticals, Whippany, NJ, 2Analysis Group, Inc., Boston, MA, 3Analysis Group, Inc., New York, NY, USA Background: No head-to-head trials comparing recombinant factor VIII (rFVIII products currently exist. This was a matching-adjusted indirect comparison (MAIC study of efficacy of BAY 81-8973 with antihemophilic factor (recombinant plasma/albumin-free method (rAHF-PFM and turoctocog alfa for the prophylaxis of severe hemophilia A. Methods: A systematic literature review was conducted to identify trials of rAHF-PFM and turoctocog alfa. Comparisons were conducted using BAY 81-8973 individual patient data (IPD from LEOPOLD trials and published data from rAHF-PFM and turoctocog alfa trials. Differences in outcome reporting were reconciled using transformation of BAY 81-8973 IPD. Patients in pooled LEOPOLD trials were weighted to match baseline characteristics for rAHF-PFM or turoctocog alfa trials using MAICs. After matching, annualized bleed rates (ABRs were compared using weighted t-tests. Results: Two rAHF-PFM trials and one turoctocog alfa trial were identified. In these trials, rFVIIIs were dosed thrice weekly or every other day; in LEOPOLD trials, BAY 81-8973 was dosed twice- or thrice weekly. Three MAICs were conducted because the two rAHF-PFM trials calculated ABRs differently, matching for age, race, and weight (turoctocog alfa only. BAY 81-8973 had similar ABR of all bleeds vs rAHF-PFM (two trials: 4.8 vs 6.3, 1.9 vs 1.8 [square root transform] and lower ABR of spontaneous bleeds and trauma bleeds (2.6 vs 4.1, 2.1 vs 4.7; both P<0.05. BAY 81-8973 showed lower ABR of all bleeds and spontaneous bleeds vs turoctocog alfa (4.3 vs 6.5, 2.8 vs 4.3; both P<0.05 and similar ABR of trauma bleeds (1.5 vs 1.6. In subgroup analysis, twice-weekly BAY 81-8973 had similar ABRs of all

  1. Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data.

    Science.gov (United States)

    Kouides, Peter; Wawra-Hehenberger, Kathrin; Sajan, Anna; Mead, Henry; Simon, Toby

    2017-10-01

    Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). We analyzed the safety of Humate-P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient-years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate-P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate-P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate-P. Reported results of company-sponsored studies showed a low incidence of adverse events possibly or probably related to Humate-P. More than 33 years of pharmacovigilance data continue to support the safety of Humate-P. © 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  2. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-04

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism.

  3. Factor VIII genotype characterization of haemophilia A affected patients with transient and permanent inhibitors: a comprehensive Argentine study of inhibitor risks.

    Science.gov (United States)

    Rossetti, L C; Szurkalo, I; Radic, C P; Abelleyro, M M; Primiani, L; Neme, D; Candela, M; Bianco, R P; de Tezanos Pinto, M; Larripa, I B; De Brasi, C D

    2013-07-01

    Inhibitor development against exogenous factor VIII is a severe impairment of replacement therapy affecting 18% of Argentine patients with severe haemophilia A (HA). To study the molecular predisposition for inhibitor development, we genotyped 260 HA patients with and without inhibitors, countrywide. The inhibitor-positive population (19 transients, 15 low responders, LR and 70 high responders, HR) of 104 severe-HA patients showed 59 Inv22 (intron 22 inversions), 18 small ins/del-frameshifts, 12 gross deletions, 12 nonsense, one splicing defect and two missense, p.Arg531Pro and p.Leu575Pro, both LR and thought to impair FVIII A2 domain secondary structure. In addition, a patient with mild HA and HR showed the missense p.Glu1704Lys associated with two neutral intronic substitutions potentially affecting the A3 domain. A case/control study (84/143) permitted estimation of F8 genotype-specific inhibitor risks [OR; prevalence (CI)] in severe-HA patients classifying a high-risk group including multi-exon deletions [3.66; 55% (19-100)], Inv22 [1.8; 24% (19-100)] and nonsense in FVIII-LCh [1.2; 21% (7-59)]; an average risk group including single-exon deletions, indel frameshifts and nonsense-HCh; and a low-risk group represented by missense defects [0.14; 3% (0.6-11)]. Analysis of inhibitor concordance/discordance in related patients indicated additional genetic factors other than F8 genotype for inhibitor formation. No significant inhibitor-predisposing factors related to FVIII product exposure were found in age- and F8 genotype-stratified populations of severe-HA patients. In conclusion, the Argentine HA patient series presents similar global and mutation-specific inhibitor risks than the HA database and other published series. This case-specific information will help in designing fitted therapies and follow-up protocols in Argentina. © 2013 John Wiley & Sons Ltd.

  4. Assessment of the frequency of regulatory T cells (CD4+CD25+CD127-) in children with hemophilia A: relation to factor VIII inhibitors and disease severity.

    Science.gov (United States)

    El-Asrar, Mohamed Abo; Hamed, Ahmed El-Saeed; Darwish, Yasser Wagih; Ismail, Eman Abdel Rahman; Ismail, Noha Ali

    2016-01-01

    A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.

  5. Anti-CD20 as the B cells targeting agent in the combined therapy to modulate anti-factor VIII immune responses in hemophilia A inhibitor mice

    Directory of Open Access Journals (Sweden)

    Chao Lien eLiu

    2014-01-01

    Full Text Available Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B cells. Anti-CD20 targets a variety of B cells (pre-B cells to mature/memory cells; therefore, we investigated the impact of B cell depletion on anti-FVIII immune responses in hemophilia A mice using anti-CD20 combined with regulatory T (Treg cell expansion using IL-2/IL-2mAb complexes plus rapamycin. We found that anti-CD20 alone can partially modulate anti-FVIII immune responses in both unprimed and FVIII-primed hemophilia A mice. Moreover, in mice treated with anti-CD20 + IL-2/IL-2mAb complexes + rapamycin + FVIII, anti-FVIII antibody titers were significantly reduced in comparison to mice treated with regimens targeting only B or T cells. In addition, titers remained low after a second challenge with FVIII plasmid . Treg cells and activation markers were transiently and significantly increased in the groups treated with IL-2/IL-2mAb complexes ; however,significant B cell depletion was obtained in anti-CD20-treated groups. Importantly, both FVIII-specific antibody-secreting cells and memory B cells were significantly reduced in mice treated with combination therapy. This study demonstrates that a combination regimen is highly promising as a treatment option for modulating anti-FVIII antibodies and facilitating induction of long-term tolerance to FVIII in hemophilia A mice.

  6. Six amino acid residues in a 1200 A2 interface mediate binding of factor VIII to an IgG4κ inhibitory antibody.

    Directory of Open Access Journals (Sweden)

    Jasper C Lin

    Full Text Available The development of neutralizing anti-factor VIII (FVIII antibodies complicates the treatment of many hemophilia A patients. The C-terminal C2 domain is a particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2 bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to bind von Willebrand factor (VWF and phospholipids, revealed that 15 amino acids in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each with a surface-exposed side chain mutated to alanine or another residue, were generated, and surface plasmon resonance studies were carried out to evaluate effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic analysis of experiments carried out at three temperatures indicated that one beta hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and F2200 plus two non-contiguous arginines (FVIII-R2215 and R2220, contributed appreciably to the affinity. B-domain-deleted (BDD FVIII-F2196A, FVIII-F2196K and FVIII-M2199A were generated and characterized. Their pro-coagulant activities and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study suggests specific sites for amino acid substitutions to rationally design FVIII variants capable of evading immunodominant neutralizing anti-FVIII antibodies.

  7. Allergic reaction in a cohort of haemophilia A patients using plasma-derived factor VIII (FVIII) concentrate is rare and not necessarily triggered by FVIII.

    Science.gov (United States)

    Montalvão, S A L; Tucunduva, A C; Siqueira, L H; Sambo, A L A; Medina, S S; Ozelo, M C

    2015-07-01

    In contrast to haemophilia B, allergic manifestations are rare complications in haemophilia A (HA) patients treated with factor VIII (FVIII) concentrates. Nevertheless, it can be serious and hamper replacement therapy in these cases. The aims of this study were to evaluate the frequency of allergic reaction in a cohort of HA patients treated only with plasma-derived FVIII (pdFVIII) concentrates, and assess the possible immune mechanisms involved. History of allergic reaction was retrospectively assessed. Patients with allergic manifestations were followed, and had plasma samples collected in different timepoints in relation to the allergic episode. These samples were analysed for the presence of inhibitor and anti-FVIII immunoglobulins subclasses. Three of 322 HA patients (0.9%) developed allergic reaction after exposure to pdFVIII products during the last 15 years in our centre. The first patient, with severe HA, without inhibitor, had anti-pdFVIII IgE and IgG4, but no anti-recombinant FVIII (rFVIII) IgE. The second patient, with severe HA, and high-responding inhibitor, presented allergic manifestation with both, pdFVIII concentrate and activated prothrombin complex concentrate. Although anti-pdFVIII and anti-rFVIII IgG4 were detected, no anti-FVIII IgE was present. The third patient, with moderate HA without inhibitor, atopic, had no anti-FVIII immunoglobulin detected, and allergic symptoms disappeared after switching to rFVIII concentrate. This study corroborates the low incidence of allergic reactions in HA patients. In the three cases presented, the anti-FVIII immunoglobulin profile demonstrated that the allergic manifestation was triggered by other proteins contained in pdFVIII products, and not directed to FVIII. © 2015 John Wiley & Sons Ltd.

  8. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study.

    Science.gov (United States)

    Tiede, Andreas; Hofbauer, Christoph J; Werwitzke, Sonja; Knöbl, Paul; Gottstein, Saskia; Scharf, Rüdiger E; Heinz, Jürgen; Groß, Jürgen; Holstein, Katharina; Dobbelstein, Christiane; Scheiflinger, Fritz; Koch, Armin; Reipert, Birgit M

    2016-05-12

    Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA. © 2016 by The American Society of Hematology.

  9. Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay

    Science.gov (United States)

    Boylan, Brian; Rice, Anne S.; Dunn, Amy L.; Tarantino, Michael D.; Brettler, Doreen B.; Barrett, John C.; Miller, Connie H.

    2015-01-01

    Summary Background The development of neutralizing antibodies, referred to as inhibitors, against factor VIII (FVIII) is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective Assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2, or IgG4 correlated qualitatively and quantitatively with the presence of a FVIII inhibitor as reported by the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and a positive anti-FVIII IgG1 later developed an inhibitor, compared to 2 of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing. PMID:25354263

  10. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight®), in patients with hemophilia A.

    Science.gov (United States)

    Jiménez-Yuste, V; Lejniece, S; Klamroth, R; Suzuki, T; Santagostino, E; Karim, F A; Saugstrup, T; Møss, J

    2015-03-01

    Turoctocog alfa (NovoEight(®)) is a human recombinant coagulation factor VIII (rFVIII) for the treatment of patients with hemophilia A. To evaluate the pharmacokinetics of turoctocog alfa in all age groups across clinical trials. Data from previously treated patients with severe hemophilia A (FVIII activity level of ≤ 1%) with no history of FVIII inhibitors, in a non-bleeding state, were included. The pharmacokinetics were assessed following a wash-out period and a subsequent single intravenous 50 IU kg(-1) dose of turoctocog alfa. Blood was sampled during a 48-h period postdose. Standard pharmacokinetic (PK) parameters were estimated on the basis of plasma FVIII activity vs. time (PK profiles) with non-compartmental methods. Furthermore, a population PK analysis was conducted. Data from 76 patients (aged 1-60 years) enrolled globally across six clinical trials were included, totaling 105 turoctocog alfa PK profiles. Single-dose PK results 3-6 months after the first dose of turoctocog alfa were comparable with the results obtained after the first dose. Similar PK characteristics were shown for different lots and strengths of the drug product. Overall, area under the plasma concentration (activity) curve from administration to infinity (AUC) and t1(/2) tended to increase with increasing age, with lower AUC and shorter t(1/2) being seen in children than in adolescents and adults. The PK profiles of turoctocog alfa and other commercially available plasma-derived FVIII and rFVIII products were similar in all age groups. The PK characteristics of turoctocog alfa have been thoroughly studied, and shown to be consistent over time, reproducible between different lots and strengths of drug product, and similar to those observed for other FVIII products. © 2014 International Society on Thrombosis and Haemostasis.

