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Sample records for viii genetic load

  1. Human genetic studies in areas of high natural radiation. VIII. Genetic load not related to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Freire-Maia, A.; Krieger, H. (Faculdade de Ciencias Medicas e Biologicas, Botucatu, Sao Paulo (Brazil))

    1975-05-01

    The genetic load disclosed by inbreeding has been analyzed in a multiple regression model for a population involving several localities in the state of Espirito Santo, Brazil. The inbreeding load has been estimated for number of pregnancies, abortions, stillbirths, children born alive, anomalies in general, sex ratio, infant mortality, post-infant mortality, and sterility and infertility of the couple. There was no evidence of either maternal or paternal inbreeding effects on the variables analyzed. The effect of inbreeding of the zygote was significant only for anomalies in general (B = 2.29 +/- 0.45) and infant mortality (B = 3.19 +/- 1.39). The latter result must be accepted with caution because of the many environmental causes affecting infant mortality. The B/A ratio suggested a predominantly mutational load for anomalies in general (B/A = 25), but with respect to infant mortality (B/A = 6), the ratio is regarded as an underestimate because of the environmental contribution to A and therefore not supportive of the segregational interpretation.

  2. Chapter VIII. Contributions of propagation techniques and genetic modification to breeding - genetic engineering for disease resistance

    Science.gov (United States)

    Genetic engineering offers an opportunity to develop flower bulb crops with resistance to fungal, viral, and bacterial pathogens. Several of the flower bulb crops, Lilium spp., Gladiolus, Zantedeschia, Muscari, Hyacinthus, Narcissus, Ornithogalum, Iris, and Alstroemeria, have been transformed with t...

  3. The Human Operator Simulator. Volume VIII. Applications to Assessment of Operator Loading.

    Science.gov (United States)

    1977-06-14

    N62269-77-C.0109 THE HUMAN OPERATOR SIMULATOR VOLUME Vill,- APPLICATIONS TO ASSESSMENT OF OPERATOR LOADING Floyd A. Glenn Melvin I.’ Strieb Robert Jj...Kristofferson, 1967). Though compelling evidence against this theory of the "psychological moment" has been raised by experiments reported by Allport (1968) and...clearly demonstrated. 31 Is REFERENCES Allport , D.A., Phenomenal simultaneity and the perceptual moment hypo- thesis. British Journal of Psychology

  4. 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

  5. Genetic loading on human loving styles.

    Science.gov (United States)

    Emanuele, Enzo; Brondino, Natascia; Pesenti, Sara; Re, Simona; Geroldi, Diego

    2007-12-01

    It has been hypothesized that cerebral neurotransmitters such as dopamine and serotonin could play a role in human romantic bonding. However, no data on the genetic basis of human romantic love are currently available. To address this issue, we looked for associations between markers in neurotransmitter genes (the serotonin transporter gene, 5-HTT; the serotonin receptor 2A, 5HT2A; the dopamine D2 receptor gene, DRD2; and the dopamine D4 receptor gene, DRD4) and the six styles of love as conceptualized by Lee (Eros, Ludus, Storge, Pragma, Mania and Agape). A total of 350 healthy young adults (165 males and 185 females, mean age: 24.1+/-3.9 years, range 18-32 years) filled the 24-item Love Attitudes Scale (LAS) and were genotyped for the following six polymorphic markers: the serotonin transporter-linked polymorphic region (5-HTTLPR), the 5HT2A T102C and C516T polymorphisms, the DRD2 TaqI A and TaqI B variants, and the DRD4 exon 3 VNTR polymorphism. Statistical analysis revealed a significant association between the DRD2 TaqI A genotypes and "Eros" (a loving style characterized by a tendency to develop intense emotional experiences based on the physical attraction to the partner), as well as between the C516T 5HT2A polymorphism and "Mania" (a possessive and dependent romantic attachment, characterized by self-defeating emotions). These associations were present in both sexes and remained significant even after adjustment for potential confounders. Our data provide the first evidence of a possible genetic loading on human loving styles.

  6. GENETIC ALGORITHM BASED CONCEPT DESIGN TO OPTIMIZE NETWORK LOAD BALANCE

    Directory of Open Access Journals (Sweden)

    Ashish Jain

    2012-07-01

    Full Text Available Multiconstraints optimal network load balancing is an NP-hard problem and it is an important part of traffic engineering. In this research we balance the network load using classical method (brute force approach and dynamic programming is used but result shows the limitation of this method but at a certain level we recognized that the optimization of balanced network load with increased number of nodes and demands is intractable using the classical method because the solution set increases exponentially. In such case the optimization techniques like evolutionary techniques can employ for optimizing network load balance. In this paper we analyzed proposed classical algorithm and evolutionary based genetic approach is devise as well as proposed in this paper for optimizing the balance network load.

  7. Load Balancing in Multi Cloud Computing Environment with Genetic Algorithm

    Science.gov (United States)

    Vhansure, Fularani; Deshmukh, Apurva; Sumathy, S.

    2017-11-01

    Cloud is a pool of resources that is available on pay per use model. It provides services to the user which is increasing rapidly. Load balancing is an issue because it cannot handle so many requests at a time. It is also known as NP complete problem. In traditional system the functions consist of various parameter values to maximise it in order to achieve best optimal individualsolutions. Challenge is when there are many parameters of solutionsin the system space. Another challenge is to optimize the function which is much more complex. In this paper, various techniques to handle load balancing virtually (VM) as well as physically (nodes) using genetic algorithm is discussed.

  8. 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.

  9. 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

  10. Genetic Variation Underlying Traumatic Brain injury (TBI) and Late Onset Alzheimer’s Disease (LOAD)

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0588 TITLE: Genetic variation underlying traumatic brain injury (TBI) and Late Onset Alzheimer’s Disease (LOAD...14 Sep 2017 4. TITLE AND SUBTITLE Late-Onset Alzheimer’s Disease (LOAD) 5a. CONTRACT NUMBER Genetic variation underlying traumatic brain injury...accelerating individual’s memory decline and possibly accelerating LOAD like neuro-degeneration. In addition, genetic risk factors including non- coding and

  11. [Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

    Science.gov (United States)

    Balanovskiĭ, O P; Koshel', S M; Zaporozhchenko, V V; Pshenichnov, A S; Frolova, S A; Kuznetsova, M A; Baranova, E E; Teuchezh, I E; Kuznetsova, A A; Romashkina, M V; Utevskaia, O M; Churnosov, M I; Villems, R; Balanovskaia, E V

    2011-11-01

    Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

  12. 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.

  13. 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.

  14. 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

  15. The power of evolutionary rescue is constrained by genetic load.

    Science.gov (United States)

    Stewart, Gavin S; Morris, Madeline R; Genis, Allison B; Szűcs, Marianna; Melbourne, Brett A; Tavener, Simon J; Hufbauer, Ruth A

    2017-08-01

    The risk of extinction faced by small isolated populations in changing environments can be reduced by rapid adaptation and subsequent growth to larger, less vulnerable sizes. Whether this process, called evolutionary rescue, is able to reduce extinction risk and sustain population growth over multiple generations is largely unknown. To understand the consequences of adaptive evolution as well as maladaptive processes in small isolated populations, we subjected experimental Tribolium castaneum populations founded with 10 or 40 individuals to novel environments, one more favorable, and one resource poor, and either allowed evolution, or constrained it by replacing individuals one-for-one each generation with those from a large population maintained in the natal environment. Replacement individuals spent one generation in the target novel environment before use to standardize effects due to the parental environment. After eight generations we mixed a subset of surviving populations to facilitate admixture, allowing us to estimate drift load by comparing performance of mixed to unmixed groups. Evolving populations had reduced extinction rates, and increased population sizes in the first four to five generations compared to populations where evolution was constrained. Performance of evolving populations subsequently declined. Admixture restored their performance, indicating high drift load that may have overwhelmed the beneficial effects of adaptation in evolving populations. Our results indicate that evolution may quickly reduce extinction risk and increase population sizes, but suggest that relying solely on adaptation from standing genetic variation may not provide long-term benefits to small isolated populations of diploid sexual species, and that active management facilitating gene flow may be necessary for longer term persistence.

  16. 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

  17. Ionizing radiation and genetic risks. Part VIII. The concept of mutation component and its use in risk estimation for multifactorial diseases

    Energy Technology Data Exchange (ETDEWEB)

    Denniston, C. [Laboratory of Genetics, University of Wisconsin-Madison, Madison (United States); Chakraborty, R. [Human Genetics Center, University of Texas School of Public Health, P.O. Box 20334, Houston, TX (United States); Sankaranarayanan, K. [Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratories, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL Leiden (Netherlands)

    1998-08-31

    mutation rate. Our investigation shows that, for a permanent increase in mutation rate of 15%, MC in the first few generations is of the order of 1-2%. This conclusion holds over a broad range of heritability values above about 30%. At equilibrium, however, MC reaches 100%. For a one-time increase in mutation rate, MC reaches its maximum value (of 1-2%) in the first generation, followed by a decline to zero in subsequent generations. These conclusions hold for so many combinations of parameter values (i.e., threshold, selection coefficient, number of loci, environmental variance, spontaneous mutation rate, increases in mutation rate, levels of `interaction` between genes and recombination rates) that it can be considered to be relatively robust. We also investigated the biological validity of the FLTM in terms of the minimum number of loci, their mutation rates and selection coefficients needed to explain the incidence of multifactorial diseases using the theory of genetic loads. We argue that for common multifactorial diseases, selection coefficients are small in present-day human populations. Consequently, with mutation rates of the order known for Mendelian genes, the FLTM with a few loci and weak selection provides a good approximation for studying the responsiveness of multifactorial diseases to radiation exposures

  18. Genetic algorithms for nuclear reactor fuel load and reload optimization problems

    Directory of Open Access Journals (Sweden)

    A.V. Sobolev

    2017-09-01

    The efficiency of use of the developed model of the genetic algorithm is demonstrated by the test example of a BN type reactor. The results of the test run demonstrated that the use of the proposed approach allows searching for optimal reactor load mapping for each separate core reshuffling operation. The main objective of the performed study was to demonstrate the applicability and efficiency of the new up-to-date approach to solving the problem of fuel loading into a nuclear reactor.

  19. 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.

  20. Multiobjective Economic Load Dispatch in 3-D Space by Genetic Algorithm

    Science.gov (United States)

    Jain, N. K.; Nangia, Uma; Singh, Iqbal

    2017-08-01

    This paper presents the application of genetic algorithm to Multiobjective Economic Load Dispatch (MELD) problem considering fuel cost, transmission losses and environmental pollution as objective functions. The MELD problem has been formulated using constraint method. The non-inferior set for IEEE 5, 14 and 30-bus system has been generated by using genetic algorithm and the target point has been obtained by using maximization of minimum relative attainments.

  1. Multiobjective Economic Load Dispatch in 3-D Space by Genetic Algorithm

    Science.gov (United States)

    Jain, N. K.; Nangia, Uma; Singh, Iqbal

    2017-10-01

    This paper presents the application of genetic algorithm to Multiobjective Economic Load Dispatch (MELD) problem considering fuel cost, transmission losses and environmental pollution as objective functions. The MELD problem has been formulated using constraint method. The non-inferior set for IEEE 5, 14 and 30-bus system has been generated by using genetic algorithm and the target point has been obtained by using maximization of minimum relative attainments.

  2. A Web-Based Tool to Interpolate Nitrogen Loading Using a Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Youn Shik Park

    2014-09-01

    Full Text Available Water quality data may not be collected at a high frequency, nor over the range of streamflow data. For instance, water quality data are often collected monthly, biweekly, or weekly, since collecting and analyzing water quality samples are costly compared to streamflow data. Regression models are often used to interpolate pollutant loads from measurements made intermittently. Web-based Load Interpolation Tool (LOADIN was developed to provide user-friendly interfaces and to allow use of streamflow and water quality data from U.S. Geological Survey (USGS via web access. LOADIN has a regression model assuming that instantaneous load is comprised of the pollutant load based on streamflow and the pollutant load variation within the period. The regression model has eight coefficients determined by a genetic algorithm with measured water quality data. LOADIN was applied to eleven water quality datasets from USGS gage stations located in Illinois, Indiana, Michigan, Minnesota, and Wisconsin states with drainage areas from 44 km2 to 1,847,170 km2. Measured loads were calculated by multiplying nitrogen data by streamflow data associated with measured nitrogen data. The estimated nitrogen loads and measured loads were evaluated using Nash-Sutcliffe Efficiency (NSE and coefficient of determination (R2. NSE ranged from 0.45 to 0.91, and R2 ranged from 0.51 to 0.91 for nitrogen load estimation.

  3. A hypothesis for using pathway genetic load analysis for understanding complex outcomes in bilirubin encephalopathy

    Directory of Open Access Journals (Sweden)

    Sean M. Riordan

    2016-08-01

    Full Text Available Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a load is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load that affects the response to a specific insult has been previously reported as a pathway genetic load (PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system’s response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin-induced neurological disorders (BIND such as kernicterus and could be the key to understanding

  4. Simultaneous optimization of the cavity heat load and trip rates in linacs using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Balša Terzić

    2014-10-01

    Full Text Available In this paper, a genetic algorithm-based optimization is used to simultaneously minimize two competing objectives guiding the operation of the Jefferson Lab’s Continuous Electron Beam Accelerator Facility linacs: cavity heat load and radio frequency cavity trip rates. The results represent a significant improvement to the standard linac energy management tool and thereby could lead to a more efficient Continuous Electron Beam Accelerator Facility configuration. This study also serves as a proof of principle of how a genetic algorithm can be used for optimizing other linac-based machines.

  5. Advanced and flexible genetic algorithms for BWR fuel loading pattern optimization

    Energy Technology Data Exchange (ETDEWEB)

    Martin-del-Campo, Cecilia [Departamento de Sistemas Energeticos, Facultad de Ingenieria, Universidad Nacional Autonoma de Mexico, Paseo Cuauhnahuac 8532, Jiutepec, Mor., 62550 (Mexico)], E-mail: cmcm@fi-b.unam.mx; Palomera-Perez, Miguel-Angel [Instituto de Investigaciones en Matematicas Aplicadas y Sistemas, Universidad Nacional Autonoma de Mexico, Circuito Escolar, Ciudad Universitaria, 04510 DF (Mexico)], E-mail: mapp@uxmcc2.iimas.unam.mx; Francois, Juan-Luis [Departamento de Sistemas Energeticos, Facultad de Ingenieria, Universidad Nacional Autonoma de Mexico, Paseo Cuauhnahuac 8532, Jiutepec, Mor., 62550 (Mexico)], E-mail: jlfl@fi-b.unam.mx

    2009-10-15

    This work proposes advances in the implementation of a flexible genetic algorithm (GA) for fuel loading pattern optimization for Boiling Water Reactors (BWRs). In order to avoid specific implementations of genetic operators and to obtain a more flexible treatment, a binary representation of the solution was implemented; this representation had to take into account that a little change in the genotype must correspond to a little change in the phenotype. An identifier number is assigned to each assembly by means of a Gray Code of 7 bits and the solution (the loading pattern) is represented by a binary chain of 777 bits of length. Another important contribution is the use of a Fitness Function which includes a Heuristic Function and an Objective Function. The Heuristic Function which is defined to give flexibility on the application of a set of positioning rules based on knowledge, and the Objective Function that contains all the parameters which qualify the neutronic and thermal hydraulic performances of each loading pattern. Experimental results illustrating the effectiveness and flexibility of this optimization algorithm are presented and discussed.

  6. A Hypothesis for Using Pathway Genetic Load Analysis for Understanding Complex Outcomes in Bilirubin Encephalopathy

    Science.gov (United States)

    Riordan, Sean M.; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Gazzin, Silvia; Tiribelli, Claudio; Watchko, Jon F.; Wennberg, Richard P.; Shapiro, Steven M.