  11. Influence of factor VIII level and its inhibitor titer on the therapeutic response to corticosteroids alone in the management of acquired hemophilia

    Science.gov (United States)

    Vautier, Mathieu; de Boysson, Hubert; Creveuil, Christian; Repesse, Yohan; Borel-Derlon, Annie; Troussard, Xavier; Damaj, Gandhi L.; Bienvenu, Boris; Gautier, Philippe; Aouba, Achille

    2016-01-01

    Abstract The treatment of acquired hemophilia (AH) involves discussing whether corticosteroids should be administered alone or combined with immunosuppressant drugs, which increase the risk of infection especially in elderly patients and/or those with autoimmunity or neoplastic diseases, who represent the target population of the disease. Prognostic factors highlighting adequate responses to corticosteroids alone must be identified for satisfactory clinical response and lower infectious risk. We aimed to evaluating the efficacy of corticosteroids alone in the management of AH depending on factor VIII (FVIII, ≥ or 20 Bethesda units per milliliter [BU/mL]) titer. We conducted a retrospective single-center study including 24 patients treated for AH with corticosteroids alone. Time to achieve partial remission (PR: absence of hemorrhage and FVIII levels >50 IU/dL) was significantly shorter in the FVIII ≥ 1 IU/dL group than in the FVIII  20 BU/mL group (15 [11–35] vs 41 [20–207] days, P = 0.003). In both subgroups, time to achieve complete remission (CR: negative INH and corticosteroids below 10 mg/d) was also significantly shorter than that observed in the opposite subgroups. INH titer, considered alone, did not affect the length of time to onset of PR or CR. CR and PR rates did not differ significantly depending on these variables. Our study suggests that in AH, patients with FVIII levels ≥1 IU/dL considered alone or combined with INH titer ≤20 BU/mL could be treated by corticosteroids alone, given that this subgroup of patients displayed faster therapeutic responses to this strategy. PMID:27902587

  12. Influence of factor VIII level and its inhibitor titer on the therapeutic response to corticosteroids alone in the management of acquired hemophilia: A retrospective single-center study.

    Science.gov (United States)

    Vautier, Mathieu; de Boysson, Hubert; Creveuil, Christian; Repesse, Yohan; Borel-Derlon, Annie; Troussard, Xavier; Damaj, Gandhi L; Bienvenu, Boris; Gautier, Philippe; Aouba, Achille

    2016-11-01

    The treatment of acquired hemophilia (AH) involves discussing whether corticosteroids should be administered alone or combined with immunosuppressant drugs, which increase the risk of infection especially in elderly patients and/or those with autoimmunity or neoplastic diseases, who represent the target population of the disease. Prognostic factors highlighting adequate responses to corticosteroids alone must be identified for satisfactory clinical response and lower infectious risk.We aimed to evaluating the efficacy of corticosteroids alone in the management of AH depending on factor VIII (FVIII, ≥ or 20 Bethesda units per milliliter [BU/mL]) titer.We conducted a retrospective single-center study including 24 patients treated for AH with corticosteroids alone.Time to achieve partial remission (PR: absence of hemorrhage and FVIII levels >50 IU/dL) was significantly shorter in the FVIII ≥ 1 IU/dL group than in the FVIII  20 BU/mL group (15 [11-35] vs 41 [20-207] days, P = 0.003). In both subgroups, time to achieve complete remission (CR: negative INH and corticosteroids below 10 mg/d) was also significantly shorter than that observed in the opposite subgroups. INH titer, considered alone, did not affect the length of time to onset of PR or CR. CR and PR rates did not differ significantly depending on these variables.Our study suggests that in AH, patients with FVIII levels ≥1 IU/dL considered alone or combined with INH titer ≤20 BU/mL could be treated by corticosteroids alone, given that this subgroup of patients displayed faster therapeutic responses to this strategy.

  13. Recombinant porcine sequence factor VIII (rpFVIII) for acquired haemophilia A: practical clinical experience of its use in seven patients.

    Science.gov (United States)

    Tarantino, M D; Cuker, A; Hardesty, B; Roberts, J C; Sholzberg, M

    2017-01-01

    A recombinant porcine factor VIII B-domain-deleted product (rpFVIII; OBIZUR, Baxalta Incorporated, Deerfield, IL 60015, USA) was recently approved for treatment of bleeding episodes in adults with acquired haemophilia A (AHA) in the United States. To date, no clinical experience outside the registration study has been reported. To describe early clinical experience using rpFVIII for AHA. A retrospective chart review of seven patients with AHA treated with rpFVIII at four institutions from November 2014 to October 2015. The time to diagnosis of AHA ranged from 5 days to 6 weeks. Six major and one other bleed were treated with rpFVIII following unsatisfactory bypassing agent (BPA) therapy. Good haemostatic efficacy was seen in five of seven cases. rpFVIII loading doses of 100 (n = 6) or 200 U kg-1 (n = 1) increased FVIII activity from <1 to 9% at baseline to 109-650% within 0.25-7 h in six of seven cases. Subsequent median doses ranged from 30 to 100 U kg-1 for 3-26 days. No rpFVIII-related adverse events were reported. Three patients survived with inhibitor eradication, one with persistent inhibitor, two died with inhibitors present and one was discharged and later died from unrelated causes. rpFVIII showed good haemostatic efficacy with no recurrences in most cases, with consumption substantially less than in the registration study. Treatment decisions were based on FVIII activity levels and clinical assessment. The ability to titrate rpFVIII dose using FVIII activity was considered advantageous compared with BPA therapy. Notable delays in diagnosis were observed. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  14. Assessing patients' and caregivers' perspectives on stability of factor VIII products for haemophilia A: a web-based study in the United States and Canada.

    Science.gov (United States)

    DiBenedetti, D B; Coles, T M; Sharma, T; Pericleous, L; Kulkarni, R

    2014-07-01

    Haemophilia A is a rare inherited bleeding disorder characterized by an inability of the blood to clot normally. Patients can experience spontaneous or trauma-induced joint and soft tissue bleeding and must keep coagulation factor VIII (FVIII) accessible at all times; thus, FVIII product storage and stability are critical. Our primary objective was to assess haemophilia A patients' and caregivers' experiences and preferences with FVIII product storage and stability. A secondary objective was to evaluate the use of the social media site Facebook in recruitment. In this cross-sectional study, 145 English-speaking adult patients and caregivers of children with haemophilia A were recruited through two state-based haemophilia organizations in the United States (US) and one national organization in Canada for a web-based survey assessing demographics and FVIII product ordering, usage, and storage practices. Of the 101 individuals who completed the survey, 60% resided in Canada; 57% were recruited through Facebook. Caregivers and patients responded similarly to questions about ordering practices and product usage, with some distinction between groups in storage practices. Two-thirds of participants noted challenges with storing FVIII products, especially storage away from home. More than half preferred storing FVIII products at room temperature vs. in the refrigerator for long periods of time. FVIII product accessibility, usage and storage affect disease management. Results support the need for more convenient and accessible FVIII products for patients in daily life and while travelling. In addition, the use of social media has potential value in recruiting this population. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  15. Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients.

    Science.gov (United States)

    Pinto, P; Ghosh, K; Shetty, S

    2012-09-01

    Development of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR-RFLP, DNA sequencing and allele-specific PCRs. The IL10 promoter 'GCC' haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607-7.416), and 'GCC/ATA' (P: 0.011, OR: 3.492, 95% CI: 1.402-8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the 'non-GCC' haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135-0.622) and 'ATA/ATA' haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096-0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273-7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients. © 2012 Blackwell Publishing Ltd.

  16. [Relationship between factor VIII inhibitor development and polymorphisms of TNFα and CTLA-4 gene in Chinese Han patients with hemophilia A].

    Science.gov (United States)

    Zhang, Lu-lu; Yu, Zi-qiang; Zhang, Wei; Cao, Li-juan; Su, Jian; Bai, Xia; Ruan, Chang-geng

    2011-03-01

    To investigate the potential association between factor VIII inhibitor development and polymorphisms of tumor necrosis factor-α (TNF-α)-308 and cytotoxic T-lymphocyte associated protein-4 gene in Chinese Han patients with hemophilia A (HA). The single base change polymorphism in TNF-α and CTLA-4 gene was analyzed in 140 Chinese Han patients with hemophilia A who have been treated with plasma-derived FVIII concentrates and 108 normal controls by using PCR-restrictive fragment length polymorphism (RFLP). All of the HA patients' plasma samples were measured by modified-Nijmegen assay simultaneously. In HA patients, G/G genotype, G/A genotype and A/A genotype were detected in 118 (84.3%), 18 (12.8%) and 4 cases (2.9%) respectively; C/C genotype, C/T genotype and T/T genotype were detected in 108 (77.2%), 30 (21.4%) and 2 cases (1.4%) respectively. The difference in the genotype frequencies between HA patients and controls was nonsignificant (P > 0.05). Patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 7.519, 95% CI = 3.168 - 17.844). Severe HA patients who were carriers of homozygotes for A allele had a higher risk of inhibitor development compared with those who were not (OR = 8.163, 95% CI = 2.521 - 26.434). There was no statistical difference in the risk of inhibitor development between the patients who were carriers or not (OR = 1.586, 95% CI = 0.729 - 3.450). TNF-α-308 gene polymorphism is significantly associated with inhibitor development in Chinese Han patients with severe hemophilia A. TNF-α gene may be a useful marker and potential modulator of the immune response to replacement therapy for hemophilia A patients.

  17. Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity.

    Science.gov (United States)

    Kuether, E L; Schroeder, J A; Fahs, S A; Cooley, B C; Chen, Y; Montgomery, R R; Wilcox, D A; Shi, Q

    2012-08-01

    The development of inhibitory antibodies, referred to as inhibitors, against exogenous factor VIII in a significant subset of patients with hemophilia A remains a persistent challenge to the efficacy of protein replacement therapy. Our previous studies using the transgenic approach provided proof-of-principle that platelet-specific expression could be successful in treating hemophilia A in the presence of inhibitory antibodies. To investigate a clinically translatable approach for platelet gene therapy of hemophilia A with pre-existing inhibitors. Platelet FVIII expression in preimmunized FVIII(null) mice was introduced by transplantation of lentivirus-transduced bone marrow or enriched hematopoietic stem cells. FVIII expression was determined with a chromogenic assay. The transgene copy number per cell was quantitated with real-time PCR. Inhibitor titer was measured with the Bethesda assay. Phenotypic correction was assessed by the tail clipping assay and an electrolytically induced venous injury model. Integration sites were analyzed with linear amplification-mediated PCR. Therapeutic levels of platelet FVIII expression were sustained in the long term without evoking an anti-FVIII memory response in the transduced preimmunized recipients. The tail clip survival test and the electrolytic injury model confirmed that hemostasis was improved in the treated animals. Sequential bone marrow transplants showed sustained platelet FVIII expression resulting in phenotypic correction in preimmunized secondary and tertiary recipients. Lentivirus-mediated platelet-specific gene transfer improves hemostasis in mice with hemophilia A with pre-existing inhibitors, indicating that this approach may be a promising strategy for gene therapy of hemophilia A even in the high-risk setting of pre-existing inhibitory antibodies. © 2012 International Society on Thrombosis and Haemostasis.

  18. Absence of a desmopressin response after therapeutic expression of factor VIII in hemophilia A dogs with liver-directed neonatal gene therapy

    Science.gov (United States)

    Xu, Lingfei; Nichols, Timothy C.; Sarkar, Rita; McCorquodale, Stephanie; Bellinger, Dwight A.; Ponder, Katherine P.

    2005-01-01

    Hemophilia A (HA) is a bleeding disorder caused by factor VIII (FVIII) deficiency. FVIII replacement therapy can reduce bleeding but is expensive, inconvenient, and complicated by development of antibodies that inhibit FVIII activity in 30% of patients. Neonatal hepatic gene therapy could result in continuous secretion of FVIII into blood and might reduce immunological responses. Newborn HA mice and dogs that were injected i.v. with a retroviral vector (RV) expressing canine B domain-deleted FVIII (cFVIII) achieved plasma cFVIII activity that was 139 ± 22% and 116 ± 5% of values found in normal dogs, respectively, which was stable for 1.5 yr. Coagulation tests were normalized, no bleeding had occurred, and no inhibitors were detected. This is a demonstration of long-term fully therapeutic gene therapy for HA in a large animal model. Desmopressin (DDAVP; 1-deamino-[d-Arg8]vasopressin) is a drug that increases FVIII activity by inducing release of FVIII complexed with von Willebrand factor from endothelial cells. It has been unclear, however, if the FVIII is synthesized by endothelial cells or is taken up from blood. Because the plasma cFVIII in these RV-treated dogs derives primarily from transduced hepatocytes, they provided a unique opportunity to study the biology of the DDAVP response. Here we show that DDAVP did not increase plasma cFVIII levels in the RV-treated dogs, although von Willebrand factor was increased appropriately. This result suggests that the increase in FVIII in normal dogs after DDAVP is due to release of FVIII synthesized by endothelial cells. PMID:15837921

  19. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety.

    Science.gov (United States)

    Maas Enriquez, Monika; Thrift, John; Garger, Stephen; Katterle, Yvonne

    2016-11-01

    BAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial.

    Science.gov (United States)

    Saxena, K; Lalezari, S; Oldenburg, J; Tseneklidou-Stoeter, D; Beckmann, H; Yoon, M; Maas Enriquez, M

    2016-09-01

    BAY 81-8973 (Kovaltry(®) ) is a full-length, unmodified recombinant human factor VIII (FVIII) with the same amino acid sequence as sucrose-formulated recombinant FVIII and is produced using additional advanced manufacturing technologies. To demonstrate efficacy and safety of BAY 81-8973 for treatment of bleeds and as prophylaxis based on two different potency assignments. In LEOPOLD I (ClinicalTrials.gov identifier, NCT01029340), males aged 12-65 years with severe haemophilia A and ≥150 exposure days received BAY 81-8973 20-50 IU kg(-1) two or three times per week for 12 months. Potency was based on chromogenic substrate assay per European Pharmacopoeia and label adjusted to mimic one-stage assay potency. Patients were randomized for potency sequence and crossed over potency groups after 6 months, followed by an optional 12-month extension. Primary efficacy endpoint was annualized bleeding rate (ABR). Patients also received BAY 81-8973 during major surgeries. Sixty-two patients received BAY 81-8973 prophylaxis and were included in the analysis. Median ABR was 1.0 (quartile 1, 0; quartile 3, 5.1) without clinically relevant differences between potency periods. Median ABR was similar for twice-weekly vs. three times-weekly dosing (1.0 vs. 2.0). Haemostasis was maintained during 12 major surgeries. Treatment-related adverse event (AE) incidence was ≤7% overall; no patient developed inhibitors. One patient with risk factors for cardiovascular disease developed a myocardial infarction. BAY 81-8973 was efficacious in preventing and treating bleeding episodes, irrespective of the potency assignment method, with few treatment-related AEs. Caution should be used when treating older patients with cardiovascular risk factors. © 2016 Bayer. Haemophilia Published by John Wiley & Sons Ltd.

  1. A protective effect of milk fat globule EGF factor VIII (MFG-E8) on the spontaneous fusion of milk fat globules in breast milk.

    Science.gov (United States)

    Yasueda, Takehiko; Oshima, Kenzi; Nakatani, Hajime; Tabuchi, Kanji; Nadano, Daita; Matsuda, Tsukasa

    2015-07-01

    Lipid droplets synthesized in mammary epithelial cells are secreted into breast milk by the budding-off mechanism. The milk lipids, termed mik fat globules (MFGs), are surrounded with the cell plasma membrane and contain various membrane proteins, including milk fat globule epidermal growth factor (EGF)-factor VIII (MFG-E8), on their surface. We report here that the MFGs in the milk of MFG-E8-deficient mice fused each other and turned into abnormally large size of lipid droplets within ∼48 h after being secreted into mammary alveolar lumen in situ or being incubated at 37°C in vitro. This biophysical degeneration of MFGs in the MFG-E8-deficient milk was efficiently rescued in vitro by adding the milk serum of wild-type mice, isolated MFG-E8 or annexin V. Moreover, addition of ethylenediaminetetraacetic acid (30 mM) also protected the MFG fusion remarkably in vitro. In addition, bovine MFGs also fused each other when isolated from milk serum, and the fusion was inhibited by adding isolated MFG-E8 or mouse milk serum, but not the milk serum of MFG-E8-deficient mice. MFG-E8 in breast milk may mask the phosphatidylserine exposed on the surface of MFGs with time after secretion and thereby suppress the membrane fusion among MFGs resulting in the enlargement of MFGs in the breast milk. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  2. PENGARUH PENGGUNAAN MODEL COOPERATIVE LEARNING TIPE GROUP INVESTIGATION (GI TERHADAP HASIL BELAJAR IPS TERPADU KELAS VIII SEMESTER GENAP SMPYPI 1 BANDAR MATARAM LAMPUNG TENGAH T.P 2015/2016

    Directory of Open Access Journals (Sweden)

    Desi Fatmawati Maryatun

    2016-05-01

    Full Text Available Metode cooperative learning tipe group investigation merupakan model pembelajaran kooperatif yang dapat melibatkan peserta didik secara aktif dalam kegiatan pembelajaran mulai dari merencanakan topik-topik yang akan dipelajari, bagaimana melaksanakan investigasinya, hingga melakukan presentasi kelompok dan evaluasi. Tujuan penelitian ini adalah untuk mengetahui adanya pengaruh penggunaan model pembelajaran cooperative learning tipe Group Investigation terhadap hasil belajar IPS Terpadu peserta didik kelas VIII semester genap SMP YPI 1 Bandar Mataram  Lampung Tengah tahun pelajaran 2015/2016. Hipotesis yang penulis ajukan adalah “Ada pengaruh yang positif pada model pembelajaran cooperative learning tipe Group Investigation terhadap hasil belajar IPS Terpadu peserta didik kelas VIII semester genap SMP YPI 1 Bandar Mataram  Lampung Tengah tahun pelajaran 2015/2016. Populasi dalam penelitian ini adalah siswa kelas VIII SMP YPI 1 Bandar Mataram Lampung Tengah Tahun Pelajaran 2015/2016 yaitu berjumlah 48 orang siswa dan diantaranya terdiri dari 2 kelas. Dan yang menjadi sampel dalam penelitian ini adalah kelas VIIIa dan VIIIb. Kelas VIIIa sebagai kelas eksperimen dan kelas VIIIb sebagai kelas control, sampel diambil menggunakan teknik purposive sampling, Eksperimen dilaksanakan pada siswa kelas VIIIa Semester Genap SMP YPI 1 Bandar Mataram Lampung Tengah Tahun Pelajaran 2015/2016 yang berjumlah 24 peserta didik. Data penelitian ini dikumpulkan dengan menggunakan  metode observasi, wawancara, dokumentasi, dan tes. Sedangkan untuk mengetahui tingkat validitas dan reliabilitas penulis menggunakan rumus K-R 20. Kemudian untuk menguji/membuktikan hipotesis digunakan rumus Regresi Linier Sederhana yaitu  Ŷ = a + bx. Nilai Ŷ = 73,33+ 0,5 X yang dilanjutkan dengan rumus thitung > ttabel.pada daftar signifikan 5% yaitu 4 > 1,72  dan pada taraf signifikan 1% yaitu 4 > 2,52. Dengan demikian hipotesisnya diterima karena ada pengaruh yang positif

  3. TIRO Y LAS FLUCTUACIONES DE LA ECONOMÍA FENICIA DURANTE EL SIGLO VIII ANTES DE NUESTRA ERA (Tyre and the Fluctuations of Phoenician Economy during the 8th Century BC

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    Pascual Izquierdo-Egea

    2014-12-01

    Full Text Available La aplicación del método de valoración contextual al análisis de los ajuares funerarios hasta ahora publicados de la necrópolis fenicia de Tiro-Al Bass, Líbano, permite aislar las fluctuaciones económicas y los cambios sociales experimentados por la población tiria durante el siglo VIII a. C. En concreto, se detecta una larga prosperidad desde mediados del siglo IX hasta mediados del VIII antes de nuestra era, con un máximo de bonanza a lo largo del periodo 775-750 a. C. En cambio, la segunda mitad del siglo VIII muestra una aguda crisis económica asociada a una elevada conflictividad social. Estos resultados coinciden plenamente con los acontecimientos históricos conocidos a través de las fuentes literarias antiguas, aportando evidencias que las complementan. En todo caso, con este nuevo ejemplo se confirma, una vez más, la universalidad de la metodología empleada y su irrefutable validez científica. ENGLISH: By applying the contextual valuation method to the analysis of grave goods from the Phoenician cemetery of Tyre-Al Bass, Lebanon, we can isolate the economic fluctuations and social changes experienced by the Tyrian population during the 8th century BC. Based on the evidence, the mid-9th to the mid-8th century BC was a period of prosperity, with the most pronounced economic boom between 775-750 BC. In contrast, the second half of the 8th century BC shows a sharp economic crisis associated with a high level of social conflict. These results are fully consistent with the historical events known through ancient literary sources. This new example confirms the universality of this methodology and its irrefutable scientific validity.

  4. «Ladinia», Sföi cultural dai Ladins dies Dolomites, numm.V. (1981- VIII (1984, Institut Ladin «Micurà de Rü”, San Martin de Tor, Piccolino (Val Badia.

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    Pavao Tekavčić

    1986-12-01

    Full Text Available La rivista «Ladinia», le cui prime quattro annate sono state recensite in «Linguistica» 21 (1981, pp. 325-331, continua ad uscire, conservando il suo profilo, Ia vastità degli argomenti che concernono il mondo ladino ed arricchendosi an­ che di rubriche nuove. Offriamo ai lettori Ia recensione delle annate 1981-1984, concentrandoci anche qui sui contributi linguistici (tanto piu che nei numeri V-VIII, e particolarmente negli ultimi due, i contributi di argomento linguistico occupano più spazio di prima.

  5. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population

    Directory of Open Access Journals (Sweden)

    Zongkui Wang

    2017-03-01

    Full Text Available Background ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII and von Willebrand factor (VWF. Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg, and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13. We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. Methods A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag, collagen-binding activity (VWF:CBA, and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof was performed by agglutination of platelets with ristocetin. Results Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof were significantly higher in non-O than in O type subjects (p < 0.05 for all comparison. ADAMTS13 antigen decreased with increasing age, whereas the other parameters increased. Other than ADAMTS13 (p < 0.01, no gender-related variations were observed in the other parameters. Moreover, FVIII:C, Fbg, VWF:Ag, VWF:CBA, and VWF:Rcof showed significant and positive relationships with age (r = 0.421, 0.445, 0.410, 0.401, and 0.589, resp.; all p < 0.001, whereas a negative relationship was observed for ADAMTS13 antigen (r = 0.306; p = 0.006. Furthermore, FVIII:C were strongly correlated with VWF:Ag, VWF:CBA, and VWF:Rcof (r = 0.746, r = 0.746, and r = 0.576, resp.; p < 0.0001. VWF parameters were also strongly correlated with each other (r = 0.0.847 for VWF:Ag and VWF:CBA; r = 0.722 for VWF:Ag and VWF:Rcof; p < 0.0001. Conclusions ABO blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  6. Immune tolerance induced by platelet-targeted factor VIII gene therapy in hemophilia A mice is CD4 T cell mediated.