    2016-01-01

    Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60–80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. The lack of a monogenetic source for this risk of bilirubin neurotoxicity suggests that disease progression is dependent upon an overall decrease in the functionality of one or more essential genetically controlled metabolic pathways. In other words, a “load” is placed on key pathways in the form of multiple genetic variants that combine to create a vulnerable phenotype. The idea of epistatic interactions creating a pathway genetic load (PGL) that affects the response to a specific insult has been previously reported as a PGL score. We hypothesize that the PGL score can be used to investigate whether increased susceptibility to bilirubin-induced CNS damage in neonates is due to a mutational load being placed on key genetic pathways important to the central nervous system's response to bilirubin neurotoxicity. We propose a modification of the PGL score method that replaces the use of a canonical pathway with custom gene lists organized into three tiers with descending levels of evidence combined with the utilization of single nucleotide polymorphism (SNP) causality prediction methods. The PGL score has the potential to explain the genetic background of complex bilirubin induced neurological disorders (BIND) such as kernicterus and could be the key to understanding ranges of outcome severity

  7. Applications of the Chaotic Quantum Genetic Algorithm with Support Vector Regression in Load Forecasting

    Directory of Open Access Journals (Sweden)

    Cheng-Wen Lee

    2017-11-01

    Full Text Available Accurate electricity forecasting is still the critical issue in many energy management fields. The applications of hybrid novel algorithms with support vector regression (SVR models to overcome the premature convergence problem and improve forecasting accuracy levels also deserve to be widely explored. This paper applies chaotic function and quantum computing concepts to address the embedded drawbacks including crossover and mutation operations of genetic algorithms. Then, this paper proposes a novel electricity load forecasting model by hybridizing chaotic function and quantum computing with GA in an SVR model (named SVRCQGA to achieve more satisfactory forecasting accuracy levels. Experimental examples demonstrate that the proposed SVRCQGA model is superior to other competitive models.

  8. Core loading pattern optimization of thorium fueled heavy water breeder reactor using genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Soewono, C. N.; Takaki, N. [Dept. of Applied Science Engineering, Faculty Tokai Univ., Kanagawa-ken, Hiratsuka-shi Kitakaname 4-1-1 (Japan)

    2012-07-01

    In this work genetic algorithm was proposed to solve fuel loading pattern optimization problem in thorium fueled heavy water reactor. The objective function of optimization was to maximize the conversion ratio and minimize power peaking factor. Those objectives were simultaneously optimized using non-dominated Pareto-based population ranking optimal method. Members of non-dominated population were assigned selection probabilities based on their rankings in a manner similar to Baker's single criterion ranking selection procedure. A selected non-dominated member was bred through simple mutation or one-point crossover process to produce a new member. The genetic algorithm program was developed in FORTRAN 90 while neutronic calculation and analysis was done by COREBN code, a module of core burn-up calculation for SRAC. (authors)

  9. Genetic load and transgenic mitigating genes in transgenic Brassica rapa (field mustard × Brassica napus (oilseed rape hybrid populations

    Directory of Open Access Journals (Sweden)

    Warwick Suzanne I

    2009-10-01

    Full Text Available Abstract Background One theoretical explanation for the relatively poor performance of Brassica rapa (weed × Brassica napus (crop transgenic hybrids suggests that hybridization imparts a negative genetic load. Consequently, in hybrids genetic load could overshadow any benefits of fitness enhancing transgenes and become the limiting factor in transgenic hybrid persistence. Two types of genetic load were analyzed in this study: random/linkage-derived genetic load, and directly incorporated genetic load using a transgenic mitigation (TM strategy. In order to measure the effects of random genetic load, hybrid productivity (seed yield and biomass was correlated with crop- and weed-specific AFLP genomic markers. This portion of the study was designed to answer whether or not weed × transgenic crop hybrids possessing more crop genes were less competitive than hybrids containing fewer crop genes. The effects of directly incorporated genetic load (TM were analyzed through transgene persistence data. TM strategies are proposed to decrease transgene persistence if gene flow and subsequent transgene introgression to a wild host were to occur. Results In the absence of interspecific competition, transgenic weed × crop hybrids benefited from having more crop-specific alleles. There was a positive correlation between performance and number of B. napus crop-specific AFLP markers [seed yield vs. marker number (r = 0.54, P = 0.0003 and vegetative dry biomass vs. marker number (r = 0.44, P = 0.005]. However under interspecific competition with wheat or more weed-like conditions (i.e. representing a situation where hybrid plants emerge as volunteer weeds in subsequent cropping systems, there was a positive correlation between the number of B. rapa weed-specific AFLP markers and seed yield (r = 0.70, P = 0.0001, although no such correlation was detected for vegetative biomass. When genetic load was directly incorporated into the hybrid genome, by inserting a

  10. Accumulation, elimination, sequestration, and genetic variation of lead (Pb(2+)) loads within and between generations of Drosophila melanogaster.

    Science.gov (United States)

    Peterson, Elizabeth K; Wilson, Diane T; Possidente, Bernard; McDaniel, Phillip; Morley, Eric J; Possidente, Debra; Hollocher, Kurt T; Ruden, Douglas M; Hirsch, Helmut V B

    2017-08-01

    We examined accumulation, sequestration, elimination, and genetic variation for lead (Pb) loads within and between generations of Drosophila melanogaster. Flies were reared in control or leaded medium at various doses and tested for their Pb loads at different stages of development (larvae, eclosion, newly-eclosed adults, and mature adults). Pb loads were tested using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). We found that D. melanogaster readily accumulated Pb throughout their lifespan and the levels of accumulation increased with Pb exposure in the medium. Wandering third-instar larvae accumulated more Pb than mature adults; this phenomenon may be due to elimination of Pb in the pupal cases during eclosion and/or depuration in adults post-eclosion. The accumulated Pb in mature adults was not transferred to F1 mature adult offspring. Using a set of recombinant inbred strains, we identified a quantitative trait locus for adult Pb loads and found that genetic variation accounted for 34% of the variance in Pb load. We concluded that D. melanogaster is a useful model organism for evaluating changes in Pb loads during development, as well as between generations. Furthermore, we found that genetic factors can influence Pb loads; this provides an essential foundation for evaluating phenotypic variation induced by the toxic effects of Pb. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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.

  13. Comparison of genetic algorithm and imperialist competitive algorithms in predicting bed load transport in clean pipe.

    Science.gov (United States)

    Ebtehaj, Isa; Bonakdari, Hossein

    2014-01-01

    The existence of sediments in wastewater greatly affects the performance of the sewer and wastewater transmission systems. Increased sedimentation in wastewater collection systems causes problems such as reduced transmission capacity and early combined sewer overflow. The article reviews the performance of the genetic algorithm (GA) and imperialist competitive algorithm (ICA) in minimizing the target function (mean square error of observed and predicted Froude number). To study the impact of bed load transport parameters, using four non-dimensional groups, six different models have been presented. Moreover, the roulette wheel selection method is used to select the parents. The ICA with root mean square error (RMSE) = 0.007, mean absolute percentage error (MAPE) = 3.5% show better results than GA (RMSE = 0.007, MAPE = 5.6%) for the selected model. All six models return better results than the GA. Also, the results of these two algorithms were compared with multi-layer perceptron and existing equations.

  14. Using Clinical Characteristics to Identify Which Patients With Major Depressive Disorder Have a Higher Genetic Load for Three Psychiatric Disorders

    NARCIS (Netherlands)

    Verduijn, Judith; Milaneschi, Yuri; Peyrot, Wouter J; Hottenga, Jouke Jan; Abdellaoui, A.; de Geus, Eco J C; Smit, Johannes H; Breen, Gerome; Lewis, Cathryn M; Boomsma, Dorret I; Beekman, Aartjan T F; Penninx, Brenda W J H

    2017-01-01

    BACKGROUND: Limited successes of gene finding for major depressive disorder (MDD) may be partly due to phenotypic heterogeneity. We tested whether the genetic load for MDD, bipolar disorder, and schizophrenia (SCZ) is increased in phenotypically more homogenous MDD patients identified by specific

  15. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    Science.gov (United States)

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  16. An {epsilon}-dominance-based multiobjective genetic algorithm for economic emission load dispatch optimization problem

    Energy Technology Data Exchange (ETDEWEB)

    Osman, M.S. [High Institute of Technology, 10th Ramadan City (Egypt); Abo-Sinna, M.A.; Mousa, A.A. [Faculty of Engineering, Shebin El-Kom, Menoufia University (Egypt)

    2009-11-15

    In this paper, a novel multiobjective genetic algorithm approach for economic emission load dispatch (EELD) optimization problem is presented. The EELD problem is formulated as a non-linear constrained multiobjective optimization problem with both equality and inequality constraints. A new optimization algorithm which is based on concept of co-evolution and repair algorithm for handling non-linear constraints is presented. The algorithm maintains a finite-sized archive of non-dominated solutions which gets iteratively updated in the presence of new solutions based on the concept of {epsilon}-dominance. The use of {epsilon}-dominance also makes the algorithms practical by allowing a decision maker to control the resolution of the Pareto-set approximation by choosing an appropriate {epsilon} value. The proposed approach is carried out on the standard IEEE 30-bus 6-genrator test system. The results demonstrate the capabilities of the proposed approach to generate true and well-distributed Pareto-optimal non-dominated solutions of the multiobjective EELD problem in one single run. Simulation results with the proposed approach have been compared to those reported in the literature. The comparison demonstrates the superiority of the proposed approach and confirms its potential to solve the multiobjective EELD problem. (author)

  17. 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

  18. 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 ...

  19. Impact of genetic heterogeneity in polymerase of hepatitis B virus on dynamics of viral load and hepatitis B progression.

    Directory of Open Access Journals (Sweden)

    Chi-Jung Huang

    Full Text Available OBJECTIVE: The hepatitis B virus (HBV-polymerase region overlaps pre-S/S genes with high epitope density and plays an essential role in viral replication. We investigated whether genetic variation in the polymerase region determined long-term dynamics of viral load and the risk of hepatitis B progression in a population-based cohort study. METHODS: We sequenced the HBV-polymerase region using baseline plasma from treatment-naïve individuals with HBV-DNA levels≥1000 copies/mL in a longitudinal viral-load study of participants with chronic HBV infection followed-up for 17 years, and obtained sequences from 575 participants (80% with HBV genotype Ba and 17% with Ce. RESULTS: Patterns of viral sequence diversity across phases (i.e., immune-tolerant, immune-clearance, non/low replicative, and hepatitis B e antigen (HBeAg-negative hepatitis phases of HBV-infection, which were associated with viral and clinical features at baseline and during follow-up, were similar between HBV genotypes, despite greater diversity for genotype Ce vs. Ba. Irrespective of genotypes, however, HBeAg-negative participants had 1.5-to-2-fold higher levels of sequence diversity than HBeAg-positive participants (P<0.0001. Furthermore, levels of viral genetic divergence from the population consensus sequence, estimated by numbers of nucleotide substitutions, were inversely associated with long-term viral load even in HBeAg-negative participants. A mixed model developed through analysis of the entire HBV-polymerase region identified 153 viral load-associated single nucleotide polymorphisms in overall and 136 in HBeAg-negative participants, with distinct profiles between HBV genotypes. These polymorphisms were most evident at sites within or flanking T-cell epitopes. Seven polymorphisms revealed associations with both enhanced viral load and a more than 4-fold increased risk of hepatocellular carcinoma and/or liver cirrhosis. CONCLUSIONS: The data highlight a role of viral

  20. 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.

  1. 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.

  2. Determination of combined hardening material parameters under strain controlled cyclic loading by using the genetic algorithm method

    Energy Technology Data Exchange (ETDEWEB)

    Badnava, H. [Islamic Azad Univ., Ahvaz (Iran, Islamic Republic of); Pezeshki, S. M.; Fallah Najad, Kh.; Farhoudi, H. R. [Bu Ali Sina Univ., Hamedan (Iran, Islamic Republic of)

    2012-10-15

    In this paper, experimental and numerical investigations on mechanical behaviors of SS304 stainless steel under fully reversed straincontrolled, relaxation, ratcheting and multiple step strain-controlled cyclic loading have been performed. The kinematic and isotropic hardening theories based on the Chaboche model are used to predict the plastic behavior. An iterative method is utilized to analyze the mechanical behavior under cyclic loading conditions based on the Chaboche hardening model. A set of kinematic and isotropic parameters was obtained by using the genetic algorithm optimization approach. In order to analyze the effectiveness of this optimization procedure, numerical and experimental results for an SS304 stainless steel are compared. Finally, the results of this research show that by using the material parameters optimized based on the strain controlled and relaxation data, good agreement with the experimental data for ratcheting is achieved.

  3. THE SIGNIFICANCE OF GENETIC EROSION IN THE PROCESS OF EXTINCTION .4. INBREEDING LOAD AND HETEROSIS IN RELATION TO POPULATION-SIZE IN THE MINT SALVIA-PRATENSIS

    NARCIS (Netherlands)

    OUBORG, NJ; VANTREUREN, R

    If, because of genetic erosion, the level of homozygosity in small populations is high, additional selfing will result in small reductions of fitness. In addition, in small populations with a long inbreeding history selection may have purged the population of its genetic load. Therefore, a positive

  4. 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.

  5. Load balancing prediction method of cloud storage based on analytic hierarchy process and hybrid hierarchical genetic algorithm.

    Science.gov (United States)

    Zhou, Xiuze; Lin, Fan; Yang, Lvqing; Nie, Jing; Tan, Qian; Zeng, Wenhua; Zhang, Nian

    2016-01-01

    With the continuous expansion of the cloud computing platform scale and rapid growth of users and applications, how to efficiently use system resources to improve the overall performance of cloud computing has become a crucial issue. To address this issue, this paper proposes a method that uses an analytic hierarchy process group decision (AHPGD) to evaluate the load state of server nodes. Training was carried out by using a hybrid hierarchical genetic algorithm (HHGA) for optimizing a radial basis function neural network (RBFNN). The AHPGD makes the aggregative indicator of virtual machines in cloud, and become input parameters of predicted RBFNN. Also, this paper proposes a new dynamic load balancing scheduling algorithm combined with a weighted round-robin algorithm, which uses the predictive periodical load value of nodes based on AHPPGD and RBFNN optimized by HHGA, then calculates the corresponding weight values of nodes and makes constant updates. Meanwhile, it keeps the advantages and avoids the shortcomings of static weighted round-robin algorithm.

  6. 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.

  7. 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...

  8. Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes.

    Science.gov (United States)

    de Valles-Ibáñez, Guillem; Hernandez-Rodriguez, Jessica; Prado-Martinez, Javier; Luisi, Pierre; Marquès-Bonet, Tomàs; Casals, Ferran

    2016-03-26

    Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual's viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Analysis of seven stages supply chain management in electronic component inventory optimization for warehouse with economic load dispatch using genetic algorithm

    Directory of Open Access Journals (Sweden)

    Ajay Singh Yadav

    2017-06-01

    Full Text Available The purpose of the proposed study is to give a new dimension on warehouse with Economic Load Dispatch using genetic algorithm processes in Seven Stages - 10 Member Supply Chain in Electronic component inventory optimization to describe the certain and uncertain market demand which is based on supply reliability and to develop more realistic and more flexible models. we hope that the proposed study has a great potential to solve various practical tribulations related to the warehouse using genetic algorithm processes in Seven Stages - 10 Member Supply Chain in Electronic component inventory optimization and also provide a general review for the application of soft computing techniques like genetic algorithms to use for improve the effectiveness and efficiency for various aspect of warehouse with Economic Load Dispatch using genetic algorithm.

  10. [Demographic consequences of genetic load: a model of the origin of the incest taboo].

    Science.gov (United States)

    Buzin, A Iu

    1987-12-01

    The prohibition of copulations among near relatives may raise the fitness of population. This effect being irregular and insignificant for a distinct generation, becomes apparent in evolutionary time intervals through the natural selection of populations with incest-taboo. The "characteristic selection time" theta depends on typical population size, genetic damage and the mean rate of population growth. The estimation obtained for theta permit us to assert that the model describes the phenomenon of "socio-cultural selection" in prehistory. The model shows the demographic specificity of small populations. The problem of the number of consanguineous marriages is considered in detail. New explanation for deviation of the observed frequency of consanguineous marriages from classical estimations is proposed.