    Science.gov (United States)

    Chen, Y; Luo, X; Schroeder, J A; Chen, J; Baumgartner, C K; Hu, J; Shi, Q

    2017-10-01

    Essentials The immune response is a significant concern in gene therapy. Platelet-targeted gene therapy can restore hemostasis and induce immune tolerance. CD4 T cell compartment is tolerized after platelet gene therapy. Preconditioning regimen affects immune tolerance induction in platelet gene therapy. Background Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted factor VIII (FVIII) (2bF8) gene therapy together with in vivo drug selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. Objective To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy. Methods Platelet-FVIII expression was introduced by 2bF8LV transduction and transplantation. FVIII assays and tail bleeding tests were used to confirm the success of platelet gene therapy. Animals were challenged with rhF8 to explore if immune tolerance was induced after gene therapy. Treg cell analysis, T-cell proliferation assay and memory B-cell-mediated ELISPOT assay were used to investigate the potential mechanisms of immune tolerance. Results We showed that platelet-FVIII expression was sustained and the bleeding diathesis was restored in FVIII(null) mice after 2bF8LV gene therapy. None of the transduced recipients developed anti-FVIII inhibitory antibodies in the groups preconditioned with 660 cGy irradiation or busulfan plus ATG treatment even after rhF8 challenge. Treg cells significantly increased in 2bF8LV-transduced recipients and the immune tolerance developed was transferable. CD4(+) T cells from treated animals failed to proliferate in response to rhF8 re-stimulation, but memory B cells could differentiate into antibody secreting cells in 2bF8LV-transduced recipients. Conclusion 2bF8LV gene transfer without in vivo selection of

  7. PENINGKATAN AKTIVITAS DAN HASIL BELAJAR BENTUK PASAR DENGAN METODE COURSE REVIEW HORAY (CRH BERBANTUAN MEDIA GAMBAR KELAS VIII SMP N 1 BULU KABUPATEN SUKOHARJO

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    Setyaningsih Setyaningsih

    2013-11-01

    Full Text Available Penelitian ini bertujuan untuk meningkatkan aktivitas dan hasil belajar siswa pada materi bentuk pasar dengan metode Course Review Horay (CRH berbantuan media gambar kelas VIII SMP N 1 Bulu Kabupaten Sukoharjo. Jenis penelitian ini adalah penelitian tindakan kelas yang terdiri dari dua siklus. Setiap siklus memiliki empat tahap yaitu perencanaan, pelaksanaan, pengamatan, dan refleksi. Subjek penelitian ini adalah siswa kelas VIIIA SMP N 1 Bulu. Data aktivitas siswa dan guru diperoleh dari lembar observasi. Data hasil belajar diperoleh dari soal evaluasi siklus I dan siklus II. Berdasarkan hasil penelitian diperoleh aktivitas siswa siklus I sebesar 70,83% meningkat menjadi 87,50% pada siklus II. Sedangkan aktivitas guru dalam siklus I sebesar 71,86% meningkat menjadi 90,6% pada siklus II. Rata-rata hasil belajar kognitif menunjukkan pada siklus I sebesar 72,67 meningkat menjadi 83,20 pada siklus II. Sedangkan ketuntasan klasikal pada siklus I sebesar 70% meningkat menjadi 83,33% pada siklus II. Dari hasil penelitian tersebut dapat disimpulkan bahwa terjadi peningkatan aktivitas dan hasil belajar siswa pada materi bentuk pasar dengan metode Course Review Horay (CRH berbantuan media gambar siswa kelas VIIIA SMP N 1 Bulu Kabupaten Sukoharjo. This research is aimed to increasing activity and student learning results in the subject matter of market forms material by using Course Review Horay (CRH method and image as media in VIIIA class of SMP N 1 Bulu. The design is Classroom Action Research (CAR consisting of two cycles, each cycle including planning, action, observation and reflection. The subjects of research were 30 students of the VIIIA class of SMP N 1 Bulu. Student and teacher activity data were obtained from observation sheet. Results learning data were obtained from test evaluation of the first cycle and second cycle. Based on the results research was obtained in the first cycle of student activities at 70,83% increased to 87,50 in the

  8. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: Family studies indicate a mutation type-dependent sex ratio of mutation frequencies

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J.; Schmidt, W.; Olek, K. [Univ. of Bonn (Germany)] [and others

    1996-04-01

    The clinical manifestation of hemophilia A is caused by a wide range of different mutations. In this study the factor VIII genes of 147 severe hemophilia A patients-all exclusively from sporadic families-were screened for mutations by use of the complete panel of modern DNA techniques. The pathogenous defect could be characterized in 126 patients (85.7%). Fifty-five patients (37.4%) showed a F8A-gene inversion, 47 (32.0%) a point mutation, 14 (9.5%) a small deletion, 8 (5.4%) a large deletion, and 2 (1.4%) a small insertion. Further, four (2.7%) mutations were localized but could not be sequenced yet. No mutation could be identified in 17 patients (11.6%). Sixteen (10.9%) of the P identified mutations occurred in the B domain. Four of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicisms were detected in 3 (3.9%) of 76 patients` mothers, comprising 3 of 16 de novo mutations in the patients` mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 two-generation and 28 of 34 three-generation families. On the basis of these data, the male:female ratio of mutation frequencies (k) was estimated as k = 3.6. By use of the quotients of mutation origin in maternal grandfather to patient`s mother or to maternal grandmother, k was directly estimated as k = 15 and k = 7.5, respectively. Considering each mutation type separately, we revealed a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a >10-fold- higher mutation rate in male germ cells, whereas deletions showed a >5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other diseases like Duchenne muscular dystrophy, our results indicate that at least for X-chromosomal disorders the male:female mutation rate of a disease is determined by its proportion of the different mutation types. 68 refs., 1 fig., 5 tabs.

  9. Capitolo VIII. Note e corollari

    OpenAIRE

    Tarde, Gabriel

    2016-01-01

    La presunzione di superiorità che, a parità di valore logico, favorisce un esempio tra mille altri, non riguarda soltanto le persone, le classi e i luoghi da cui esso proviene, ma anche la sua data di nascita antica o recente. Questo capitolo sarà dedicato proprio a quest’ultima tipologia di influenze. Si tratta soltanto di una conseguenza della legge dell’imitazione del superiore, considerata da un punto di vista diverso. Cominciamo con lo stabilire, in linea di massima, che, anche nelle soc...

  10. 31. VIII avati Vaala galeriis...

    Index Scriptorium Estoniae

    2004-01-01

    Näitus "Märkmed maalist. Eesti ja Leedu noor kunst". Kuraatorid Margaret Tali ja Milda Zvirblyte. Osalevad Maarit Murka, Tõnis Saadoja, Kristi Laanemäe, Vilius Vanagas, Agile Mazonaite, Jolanta Kyzikaite, Ieva Baranauskaite. Kõlab Taavi Laatsiti originaalmuusika

  11. 24. VIII avati Eesti meremuuseumis...

    Index Scriptorium Estoniae

    2005-01-01

    Mallorcal elava eesti kunstniku Erik Schmidti elu ja kirjandusliku loomingu näitus. Kunstnik andis Eesti Kaitsejõudude staabile üle admiral Pitka portree. Koos Vaal-galeriiga kavandatavasse 2006. a. Mallorcal toimuvasse E. Schmidti juhendatavasse eesti maalikunstnike laagrisse sõidavad Maarit Murka, Anna Litvinova, Lauri Sillak (Laurentsius), Karl Nagel ja Rait Rosin

  12. Recombinant factor VIIa (eptacog alfa): a pharmacoeconomic review of its use in haemophilia in patients with inhibitors to clotting factors VIII or IX.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A; Plosker, Greg L

    2007-01-01

    Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment. Prophylactic treatment with recombinant factor VIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia. In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters. Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients

  13. NMR and theoretical investigations on the structures and dynamics of octahedral bis(chelate)dichloro V(III) compounds isolated by an unusual reduction of non-oxo V(IV) species.

    Science.gov (United States)

    Rikkou, Maria; Manos, Manolis; Tolis, Evangelos; Sigalas, Michael P; Kabanos, Themistoklis A; Keramidas, Anastasios D

    2003-07-28

    Reaction of the non-oxo V(IV) species [V(IV)Cl(2)(L(OO))(2)] [L(OO) = acetylacetonate (acac(-)) or benzoylacetonate (bzac(-))] with a chelate nitrogen-donor ligand L(NN) in acetonitrile leads to the reduction of V(IV) to V(III) and the formation of the mononuclear V(III) compounds of the general formula [V(III)Cl(2)(L(OO))(L(NN))] (L(OO) and L(NN) are acac(-) and bipy for 1; acac- and 5,5'-me(2)bipy for 2; acac(-) and 4,4'-tb(2)bipy for 3; acac(-) and phen for 4; bzac(-) and bipy for 5; bzac(-) and phen for 6). The reduction of the V(IV) complexes was monitored by GC-MS and (1)H NMR spectroscopy. Both one- and two-dimensional (2D COSY and 2D EXSY) (1)H NMR techniques were used to assign the observed (1)H NMR resonances of 1-6 in CD(2)Cl(2) or CDCl(3) solution. It appeared that in solution these V(III) complexes form two isomers which are in equilibrium: cis-[V(III)Cl(2)(L(OO))(L(NN))] trans-[V(III)Cl(2)(L(OO))(L(NN))]. 2D EXSY cross-peaks were clearly observed between bipy- and acac-hydrogen atoms of the two geometrical isomers of 1-3 as well as between bipy and acac(-) protons of the cis isomer, indicating a dynamic process that corresponds to cis-trans isomerization and a cis-cis racemization. The thermodynamic and kinetic parameters of the equilibrium between these two isomers were calculated for compounds 1 and 2 by using variable temperature (VT) NMR data. Both cis-trans isomerization and cis-cis racemization processes probably proceed with an intramolecular twist mechanism involving a trigonal prismatic transition state. Density functional calculations (DFT) also indicated such a rearrangement mechanism.

  14. VIII ВСЕРОССИЙСКИЙ СЪЕЗД ТРАНСПЛАНТОЛОГОВ

    Directory of Open Access Journals (Sweden)

    2016-01-01

    Full Text Available VIII ВСЕРОССИЙСКИЙ СЪЕЗД ТРАНСПЛАНТОЛОГОВ.МАТЕРИАЛЫ СЪЕЗДА.ТЕЗИСЫ ДОКЛАДОВ.Под редакцией академика РАН С.В. Готье.27–29 июня 2016г. Москва

  15. Cambio de uso del suelo y escorrentía superficial: aplicación de un modelo de simulación espacial en Los Ángeles, VIII Región del Biobío, Chile

    OpenAIRE

    Henríquez,Cristián; Azócar,Gerardo

    2006-01-01

    Mediante el desarrollo de un modelo de simulación espacial del cambio de uso del suelo, se evalúa y simula el cambio en el coeficiente de escorrentía superficial para la ciudad de Los Ángeles y sus alrededores, VIII Región del Biobío, para el período 1998-2022. El modelo se ha desarrollado en el SIG Idrisi Kilimanjaro, integrando los métodos de Cadenas de Markov, Evaluación Multi Criterio y Autómatas Celulares. La evaluación del coeficiente de escorrentía se basa en el método del Servicio de ...

  16. PENERAPAN METODE DISKUSI SYNDICATE GROUP UNTUK MENINGKATKAN AKTIVITAS DAN HASIL BELAJAR PADA POKOK BAHASAN MENDESKRIPSIKAN HUBUNGAN ANTARA KELANGKAAN SUMBER DAYA DENGAN KEBUTUHAN MANUSIA YANG TIDAK TERBATAS SISWA KELAS VIII B DI SMP NEGERI 2 BANYUBIRU

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    Meita Lusianti

    2013-11-01

    Full Text Available Aktivitas siswa dalam kegiatan belajar mengajar di SMP Negeri 2 Banyubiru belum terlihat optimal. Proses pembelajaran berpusat pada guru sehingga siswa belum terlibat langsung untuk aktif dalam pembelajaran. Kondisi tersebut mempengaruhi hasil penerimaan siswa terhadap materi pembelajaran yang berakibat rendahnya hasil ulangan harian siswa. Penelitian ini bertujuan untuk meningkatkan aktivitas dan hasil belajar siswa. Penelitian ini dilaksanakan dalam 2 (dua siklus. Kegiatan dalam setiap siklus meliputi kegiatan perencanaan, pelaksanaan, observasi, dan refleksi. Hasil penelitian diperoleh nilai rata-rata hasil belajar kognitif siswa pada siklus I sebesar 72,93 dengan ketuntasan klasikal 67%. Rata-rata hasil belajar pada siklus II sebesar 79,20 dengan ketuntasan klasikal 90%. Adapun hasil analisis aktivitas siswa pada siklus I mencapai 61% dan pada siklus II meningkat menjadi 81%. Berdasarkan hasil penelitian tersebut, dapat diambil kesimpulan bahwa penerapan metode diskusi Syndicate Group dapat peningkatan aktivitas dan hasil belajar siswa kelas VIII B SMP Negeri 2 Banyubiru tahun ajaran 2013/2014. Student activity in learning activities at SMP Negeri 2 Banyubiru seen optimum yet. Learning proces centre on teacher so the student not involve direct to active in the learning. That condition influential student outcome about learning material that come about student daily test outcome low. The research as a purpose to increase activity and student outcome learning. This research doing on two cycle. Activity in every cycle includes planning, implementation, observation, and reflection. Research result got average of cognitive learning outcome in cycle I is 72,93 with classical totally 67%. Average of learning outcome in cycle II is 79,20 with classical totally 90%. There is student activity analysis outcome on cycle I reach 61% and on cycle II rises become 81%. Grounded on research result that, be able take conclusion that implementation Syndicate

  17. Meningkatkan Ketuntasan Hasil Belajar Peserta Didik Kelas VIII-F SMP Negeri 33 Surabaya Melalui Penerapan Model Pengajaran Langsung Dengan Kegiatan Laboratorium Mini Pada Materi Pembentukan Harga Pasar

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    Mudjianingsih .

    2017-01-01

    Full Text Available Penelitian ini dilaksanakan dengan latar belakang masih banyak kesulitan  yang ditemui peserta didik dalam mempelajari IPS. Berdasarkan observasi yang telah dilakukan, pembelajaran di kelas VIII-F SMPN 33 Surabaya menggunakan metode ceramah dan tanya jawab. Penerapan metode ini menjadikan peserta didik hanya sebagai obyek belajar, peserta didik yang duduk di belakang cenderung pasif dan kemungkinan hasil belajarnya tidak tuntas. Untuk mengatasi pemasalahan tersebut peneliti mengunakan model pengajaran langsung dengan kegiatan praktikum. Kegiatan praktikum ini merupakan bagian pengetahuan prosedural. Penelitian ini adalah penelitian tindakan kelas dengan tahapan  berupa rancangan, kegiatan dan pengamatan, refleksi dan revisi. Penelitian ini terdiri dari 3 putaran. Data penelitian diambil dengan menggunakan lembar observasi dan tes yang dilakukan pada bulan Maret s/d April 2013. Berdasarkan analisis data diperoleh informasi tentang keterampilan guru dalam pengelolaan model pengajaran langsung pada putaran I sampai putaran III mengalami peningkatan dari kriteria kurang baik menjadi baik. Keterampilan psikomotor peserta didik pada aspek transaksi pada putaran I mencapai skor 2,6 (kategori baik, sedangkan putaran II mencapai 2,4 (kategori kurang baik, hal ini peserta didik kurang serius pada saat melakukan kegiatan dan pengamatan, kemudian pada putaran III meningkat menjadi 3,8 (kategori sangat baik. Keterampilan afektif peserta didik dalam bertanya/ mengemukakan pendapat pada putaran I mencapai 2,8 (kategori baik, sedangkan putaran II menurun mencapai 2,4 (kategori kurang baik, dan putaran III mengalami peningkatan menjadi 3,3 (kategori sangat baik. Hasil belajar peserta didik sudah mencapai standar ketuntasan di sekolah. Pada putaran I ketuntasan belajar 70%, putaran II mencapai 91,06% sedangkan putaran III mencapai 88,62%. Dengan demikian dapat disimpulkan bahwa hasil belajar peserta didik sudah mencapai standar ketuntasan belajar di sekolah

  18. Diagnostico por PCR del complejo Sigatoka en Colombia.

    Directory of Open Access Journals (Sweden)

    Romero Magally

    1999-06-01

    Full Text Available Las Sigatokas negra y amarilla son enfermedades causadas por Mycosphaerella fijiensis y Mycosphaerella musicola respectivamente. Estas dos especies de hongos estrechamente relacionadas y morfológicamente similares, causan necrosis severa en las hojas de banano y plátano disminuyendo el área de tejido fotosintético y acelerando la maduración del fruto. Las enfermedades producidas por estos hongos afectan la mayoría de las áreas cultivadas de banano y plátano a nivel mundial, generando un gran problema económico y ambiental. Los síntomas que produce cada uno de estos patógenos en el cultivo son similares, por lo que su correcta identificación en campo se hace difícil. Con el fin de hacer una identificación precisa de cada uno de ellos decidimos estandarizar una prueba diagnóstica basada en la reacción en cadena de la polimerasa (PCR utilizando dos oligonucleótidos de 21 bases (MF 137 y MM 137 específicos para cada una de las especies M. fijiensis y M. musicola respectivamente. MF 137 y MM 137 codifican regiones variables identificadas en las secuencias interespaciadoras (ITS del DNA ribosomal.

  19. Diagnostico laboratorial das leucemias mielóides agudas

    OpenAIRE

    Silva,Graziele C. da; Pilger, Diogo Andre; Castro,Simone Martins de; Wagner,Sandrine Comparsi

    2006-01-01

    As leucemias agudas caracterizam-se pela proliferação clonal e pelo bloqueio maturativo das células hematopoéticas, com substituição difusa da medula óssea por células neoplásicas. A leucemia mielóide aguda (LMA) é um grupo heterogêneo de doenças clonais do tecido hematopoético, que acomete predominantemente idosos acima de 60 anos de idade. A LMA apresenta oito subtipos distintos morfologicamente: LMA M0 a M7. Os métodos diagnósticos para identificação da LMA e classificação dos subtipos são...

  20. Diagnostico da tuberculose: atencao basica ou pronto atendimento?

    Directory of Open Access Journals (Sweden)

    Rubia Laine de Paula Andrade

    2013-12-01

    Full Text Available OBJETIVO : Avaliar a qualidade dos serviços de saúde de atenção básica e pronto atendimento quanto ao diagnóstico da tuberculose pulmonar. MÉTODOS : Estudo transversal, com 90 profissionais de saúde da atenção básica e 68 de pronto atendimento de Ribeirão Preto, em 2009. Foi utilizado questionário estruturado com base em um instrumento de avaliação da atenção à tuberculose. Utilizaram-se os testes Qui-quadrado e exato de Fisher (ambos com nível de significância estatística de 5% e a análise de correspondência múltipla para estimar associação entre serviço de saúde e as variáveis de estrutura e processo para o diagnóstico da tuberculose. RESULTADOS : Atenção básica esteve associada à adequada provisão de insumos e recursos humanos, bem como com a solicitação de baciloscopia de escarro. O pronto atendimento associou-se à disponibilidade de equipamento de raio-X, sobrecarga de trabalho e rotatividade de recursos humanos, deficiências na quantidade de profissionais de saúde, disponibilidade de recipiente para coleta de escarro e solicitação baciloscópica de escarro. As ações de diagnóstico permaneceram centradas no médico em ambos os serviços. CONCLUSÕES : Os serviços de pronto atendimento apresentaram fragilidades em sua estrutura para identificar os casos de tuberculose. Lacunas no processo foram identificadas em ambos os serviços de atenção básica e pronto atendimento. É necessária a qualificação dos serviços de saúde que constituem as principais portas de entrada ao sistema de saúde para atender as reformas setoriais que priorizam o diagnóstico oportuno e o controle da tuberculose.

  1. DIAGNOSTICO DE AFECCIONES RESPIRATORIAS EN CAMPO QUIJANO SALTA -ARGENTINA

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    Marta Leonor de Viana

    2008-01-01

    Full Text Available Campo Quijano está a 30 Km. de la ciudad de Salta y cuenta aproximadamente con 8300 habitantes. En el éjido urbano existen dos borateras que constituyen una fuente puntual de contaminación del aire, suelo y aguas. Se estudió la prevalencia de enfermedades respiratorias en la población urbana en el año 2005. Se trabajó con los datos de las planillas de consultas diarias externas del Hospital Francisco Herrera. Se consideraron cuatro grupos de afecciones, seleccionados por la sintomatología y su posible asociación con las emisiones gaseosas de las borateras: Rinitis; Catarro en vías aéreas superiores, Espasmos y Tos irritativa. Se estimó y comparó la prevalencia de las enfermedades por barrio con la prueba de X2 y la de los residuales ajustados de Haberman. Los espasmos y catarros en vías aéreas superiores fueron las afecciones más frecuentes en la población de Campo Quijano. En rinitis no se encontraron diferencias entre barrios. El barrio San Roque presentó las mayores prevalencias en CVAs, espasmos y tos irritativa. Barrios cercanos a las borateras presentaron prevalencias dispares, lo que podría relacionarse con características socio-culturales, sanitarias y económicas, entre otros factores de riesgo, no considerados en este diagnóstico.

  2. BIOPSIA DE ENCIA EN EL DIAGNOSTICO DE LA MICROANGIOPATIA DIABETICA

    OpenAIRE

    Vega, L.; Profesores de la Cátedra de Clínica Médica II de la Facultad de Medicina de la U.N.M.S.M. Lima - Perú.; Garmendia, Fausto; Profesores de la Cátedra de Clínica Médica II de la Facultad de Medicina de la U.N.M.S.M. Lima - Perú.; Sotelo, J.; Profesores de la Cátedra de Clínica Médica II de la Facultad de Medicina de la U.N.M.S.M. Lima - Perú.; Glodszmidt, Moises; Profesores de la Cátedra de Clínica Médica II de la Facultad de Medicina de la U.N.M.S.M. Lima - Perú.; Romero, Roberto; Profesor Estomatólogo de la Cátedra Clínica Estomatológica y Clínica Médica II de la Facultad de Odontología y Facultad de Medicina de la U.N.M.S.M. Lima - Perú.

    2014-01-01

    A study was made of gingival biopsies perfomed in 42 patients, 24 of the patients. Were diabetics and 18 were non diabeties used as controls. Capillary lesions were found in all diabetic patients. These lesions varied from a minimal thickening of the basement membrane. This thickening was P.A.S. positive. In 90% of the diabetic patients a thickening of the nodular type in the walls of the thickened capillaries and too were fonud a series of pictures of transition between the diffuse, more or ...

  3. Lipoma arborescens: diagnosis and image; Lipoma arborescens: diagnostico e imagem

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, Marcela; Len, Claudio Arnaldo; Terreri, Maria Teresa Ramos Ascencao [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Setor de Reumatologia Pediatrica; Fernandes, Artur da Rocha Correa [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Diagnostico por Imagem; Hilario, Maria Odete Esteves [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Alergia, Imunologia e Reumatologia]. E-mail: odetehilario@terra.com.br

    2004-08-01

    Lipoma arborescens is an intraarticular lesion of unknown etiology, consisting of a chronic villous fat proliferation of the synovial membrane. The disease has occasionally been associated with diabetes mellitus, degenerative diseases, juvenile rheumatoid arthritis and also rheumatoid arthritis. The diagnosis relies on magnetic resonance imaging evaluation and synovial biopsy. We report a case of a 8-year-old girl with a two year history of bilateral swelling of the knees and elbows. The patient had improvement of the arthritis after starting treatment with conventional drugs. (author)

  4. Infezione da Bartonella henselae: caso clinico e supporto diagnostico

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    Salvatore Nisticò

    2006-03-01

    Full Text Available Cat scratch disease is due to a bacterial infection sustained by Bartonella strains, transmitted to the human through the bite, scratch or lick of cats.We report a case about a young man who showed up to the Pediatrics outpatient clinic after he noticed a growing mass in his left armpit, preceded by malaise, fatigue and mild fever. The detection of the scar as a consequence of a cat scratch suggested the Bartonella infection diagnosis. Thus the patient had a blood test, the erythrocyte sedimentation velocity and specific antibodies assay: the measurement of serum Bartonella specific antibodies yelded high levels of IgM and IgG which confirmed the diagnosis.The patient was treated with a course of oral antibiotic, specifically Claritromicin 250 mg tablets BID for two weeks.After 30 days the axillary nodal mass downsized.The serum immunoglobulin assay cut down the time required for the formulation of the causative diagnosis and allowed for a prompt and aimed antimicrobial therapy. Compared with the blood culture, the antibodies test screening is quicker and highly reliable.