  11. 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.

  12. 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.

  13. Optimal shape control of piezolaminated beams with different boundary condition and loading using genetic algorithm

    Science.gov (United States)

    Bendine, Kouider; Wankhade, Rajan L.

    2017-12-01

    Piezoelectric actuators are effectively used to control the response of light weight structures in shape, vibration and buckling. Optimization for the shape control of piezoelectric beam is the recent challenge which requires proper numerical technique to perform. The shape control of a composite beam using surface-bounded piezoelectric actuators has been investigated in the present work. The mathematical model is developed using two-node Timoshenko beam element coupling with the theory of linear piezoelectricity. First-order shear deformation theory is employed in the formulation to consider the effect of shear. In the analysis, the effect of the actuators position for different set of boundary conditions is investigated. For different boundary conditions which include clamped-free-, clamped-clamped- and simply supported beam, optimisation of piezoelectric patch location is investigated. Moreover, a genetic algorithm is adopted and implemented to optimize the required voltage to maintain the desired shape of the beam. This optimization technique is applied to different cases of composite beams with varying the boundary condition.

  14. Optimal shape control of piezolaminated beams with different boundary condition and loading using genetic algorithm

    Science.gov (United States)

    Bendine, Kouider; Wankhade, Rajan L.

    2017-10-01

    Piezoelectric actuators are effectively used to control the response of light weight structures in shape, vibration and buckling. Optimization for the shape control of piezoelectric beam is the recent challenge which requires proper numerical technique to perform. The shape control of a composite beam using surface-bounded piezoelectric actuators has been investigated in the present work. The mathematical model is developed using two-node Timoshenko beam element coupling with the theory of linear piezoelectricity. First-order shear deformation theory is employed in the formulation to consider the effect of shear. In the analysis, the effect of the actuators position for different set of boundary conditions is investigated. For different boundary conditions which include clamped-free-, clamped-clamped- and simply supported beam, optimisation of piezoelectric patch location is investigated. Moreover, a genetic algorithm is adopted and implemented to optimize the required voltage to maintain the desired shape of the beam. This optimization technique is applied to different cases of composite beams with varying the boundary condition.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Genetic polymorphisms regulating dopamine signaling in the frontal cortex interact to affect target detection under high working memory load.

    Science.gov (United States)

    Smith, Christopher T; Swift-Scanlan, Theresa; Boettiger, Charlotte A

    2014-02-01

    Frontal-dependent task performance is typically modulated by dopamine (DA) according to an inverted-U pattern, whereby intermediate levels of DA signaling optimizes performance. Numerous studies implicate trait differences in DA signaling based on differences in the catechol-O-methyltransferase (COMT) gene in executive function task performance. However, little work has investigated genetic variations in DA signaling downstream from COMT. One candidate is the DA- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), which mediates signaling through the D1-type DA receptor, the dominant DA receptor in the frontal cortex. Using an n-back task, we used signal detection theory to measure performance in a healthy adult population (n = 97) genotyped for single nucleotide polymorphisms in the COMT (rs4680) and DARPP-32 (rs907094) genes. Correct target detection (hits) and false alarms were used to calculate d' measures for each working memory load (0-, 2-, and 3-back). At the highest load (3-back) only, we observed a significant COMT × DARPP-32 interaction, such that the DARPP-32 T/T genotype enhanced target detection in COMT(ValVal) individuals, but impaired target detection in COMT(Met) carriers. These findings suggest that enhanced dopaminergic signaling via the DARPP-32 T allele aids target detection in individuals with presumed low frontal DA (COMT(ValVal)) but impairs target detection in those with putatively higher frontal DA levels (COMT(Met) carriers). Moreover, these data support an inverted-U model with intermediate levels of DA signaling optimizing performance on tasks requiring maintenance of mental representations in working memory.

  20. 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.

  1. 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...

  2. Improved genetic algorithm for economic load dispatch in hydropower plants and comprehensive performance comparison with dynamic programming method

    Science.gov (United States)

    Shang, Yizi; Lu, Shibao; Gong, Jiaguo; Liu, Ronghua; Li, Xiang; Fan, Qixiang

    2017-11-01

    This paper presents a practical genetic algorithm (GA)-based solution for solving the economic load dispatch problem (ELDP) and further compares the performance of the improved GA (IGA) with that of dynamic programming (DP). Specifically, their performance is comprehensively evaluated in terms of addressing the ELDP through a case study of 26 turbines in the Three Gorges Hydropower Plant with a focus on calculation accuracy, calculation time, and algorithm stability. Evaluation results show that the improved GA method can significantly reduce the ineffectiveness of the GA in current use and could avoid the running of the turbines in the cavitation/vibration zone, thereby ensuring the safety of the turbines during generating operations. Further, the analysis comparing the performance of the IGA and DP show that the IGA is superior to DP when a small number of turbines are involved. However, as the number of turbines increases, the IGA requires more calculation time than DP; moreover, its calculation accuracy and convergence rate are significantly reduced. It is difficult to guarantee the stability of IGA in high-dimension space even though the population grows, on account of the exponential expansion of the calculation dimension, the algorithm's premature convergence, and the lack of a local search capability. The improvement of the GA as well as the evaluation method proposed in this paper provide a new approach for choosing and improving optimization algorithms to solve the ELDP of large-scale hydropower plants.

  3. 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.

  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. 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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Genetics

    Science.gov (United States)

    ... Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... mother and medications). These include: Asthma Cancer Coronary heart disease Diabetes Hypertension Stroke MITOCHONDRIAL DNA-LINKED DISORDERS Mitochondria ...

  9. 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"

  10. 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:

  11. 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 ...

  12. 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

  13. 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.

  14. Disease ecology in the Galápagos Hawk (Buteo galapagoensis): host genetic diversity, parasite load and natural antibodies

    NARCIS (Netherlands)

    Whiteman, N.K.; Matson, K.D.; Bollmer, J.L.; Parker, P.G.

    2006-01-01

    An increased susceptibility to disease is one hypothesis explaining how inbreeding hastens extinction in island endemics and threatened species. Experimental studies show that disease resistance declines as inbreeding increases, but data from in situ wildlife systems are scarce. Genetic diversity

  15. Blastocystis Isolates from Patients with Irritable Bowel Syndrome and from Asymptomatic Carriers Exhibit Similar Parasitological Loads, but Significantly Different Generation Times and Genetic Variability across Multiple Subtypes.

    Directory of Open Access Journals (Sweden)

    Gie-Bele Vargas-Sanchez

    Full Text Available Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS; however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret's and in Pavlova's media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST. Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π as compared to the control group (0.011±0.016 and 0.118±0.177, respectively, whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima's D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret's than in Pavlova's medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (p<0.05. We propose that generation times of Blastocystis might be easily affected by intestinal environmental changes due to IBS probably because virulent strains with slow growth may be

  16. Blastocystis Isolates from Patients with Irritable Bowel Syndrome and from Asymptomatic Carriers Exhibit Similar Parasitological Loads, but Significantly Different Generation Times and Genetic Variability across Multiple Subtypes.

    Science.gov (United States)

    Vargas-Sanchez, Gie-Bele; Romero-Valdovinos, Mirza; Ramirez-Guerrero, Celedonio; Vargas-Hernandez, Ines; Ramirez-Miranda, Maria Elena; Martinez-Ocaña, Joel; Valadez, Alicia; Ximenez, Cecilia; Lopez-Escamilla, Eduardo; Hernandez-Campos, Maria Elena; Villalobos, Guiehdani; Martinez-Hernandez, Fernando; Maravilla, Pablo

    2015-01-01

    Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS); however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret's and in Pavlova's media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST). Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π) as compared to the control group (0.011±0.016 and 0.118±0.177, respectively), whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima's D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret's than in Pavlova's medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (pBlastocystis might be easily affected by intestinal environmental changes due to IBS probably because virulent strains with slow growth may be selected, reducing their genetic variability.

  17. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  18. 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.

  19. [Genetic epidemiological study of monogenic hereditary diseases in the Republic of Tatarstan: population dynamic factors determining the differentiation of the load of hereditary diseases in five districts].

    Science.gov (United States)

    Ginter, E K; El'chinova, G I; Petrin, A N; Bessonova, L A; Kadyshev, V V; Gavrilina, S G; Vafina, Z I; Zinchenko, R A

    2012-09-01

    A genetic epidemiological study has been performed in five districts of the Republic of Tatarstan, Russia: Arsky, Atninsky, Kukmorsky, Buinsky and Drozhzhanovsky raions. The total size of the population surveyed is 188 397 people. Tatars accounted for 77.13% of the population analyzed (145466 people) and were represented by two main ethnic groups: Kazan Tatars and Mishars. The medical genetic study encompassed the total population of the districts, irrespective of ethnicity, and was carried out according to the standard protocol developed in the Laboratory of Genetic Epidemiology of the Research Center for Medical Genetics of the Russian Academy of Medical Sciences. After segregation analysis, the prevalence rates of the main types of monogenic hereditary disorders (MHDs), i.e., autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases, have been calculated for the total population of the five districts and for Tatars alone. The prevalence rates ofAD, AR, and X-linked diseases considerably vary in different subpopulations. The largest difference in the MHD prevalence rate has been found between the rural and urban populations. The overall prevalence rate of MHDs was one patient per 293 urban residents and populations and one patient per 134 rural residents, with a wide variation between subpopulations, from 1 : 83 people in the rural population of Atninsky raion to 1: 351 people in the town of Kukmor. Comparison of the MHD prevalence rate in Tatars with those in populations surveyed earlier has shown that the characteristics of the load of MHDs in the Tatar population are similar to those in some districts of the republics of Bashkortostan, Udmurtia, Mari El, and Chuvachia. In Russian populations of European Russia, the MHD prevalence rates are substantially lower. Correlation analysis has shown high (r = 0.5-0.9) significant correlations between the local inbreeding (a), the im index, the random inbreeding (F(ST)), and the AD and AR prevalence rates

  20. 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.

  1. 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...

  2. 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 ...

  3. 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 ...

  4. Central composite design and genetic algorithm applied for the optimization of ultrasonic-assisted removal of malachite green by ZnO Nanorod-loaded activated carbon.

    Science.gov (United States)

    Ghaedi, M; Azad, F Nasiri; Dashtian, K; Hajati, S; Goudarzi, A; Soylak, M

    2016-10-05

    Maximum malachite green (MG) adsorption onto ZnO Nanorod-loaded activated carbon (ZnO-NR-AC) was achieved following the optimization of conditions, while the mass transfer was accelerated by ultrasonic. The central composite design (CCD) and genetic algorithm (GA) were used to estimate the effect of individual variables and their mutual interactions on the MG adsorption as response and to optimize the adsorption process. The ZnO-NR-AC surface morphology and its properties were identified via FESEM, XRD and FTIR. The adsorption equilibrium isotherm and kinetic models investigation revealed the well fit of the experimental data to Langmuir isotherm and pseudo-second-order kinetic model, respectively. It was shown that a small amount of ZnO-NR-AC (with adsorption capacity of 20mgg(-1)) is sufficient for the rapid removal of high amount of MG dye in short time (3.99min). Copyright © 2016 Elsevier B.V. All rights reserved.

  5. ARCHITECT® HIV Ag/Ab Combo assay: correlation of HIV-1 p24 antigen sensitivity and RNA viral load using genetically diverse virus isolates.

    Science.gov (United States)

    Brennan, Catherine A; Yamaguchi, Julie; Vallari, Ana; Swanson, Priscilla; Hackett, John R

    2013-06-01

    HIV antigen/antibody (Ag/Ab) combination assays represent a significant advancement in assays used for diagnosing HIV infection based on their ability to detect acute and chronic infections. During acute HIV infection (AHI), detection depends on assay sensitivity for p24 Ag. To directly compare the Ag sensitivity of the ARCHITECT(®) HIV Ag/Ab Combo assay to RNA viral load using cell culture supernatants of virus isolates. HIV-1 isolates allow correlation in the total absence of an antibody response to infection and across genetically diverse HIV-1 group M strains. Thirty-five HIV-1 isolates comprising subtypes A-D, F and G, CRF01_AE, CRF02_AG, and unique recombinant forms were evaluated. Cell-free culture supernatant for each isolate was diluted to four levels and tested in the HIV Combo assay to determine a signal to cutoff ratio and the RealTime(®) HIV-1 assay to quantify RNA. The RNA copies/mL at the HIV Combo assay cutoff was determined. The median RNA copies/mL at the HIV Combo assay cutoff was 57,900 for individual virus isolates (range 26,440-102,400). A single plot of all the data gave a value of 58,500RNA copies/mL. An analysis of data published for acute HIV infection in human subjects gave a similar result; HIV Combo detected 97% of AHIs with RNA copies/mL > 30,700. Based on analysis of virus isolates, the ARCHITECT HIV Combo assay can detect p24 Ag when RNA is above approximately 58,000copies/mL. The correlation of viral load and Ag sensitivity was consistent across genetically diverse HIV-1 group M strains. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Inflammatory lesion and parasite load are inversely associated in Leishmania amazonensis infected mice genetically selected according to oral tolerance susceptibility.

    Science.gov (United States)

    Tavares, Daniel; da Conceição Ribeiro, Ricardo; Carlos da Silva, Antonio

    2006-04-01

    Two strains of mice selected according to extreme phenotypes of susceptibility and resistance to oral tolerance (TS and TR mice, respectively) were infected with 1 x 10(7) Leishmania amazonensis promastigotes and studied comparatively. TS mice developed a minor pathology while permitting parasite growth with the presence of increased IL-4, IL-10 and IFN-gamma, and lower NO and IL-2 levels and delayed-type hypersensitivity (DTH). In contrast, in TR mice, footpad swelling was increased but parasite growth was reduced. They produced lower IL-4, IL-10 and IFN-gamma but increased NO, IL-2 levels, DTH, activated spleen macrophages and periarteriolar lymphoid sheaths. The results suggest that the tolerogenic TS mouse profile, with higher IL-10 production, impaired lesion development but also avoided macrophage leishmanicidal activity, maintaining in this manner a silent parasite load. On the other hand, the TR mouse profile contributed to lesion progression with controlled parasite load. To directly address the influence of oral tolerance on infection, mice were gavaged with OVA, and 7 days afterwards were infected and challenged to bystander suppression with OVA in the same footpad. In TR mice gavaged with 25 mg OVA the inflammatory lesion was largely enhanced, while with 5 mg OVA the lesion was diminished. In TS mice the footpad swelling was always lower. However, the bystander effect did not modify the establishment of infection; and similarly to the control non-bystander mice, parasite clearance was maintained in TR and prevented in TS mice. Therefore, a better comprehension of immunoregulation of innate and adaptive immunity in the early stages of infection is necessary for the development of protocols preventing inflammation and contributing to the elimination of parasites.

  7. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    Directory of Open Access Journals (Sweden)

    Rembeck Karolina

    2012-09-01

    Full Text Available Abstract Background Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. Methods Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study, in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. Results In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023 and lower viral load (P = 0.005 at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. Conclusions Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Prediction of crack growth direction by Strain Energy Sih's Theory on specimens SEN under tension-compression biaxial loading employing Genetic Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-MartInez R; Lugo-Gonzalez E; Urriolagoitia-Calderon G; Urriolagoitia-Sosa G; Hernandez-Gomez L H; Romero-Angeles B; Torres-San Miguel Ch, E-mail: rrodriguezm@ipn.mx, E-mail: urrio332@hotmail.com, E-mail: guiurri@hotmail.com, E-mail: luishector56@hotmail.com, E-mail: romerobeatriz98@hotmail.com, E-mail: napor@hotmail.com [INSTITUTO POLITECNICO NACIONAL Seccion de Estudios de Posgrado e Investigacion (SEPI), Escuela Superior de Ingenieria Mecanica y Electrica (ESIME), Edificio 5. 2do Piso, Unidad Profesional Adolfo Lopez Mateos ' Zacatenco' Col. Lindavista, C.P. 07738, Mexico, D.F. (Mexico)

    2011-07-19

    Crack growth direction has been studied in many ways. Particularly Sih's strain energy theory predicts that a fracture under a three-dimensional state of stress spreads in direction of the minimum strain energy density. In this work a study for angle of fracture growth was made, considering a biaxial stress state at the crack tip on SEN specimens. The stress state applied on a tension-compression SEN specimen is biaxial one on crack tip, as it can observed in figure 1. A solution method proposed to obtain a mathematical model considering genetic algorithms, which have demonstrated great capacity for the solution of many engineering problems. From the model given by Sih one can deduce the density of strain energy stored for unit of volume at the crack tip as dW = [1/2E({sigma}{sup 2}{sub x} + {sigma}{sup 2}{sub y}) - {nu}/E({sigma}{sub x}{sigma}{sub y})]dV (1). From equation (1) a mathematical deduction to solve in terms of {theta} of this case was developed employing Genetic Algorithms, where {theta} is a crack propagation direction in plane x-y. Steel and aluminium mechanical properties to modelled specimens were employed, because they are two of materials but used in engineering design. Obtained results show stable zones of fracture propagation but only in a range of applied loading.