  5. La odontologia en el diagnostico del maltrato infantil

    National Research Council Canada - National Science Library

    Doria Martinez, Ana Milena; Navarro Chong, Melissa Ivette

    2016-01-01

    Antecedentes: El maltrato infantil fue descrito por primera vez en 1868 por el patologo Ambrosio Tardieu, pero solo hasta el siglo pasado el papel del odontologo se torno relevante para diagnosticar el sindrome...

  6. ACTIVIDADES DOMÉSTICAS DURANTE LOS SIGLOS III -VIII D.C. EN EL VALLE DE POTRERILLOS (SAN IGNACIO-MENDOZA. UN ACERCAMIENTO DESDE LA OSTEOMETRÍA Y LA TECNOLOGÍA CERÁMICA Y LÍTICA / Domestic activities during the III-VIII centuries AD in Potrerillos Valley

    Directory of Open Access Journals (Sweden)

    Alejandra Valeria Gasco

    2011-12-01

    Full Text Available San Ignacio, en el Valle de Potrerillos, fue habitado durante los siglos III-VIII D.C. por grupos humanos que construyeron hornillos y ocuparon casas semi-subterráneas. Constituye uno de los escasos registros sistemáticos de contextos domésticos para el valle. Se presenta y caracteriza el sitio mediante el análisis osteométrico de camélidos, la organización de la tecnología lítica y el análisis tipológico y morfo-funcional cerámico. Las diversas actividades domésticas desarrolladas combinaron la explotación de camélidos silvestres y domésticos, además de cultígenos. Los rasgos arquitectónicos y los patrones materiales del interior de la unidad habitacional, se relacionan con una ocupación anticipada de tipo permanente. La cerámica analizada fue asignada al estilo Agrelo-Calingasta del período Agro-alfarero Temprano-Medio de la arqueología regional. El asentamiento podría insertarse en un circuito de movilidad para el aprovechamiento de diversos recursos en ambientes de altura. Además se sugiere la participación en redes de intercambio, evidenciada por la presencia de cerámica similar a la de los complejos culturales que se desarrollaron en la vertiente occidental de Los Andes y por la identificación de un morfotipo de camélido especialmente grande, propicio para la realización de caravanas.   Palabras clave: Valle de Potrerillos; Período Agro-alfarero regional; Contexto Doméstico; Camélidos silvestres y domésticos; Redes de Intercambio.   Abstract San Ignacio, in the Valley of Portrerillos was occupied during the third to eighth centuries A.D. by groups that constructed pit ovens and occupied semi-subterranean houses. It is one of the few systematically recorded domestic contexts in the valley. The site is presented and characterized through the osteometric analysis of camelids, the organization of lithic technology, and typological and morphofunctional analyses of ceramics. Diverse domestic activities

  7. III. Mezquita de Córdoba. El trazado de la portada interior de la Bāb al-Wuzarā’. La Puerta de los Deanes (s. VIII, su trazado interior y exterior

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    Fernández-Puertas, Antonio

    2009-06-01

    Full Text Available The design of the inner façade of the Bāb al-Wuzarā’ is based on a square and its diagonal √2, with the use of a set-square of 90°, 45°, 45°, another of 90°, 60°, 30° and a compass. The ashlars alternate correctly in depth and width. The lintel space is carried by a horse-shoe arch with a merlon frieze. The intrados of the jambs reveals, by the differing ashlars, the consolidation of the Bāb al-Wuzarā’ undertaken in 855/856. The inner façade of the Puerta de los Deanes belongs to the eighth century, the outer façade was consolidated in the fourteenth. The steps are done with both set-squares and a compass. The left jamb on the N. side shows the larger ashlars of the eighth century and the smaller ones of the tenth century.

    El trazado de la portada interior de la Bāb al-Wuzarā’ obedece al cuadrado y su diagonal √2, y al uso de la escuadra, el cartabón y el compás. La cantería del muro está bien despiezada a soga y tizón. El hueco adintelado se descarga por arco enjarjado de herradura con alfiz y friso de almenas. En el intradós de las jambas del hueco se ve, en el despiece de la cantería, la obra de consolidación de la Bāb al-Wuzarā’ del 855/856. La Puerta de los Deanes en su fachada interior es obra del siglo VIII y la exterior fue consolidada en el siglo XIV. Su trazado se ha hecho con la escuadra, el cartabón y el compás. En la jamba izquierda, a N., se ve la unión de la cantería del siglo VIII con la de menor sección del siglo X.

  8. Polymorphisms in the F8 gene and MHC-II variants as risk factors for the development of inhibitory anti-factor VIII antibodies during the treatment of hemophilia a: a computational assessment.

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey

    Full Text Available The development of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most significant impediment to the effective management of hemophilia A. Common non-synonymous single nucleotide polymorphisms (ns-SNPs in the F8 gene occur as six haplotypes in the human population (denoted H1 to H6 of which H3 and H4 have been associated with an increased risk of developing anti-drug antibodies. There is evidence that CD4+ T-cell response is essential for the development of anti-drug antibodies and such a response requires the presentation of the peptides by the MHC-class-II (MHC-II molecules of the patient. We measured the binding and half-life of peptide-MHC-II complexes using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that these wild type peptides form stable complexes with six common MHC-II alleles, representing 46.5% of the North American population. Next, we compared the affinities computed by NetMHCIIpan, a neural network-based algorithm for MHC-II peptide binding prediction, to the experimentally measured values and concluded that these are in good agreement (area under the ROC-curve of 0.778 to 0.972 for the six MHC-II variants. Using a computational binding predictor, we were able to expand our analysis to (a include all wild type peptides spanning each polymorphic position; and (b consider more MHC-II variants, thus allowing for a better estimation of the risk for clinical manifestation of anti-drug antibodies in the entire population (or a specific sub-population. Analysis of these computational data confirmed that peptides which have the wild type sequence at positions where the polymorphisms associated with haplotypes H3, H4 and H5 occur bind MHC-II proteins significantly more than a negative control. Taken together, the experimental and computational results suggest that wild type peptides from polymorphic regions of FVIII constitute potential T-cell epitopes

  9. Status and trend analysis of prophylactic usage of recombinant factor VIII in Chinese pediatric patients with hemophilia A: ReCare - a retrospective, phase IV, non-interventional study.

    Science.gov (United States)

    Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Vicky; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

    2017-09-01

    No study has reported the status and chronological trend of prophylactic recombinant factor VIII (rFVIII) use in Chinese pediatric patients with hemophilia A (HA). We aimed to analyze the status and trend of rFVIII-containing prophylaxis in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained REgular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers across China. The trend of prophylaxis was evaluated by determining the mean duration of prophylaxis, mean injection frequency (per week), mean dose of each injection (IU/kg), mean total dose injected/week (IU) and proportion of rFVIII consumption relative to factor VIII (FVIII) consumption over the study period. We analyzed 183 male pediatric patients with HA (mean age, 7.1 ± 4.23 years), who received intermittent prophylaxis between 1 November 2007 and 31 May 2013. The mean duration of prophylaxis with rFVIII increased from 16.72 weeks in 2008 to 32.77 in 2012. Per injection dose of rFVIII increased significantly from 2008 to 2013 (25.89 to 28.31 IU/kg, p < .001). An increase was also reported in the mean total FVIII consumed (699.97 ± 173.25 IU in 2008 and 891.30 ± 730.341 in 2013) and mean proportion of rFVIII used (33.33 ± 57.73% in 2008 to 85.50 ± 29.077% in 2013). Our data revealed an overall improvement in treatment dosage and duration with an increase in the number of patients receiving prophylaxis. The total proportion of rFVIII also increased gradually indicating the development of economy and safety awareness. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02263066).

  10. Polymorphisms in the F8 gene and MHC-II variants as risk factors for the development of inhibitory anti-factor VIII antibodies during the treatment of hemophilia a: a computational assessment.

    Science.gov (United States)

    Pandey, Gouri Shankar; Yanover, Chen; Howard, Tom E; Sauna, Zuben E

    2013-01-01

    The development of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most significant impediment to the effective management of hemophilia A. Common non-synonymous single nucleotide polymorphisms (ns-SNPs) in the F8 gene occur as six haplotypes in the human population (denoted H1 to H6) of which H3 and H4 have been associated with an increased risk of developing anti-drug antibodies. There is evidence that CD4+ T-cell response is essential for the development of anti-drug antibodies and such a response requires the presentation of the peptides by the MHC-class-II (MHC-II) molecules of the patient. We measured the binding and half-life of peptide-MHC-II complexes using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that these wild type peptides form stable complexes with six common MHC-II alleles, representing 46.5% of the North American population. Next, we compared the affinities computed by NetMHCIIpan, a neural network-based algorithm for MHC-II peptide binding prediction, to the experimentally measured values and concluded that these are in good agreement (area under the ROC-curve of 0.778 to 0.972 for the six MHC-II variants). Using a computational binding predictor, we were able to expand our analysis to (a) include all wild type peptides spanning each polymorphic position; and (b) consider more MHC-II variants, thus allowing for a better estimation of the risk for clinical manifestation of anti-drug antibodies in the entire population (or a specific sub-population). Analysis of these computational data confirmed that peptides which have the wild type sequence at positions where the polymorphisms associated with haplotypes H3, H4 and H5 occur bind MHC-II proteins significantly more than a negative control. Taken together, the experimental and computational results suggest that wild type peptides from polymorphic regions of FVIII constitute potential T-cell epitopes and thus

  11. Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis: 4. Classificação histopatológica

    Directory of Open Access Journals (Sweden)

    Albino Verçosa de Magalhães

    1986-12-01

    Full Text Available Os A A. analisaram as alterações histológicas encontradas em 162 casos de Leishmaniose Tegumentar da localidade de Três Braços, Estado da Bahia, dos quais 131 (80,9% eram de portadores de lesões cutâneas e 31 (19,1% de portadores de lesões mucosas. Analisaram, também, o comportamento clínico dos cinco padrões histopatológicos, já antes descritos, em relação à terapêutica. O melhor prognóstico esteve sempre ligado ao padrão de Reação Exsudativa e Granulomatosa, ou seja, a uma fase na qual o organismo, tendo lançado mão de um mecanismo endógeno de lise parasitária, já circunscreveu a área de necrose por uma reação granulomatosa, e esta é agora apenas o elemento residual. A ação terapêutica nessa fase somente acelera a resolução natural do caso. O grupo seguinte é amplo, e compreende os casos em que a lesão pertence aos padrões de Reação Exsudativa Celular (formas cutâneas, Reação Exsudativa e Necrótica e Reação Exsudativa e Necrótico-Granulomatosa. Nesses casos, o mecanismo de auto-controle da lesão encontra-se ainda em curso, e a ação terapêutica encurta o período de evolução natural. Os f.asos do padrão de Reação Exsudativa e Tuberculóide tiveram um prognóstico variável. Houve boa resposta à terapêutica quando o granuloma tuberculóide característico desse padrão surgiu em pacientes jovens, com curto tempo de evolução da doença e intradermorreação não exacerbada. Nos demais casos tuberculóides —. principalmente em pacientes adultos, com longo tempo de evolução da doença e intradermorreação exacerbada —, a resposta foi menos satisfatória. Em último lugar, com prognóstico reservado, ficaram os casos da forma mucosa que apresentaram o padrão de Reação Exsudativa Celular, onde o infiltrado pode estar desempenhando papel de auto-agressão. O presente estudo evoluiu para a proposição de uma classificação da Leishmaniose Tegumentar, baseada nos padrões histopatológicos observados. Esta classificação, estritamente morfológica, deverá ser de fácil aplicação para o Patologista e, como apresenta também uma correspondência clínico-evolutiva poderá constituir auxílio valioso ao médico envolvido no diagnóstico e tratamento da Leishmaniose Tegumentar.