  14. 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.)

  15. 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.

  16. 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…

  17. 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...

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. Ethanol mediated As(III) adsorption onto Zn-loaded pinecone biochar: Experimental investigation, modeling, and optimization using hybrid artificial neural network-genetic algorithm approach.

    Science.gov (United States)

    Zafar, Mohd; Van Vinh, N; Behera, Shishir Kumar; Park, Hung-Suck

    2017-04-01

    Organic matters (OMs) and their oxidization products often influence the fate and transport of heavy metals in the subsurface aqueous systems through interaction with the mineral surfaces. This study investigates the ethanol (EtOH)-mediated As(III) adsorption onto Zn-loaded pinecone (PC) biochar through batch experiments conducted under Box-Behnken design. The effect of EtOH on As(III) adsorption mechanism was quantitatively elucidated by fitting the experimental data using artificial neural network and quadratic modeling approaches. The quadratic model could describe the limiting nature of EtOH and pH on As(III) adsorption, whereas neural network revealed the stronger influence of EtOH (64.5%) followed by pH (20.75%) and As(III) concentration (14.75%) on the adsorption phenomena. Besides, the interaction among process variables indicated that EtOH enhances As(III) adsorption over a pH range of 2 to 7, possibly due to facilitation of ligand-metal(Zn) binding complexation mechanism. Eventually, hybrid response surface model-genetic algorithm (RSM-GA) approach predicted a better optimal solution than RSM, i.e., the adsorptive removal of As(III) (10.47μg/g) is facilitated at 30.22mg C/L of EtOH with initial As(III) concentration of 196.77μg/L at pH5.8. The implication of this investigation might help in understanding the application of biochar for removal of various As(III) species in the presence of OM. Copyright © 2016. Published by Elsevier B.V.

  8. 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.

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. piggyBac-mediated phenotypic correction of factor VIII deficiency

    Directory of Open Access Journals (Sweden)

    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.

  14. Age-specific incidence rates for dementia and Alzheimer disease in NIA-LOAD/NCRAD and EFIGA families: National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA).

    Science.gov (United States)

    Vardarajan, Badri N; Faber, Kelley M; Bird, Thomas D; Bennett, David A; Rosenberg, Roger; Boeve, Bradley F; Graff-Radford, Neill R; Goate, Alison M; Farlow, Martin; Sweet, Robert A; Lantigua, Rafael; Medrano, Martin Z; Ottman, Ruth; Schaid, Daniel J; Foroud, Tatiana M; Mayeux, Richard

    2014-03-01

    Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia. Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD. To determine the incidence rates of dementia and LOAD in unaffected members in the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) family studies. Families with 2 or more affected siblings who had a clinical or pathological diagnosis of LOAD were recruited as a part of the NIA-LOAD/NCRAD Family Study. A cohort of Caribbean Hispanics with familial LOAD was recruited in a different study at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain in New York and from clinics in the Dominican Republic as part of the EFIGA study. Age-specific incidence rates of LOAD were estimated in the unaffected family members in the NIA-LOAD/NCRAD and EFIGA data sets. We restricted analyses to families with follow-up and complete phenotype information, including 396 NIA-LOAD/NCRAD and 242 EFIGA families. Among the 943 at-risk family members in the NIA-LOAD/NCRAD families, 126 (13.4%) developed dementia, of whom 109 (86.5%) met criteria for LOAD. Among 683 at-risk family members in the EFIGA families, 174 (25.5%) developed dementia during the study period, of whom 145 (83.3%) had LOAD. The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families per person-year were 0.03 and 0.03, respectively, in participants aged 65 to 74 years; 0.07 and 0.06, respectively, in those aged 75 to 84 years; and 0.08 and 0.07, respectively, in those 85 years or older. Incidence rates in the EFIGA families were slightly higher, at 0.03 and 0.02, 0.06 and 0.05, 0.10 and 0.08, and 0.10 and 0.07, respectively, in the same age groups. Contrasting these

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Bhavya S Doshi

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

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Higher viral load and genetic diversity of HIV-1 in seminal compartments than in blood of seven Chinese men who have sex with men and have early HIV-1 infection.

    Science.gov (United States)

    Jiao, Yan-Mei; Chen, Guang-Lei; Zhu, Wei-Jun; Huang, Hui-Huang; Fu, Jun-Liang; Chen, Wei-Wei; Shi, Ming; Zhang, Tong; Wu, Hao; Wang, Fu-Sheng

    2017-06-01

    To date, there have been no reports characterizing HIV-1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection were examined. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co-receptor usage. It was found that there was more HIV-1 RNA in seminal plasma than in blood plasma and total, and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV-infection. There was also greater HIV-1 genetic diversity in seminal than in blood compartments. HIV-1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  2. 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.

  3. 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.

  4. 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.

  5. Molecular genetics of hemophilia A: Clinical perspectives | Tantawy ...

    African Journals Online (AJOL)

    Since the publication of the sequence of the factor VIII (F8) gene in 1984, a large number of mutations that cause hemophilia A have been identified and a significant progress has been made in translating this knowledge for clinical diagnostic and therapeutic purposes. Molecular genetic testing is used to determine the ...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.).

  8. 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.

  9. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    Science.gov (United States)

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission.

  10. 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...

  11. 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.

  12. Lack of Evidence for Increased Genetic Loading for Autism among Families of Affected Females: A Replication from Family History Data in Two Large Samples

    Science.gov (United States)

    Goin-Kochel, Robin P.; Abbacchi, Anna; Constantino, John N.

    2007-01-01

    Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD…

  13. Genetic analysis of haemophilia A in Bulgaria

    OpenAIRE

    Kremensky Ivo; Chakarov Stoian; Petkova Rumena

    2004-01-01

    Abstract Background Haemophilias are the most common hereditary severe disorders of blood clotting. In families afflicted with heamophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostical strategy for carriership determination and prenatal diagnostics of haemophilia A in Bulgarian haemophilic population. Methods A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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 ...

  20. 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

  1. 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...

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 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.

  9. 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%,

  10. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    DEFF Research Database (Denmark)

    Rembeck, Karolina; Maglio, Cristina; Lagging, Martin

    2012-01-01

    ABSTRACT: BACKGROUND: Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequ...

  11. 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.

  12. 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.

  13. [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.

  14. 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...

  15. 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...

  16. 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.

  17. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients: Increased Genetic Load of Islet-Expressed and Cytokine-Regulated Candidate Genes Predicts Poorer Glycemic Control

    Directory of Open Access Journals (Sweden)

    Caroline A. Brorsson

    2016-01-01

    Full Text Available Genome-wide association studies (GWAS have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type 1 diabetes (T1D. As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs from each locus, we constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO analyses revealed that several of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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)

  3. 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...

  4. Extremity War Injuries VIII: sequelae of combat injuries.

    Science.gov (United States)

    Andersen, Romney C; D'Alleyrand, Jean-Claude G; Swiontkowski, Marc F; Ficke, James R

    2014-01-01

    The 2013 Extremity War Injury symposium focused on the sequelae of combat-related injuries, including posttraumatic osteoarthritis, amputations, and infections. Much remains to be learned about posttraumatic arthritis, and there are few circumstances in which a definitive arthroplasty should be performed in an acutely injured and open joint. Although the last decade has seen tremendous advances in the treatment of combat upper extremity injuries, many questions remain unanswered, and continued research focusing on improving reconstruction of large segmental defects remains critical. Discussion of infection centered on the need for novel methods to reduce the bacterial load following the initial débridement procedures. Novel methods of delivering antimicrobial therapy and anti-inflammatory medications directly to the wound were discussed as well as the need for near real-time assessment of bacterial and fungal burden and further means of prevention and treatment of biofilm formation and the importance of animal models to test therapies discussed. Moderators and lecturers of focus groups noted the continuing need for improved prehospital care in the management of junctional injuries, identified optimal strategies for both surgical repair and/or reconstruction of the ligaments in multiligamentous injuries, and noted the need to mitigate bone mineral density loss following amputation and/or limb salvage as well as the necessity of developing better methods of anticipating and managing heterotopic ossification.

  5. 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.

  6. 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 ...

  7. 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.

  8. 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)

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. [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.

  14. Combined deficiency of coagulation factors V and VIII: an update.

    Science.gov (United States)

    Zheng, Chunlei; Zhang, Bin

    2013-09-01

    Combined deficiency of factor V (FV) and FVIII (F5F8D) is an autosomal recessive bleeding disorder characterized by simultaneous decreases of both coagulation factors. This review summarizes recent reports on the clinical presentations, treatments, and molecular mechanism of F5F8D. Genetic studies identified LMAN1 and MCFD2 as causative genes for this disorder, revealing a previously unknown intracellular transport pathway shared by the two important blood coagulation factors. LMAN1 and MCFD2 form a Ca2+-dependent cargo receptor complex that functions in the transport of FV/FVIII from the endoplasmic reticulum (ER) to the Golgi. Disrupting the LMAN1-MCFD2 receptor, complex formation is the primary molecular defect of missense mutations leading to F5F8D. The EF-hand domains of MCFD2 are necessary and sufficient for the interactions with both LMAN1 and FV/FVIII. Similarly, the carbohydrate recognition domain of LMAN1 contains distinct and separable binding sites for both MCFD2 and FV/FVIII. Therefore, FV and FVIII likely carry duel sorting signals that are separately recognized by LMAN1 and MCFD2 and necessary for the efficient ER-to-Golgi transport. FV and FVIII likely bind LMAN1 through the high-mannose N-linked glycans under the higher Ca2+ conditions in the ER and dissociate in the lower Ca2+ environment of the ER-Golgi intermediate compartment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. 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

  16. Balance de carga en circuitos de distribución primaria por algoritmo genético; Load Balance of Primary Distribution Circuits by Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Ignacio Pérez Abril

    2011-02-01

    Full Text Available Aún cuando la operación más eficiente de un circuito trifásico se obtiene cuando la carga está totalmentebalanceada entre las fases, desde el punto de vista operativo es prácticamente imposible mantener dichobalance las 24 h del día y en todos los nodos del circuito de distribución. La existencia de desbalance entre lascorrientes de fase provoca un incremento de las pérdidas de potencia y energía en toda la longitud del circuitoprimario, al mismo tiempo que empobrece la calidad de la energía servida al contribuir al desbalance de losvoltajes en los distintos nodos del circuito. El presente trabajo implementa un algoritmo gético simple SGA paraseleccionar óptimamente las fases del circuito primario a que se deben conectar tanto los distintos bancos detransformadores de distribución, como los ramales bifásicos y monofásicos del circuito, de forma que se minimicenlos costos de las pérdidas de energía a lo largo del mismo In spite of the must efficient operation of a three phase circuit is obtained when the load is fully balanced, fromthe operative point of view, it is practically impossible to maintain that balance for the 24 hours of the day in allbuses of the distribution network. The existence of unbalance in the phase currents produces an increase inpower and energy losses in all the primary circuit length, at the same time that the power quality served tocustomers is decreased by the voltage unbalance in the circuit buses. The presented paper implements a simplegenetic algorithm SGA to optimize the phase selection for the distribution transformers and transformers banksconnection, as well as two and single phase feeder's connection to the circuit. 

  17. Isotherm and kinetics study of malachite green adsorption onto copper nanowires loaded on activated carbon: artificial neural network modeling and genetic algorithm optimization.

    Science.gov (United States)

    Ghaedi, M; Shojaeipour, E; Ghaedi, A M; Sahraei, Reza

    2015-05-05

    In this study, copper nanowires loaded on activated carbon (Cu-NWs-AC) was used as novel efficient adsorbent for the removal of malachite green (MG) from aqueous solution. This new material was synthesized through simple protocol and its surface properties such as surface area, pore volume and functional groups were characterized with different techniques such XRD, BET and FESEM analysis. The relation between removal percentages with variables such as solution pH, adsorbent dosage (0.005, 0.01, 0.015, 0.02 and 0.1g), contact time (1-40min) and initial MG concentration (5, 10, 20, 70 and 100mg/L) was investigated and optimized. A three-layer artificial neural network (ANN) model was utilized to predict the malachite green dye removal (%) by Cu-NWs-AC following conduction of 248 experiments. When the training of the ANN was performed, the parameters of ANN model were as follows: linear transfer function (purelin) at output layer, Levenberg-Marquardt algorithm (LMA), and a tangent sigmoid transfer function (tansig) at the hidden layer with 11 neurons. The minimum mean squared error (MSE) of 0.0017 and coefficient of determination (R(2)) of 0.9658 were found for prediction and modeling of dye removal using testing data set. A good agreement between experimental data and predicted data using the ANN model was obtained. Fitting the experimental data on previously optimized condition confirm the suitability of Langmuir isotherm models for their explanation with maximum adsorption capacity of 434.8mg/g at 25°C. Kinetic studies at various adsorbent mass and initial MG concentration show that the MG maximum removal percentage was achieved within 20min. The adsorption of MG follows the pseudo-second-order with a combination of intraparticle diffusion model. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. In vitro responses of chicken macrophage-like monocytes following exposure to pathogenic and non-pathogenic E. coli ghosts loaded with a rational design of conserved genetic materials of influenza and Newcastle disease viruses.

    Science.gov (United States)

    Lagzian, Milad; Bassami, Mohammad Reza; Dehghani, Hesam

    2016-08-01

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two important viral diseases in the poultry industry. Therefore, new disease-fighting strategies, especially effective genetic vaccination, are in high demand. Bacterial Ghost (BG) is a promising platform for delivering genetic materials to macrophages, cells that are among the first to encounter these viruses. However, there is no investigation on the immune response of these macrophage-targeted treatments. Here, we investigated the effect of genetic materials of AIV and NDV on the gene expression profile of important pro-inflammatory cytokines, a chemokine, a transcription factor, major histocompatibility complexes, and the viability of the chicken macrophage-like monocyte cells (CMM). Our genetic construct contained the external domain of matrix protein 2 and nucleoprotein gene of AIV, and immunodominant epitopes of fusion and hemagglutinin-neuraminidase proteins of NDV (hereinafter referred to as pAIV-Vax), delivered via the pathogenic and non-pathogenic BGs (Escherichia coli O78K80 and E. coli TOP10 respectively). The results demonstrated that both types of BGs were able to efficiently deliver the construct to the CMM, although the pathogenic strain derived BG was a significantly better stimulant and delivery vehicle. Both BGs were safe regarding LPS toxicity and did not induce any cell death. Furthermore, the loaded BGs were more powerful in modulating the pro-inflammatory cytokines' responses and antigen presentation systems in comparison to the unloaded BGs. Nitric oxide production of the BG-stimulated cells was also comparable to those challenged by the live bacteria. According to the results, the combination of pAIV-Vax construct and E. coli O78K80 BG is promising in inducing a considerable innate and adaptive immune response against AIV-NDV and perhaps the pathogenic E. coli, provided that the current combination be a potential candidate for in vivo testing regarding the development of an

  19. 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.

  20. 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.

  1. 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.

  2. Carbohydrate Loading.

    Science.gov (United States)

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  3. Plastic instabilities in statically and dynamically loaded spherical vessels

    Energy Technology Data Exchange (ETDEWEB)

    Duffey, Thomas A [Los Alamos National Laboratory; Rodriguez, Edward A [Los Alamos National Laboratory

    2010-01-01

    Significant changes were made in design limits for pressurized vessels in the 2007 version of the ASME Code (Section VIII, Div. 3) and 2008 and 2009 Addenda. There is now a local damage-mechanics based strain-exhaustion limit as well as the well-known global plastic collapse limit. Moreover, Code Case 2564 (Section VIII, Div. 3) has recently been approved to address impulsively loaded vessels. It is the purpose of this paper to investigate the plastic collapse limit as it applies to dynamically loaded spherical vessels. Plastic instabilities that could potentially develop in spherical shells under symmetric loading conditions are examined for a variety of plastic constitutive relations. First, a literature survey of both static and dynamic instabilities associated with spherical shells is presented. Then, a general plastic instability condition for spherical shells subjected to displacement controlled and impulsive loading is given. This instability condition is evaluated for six plastic and visco-plastic constitutive relations. The role of strain-rate sensitivity on the instability point is investigated. Calculations for statically and dynamically loaded spherical shells are presented, illustrating the formation of instabilities as well as the role of imperfections. Conclusions of this work are that there are two fundamental types of instabilities associated with failure of spherical shells. In the case of impulsively loaded vessels, where the pulse duration is short compared to the fundamental period of the structure, one instability type is found not to occur in the absence of static internal pressure. Moreover, it is found that the specific role of strain-rate sensitivity on the instability strain depends on the form of the constitutive relation assumed.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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".

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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…

  12. 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...

  13. 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.

  14. 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

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. A genetical approach to deep venous thrombosis

    Directory of Open Access Journals (Sweden)

    Celal Yavuz

    2012-06-01

    Full Text Available Deep venous thrombosis (DVT is a common disorderthat frequently occurs after surgical procedures andtrauma and in the presence of cancer or immobilizationconditions. However, it can also develop without any ofthese predisposing factors. This condition directs theresearcher’s enquiry to investigating the basis of organismalthrombotic predisposition. The common prothromboticgenetic mutations include factor V Leiden, factor IIG20210 A, plasminogen activator inhibitor-1, prothrombinA20210, and factor XIII - VIII. Nevertheless, current studiessuggest that the thrombotic events are not connectedwith single gene deletion or homeostatic regulation is alsoaffected by other genetic risk factors. Complex interactionsof genetic mutations can be affects different levels ofthrombotic system or reinforce each other’s effects on homeostaticmechanisms. The analysis of literature, togetherwith the action mechanisms of the classic geneticalfactors and new suggestions, may contribute significantlyto our understanding of the genetic predisposition to venousthrombosis. J Clin Exp Invest 2012; 3(2: 303-306

  8. 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...

  9. 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. 

  10. 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.

  11. Load testing circuit

    DEFF Research Database (Denmark)

    2009-01-01

    A load testing circuit a circuit tests the load impedance of a load connected to an amplifier. The load impedance includes a first terminal and a second terminal, the load testing circuit comprising a signal generator providing a test signal of a defined bandwidth to the first terminal of the load...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Electrical load detection aparatus

    DEFF Research Database (Denmark)

    2010-01-01

    A load detection technique for a load comprising multiple frequency-dependant sub-loads comprises measuring a representation of the impedance characteristic of the load; providing stored representations of a multiplicity of impedance characteristics of the load; each one of the stored representat...

  18. Direct detection of common and rare inversion mutations in the genetic diagnosis of severe hemophilia A

    Energy Technology Data Exchange (ETDEWEB)

    Windsor, A.S.; Lillicrap, D.P.; Taylor, S.A.M. [Queen`s Univ., Ontario (Canada)

    1994-09-01

    Approximately 50% of the cases of severe hemophilia A (factor VIII:C < 0.01 units/ml) may be due to gross rearrangements of the factor VIII gene. The mutation involves homologous sequences upstream of the factor VIII locus and within intron 22 in an intrachromosomal recombination, inversion, event. The rearrangements can readily be detected on a Southern blot using a probe that is complementary to sequences from within intron 22. We describe here the analysis of this mutation in 71 severe hemophilia A patients. Thirty two of the patients (45%) showed evidence of a rearrangement. Five different patterns of rearrangements were seen, two of which have previously been described and account for the majority of cases (pattern 1, 70% and pattern 2, 16%). Three other abnormal patterns were observed. The inversion mechanism does not usually result in the loss or gain of any genetic material, but in one patient, in whom a unique rearrangement pattern was observed (pattern 3), we have previously documented a gross deletion which removes exons 1-22 of the factor VII gene as well as sequences 5{prime} to the gene. In another individual a fourth pattern in which an extra 19.0 kb band is present was detected. In this case it is unclear as to whether the rearrangement is responsible for the disease or is simply coincident normal variation. A fifth pattern, in which an extra 16.0 kb band was detected, was observed in a family with a new mutation causing hemophilia A. The affected individual and his mother inherited a de novo rearrangement of the factor VIII gene from his unaffected grandfather, implicating it as the cause of the disease. In conclusion, testing for the factor VIII inversion mutation was positive in approximately 45% of severe hemophiliacs, 72% of whom were isolated cases, and as such should constitute the initial stage in the genetic testing protocol for these patients` families.

  19. 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

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. 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

  3. 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.

  4. [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.

  5. 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.

  6. 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.

  7. 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...

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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...

  11. 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

  12. Distribution load estimation (DLE)

    Energy Technology Data Exchange (ETDEWEB)

    Seppaelae, A.; Lehtonen, M. [VTT Energy, Espoo (Finland)

    1998-08-01

    The load research has produced customer class load models to convert the customers` annual energy consumption to hourly load values. The reliability of load models applied from a nation-wide sample is limited in any specific network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to find improvements to the load models or, in general, improvements to the load estimates. In Distribution Load Estimation (DLE) the measurements from the network are utilized to improve the customer class load models. The results of DLE will be new load models that better correspond to the loading of the distribution network but are still close to the original load models obtained by load research. The principal data flow of DLE is presented

  13. 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.

  14. 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.

  15. Distribution load estimation - DLE

    Energy Technology Data Exchange (ETDEWEB)

    Seppaelae, A. [VTT Energy, Espoo (Finland)

    1996-12-31

    The load research project has produced statistical information in the form of load models to convert the figures of annual energy consumption to hourly load values. The reliability of load models is limited to a certain network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to make improvements in the load models. Distribution load estimation (DLE) is the method developed here to improve load estimates from the load models. The method is also quite cheap to apply as it utilises information that is already available in SCADA systems

  16. Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models.

    Science.gov (United States)

    Ferreira, A E R; Castro, B F M; Vieira, L C; Cassali, G D; Souza, C M; Fulgêncio, G O; Ayres, E; Oréfice, R L; Jorge, R; Silva-Cunha, A; Fialho, S L

    2017-03-01

    To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization. The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression. In the evaluated models, the use of bevacizumab (Avastin®) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization. The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. 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.

  18. 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.

  19. [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.

  20. 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.

  1. [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.

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Medical genetics

    Energy Technology Data Exchange (ETDEWEB)

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  11. Genetic analysis of haemophilia A in Bulgaria.

    Science.gov (United States)

    Petkova, Rumena; Chakarov, Stoian; Kremensky, Ivo

    2004-01-01

    Haemophilias are the most common hereditary severe disorders of blood clotting. In families afflicted with heamophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostical strategy for carriership determination and prenatal diagnostics of haemophilia A in Bulgarian haemophilic population. A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a panel of eight linked to the factor VIII gene locus polymorphisms was established. Polymorphic analysis for carrier status determination of haemophilia A was successful in 30 families out of 32 (94%). Carrier status was determined in 25 of a total of 28 women at risk (89%). Fourteen prenatal diagnoses in women at high risk of having a haemophilia A - affected child were performed, resulting in 6 healthy boys and 5 girls. The compound approach proves to be a highly informative and cost-effective strategy for prevention of recurrence of haemophilia A in Bulgaria. DNA analysis facilitates carriership determination and subsequent prenatal diagnosis in the majority of Bulgarian families affected by haemophilia A.

  12. Genetic analysis of haemophilia A in Bulgaria

    Directory of Open Access Journals (Sweden)

    Kremensky Ivo

    2004-03-01

    Full Text Available Abstract Background Haemophilias are the most common hereditary severe disorders of blood clotting. In families afflicted with heamophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostical strategy for carriership determination and prenatal diagnostics of haemophilia A in Bulgarian haemophilic population. Methods A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a panel of eight linked to the factor VIII gene locus polymorphisms was established. Results Polymorphic analysis for carrier status determination of haemophilia A was successful in 30 families out of 32 (94%. Carrier status was determined in 25 of a total of 28 women at risk (89%. Fourteen prenatal diagnoses in women at high risk of having a haemophilia A – affected child were performed, resulting in 6 healthy boys and 5 girls. Conclusion The compound approach proves to be a highly informative and cost-effective strategy for prevention of recurrence of haemophilia A in Bulgaria. DNA analysis facilitates carriership determination and subsequent prenatal diagnosis in the majority of Bulgarian families affected by haemophilia A.

  13. Genetic algorithms

    Science.gov (United States)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  14. High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression

    National Research Council Canada - National Science Library

    Hamshere, Marian L; Langley, Kate; Martin, Joanna; Agha, Sharifah Shameem; Stergiakouli, Evangelia; Anney, Richard J.L; Buitelaar, Jan; Faraone, Stephen V; Lesch, Klaus-Peter; Neale, Benjamin M; Franke, Barbara; Sonuga-Barke, Edmund; Asherson, Philip; Merwood, Andrew; Kuntsi, Jonna; Medland, Sarah E; Ripke, Stephan; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Roeyers, Herbert; Biederman, Joseph; Doyle, Alysa E; Hakonarson, Hakon; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D; McGough, James J; Kent, Lindsey; Williams, Nigel; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C; Thapar, Anita

    2013-01-01

    ...) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity...

  15. 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

  16. 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%.

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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.

  1. Genetic Counseling

    Science.gov (United States)

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  2. Genetic Counseling

    Science.gov (United States)

    ... been added to your dashboard . KEY POINTS Genetic counseling helps you understand how genes, birth defects and medical ... in your area. What is genetic counseling? Genetic counseling helps you understand how genes , birth defects and other ...

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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?

  10. 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

  11. Parametric Identification of Aircraft Loads: An Artificial Neural Network Approach

    Science.gov (United States)

    2016-03-30

    Undergraduate Student Paper Postgraduate Student Paper Parametric Identification of Aircraft Loads: An Artificial Neural Network Approach...monitoring, flight parameter, nonlinear modeling, Artificial Neural Network , typical loadcase. Introduction Aircraft load monitoring is an... Neural Networks (ANN), i.e. the BP network and Kohonen Clustering Network , are applied and revised by Kalman Filter and Genetic Algorithm to build

  12. Carbohydrate-Loading Diet

    Science.gov (United States)

    ... of your calories from carbohydrates. The role of carbohydrates Carbohydrates, also known as starches and sugars, are ... to consume some energy sources during your event. Carbohydrate loading Carbohydrate loading is done the week before ...

  13. 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.

  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

    Directory of Open Access Journals (Sweden)

    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. Spatial electric load forecasting

    CERN Document Server

    Willis, H Lee

    2002-01-01

    Spatial Electric Load Forecasting Consumer Demand for Power and ReliabilityCoincidence and Load BehaviorLoad Curve and End-Use ModelingWeather and Electric LoadWeather Design Criteria and Forecast NormalizationSpatial Load Growth BehaviorSpatial Forecast Accuracy and Error MeasuresTrending MethodsSimulation Method: Basic ConceptsA Detailed Look at the Simulation MethodBasics of Computerized SimulationAnalytical Building Blocks for Spatial SimulationAdvanced Elements of Computerized SimulationHybrid Trending-Simulation MethodsAdvanced

  18. Cognitive Load and Cooperation

    DEFF Research Database (Denmark)

    Døssing, Felix Sebastian; Piovesan, Marco; Wengström, Erik Roland

    2017-01-01

    We study the effect of intuitive and reflective processes on cooperation using cognitive load. Compared with time constraint, which has been used in the previous literature, cognitive load is a more direct way to block reflective processes, and thus a more suitable way to study the link between...... intuition and cooperation. Using a repeated public goods game, we study the effect of different levels of cognitive load on contributions. We show that a higher cognitive load increases the initial level of cooperation. In particular, subjects are significantly less likely to fully free ride under high...... cognitive load....

  19. 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

  20. 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.

  1. Optimisation of load control

    Energy Technology Data Exchange (ETDEWEB)

    Koponen, P. [VTT Energy, Espoo (Finland)

    1998-08-01

    Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

  2. Tightness and Material Aspects of Bolted Flange Connections With Gaskets of Nonlinear Properties Exposed to Variable Loads

    Directory of Open Access Journals (Sweden)

    Walczak R.

    2016-09-01

    Full Text Available The paper presents the problems regarding bolted flange connections with gaskets used in chemical, petrochemical and energy industry. The aim of the research is to present state of knowledge regarding pipelines and apparatus in industrial installations and rules and regulations regarding flange connections tightness. Additionally a calculation example regarding flange connection according to ASME VIII DIV 1 requirement and then detailed Finite Element Analysis presented; impact of nonlinear material properties (gasket loading unloading curves on the connection tightness for complex loading programme is shown. It is finally concluded that in addition to usual design calculations more precise calculation is needed to fully verify behaviour of sealed connection at complex extreme variable loadings. Material aspect is very important at designing, testing, service and maintenance; taking it into consideration may avoid many problems related to safe exploitation.

  3. 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.

  4. 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

  5. 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

  6. Concentrated loads on concrete

    DEFF Research Database (Denmark)

    Lorenzen, Karen Grøndahl; Nielsen, Mogens Peter

    1997-01-01

    This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas are devel......This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas...

  7. Electrical load modeling

    Energy Technology Data Exchange (ETDEWEB)

    Valgas, Helio Moreira; Pinto, Roberto del Giudice R.; Franca, Carlos [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil); Lambert-Torres, Germano; Silva, Alexandre P. Alves da; Pires, Robson Celso; Costa Junior, Roberto Affonso [Escola Federal de Engenharia de Itajuba, MG (Brazil)

    1994-12-31

    Accurate dynamic load models allow more precise calculations of power system controls and stability limits, which are critical mainly in the operation planning of power systems. This paper describes the development of a computer program (software) for static and dynamic load model studies using the measurement approach for the CEMIG system. Two dynamic load model structures are developed and tested. A procedure for applying a set of measured data from an on-line transient recording system to develop load models is described. (author) 6 refs., 17 figs.

  8. Critical Axial Load

    Directory of Open Access Journals (Sweden)

    Walt Wells

    2008-01-01

    Full Text Available Our objective in this paper is to solve a second order differential equation for a long, simply supported column member subjected to a lateral axial load using Heun's numerical method. We will use the solution to find the critical load at which the column member will fail due to buckling. We will calculate this load using Euler's derived analytical approach for an exact solution, as well as Euler's Numerical Method. We will then compare the three calculated values to see how much they deviate from one another. During the critical load calculation, it will be necessary to calculate the moment of inertia for the column member.

  9. [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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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. ...

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. Genetic Disorders

    Science.gov (United States)

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  3. Genetic Counseling

    Science.gov (United States)

    ... and their families. Clinical Geneticists Clinical geneticists are medical doctors with special training in genetics. In addition to educating families about genetic conditions, they perform clinical exams and order lab tests to diagnose the causes ...

  4. Genetic modification and genetic determinism

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  5. Genetic modification and genetic determinism.

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  6. Imaging Genetics

    Science.gov (United States)

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  7. 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.

  8. 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...

  9. 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.

  10. 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...

  11. 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.

  12. 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...