  12. Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 3. Reação celular nos tecidos

    Directory of Open Access Journals (Sweden)

    Albino Verçosa de Magalhães

    1986-10-01

    Full Text Available Os A.A. analisam as alterações histopatológicas observadas em 378 casos de Leishmaniose Tegumentar da localidade de Três Braços Estado da Bahia, dos quais 307 eram de portadores de lesões exclusivamente cutâneas, 54 de portadores de lesões exclusivamnte mucosas e 17 de portadores de lesões cutâneo-mucosas. A infiltração histiolinfoplasmocitária, na maioria dos casos, parece desempenhar o papel de resposta celular inespecífica à presença de um irritante tecidual, porém, nos casos de forma mucosa, não se pode afastar a possibilidade de que esse infiltrado esteja participando de uma reação de tipo autoagressivo. O plasmócito constitui um elemento quase constante nas lesões desenvolvidas, mas não tem sido observado nas lesões residuais, quer em via de cura ou já cicatrizadas; sua presença nestes casos denota, quase sempre, tendência à recidiva. Os mastdcitos foram observados em lesões tanto da forma cutânea como da forma mucosa, mas predominavam nas primeiras. Seu número foi significantemente maior no padrão de Reação Exsudativa e Neerótico Granulomatosa, onde os fenômenos necróticos são bem desenvolvidos. Os eosinófilos apresentaram associação significativa com os mastócitos, confirmando a existência de um eixo bidirecional entre estás duas células, o qual deve participar da modulação inflamatória, na Leishmaniose Tegumentar. Dois tipos de reação granulomatosa foram observados: um desorganizado, em relação, muitas vezes, com a necrose tissular, e outro organizado, mais raro, do tipo tuberculóide. O primeiro foi interpretado como de origem pós-necrótica, surgindo com a redução da carga parasitária, propiciada pelos fenômenos necróticos: eliminado o antígeno e mantidos os níveis de anticorpos, surgem as condições necessárias ao estabelecimento do granuloma, semelhante àquele observado nas lesões por imunocomplexo em excesso de anticorpos. O outro tipo de reação foi o granuloma de células epiteliódes, que surgiu em dois grupos de pacientes. Nos pacientes jovens, com doença de curto tempo de evolução e intradermorreação não exacerbada, este tipo de granuloma talvez seja a expressão da Hipersensibilidade Granulomatosa Específica, descrita por EPSTEIN (1977. No outro grupo de pacientes, havia em todos intradermorreação exacerbada. Nestes casos a hipersensibilidade granulomatosa, associando-se ã hipersensibilidade mediada por células — agora ampliada pelo seqüestro do antígeno —, reforçaria o processo granulomatoso, através da reverberação do estímulo antígênico; isso tornaria o tratamento mais difícil e pior o prognóstico para o caso.

  13. ATLAS DIGITAL DE MORFOLOGIA COMPARADA: UMA FERRA-MENTA COMPLEMENTAR AO ENSINO DE HISTOLOGIA E HISTO-PATOLOGIA

    OpenAIRE

    Burity, Carlos Henrique de Freitas; UNIGRANRIO; Cardozo, Sergian Vianna; Unigranrio

    2014-01-01

    O objetivo do presente trabalho foi estruturar um atlas de morfologia comparada digital e disponibiliza-lo, como ferramenta digital complementar de auxílio ao estudo dos alunos, junto ao portal acadêmico da Universidade, facilitando o ensino e aprendizagem nas áreas de morfologia. Avaliou-se por meio de grupos comparativos o desempenho dos alunos nas disciplinas relacionadas, de 2009 a 2012, utilizando-se os parâmetros: alunos abaixo da média e o índice de reprovação. Os resultados demonstrar...

  14. LEGAL RELATIONSHIP BETWEEN ILLEGITIMATE CHILDREN AND THEIR BIOLOGICAL FATHER: The Analysis of Constitutional Court Decree No. 46/PUU-VIII/2010 in the Perspective of Civil and Islamic Law

    Directory of Open Access Journals (Sweden)

    Marilang Marilang

    2016-12-01

    Full Text Available In Indonesia, children born out of wedlock only have legal relationship or family lineage relationship with their mother and mother’s family, not with their biological father and biological father’s family. This provisions of law are arranged in Article 43 paragraph (1 of Marriage Law No. 1 of 1974 which is highly influenced by Shafi’ite School of Islamic jurisprudence. Through judicial review of Aisyah (Machica Mochtar and her son named M. Iqbal Ramadhan, Constitutional Court has agreed to waive the provisions by means of the Decree Number 46/PUU-VIII/2010 with legal consideration that the concerned article contravenes the Constitution, then it creates new legal norm which states those children have legal relationship and family lineage with their mother and mother’s family and also the man who is their father. The Decree sparks controversies concerning the term ‘children born out of wedlock’ and ‘legal relationship’ in the decree. Contrary to many law experts, the article argues that the term ‘children born out of wedlock’ simply means children born from zina (adultery or fornication. Thus, ‘legal relationship’ only refer to limited relationship between both parties.

  15. Solution of the Skyrme-Hartree-Fock-Bogolyubovequations in the Cartesian deformed harmonic-oscillator basis. (VIII) HFODD (v2.73y): A new version of the program

    Science.gov (United States)

    Schunck, N.; Dobaczewski, J.; Satuła, W.; Bączyk, P.; Dudek, J.; Gao, Y.; Konieczka, M.; Sato, K.; Shi, Y.; Wang, X. B.; Werner, T. R.

    2017-07-01

    We describe the new version (v2.73y) of the code HFODD which solves the nuclear Skyrme Hartree-Fock or Skyrme Hartree-Fock-Bogolyubov problem by using the Cartesian deformed harmonic-oscillator basis. In the new version, we have implemented the following new features: (i) full proton-neutron mixing in the particle-hole channel for Skyrme functionals, (ii) the Gogny force in both particle-hole and particle-particle channels, (iii) linear multi-constraint method at finite temperature, (iv) fission toolkit including the constraint on the number of particles in the neck between two fragments, calculation of the interaction energy between fragments, and calculation of the nuclear and Coulomb energy of each fragment, (v) the new version 200d of the code HFBTHO, together with an enhanced interface between HFBTHO and HFODD, (vi) parallel capabilities, significantly extended by adding several restart options for large-scale jobs, (vii) the Lipkin translational energy correction method with pairing, (viii) higher-order Lipkin particle-number corrections, (ix) interface to a program plotting single-particle energies or Routhians, (x) strong-force isospin-symmetry-breaking terms, and (xi) the Augmented Lagrangian Method for calculations with 3D constraints on angular momentum and isospin. Finally, an important bug related to the calculation of the entropy at finite temperature and several other little significant errors of the previous published version were corrected.

  16. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  17. Applying cheerful disco learning for improving of motivation and learning result of PKn in grade viii c students junior high school 1 Kebumen in second semester 2013/2014 academic years

    Directory of Open Access Journals (Sweden)

    Siti Makmuroh

    2017-06-01

    Full Text Available The aim of this classroom action research is to improve students’ learning motivation, learning result of PKn on Basic Competence of Describing Indonesian Government System and the Roles of the State Institutions as the Sovereignty Executive and the characters of Grade VIII C Students of Junior High School 1 of Kebumen in Second Semester of Academic Year 2013/2014 by applying CHEERFUL DISCO learning method. The research is a classroom action research conducted in two cycles; each cycle of which includes planning, conducting, observation, and reflection. The result of the research shows that the learning method was able to improve the students’ learning motivation in learning activities from 62.37% in pre cycle to 73.74% in the first cycle, then from 78.91% in the second cycle, improved the PKn learning achievement in mastering concept of the ability to describe Indonesian Government System and the Roles of the State Institutions as the Sovereignty Executive, which can be seen that the students’ achievement test result is improving in average from 78.18 with 54.55% of mastery learning in pre cycle to 83.23 with 72.73% of mastery learning in the first cycle, then it was improved to 86.59 in average with 81.82% of mastery learning in the second cycle.

  18. 'Medusa-head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII.

    Science.gov (United States)

    Jarius, S; Wildemann, B

    2015-09-17

    Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa-head antibodies' due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects and provides a summary and outlook.

  19. Carbonic anhydrase-related protein VIII is expressed in rod bipolar cells and alters signaling at the rod bipolar to AII-amacrine cell synapse in the mammalian retina.

    Science.gov (United States)

    Puthussery, T; Gayet-Primo, J; Taylor, W R

    2011-11-01

    Mutation of the gene encoding carbonic anhydrase-related protein VIII (CAVIII) results in motor coordination deficits in mice and humans, due to loss of this protein in Purkinje cells of the cerebellum. Recent studies have indicated that the CAVIII gene, Car8, is also expressed in rod bipolar cells (RBCs), a critical glutamatergic neuron for scotopic vision. We investigated the localization of CAVIII in the mouse and macaque retina, and utilized the wdl mouse, which has a null mutation in the Car8 gene, to determine how the loss of CAVIII affects retinal signaling. CAVIII immunoreactivity was observed in RBCs, with particularly high staining intensity in the axon terminals. In addition, weaker staining was observed in a subset of cone bipolar cells and γ-aminobutyric acid (GABA)ergic amacrine cells. Light-evoked current and voltage responses of RBCs were not altered in the wdl mutant. However, light-evoked current responses from the AII-amacrine cell, a postsynaptic partner at the RBC ribbon synapse, were significantly larger, and more prolonged than in control mice. These changes could not be attributed to alterations in calcium current activation or inactivation, or to changes in the density of RBCs. Furthermore, no gross synaptic alterations were evident in the wdl mutant at the light or ultrastructural level. These data provide evidence that the CAVIII protein, which is highly conserved in vertebrates, is selectively expressed within neural circuits, and may be important for modulating retinal neurotransmission. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  20. Low risk of inhibitor formation in haemophilia A patients following en masse switch in treatment to a third generation full length plasma and albumin-free recombinant factor VIII product (ADVATE®).

    LENUS (Irish Health Repository)

    Bacon, C L

    2011-05-01

    Previous studies have suggested that development of inhibitors in previously treated patients (PTPs) may be attributable to a switch in factor VIII (FVIII) therapeutic product. Consequently, it is widely recognized that inhibitor development must be assessed in PTPs following the introduction of any new FVIII product. Following a national tender process in 2006, all patients with haemophilia A in Ireland changed their FVIII treatment product en masse to a plasma and albumin-free recombinant full-length FVIII product (ADVATE(®)). In this study, we retrospectively reviewed the case records of Irish PTPs to evaluate risk of inhibitor formation following this treatment switch. One hundred and thirteen patients participated in the study. Most patients (89%) had severe haemophilia. Only one of 96 patients with no inhibitor history developed an inhibitor. Prior to the switch in his recombinant FVIII (rFVIII) treatment of choice, this child had only experienced three exposure days (EDs). Consequently, in total he had only received 6 EDs when his inhibitor was first diagnosed. In keeping with this lack of de novo inhibitor development, we observed no evidence of any recurrent inhibitor formation in any of 16 patients with previously documented inhibitors. Similarly, following a previous en masse switch, we have previously reported that changing from a Chinese hamster ovary cell-produced to a baby hamster kidney cell-produced rFVIII was also associated with a low risk of inhibitor formation in PTPs. Our cumulative findings from these two studies clearly emphasizes that the risk of inhibitor development for PTPs following changes in commercial rFVIII product is low, at least in the Irish population.

  1. Long-term efficacy and safety of prophylaxis with recombinant factor VIII in Chinese pediatric patients with hemophilia A: a multi-center, retrospective, non-interventional, phase IV (ReCARE) study.