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Load Induced Blindness

    Science.gov (United States)

    Macdonald, James S. P.; Lavie, Nilli

    2008-01-01

    Although the perceptual load theory of attention has stimulated a great deal of research, evidence for the role of perceptual load in determining perception has typically relied on indirect measures that infer perception from distractor effects on reaction times or neural activity (see N. Lavie, 2005, for a review). Here we varied the level of…

  1. Genetic Variations in the Kir6.2 Subunit (KCNJ11 of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan

    Directory of Open Access Journals (Sweden)

    Yi-Der Jiang

    2014-01-01

    Full Text Available To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4 and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0 from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044. After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047. K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading.

  2. Mechanism isolates load weighing cell during lifting of load

    Science.gov (United States)

    Haigler, J. S.

    1966-01-01

    Load weighing cell used in conjuction with a hoist is isolated during lifting and manipulation of the load. A simple mechanism, attached to a crane hook, provides a screw adjustment for engaging the load cell during weighing of the load and isolating it from lift forces during hoisting of the load.

  3. Load flow analysis using decoupled fuzzy load flow under critical ...

    African Journals Online (AJOL)

    user

    The conventional load flow methods like Newton-Raphson load flow (NRLF), Fast Decoupled load flow (FDLF) provide poor performance under critical conditions such as high R/X ratio, heavily loading condition etc. Exploiting the decoupling properties of power system, reliable fuzzy load flow is developed to overcome the ...

  4. Load Balancing Scientific Applications

    Energy Technology Data Exchange (ETDEWEB)

    Pearce, Olga Tkachyshyn [Texas A & M Univ., College Station, TX (United States)

    2014-12-01

    The largest supercomputers have millions of independent processors, and concurrency levels are rapidly increasing. For ideal efficiency, developers of the simulations that run on these machines must ensure that computational work is evenly balanced among processors. Assigning work evenly is challenging because many large modern parallel codes simulate behavior of physical systems that evolve over time, and their workloads change over time. Furthermore, the cost of imbalanced load increases with scale because most large-scale scientific simulations today use a Single Program Multiple Data (SPMD) parallel programming model, and an increasing number of processors will wait for the slowest one at the synchronization points. To address load imbalance, many large-scale parallel applications use dynamic load balance algorithms to redistribute work evenly. The research objective of this dissertation is to develop methods to decide when and how to load balance the application, and to balance it effectively and affordably. We measure and evaluate the computational load of the application, and develop strategies to decide when and how to correct the imbalance. Depending on the simulation, a fast, local load balance algorithm may be suitable, or a more sophisticated and expensive algorithm may be required. We developed a model for comparison of load balance algorithms for a specific state of the simulation that enables the selection of a balancing algorithm that will minimize overall runtime.

  5. Heritability and Genetic Advance among Chili Pepper Genotypes for Heat Tolerance and Morphophysiological Characteristics

    Directory of Open Access Journals (Sweden)

    Magaji G. Usman

    2014-01-01

    Full Text Available High temperature tolerance is an important component of adaptation to arid and semiarid cropping environment in chili pepper. Two experiments were carried out to study the genetic variability among chili pepper for heat tolerance and morphophysiological traits and to estimate heritability and genetic advance expected from selection. There was a highly significant variation among the genotypes in response to high temperature (CMT, photosynthesis rate, plant height, disease incidence, fruit length, fruit weight, number of fruits, and yield per plant. At 5% selection intensity, high genetic advance as percent of the mean (>20% was observed for CMT, photosynthesis rate, fruit length, fruit weight, number of fruits, and yield per plant. Similarly, high heritability (>60% was also observed indicating the substantial effect of additive gene more than the environmental effect. Yield per plant showed strong to moderately positive correlations (r=0.23–0.56 at phenotypic level while at genotypic level correlation coefficient ranged from 0.16 to 0.72 for CMT, plant height, fruit length, and number of fruits. Cluster analysis revealed eight groups and Group VIII recorded the highest CMT and yield. Group IV recorded 13 genotypes while Groups II, VII, and VIII recorded one each. The results showed that the availability of genetic variance could be useful for exploitation through selection for further breeding purposes.

  6. Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women.

    Directory of Open Access Journals (Sweden)

    Maria A Matuszek

    Full Text Available To identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities.Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians.There were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000, triglycerides (P = .050, low density lipoprotein (P = .009 and non-fasting blood glucose (15 min (P = .024 were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC. Non-fasting insulin in South Asians (15-120 min, in South East/East Asians (60-120 min, and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006. The molar ratio of C-peptide AUC/Insulin AUC (P = .045 and adiponectin (P = .037 were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022 and rs10830963 (P = 0.009, which are both near the melatonin receptor MTNR1B.Elevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.

  7. Resolutions of the Coulomb operator: VIII. Parallel implementation using the modern programming language X10.

    Science.gov (United States)

    Limpanuparb, Taweetham; Milthorpe, Josh; Rendell, Alistair P

    2014-10-30

    Use of the modern parallel programming language X10 for computing long-range Coulomb and exchange interactions is presented. By using X10, a partitioned global address space language with support for task parallelism and the explicit representation of data locality, the resolution of the Ewald operator can be parallelized in a straightforward manner including use of both intranode and internode parallelism. We evaluate four different schemes for dynamic load balancing of integral calculation using X10's work stealing runtime, and report performance results for long-range HF energy calculation of large molecule/high quality basis running on up to 1024 cores of a high performance cluster machine. Copyright © 2014 Wiley Periodicals, Inc.

  8. Genetic barcodes

    Science.gov (United States)

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  9. LOADING SIMULATION PROGRAM C

    Data.gov (United States)

    U.S. Environmental Protection Agency — LSPC is the Loading Simulation Program in C++, a watershed modeling system that includes streamlined Hydrologic Simulation Program Fortran (HSPF) algorithms for...

  10. Plug Load Data

    Data.gov (United States)

    National Aeronautics and Space Administration — We provide MATLAB binary files (.mat) and comma separated values files of data collected from a pilot study of a plug load management system that allows for the...

  11. LOADING SIMULATION PROGRAM C

    Science.gov (United States)

    LSPC is the Loading Simulation Program in C++, a watershed modeling system that includes streamlined Hydrologic Simulation Program Fortran (HSPF) algorithms for simulating hydrology, sediment, and general water quality

  12. HIV Viral Load

    Science.gov (United States)

    ... Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle ... used each time. Will exercise, nutrition, and other lifestyle modifications help decrease my HIV viral load? There ...

  13. Lumbriculus variegatus loading study

    Data.gov (United States)

    U.S. Environmental Protection Agency — Results from sediment bioaccumulation tests with Lumbriculus variegatus with evaluating the effects of organism loading density. This dataset is associated with the...

  14. Static Loads Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides the capability to perform large-scale structural loads testing on spacecraft and other structures. Results from these tests can be used to verify...

  15. Composite Load Model Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ning; Qiao, Hong (Amy)

    2007-09-30

    The WECC load modeling task force has dedicated its effort in the past few years to develop a composite load model that can represent behaviors of different end-user components. The modeling structure of the composite load model is recommended by the WECC load modeling task force. GE Energy has implemented this composite load model with a new function CMPLDW in its power system simulation software package, PSLF. For the last several years, Bonneville Power Administration (BPA) has taken the lead and collaborated with GE Energy to develop the new composite load model. Pacific Northwest National Laboratory (PNNL) and BPA joint force and conducted the evaluation of the CMPLDW and test its parameter settings to make sure that: • the model initializes properly, • all the parameter settings are functioning, and • the simulation results are as expected. The PNNL effort focused on testing the CMPLDW in a 4-bus system. An exhaustive testing on each parameter setting has been performed to guarantee each setting works. This report is a summary of the PNNL testing results and conclusions.

  16. Load power device, system and method of load control and management employing load identification

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yi; Luebke, Charles John; Schoepf, Thomas J.

    2018-01-09

    A load power device includes a power input, at least one power output for at least one load, a plurality of sensors structured to sense voltage and current at the at least one power output, and a processor. The processor provides: (a) load identification based upon the sensed voltage and current, and (b) load control and management based upon the load identification.

  17. 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...

  18. 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

  19. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  20. GENETIC ASPECTS OF AUTISM

    Directory of Open Access Journals (Sweden)

    Anastas LAKOSKI

    1997-06-01

    Full Text Available In the first paper on the syndrome of autism, Kanner described it as innate and inborn. He drew attention to the abnormalities in infancy without evidence of prior normal development and the intellectual, non emotional qualities shown by many of the parents and grandparents. Subsequently, the supposed lack of parental warmth led many clinicians to abandon the notions of constitutional deficit in the child and instead to postulate a psychogenic origin etiology was likely, genetic factors probably did not play a major role. Attention was draw to the low rate of autism in siblings, the lack of chromosome anomalies, and the similarities with syndromes associated with known brain trauma. Although the rate of autism in siblings was indeed low, it was much higher than in the general population rate providing a strong pointer to the genetic factors. The recognition that this was so, associated with the parallel finding of apparently high familiar loading for language delay, stimulated the first, systematic, twin study of autism, which suggested a strong genetic component. Subsequent research has produced findings in the same direction, although many questions remain unanswered. In this paper the evidence that has accumulated on genetic influences on autism is summarized and the remained dilemmas on this field are discussed.

  1. Determinación de cargas dinámicas de camiones pesados que transitan en un puente basado en algoritmos genéticos e instrumentación Genetic algorithms and instrumentation determination of dynamic loads of heavy trucks over a bridge

    Directory of Open Access Journals (Sweden)

    Edgar Muñoz

    2011-12-01

    Full Text Available Esta investigación determina las cargas por eje de los camiones que circulan por un puente ubicado en una de las vías principales de Colombia, utilizando la técnica de control BWIM (Bridge Weight in Motion, no empleada antes en el País. Nuestro grupo de investigación implementó la Metodología de los Algoritmos genéticos, instrumentación y monitoreo, para el Puente denominado Boquerón en la vía Bogotá - Villavicencio, Colombia. Para ese fin, se instrumentaron cuatro vigas con un sistema electrónico de medición de tráfico en cada carril, además de un sistema de adquisición de datos y ensayos de laboratorio. Desarrollamos la calibración de su modelo estructural y la generación de funciones matemáticas para hacer converger líneas de influencias de cargas con pruebas experimentales y así determinar las cargas en movimiento de los camiones. En adición, se desarrolló una herramienta computacional, capaz de representar con aceptable precisión las cargas en movimiento.This research determines the axle loads of trucks traveling on a bridge located in one of the most important corridors of Colombia, using the technique of control BWIM (Bridge Weight in Motion, not used before in the country. Our research group developed a Genetic Algorithm based in a trial test, implementation and monitoring to the bridge called Boquerón of Colombian Highways (Bogota - Villavicencio. For such an effort, four girders were monitored by data acquisition electronics joined by an electronic traffic log device by lane accompanied of laboratory testing for materials. Model calibration was performed by mathematical approach of in-situ influence lines compared to those obtained by modeling, giving as outcome loads of moving trucks over the bridge. In addition, we developed a computational tool, able to represent with reasonable accuracy the moving loads.

  2. Genetic Mapping

    Science.gov (United States)

    ... at NHGRI About About the Institute Budget and Financial Information Divisions Director's Page How to Contact Us Institute ... genome, has greatly advanced genetics research. The improved quality of genetic ... for Biotechnology Information (NCBI) [ncbi.nlm.nih.gov], as well as ...

  3. Genetic Engineering

    Science.gov (United States)

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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...

  12. 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.

  13. 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...

  14. 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.

  15. 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%

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    The strings of artificial genetic systems are analogous to chromosomes. GENERAL I ARTICLE. GAs operate by combining the information present in different possible solutions for a given problem, in such a way that a better solution is obtained in future generations. Terminologies used in natural genetic systems (NGS) and.

  1. Low metal loading catalysts used for the selective hydrogenation of styrene

    Energy Technology Data Exchange (ETDEWEB)

    Badano, Juan; Lederhos, Cecilia; Quiroga, Monica; L' Argentiere, Pablo [Consejo Nacional de Investigaciones Cientificas y Tecnicas, Santa Fe (Argentina). Universidad Nacional del Litoral. Inst. de Investigaciones en Catalisis y Petroquimica; Coloma-Pascual, Fernando [Universidad de Alicante (Spain). Facultad de Ciencias. Servicios Tecnicos de Investigacion

    2010-07-01

    A series of Group VIII metal catalysts was obtained for the semi-hydrogenation of styrene. Catalysts were characterized by Hydrogen Chemisorption, TPR and XPS. Palladium, rhodium and platinum low metal loading prepared catalysts presented high activity and selectivity (ca. 98%) during the semi-hydrogenation of styrene, being palladium the most active catalyst. The ruthenium catalyst also presented high selectivity (ca. 98%), but the lowest activity. For the palladium catalyst, the influence of the precursor salt and of the reduction temperature on the activity and selectivity were studied. The following activity series was obtained: PdN-423 > PdCl-673 > PdCl-373> PtCl-673 > RhCl-673 >> RuCl-673. As determined by XPS, differences in activity could be attributed, at least in part, to electronic effects (author)

  2. 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].

  3. 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.

  4. 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].

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Dielectrically Loaded Biconical Antennas

    Science.gov (United States)

    Nusseibeh, Fouad Ahmed

    1995-01-01

    Biconical antennas are of great interest to those who deal with broadband applications including the transmission/reception of pulses. In particular, wide-angle conical antennas are an attractive choice in many applications including Electronic Support Measures (ESM) and the measurements of transient surface currents and charge densities on aircraft. Dielectric loading in the interior region of a conical antenna can be used to reduce the size of the antenna especially at low frequencies and/or for structural strength. Therefore, having an analytical solution for the input impedance and the frequency response is very helpful in optimizing the design and understanding the behavior of the antenna. From the quasi-analytical solution for the input impedance and the electric field of a wide-angle conical antenna, it can be seen that the dielectric loading in the antenna region improves the input impedance at low frequencies, but increases the number of resonance points and the magnitude of these peaks. When an inhomogeneous dielectric load is used, the magnitude of the resonance peaks is decreased (depending on the way the load is distributed), improving the input impedance of the antenna significantly. Introducing a dielectric load in the interior region of an electrically short receiving cone makes the antenna behave as an electrically longer antenna. However, this is not true for the case for electrical1y long antennas. For the case of pulse transmission, the dielectric load affects only the amplitude. Of course, if the dielectric fills the whole space, both transmitting and receiving antennas behave as electrically longer antennas.

  15. Wave Loads on Cylinders

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Frigaard, Peter

    1989-01-01

    Wave loads may be defined as time varying forces on a body resulting from the wave induced flow fields which surrounds the body in whole or in part. Such unsteady fluid forces are the net result of pressure and shear forces integrated over the instantaneous wetted area.......Wave loads may be defined as time varying forces on a body resulting from the wave induced flow fields which surrounds the body in whole or in part. Such unsteady fluid forces are the net result of pressure and shear forces integrated over the instantaneous wetted area....

  16. Load research and load estimation in electricity distribution

    Energy Technology Data Exchange (ETDEWEB)

    Seppaelae, A. [VTT Energy, Espoo (Finland). Energy Systems

    1996-12-31

    The topics introduced in this thesis are: the Finnish load research project, a simple form customer class load model, analysis of the origins of customers load distribution, a method for the estimation of the confidence interval of customer loads and Distribution Load Estimation (DLE) which utilises both the load models and measurements from distribution networks. The Finnish load research project started in 1983. The project was initially coordinated by the Association of Finnish Electric Utilities and 40 utilities joined the project. Now there are over 1000 customer hourly load recordings in a database. A simple form customer class load model is introduced. The model is designed to be practical for most utility applications and has been used by the Finnish utilities for several years. The only variable of the model is the customers annual energy consumption. The model gives the customers average hourly load and standard deviation for a selected month, day and hour. The statistical distribution of customer loads is studied and a model for customer electric load variation is developed. The model results in a lognormal distribution as an extreme case. Using the `simple form load model`, a method for estimating confidence intervals (confidence limits) of customer hourly load is developed. The two methods selected for final analysis are based on normal and lognormal distribution estimated in a simplified manner. The estimation of several cumulated customer class loads is also analysed. Customer class load estimation which combines the information from load models and distribution network load measurements is developed. This method, called Distribution Load Estimation (DLE), utilises information already available in the utilities databases and is thus easy to apply

  17. New Genetics

    Science.gov (United States)

    ... RNA, transcription, RNA splicing, translation, ribosomes, antibiotics, genetic diseases, gene chips. » more Chapter 2: RNA and DNA Revealed: New Roles, New Rules Covers microRNAs, RNAi, epigenetics, telomeres, mtDNA, recombinant DNA. » more Chapter 3: Life's ...

  18. Genetic Discrimination

    Science.gov (United States)

    Skip to main content Genetic Discrimination Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features ...

  19. 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.

  20. Laterally loaded masonry

    DEFF Research Database (Denmark)

    Raun Gottfredsen, F.

    stress and increasing shear. The results show a transition to pure friction as the cohesion is gradually destroyed. An interface model of a mortar joint that can take into account this aspect has been developed. Laterally loaded masonry panels have also been tested and it is found to be characteristic...

  1. Fuel Load (FL)

    Science.gov (United States)

    Duncan C. Lutes; Robert E. Keane

    2006-01-01

    The Fuel Load method (FL) is used to sample dead and down woody debris, determine depth of the duff/ litter profile, estimate the proportion of litter in the profile, and estimate total vegetative cover and dead vegetative cover. Down woody debris (DWD) is sampled using the planar intercept technique based on the methodology developed by Brown (1974). Pieces of dead...

  2. Probabilistic Load Flow

    DEFF Research Database (Denmark)

    Chen, Peiyuan; Chen, Zhe; Bak-Jensen, Birgitte

    2008-01-01

    This paper reviews the development of the probabilistic load flow (PLF) techniques. Applications of the PLF techniques in different areas of power system steady-state analysis are also discussed. The purpose of the review is to identify different available PLF techniques and their corresponding...

  3. Robust surgery loading

    NARCIS (Netherlands)

    Hans, Elias W.; Wullink, Gerhard; van Houdenhoven, Mark; Kazemier, Geert

    2008-01-01

    We consider the robust surgery loading problem for a hospital’s operating theatre department, which concerns assigning surgeries and sufficient planned slack to operating room days. The objective is to maximize capacity utilization and minimize the risk of overtime, and thus cancelled patients. This

  4. Duration of load revisited

    DEFF Research Database (Denmark)

    Hoffmeyer, Preben; Sørensen, John Dalsgaard

    2007-01-01

    A duration of load study representing 13 years of testing was recently terminated. Preliminary results have been published over the years. This paper represents the final account of the study, which was focused on the influ-ence of moisture content on time to failure for structural timber subject...

  5. Genetic counseling.

    Science.gov (United States)

    Pina-Neto, João Monteiro de

    2008-08-01

    The objective of this review of genetic counseling (GC) is to describe the current concepts and philosophical and ethical principles accepted by the great majority of countries and recommended by the World Health Organization, the stages of the process, its results and the psychological impact that a genetic disease has on a family. The concepts presented are based on an historical synthesis of the literature on GC since the 1930s until today, and the articles cited represent the most important research published which today provides the foundation for the theory and practice of GC. The modern definition of GC is a process of communication that deals with the human problems related with the occurrence of a genetic disease in a family. It is of fundamental importance that health professionals are aware of the psychological aspects triggered by genetic diseases and the ways in which these can be managed. In the field of human and medical genetics we are still living in a phase in which technical and scientific aspects predominate, with little emphasis on the study of emotional reactions and people's processes of adaptation to these diseases, which leads to clients having a low level of understanding of the events that have taken place, with negative consequences for family life and for society. The review concludes by discussing the need to refer families with genetic diseases for GC and the need for professionals working in this area to invest more in humanizing care and developing non-directive psychological GC techniques.

  6. Load research manual. Volume 1. Load research procedures

    Energy Technology Data Exchange (ETDEWEB)

    Brandenburg, L.; Clarkson, G.; Grund, Jr., C.; Leo, J.; Asbury, J.; Brandon-Brown, F.; Derderian, H.; Mueller, R.; Swaroop, R.

    1980-11-01

    This three-volume manual presents technical guidelines for electric utility load research. Special attention is given to issues raised by the load data reporting requirements of the Public Utility Regulatory Policies Act of 1978 and to problems faced by smaller utilities that are initiating load research programs. In Volumes 1 and 2, procedures are suggested for determining data requirements for load research, establishing the size and customer composition of a load survey sample, selecting and using equipment to record customer electricity usage, processing data tapes from the recording equipment, and analyzing the data. Statistical techniques used in customer sampling are discussed in detail. The costs of load research also are estimated, and ongoing load research programs at three utilities are described. The manual includes guides to load research literature and glossaries of load research and statistical terms.

  7. Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

    DEFF Research Database (Denmark)

    Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo

    2013-01-01

    the causative mutation is unknown. More rare bleeding disorders are generally recessively inherited, and are often caused by mutations that are specific for individual families, and mutations are scattered throughout the genes. Laboratories performing molecular genetic analyses must have validated internal......Hemophilia is an inherited bleeding disorder primarily caused by deficiency of coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B). Both conditions are X-linked. More than 2100 different F8 mutations have been described, the most common being a 500 kb inversion involving exon 1 to exon...... 22. In hemophilia B, more than 1100 unique F9 mutations have been described scattered all over the gene. Carrier analysis, genetic counseling, prenatal and pre-implantation genetic diagnosis are all based on correct identifying the disease-causing mutation. Linkage analysis can be considered when...

  8. J. Genet. classic 17

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 1, April 2004. 17. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 1, April 2004. 18. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 1, April 2004. 19. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 1, April 2004. 20. Page 5. J. Genet. classic. Journal of ...

  9. J. Genet. classic 99

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 2, August 2005. 99. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 2, August 2005. 100. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 2, August 2005. 101. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 2, August 2005. 102. Page 5. J. Genet. classic.

  10. J. Genet. classic 37

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 1, April 2005. 37. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 38. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 39. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 40. Page 5. J. Genet. classic. Journal of ...

  11. J. Genet. classic 101

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 85, No. 2, August 2006. 101. Page 2. J. Genet. classic. 102. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 3. J. Genet. classic. Journal of Genetics, Vol. 85, No. 2, August 2006. 103. Page 4. J. Genet. classic. 104. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 5. J. Genet. classic.

  12. J. Genet. classic 125

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 2, August 2004. 125. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 2, August 2004. 126. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 2, August 2004. 127. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 2, August 2004. 128. Page 5. J. Genet. classic.

  13. J. Genet. classic 17

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 1, April 2005. 17. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 18. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 19. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 20. Page 5. J. Genet. classic. Journal of ...

  14. About Genetic Counselors

    Science.gov (United States)

    ... seeing a genetic counselor? Q. What is a genetic counselor? A. Genetic counselors are healthcare professionals with ... and serve as patient advocates. Q. What is genetic counseling? A. Genetic counseling is the process of ...

  15. Coordination of Economic Load Dispatch and Load Frequency Control for Interconnected Power System

    Science.gov (United States)

    Shankar, R.; Chatterjee, K.; Chatterjee, T. K.

    2015-03-01

    This paper deals with the coordination of economic load dispatch and load frequency control concepts of the interconnected power system. The total change in the particular control area is shared by each unit according to their participation factor obtained from the calculation of the economic load dispatch. In this work, two control areas are considered, the first control area contains the combination of hydro, thermal and gas generating unit and in the second control area, it contains the combination of the thermal and hydro generating units. Integral controller is used for secondary controller for load frequency control mechanism. A digital simulation is used in conjunction with the genetic algorithm (GA) technique to determine the optimum parameters of the individual gain of integral controller. Three different types of performance indices are considered to measure the appropriateness of the proposed controller. The optimum values of the gains improve the dynamic performance of the controller and reduce the overshoot and maximum frequency deviation and net tie-line power flow deviation error for a particular load change. To show the effectiveness of the proposed controller, simulation result is shown in result and discussion section.

  16. A case study of high genetic loading and subsequent development ...

    African Journals Online (AJOL)

    became depressed and her school functioning declined even more. A child psychiatrist diagnosed a major depressive disorder and ADHD. She was prescribed citalopram 10 mg daily and methylphenidate. She became hyperactive on the antidepressant, which was subsequently discontinued. The methylphenidate was ...

  17. Transancestral mapping and genetic load in systemic lupus erythematosus

    NARCIS (Netherlands)

    Langefeld, Carl D.; Ainsworth, Hannah C.; Graham, Deborah S. Cunninghame; Kelly, Jennifer A.; Comeau, Mary E.; Marion, Miranda C.; Howard, Timothy D.; Ramos, Paula S.; Croker, Jennifer A.; Morris, David L.; Sandling, Johanna K.; Almlof, Jonas Carlsson; Acevedo-Vasquez, Eduardo M.; Alarcon, Graciela S.; Babini, Alejandra M.; Baca, Vicente; Bengtsson, Anders A.; Berbotto, Guillermo A.; Bijl, Marc; Brown, Elizabeth E.; Brunner, Hermine I.; Cardiel, Mario H.; Catoggio, Luis; Cervera, Ricard; Cucho-Venegas, Jorge M.; Dahlqvist, Solbritt Rantapaa; D'Alfonso, Sandra; Da Silva, Berta Martins; de la Rua Figueroa, Inigo; Doria, Andrea; Edberg, Jeffrey C.; Endreffy, Emoke; Esquivel-Valerio, Jorge A.; Fortin, Paul R.; Freedman, Barry I.; Frostegard, Johan; Garcia, Mercedes A.; Garcia de la Torre, Ignacio; Gilkeson, Gary S.; Gladman, Dafna D.; Gunnarsson, Iva; Guthridge, Joel M.; Huggins, Jennifer L.; James, Judith A.; Kallenberg, Cees G. M.; Kamen, Diane L.; Karp, David R.; Kaufman, Kenneth M.; Kottyan, Leah C.; Kovacs, Laszlo; Laustrup, Helle; Lauwerys, Bernard R.; Li, Quan-Zhen; Maradiaga-Cecena, Marco A.; Martin, Javier; McCune, Joseph M.; McWilliams, David R.; Merrill, Joan T.; Miranda, Pedro; Moctezuma, Jose F.; Nath, Swapan K.; Niewold, Timothy B.; Orozco, Lorena; Ortego-Centeno, Norberto; Petri, Michelle; Pineau, Christian A.; Pons-Estel, Bernardo A.; Pope, Janet; Raj, Prithvi; Ramsey-Goldman, Rosalind; Reveille, John D.; Russell, Laurie P.; Sabio, Jose M.; Aguilar-Salinas, Carlos A.; Scherbarth, Hugo R.; Scorza, Raffaella; Seldin, Michael F.; Sjowall, Christopher; Svenungsson, Elisabet; Thompson, Susan D.; Toloza, Sergio M. A.; Truedsson, Lennart; Tusie-Luna, Teresa; Vasconcelos, Carlos; Vila, Luis M.; Wallace, Daniel J.; Weisman, Michael H.; Wither, Joan E.; Bhangale, Tushar; Oksenberg, Jorge R.; Rioux, John D.; Gregersen, Peter K.; Syvanen, Ann-Christine; Ronnblom, Lars; Criswell, Lindsey A.; Jacob, Chaim O.; Sivils, Kathy L.; Tsao, Betty P.; Schanberg, Laura E.; Behrens, Timothy W.; Silverman, Earl D.; Alarcon-Riquelme, Marta E.; Kimberly, Robert P.; Harley, John B.; Wakeland, Edward K.; Graham, Robert R.; Gaffney, Patrick M.; Vyse, Timothy J.

    2017-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58

  18. Transancestral mapping and genetic load in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Langefeld, Carl D; Ainsworth, Hannah C; Graham, Deborah S Cunninghame

    2017-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Molecular research and genetic engineering of resistance to ...

    African Journals Online (AJOL)

    Molecular research and genetic engineering of resistance to Verticillium wilt in cotton: A review. ... African Journal of Biotechnology. Journal Home · ABOUT · Advanced Search · Current Issue ... Article Metrics. Metrics Loading ... Metrics ...

  11. Heavy-Load Lifting

    DEFF Research Database (Denmark)

    Bloomquist, Kira; Oturai, Peter; Steele, Megan L

    2017-01-01

    PURPOSE: Despite a paucity of evidence, prevention guidelines typically advise avoidance of heavy lifting in an effort to protect against breast cancer-related lymphedema. This study compared acute responses in arm swelling and related symptoms after low- and heavy-load resistance exercise among...... women at risk of lymphedema while receiving adjuvant taxane-based chemotherapy. METHODS: This is a randomized, cross-over equivalence trial. Women receiving adjuvant taxane-based chemotherapy for breast cancer who had undergone axillary lymph node dissection (n=21) participated in low- (60-65% 1...... repetition maximum (RM), two sets of 15-20 repetitions) and heavy-load (85-90% 1RM, three sets of 5-8 repetition) upper-extremity resistance exercise separated by a one-week wash-out period. Swelling was determined by bioimpedance spectroscopy and dual energy x-ray absorptiometry, with breast cancer...

  12. Genetic GIScience

    DEFF Research Database (Denmark)

    Jacquez, Geoffrey; Sabel, Clive E; Shi, Chen

    2015-01-01

    The exposome, defined as the totality of an individual's exposures over the life course, is a seminal concept in the environmental health sciences. Although inherently geographic, the exposome as yet is unfamiliar to many geographers. This article proposes a place-based synthesis, genetic...... geographic information science (genetic GIScience), that is founded on the exposome, genome+, and behavome. It provides an improved understanding of human health in relation to biology (the genome+), environmental exposures (the exposome), and their social, societal, and behavioral determinants (the behavome......). Genetic GIScience poses three key needs: first, a mathematical foundation for emergent theory; second, process-based models that bridge biological and geographic scales; third, biologically plausible estimates of space?time disease lags. Compartmental models are a possible solution; this article develops...

  13. Load responsive hydrodynamic bearing

    Science.gov (United States)

    Kalsi, Manmohan S.; Somogyi, Dezso; Dietle, Lannie L.

    2002-01-01

    A load responsive hydrodynamic bearing is provided in the form of a thrust bearing or journal bearing for supporting, guiding and lubricating a relatively rotatable member to minimize wear thereof responsive to relative rotation under severe load. In the space between spaced relatively rotatable members and in the presence of a liquid or grease lubricant, one or more continuous ring shaped integral generally circular bearing bodies each define at least one dynamic surface and a plurality of support regions. Each of the support regions defines a static surface which is oriented in generally opposed relation with the dynamic surface for contact with one of the relatively rotatable members. A plurality of flexing regions are defined by the generally circular body of the bearing and are integral with and located between adjacent support regions. Each of the flexing regions has a first beam-like element being connected by an integral flexible hinge with one of the support regions and a second beam-like element having an integral flexible hinge connection with an adjacent support region. A least one local weakening geometry of the flexing region is located intermediate the first and second beam-like elements. In response to application of load from one of the relatively rotatable elements to the bearing, the beam-like elements and the local weakening geometry become flexed, causing the dynamic surface to deform and establish a hydrodynamic geometry for wedging lubricant into the dynamic interface.

  14. Nutrient and Coliform Loading (NCL)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is a database of available fecal coliform bacteria, fecal streptococci bacteria, and nutrient loading data. Loading for contaminants other than fecal coliform...

  15. Load Estimation from Modal Parameters

    DEFF Research Database (Denmark)

    Aenlle, Manuel López; Brincker, Rune; Fernández, Pelayo Fernández

    2007-01-01

    In Natural Input Modal Analysis the modal parameters are estimated just from the responses while the loading is not recorded. However, engineers are sometimes interested in knowing some features of the loading acting on a structure. In this paper, a procedure to determine the loading from a FRF...... the accuracy in the load estimation. Finally, the results of an experimental program carried out on a simple structure are presented....