    Science.gov (United States)

    Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Weiqun; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

    2017-07-01

    The first recombinant factor VIII (rFVIII) product was launched in China in 2007. However, until now, no study has been conducted to describe the efficacy and safety of prophylaxis with rFVIII in Chinese pediatric patients with hemophilia A (HA). To summarize the efficacy and safety data on prophylaxis with rFVIII in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained regular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers (HTCs) across China. The primary endpoints included reduction in annualized bleeding rate (ABR); the secondary endpoints included evaluation of joint function (number and sites of target joints) using Gilbert score and Hemophilia Joint Health Score (HJHS), quality of life (QoL) and factors affecting treatment choices. Safety assessment of rFVIII was also conducted. We analyzed a total of 183 male pediatric patients (mean age, 7.1 ± 4.23 years) who received prophylaxis between 1 November 2007 and 31 May 2013. Compared with baseline, prophylaxis with rFVIII significantly reduced overall annualized joint bleed rate (AJBR) (p < .001) and ABR (p < .001). Inhibitor formation was reported in 5 (2.7%) patients and hemarthrosis was reported in 1 patient. The mean number of target joints was positively related to age (p < .001) and weight (p = .003) at baseline. Responses from survey questionnaires reported that effective bleeding control, joint protection, improvement in quality of life, favorable medical insurance policies, and economic capability were reasons for choosing prophylaxis. Prophylaxis with rFVIII reduced bleeding and number of target joints, even with a low-dose regimen, in Chinese pediatric patients with HA. Other than the efficacy and safety, factors such as poor disease control, improved economic stability and stable financial support made prophylaxis as an attractive treatment option. ClinicalTrials.gov ID

  2. A non-destructive spectroscopic study of the decoration of archaeological pottery: from matt-painted bichrome ceramic sherds (southern Italy, VIII-VII B.C.) to an intact Etruscan cinerary urn

    Science.gov (United States)

    Bruni, Silvia; Guglielmi, Vittoria; Della Foglia, Elena; Castoldi, Marina; Bagnasco Gianni, Giovanna

    2018-02-01

    A study is presented based on the use of entirely non-destructive spectroscopic techniques to analyze the chemical composition of the painted surface layer of archaeological pottery. This study aims to define both the raw materials and the working technology of ancient potters. Energy-dispersive X-ray analysis, micro-Raman spectroscopy, visible and near infrared (NIR) diffuse reflection spectroscopy and external reflection Fourier-transform infrared (FTIR) spectroscopy were applied to matt-painted bichrome pottery sherds (VIII-VII century B.C.) from the site of Incoronata near Metaponto in southern Italy. Two different raw materials, ochre and iron-rich clay, were recognized for the red decoration, while the dark areas resulted to have been obtained by the so-called manganese black technique. In any case, it was demonstrated that the decoration was applied before firing, in spite of its sometimes grainy aspect that could suggest a post-firing application. For the samples with a more sophisticated decorative pattern a red/black/white polychromy was recognized, as the lighter areas correspond to an ;intentional white; obtained by the firing of a calcium-rich clay. Reflection spectroscopy in the visible-NIR and mid-IR as well as micro-Raman spectroscopy were then employed to characterize the decoration of an intact ceramic urn from the Etruscan town of Chiusi, evidencing a post-firing painting based on the use of red ochre, carbon black and lime, possibly imitating the ;fresco; technique used in wall paintings.

  3. CD4+FOXP3+ regulatory T cells confer long-term regulation of factor VIII-specific immune responses in plasmid-mediated gene therapy-treated hemophilia mice.

    Science.gov (United States)

    Miao, Carol H; Harmeling, Benjamin R; Ziegler, Steven F; Yen, Benjamin C; Torgerson, Troy; Chen, Liping; Yau, Roger J; Peng, Baowei; Thompson, Arthur R; Ochs, Hans D; Rawlings, David J

    2009-11-05

    Gene transfer of a factor VIII (FVIII) plasmid into hemophilia A (HemA) mice achieved supraphysiologic FVIII expression, but triggered production of high-titer FVIII-specific antibodies and loss of functional FVIII activity. To test whether FVIII-specific regulatory T cells (Tregs) can modulate immune responses against FVIII, we developed a HemA mouse model in which all T cells overexpressed Foxp3 (HemA/Foxp3-Tg). FVIII plasmid therapy did not induce antibody production in HemA/Foxp3-Tg mice. CD4(+)Foxp3(+) T cells isolated from plasmid-treated HemA/Foxp3-Tg mice significantly suppressed proliferation of FVIII-stimulated CD4(+) effector T cells. The percentage of CD4(+) T cells expressing CD25, glucocorticoid-induced tumor necrosis factor receptor, and cytotoxic T lymphocyte antigen 4 increased significantly in spleen and peripheral blood for 9 weeks. Mice receiving adoptively transferred Tregs from FVIII-exposed HemA/Foxp3-Tg mice produced significantly reduced antibody titers compared with controls after initial challenge with FVIII plasmid and second challenge 16 weeks after first plasmid treatment. Adoptively transferred Tregs engrafted and distributed at 2% to 4% in the Treg compartment of blood, lymph nodes, and spleens of the recipient mice and induced activation of endogenous Tregs; the engraftment decreased to negligible levels over 8 to 12 weeks. Antigen-specific Tregs can provide long-lasting protection against immune responses in vivo and limit recall responses induced by a second challenge via infectious tolerance.

  4. Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer

    Science.gov (United States)

    Karlsson, P.; Sun, Z.; Braun, D.; Price, K. N.; Castiglione-Gertsch, M.; Rabaglio, M.; Gelber, R. D.; Crivellari, D.; Collins, J.; Murray, E.; Zaman, K.; Colleoni, M.; Gusterson, B. A.; Viale, G.; Regan, M. M.; Coates, A. S.; Goldhirsch, A.

    2011-01-01

    Background: The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. Patients and methods: From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of ‘classical’ CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF→ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. Results: For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF→ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). Conclusions: For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea. PMID:21325445

  5. A non-destructive spectroscopic study of the decoration of archaeological pottery: from matt-painted bichrome ceramic sherds (southern Italy, VIII-VII B.C.) to an intact Etruscan cinerary urn.

    Science.gov (United States)

    Bruni, Silvia; Guglielmi, Vittoria; Della Foglia, Elena; Castoldi, Marina; Bagnasco Gianni, Giovanna

    2018-02-15

    A study is presented based on the use of entirely non-destructive spectroscopic techniques to analyze the chemical composition of the painted surface layer of archaeological pottery. This study aims to define both the raw materials and the working technology of ancient potters. Energy-dispersive X-ray analysis, micro-Raman spectroscopy, visible and near infrared (NIR) diffuse reflection spectroscopy and external reflection Fourier-transform infrared (FTIR) spectroscopy were applied to matt-painted bichrome pottery sherds (VIII-VII century B.C.) from the site of Incoronata near Metaponto in southern Italy. Two different raw materials, ochre and iron-rich clay, were recognized for the red decoration, while the dark areas resulted to have been obtained by the so-called manganese black technique. In any case, it was demonstrated that the decoration was applied before firing, in spite of its sometimes grainy aspect that could suggest a post-firing application. For the samples with a more sophisticated decorative pattern a red/black/white polychromy was recognized, as the lighter areas correspond to an "intentional white" obtained by the firing of a calcium-rich clay. Reflection spectroscopy in the visible-NIR and mid-IR as well as micro-Raman spectroscopy were then employed to characterize the decoration of an intact ceramic urn from the Etruscan town of Chiusi, evidencing a post-firing painting based on the use of red ochre, carbon black and lime, possibly imitating the "fresco" technique used in wall paintings. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. ЗАМОВНІ ВБИВСТВА У ДАВНЬОСКАНДИНАВСЬКОМУ СУСПІЛЬСТВІ (VIII – ПОЧ. XI СТ. / CONTRACT KILLINGS IN OLD SCANDINAVIAN SOCIETY (IN THE LATE VIII - MIDDLE XI.

    Directory of Open Access Journals (Sweden)

    Олексій ТРЕТЬЯКОВ

    2016-09-01

    Full Text Available Третьяков Алексей. Заказные убийства в древнескандинавском обществе (VIII – первая половина. XI ст.. В статье автор исследует явление заказных убийств в раннесредневековом скандинавском обществе. Анализируется взаимодействие законов направленных против данного вида преступлений. Выделены основные категории убийц и показана их мотивация. Рассмотрены вопросы, связанные с самодентификацией преступников и связь их действий с мировоззренческими установками эпохи викингов.Ключевые слова: заказные убийства, раннесредневековое скандинавское общество, эпоха викингов, дружинники, человек вне закона, рабы. Olexiy Tretyakov. Contract killings in old scandinavian society (in the late VIII - middle XI.. The article deals with the phenomenon of contract killings in early medieval Scandinavian society (VIII - middle XI.. It is shown in the research that the transformation of tribal system of feudal relations gave rise to numerous political and social conflicts. It was a major factor in the increase of violence during the Viking Age. Relationships in Scandinavian society regulated early medieval oral law, what was codified later in the XII - XIII centuries. Its social function was to create a system of compromises and peace. The publication traces the main forms of liability provided for murder. All the way it explains the basic forms of the revealed outlaw, exile and, in fact, a large quantity of illegal persons. In the article was considered a significant

  7. EFEKTIVITAS PENDEKATAN CONTEXTUAL TEACHING AND LEARNING (CTL POKOK BAHASAN PERMINTAAN, PENAWARAN, DAN TERBENTUKNYA HARGA PASAR TERHADAP PENINGKATAN HASIL BELAJAR SISWA KELAS VIII SMP NEGERI 5 CILACAP TAHUN PELAJARAN 2011/2012

    Directory of Open Access Journals (Sweden)

    Febri Munda Aji Qisthy,

    2012-10-01

    Full Text Available Pembelajaran pada umumnya dilaksanakan oleh guru banyak menekankan pada aspek pengetahuan dan pemahaman. Untuk itu diperlukan metode pembelajaran yang inovatif, aktif dan kreatif salah satunya adalah pendekatan Contextual Teaching and Learning (CTL. Pembelajaran ini dapat membantu siswa dalam menguasai materi pembelajaran guna mencapai hasil yang maksimal. Permasalahannya dalam penelitian ini adalah model pembelajaran manakah yang dapat meningkatkan hasil belajar dan yang lebih efektif antara pembelajaran Contextual Teaching and Learning (CTL dengan Konvensional. Berdasarkan uji peningkatan hasil belajar pada kelas eksperimen diperoleh rata-rata post tes 81,84 dan rata-rata kelas kontrol 74,76 �maka dapat disimpulkan bahwa data akhir (post test kelompok eksperimen lebih tinggi dibanding kelas kontrol. Dari hasil observasi aktivitas siswa diperoleh rata � rata presentase keaktifsn siswa dengan model CTL lebih tinggi yaitu 68% dibandingkan dengan metode konvensional yaitu 59%. Dari hasil perhitungan uji hipotesis, penggunaan pendekatan Contextual Teaching and Learning (CTL lebih efektif dari pada metode konvensional pada pembelajaran IPS ekonomi standar kompetensi permintaan, penawaran, dan tebentuknya harga pasar pada siswa kelas VIII SMP Negeri 5 Cilacap tahun pelajaran 2011/2012. Lessons are generally held by many teachers emphasize the aspects of knowledge and understanding. It required an innovative learning method, one active and creative approach is Contextual Teaching and Learning (CTL. These lessons can help students in mastering the learning materials in order to achieve maximum results. The problem in this study is a model of learning which can improve learning outcomes and the more effective the learning Contextual Teaching and Learning (CTL with Conventional. Based on the test improved learning outcomes in the experimental class gained an average of 81.84 and a post-test control class average 74.76, it can be concluded that the

  8. The prevalence of latex sensitisation and allergy and associated risk factors among healthcare workers using hypoallergenic latex gloves at King Edward VIII Hospital, KwaZulu-Natal South Africa: a cross-sectional study

    Science.gov (United States)

    Phaswana, Shumani Makwarela; Naidoo, Saloshni

    2013-01-01

    Objectives The present study describes latex sensitisation and allergy prevalence and associated factors among healthcare workers using hypoallergenic latex gloves at King Edward VIII Hospital in KwaZulu-Natal, South Africa. Design Cross-sectional study. Setting A tertiary hospital in eThekwini municipality, KwaZulu-Natal, South Africa. Participants 600 healthcare workers were randomly selected and 501 (337 exposed and 164 unexposed) participated. Participants who were pregnant, with less than 1 year of work as a healthcare worker and a history of anaphylactic reaction were excluded from the study. Primary and secondary outcome measures Latex sensitisation and latex allergy were the outcome of interest and they were successfully measured. Results The prevalence of latex sensitisation and allergy was observed among exposed workers (7.1% and