  16. Genetic engineering for haemophilia A.

    Science.gov (United States)

    Gan, Shu Uin; Kon, Oi Lian; Calne, Roy Y

    2006-10-01

    At first sight, haemophilia A would appear to be an ideal candidate for treatment by gene therapy. There is a single gene defect; cells in different parts of the body, but especially the liver, produce Factor VIII, and only 5% of normal levels of Factor VIII are necessary to prevent the serious symptoms of bleeding. This review attempts to outline the status of gene therapy at present and efforts that have been made to overcome the difficulties and remaining problems that require solving. Undoubtedly, success will be achieved, but it is likely that considerably more work will be necessary before experimental models can be introduced into the clinic with any likelihood of success. The most successful results in animals that may have clinical application were from introducing the Factor VIII gene to newborn animals before antibodies are produced, presumably inducing a state of tolerance.

  17. Research of Impact Load in Large Electrohydraulic Load Simulator

    Directory of Open Access Journals (Sweden)

    Yongguang Liu

    2014-01-01

    Full Text Available The stronger impact load will appear in the initial phase when the large electric cylinder is tested in the hardware-in-loop simulation. In this paper, the mathematical model is built based on AMESim, and then the reason of the impact load is investigated through analyzing the changing tendency of parameters in the simulation results. The inhibition methods of impact load are presented according to the structural invariability principle and applied to the actual system. The final experimental result indicates that the impact load is inhibited, which provides a good experimental condition for the electric cylinder and promotes the study of large load simulator.

  18. Genetic Recombination

    Science.gov (United States)

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  19. Genetic counseling

    Science.gov (United States)

    ... MF, eds. Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice . 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 30. Review Date 1/25/2016 Updated by: Chad Haldeman-Englert, MD, FACMG, Fullerton Genetics Center, Asheville, NC. Review provided by VeriMed Healthcare ...

  20. Genetic Romanticism

    DEFF Research Database (Denmark)

    Tupasela, Aaro

    2016-01-01

    The role that national epic poetry has played in romantic nationalism during the nineteenth and twentieth centuries is well documented. The role that the new genetics has played in such processes, however, is less well known and understood as a form of writing national narratives of origin...

  1. A molecular genetic study of natural strains of Saccharomyces isolated from Asturian cider fermentations.

    Science.gov (United States)

    Suárez Valles, B; Pando Bedriñana, R; González García, A; Querol Simón, A

    2007-10-01

    To analyse the genetic diversity and the dynamics of Saccharomyces strains in spontaneous fermentation in ciders. The effect of the cellar, harvest and cider-making technology were evaluated. The ecology of spontaneous cider fermentations in the same cellar (Asturias) was studied for two consecutive harvests (2000 and 2001) by using mtDNA restriction analysis. Our results showed that there was a succession of genetically different strains of Saccharomyces during cider production. In general, strains of Saccharomyces bayanus species predominated at the early fermentation steps (begining and/or tumultuous fermentations), while Saccharomyces cerevisiae yeasts were the most abundant at the end of the fermentation. Five S. bayanus strains (patterns III, VII, VIII, XV and XVII) were present at significant frequencies in all the experimental tanks during the two consecutive years. The results of the cluster analysis (unweighted pair group method using average linkage) showed higher similarities for the patterns III, XV, VII and VIII. Therefore, these strains should be considered associated with the microbiota of this cellar. A high polymorphism within populations of Saccharomyces was found throughout the different stages of Asturian production of cider. In all the cider fermentations, a variable number of S. bayanus and S. cerevisiae strains was always present. Our results indicate, over the period of time studied, the existence of the natural microbiota in the cellar. This study has allowed us to gain a better understanding of the role of wild Saccharomyces yeast in Asturian cider fermentations.

  2. 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

  3. J. Genet. classic 235

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 3, December 2004. 235. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 236. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 237. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 238. Page 5 ...

  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. Non-invasive Loading Model of Murine Osteoarthritis.

    Science.gov (United States)

    Poulet, Blandine

    2016-07-01

    Osteoarthritis is the commonest degenerative joint disease, leading to joint pain and disability. The mouse has been the primary animal used for research, due to its size, relatively short lifespan, and the availability of genetically modified animals. Importantly, they show pathogenesis similar to osteoarthritis in humans. Mechanical loading is a major risk factor for osteoarthritis, and various mouse models have been developed to study the role and effects of mechanics on health and disease in various joints. This review describes the main mouse models used to non-invasively apply mechanical loads on joints. Most of the mouse models of osteoarthritis target the knee, including repetitive loading and joint injury such as ligament rupture, but a few studies have also characterised models for elbow, temporomandibular joint, and whole-body vibration spinal loading. These models are a great opportunity to dissect the influences of various types of mechanical input on joint health and disease.

  6. Pollution Load Estimation Based on Characteristic Section Load Method

    Science.gov (United States)

    Zhu, Lei; Song, JinXi; Liu, WanQing

    2017-12-01

    Weihe River Watershed above Linjiacun Section is taken as the research objective in this paper and COD is chosen as the water quality parameter. According to the discharge characteristics of point source pollutions and non-point source pollutions, a new method to estimate pollution loads-Characteristic Section Load Method(CSLM) is proposed and point source pollution and non-point source pollution loads of Weihe River Watershed above Linjiacun Section are calculated in the rainy, normal and dry season in the year 2007. The results show that the monthly point source pollution loads of Weihe River Watershed above Linjiacun Section are discharged stably, the monthly non-point source pollution loads of Weihe River Watershed above Linjiacun Section change greatly, the non-point source pollution load proportions of total pollution load of COD are gradually decreased in the rainy, normal and wet periods.

  7. J. Genet. classic 9

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 88, No. 1, April 2009. 9. Page 2. J. Genet. classic. 10. Journal of Genetics, Vol. 88, No. 1, April 2009. Page 3. J. Genet. classic. Journal of Genetics, Vol. 88, No. 1, April 2009. 11. Page 4. J. Genet. classic. 12. Journal of Genetics, Vol. 88, No. 1, April 2009. Page 5. J. Genet. classic. Journal of Genetics ...

  8. Android Fully Loaded

    CERN Document Server

    Huddleston, Rob

    2012-01-01

    Fully loaded with the latest tricks and tips on your new Android! Android smartphones are so hot, they're soaring past iPhones on the sales charts. And the second edition of this muscular little book is equally impressive--it's packed with tips and tricks for getting the very most out of your latest-generation Android device. Start Facebooking and tweeting with your Android mobile, scan barcodes to get pricing and product reviews, download your favorite TV shows--the book is positively bursting with practical and fun how-tos. Topics run the gamut from using speech recognition, location-based m

  9. Variable loading roller

    Science.gov (United States)

    Williams, Daniel M.

    1989-01-01

    An automatic loading roller for transmitting torque in traction drive devices in manipulator arm joints includes a two-part camming device having a first cam portion rotatable in place on a shaft by an input torque and a second cam portion coaxially rotatable and translatable having a rotating drive surface thereon for engaging the driven surface of an output roller with a resultant force proportional to the torque transmitted. Complementary helical grooves on the respective cam portions interconnected through ball bearings interacting with those grooves effect the rotation and translation of the second cam portion in response to rotation of the first.

  10. Epidemiology and etiology of Alzheimer's disease: from genetic to non-genetic factors.

    Science.gov (United States)

    Jiang, Teng; Yu, Jin-Tai; Tian, Yan; Tan, Lan

    2013-10-01

    At present, the etiology of Alzheimer's disease (AD) is still unclear, but both genetic and non-genetic factors are thought to take part in the etiopathogenesis of AD. Epidemiologic researches revealed that genetic factors played a decisive role in the development of both early-onset AD (EOAD) and late-onset AD (LOAD). The mutations in APP, PSEN1 and PSEN2 are inherited in a Mendelian fashion and directly lead to the EOAD, while recent genome-wide association studies have identified numbers of risky genes, which influences the susceptibility to LOAD. Although genetic factors are inherited and fixed, non-genetic factors, such as occupational exposures (exposure to pesticides, electromagnetic fields, organic solvents and volatile anesthetics), pre-existing medical conditions (cerebrovascular disease, hypertension, diabetes, dyslipidemia, traumatic brain injury, depression and cancer) and lifestyle factors (smoking, consumptions of alcohol and coffee, body mass index, physical activity and cognitive activity), are partly environmentally-determined. Timely interventions targeted at these non-genetic risk factors may offer opportunities for prevention and treatment of AD. In the future, more high-quality and large-sample epidemiologic studies are needed to identify risk factors for AD, and the interaction models between genetic and non-genetic risk factors required further investigation. In addition, public health campaigns targeted at modification of non-genetic risk factors should be developed among population at high risk of AD.

  11. Laterally Loaded Nail-Plates

    DEFF Research Database (Denmark)

    Nielsen, Jacob; Rathkjen, Arne

    Load-displacement curves from about 200 short-term and laterally loaded nail-plate joints are analysed. The nail-plates are from Gang-Nail Systems, type GNA 20 S. The test specimens and the measuring systems are described. The tests are divided into 32 different series. The influence of the number...... of nail row, edge distance, fixed nail-plate, bending direction, unloading, and grain direction, plate and load direction on the load-displacement curves are analysed. Mean load-displacement curves from all the tests are given....

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Load Control System Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Trudnowski, Daniel [Montana Tech of the Univ. of Montana, Butte, MT (United States)

    2015-04-03

    This report summarizes the results of the Load Control System Reliability project (DOE Award DE-FC26-06NT42750). The original grant was awarded to Montana Tech April 2006. Follow-on DOE awards and expansions to the project scope occurred August 2007, January 2009, April 2011, and April 2013. In addition to the DOE monies, the project also consisted of matching funds from the states of Montana and Wyoming. Project participants included Montana Tech; the University of Wyoming; Montana State University; NorthWestern Energy, Inc., and MSE. Research focused on two areas: real-time power-system load control methodologies; and, power-system measurement-based stability-assessment operation and control tools. The majority of effort was focused on area 2. Results from the research includes: development of fundamental power-system dynamic concepts, control schemes, and signal-processing algorithms; many papers (including two prize papers) in leading journals and conferences and leadership of IEEE activities; one patent; participation in major actual-system testing in the western North American power system; prototype power-system operation and control software installed and tested at three major North American control centers; and, the incubation of a new commercial-grade operation and control software tool. Work under this grant certainly supported the DOE-OE goals in the area of “Real Time Grid Reliability Management.”

  17. Reducing mutation load through sexual selection on males.

    Science.gov (United States)

    McGuigan, Katrina; Petfield, Donna; Blows, Mark W

    2011-10-01

    Mutation load is a key parameter in evolutionary theories, but relatively little empirical information exists on the mutation load of populations, or the elimination of this load through selection. We manipulated the opportunity for sexual selection within a mutation accumulation divergence experiment to determine how sexual selection on males affected the accumulation of mutations contributing to sexual and nonsexual fitness. Sexual selection prevented the accumulation of mutations affecting male mating success, the target trait, as well as reducing mutation load on productivity, a nonsexual fitness component. Mutational correlations between mating success and productivity (estimated in the absence of sexual selection) were positive. Sexual selection significantly reduced these fitness component correlations. Male mating success significantly diverged between sexual selection treatments, consistent with the fixation of genetic differences. However, the rank of the treatments was not consistent across assays, indicating that the mutational effects on mating success were conditional on biotic and abiotic context. Our experiment suggests that greater insight into the genetic targets of natural and sexual selection can be gained by focusing on mutational rather than standing genetic variation, and on the behavior of trait variances rather than means. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  18. [Autism: genetics].

    Science.gov (United States)

    Gupta, Abha R; State, Matthew W

    2006-05-01

    Autism is a strongly genetic disorder, with an estimated heritability of greater than 90%. A combination of phenotypic heterogeneity and the likely involvement of multiple interacting loci have hampered efforts at gene discovery. As a consequence, the genetic etiology of the spectrum of autism related disorders remains largely unknown. Over the past several years, the convergence of rapidly advancing genomic technologies, the completion of the human genome project, and increasingly successful collaborative efforts to increase the number of patients available for study have led to the first solid clues to the biological origins of these disorders. This paper will review the literature to date summarizing the results of linkage, cytogenetic, and candidate gene studies with a focus on recent progress. In addition, promising avenues for future research are considered.

  19. Genetic Prediction.

    Science.gov (United States)

    Turkheimer, Eric

    2015-01-01

    The fundamental reason that the genetics of behavior has remained so controversial for so long is that the layer of theory between data and their interpretation is thicker and more opaque than in more established areas of science. The finding that variations in tiny snippets of DNA have small but detectable relations to variation in behavior surprises no one, at least no one who was paying attention to the twin studies. How such snippets of DNA are related to differences in behavior-known as the gene-to-behavior pathway-is the great theoretical problem of modern behavioral genetics. Given that intentional human breeding is a horrific prospect, what kind of technology might we want (or fear) out of human behavioral genetics? One possibility is a technology that could predict important behavioral characteristics of humans based on their genomes alone. A moment's thought suggests significant benefits and risks that might be associated with such a possibility, but for the moment, just consider how convincing it would be if on the day of a baby's birth we could make meaningful predictions about whether he or she would become a concert pianist or an alcoholic. This article will consider where we are right now as regards that possibility, using human height and intelligence as the primary examples. © 2015 The Hastings Center.

  20. 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

  1. Melanoma genetics.

    Science.gov (United States)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2016-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other medium to high penetrance melanoma predisposition genes have been associated with renal cell carcinoma (MITF, BAP1) and glioma (POT1). These associations between melanoma and other cancers hint at the possibility of common pathways for oncogenesis, and better knowledge of these pathways may improve understanding of the genetic basis underpinning familial melanoma. It is likely that 'melanoma' risk genes will impact on mutation screening and genetic counselling not only for melanoma but

  2. 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.

  3. 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.

  4. 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. 

  5. About Genetic Counselors

    Science.gov (United States)

    ... degrees and experience in the areas of both medical genetics and counseling. Genetic counselors work as members of ... and worried. Genetic counselors have advanced training in medical genetics and counseling to interpret tests, and guide and ...

  6. Genetic Testing (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Genetic Testing KidsHealth / For Parents / Genetic Testing What's in ... blood, skin, bone, or other tissue is needed. Genetic Testing During Pregnancy For genetic testing before birth, ...

  7. Estimating constituent loads

    Science.gov (United States)

    Cohn, T.A.; DeLong, L.L.; Gilroy, E.J.; Hirsch, R.M.; Wells, D.K.

    1989-01-01

    This paper compares the bias and variance of three procedures that can be used with log linear regression models: the traditional rating curve estimator, a modified rating curve method, and a minimum variance unbiased estimator (MVUE). Analytical derivations of the bias and efficiency of all three estimators are presented. It is shown that for many conditions the traditional and the modified estimator can provide satisfactory estimates. However, other conditions exist where they have substantial bias and a large mean square error. These conditions commonly occur when sample sizes are small, or when loads are estimated during high-flow conditions. The MVUE, however, is unbiased and always performs nearly as well or better than the rating curve estimator or the modified estimator provided that the hypothesis of the log linear model is correct. Since an efficient unbiased estimator is available, there seems to be no reason to employ biased estimators. -from Authors

  8. Sustaining global agriculture through rapid detection and deployment of genetic resistance to deadly crop diseases.

    Science.gov (United States)

    Periyannan, Sambasivam

    2017-12-04

    Contents I. II. III. IV. V. VI. VII. VIII. References SUMMARY: Genetically encoded resistance is a major component of crop disease management. Historically, gene loci conferring resistance to pathogens have been identified through classical genetic methods. In recent years, accelerated gene cloning strategies have become available through advances in sequencing, gene capture and strategies for reducing genome complexity. Here, I describe these approaches with key emphasis on the isolation of resistance genes to the cereal crop diseases that are an ongoing threat to global food security. Rapid gene isolation enables their efficient deployment through marker-assisted selection and transgenic technology. Together with innovations in genome editing and progress in pathogen virulence studies, this creates further opportunities to engineer long-lasting resistance. These approaches will speed progress towards a future of farming using fewer pesticides. © 2017 Commonwealth of Australia. New Phytologist © 2017 New Phytologist Trust.

  9. Application of Genetic Algorithm for Solving Optimum Power Flow Problems

    OpenAIRE

    Vennila, H.; T. Ruban Deva Prakash; B.G. Malini; M.S. Birundha; V. Evangelin Jeba; L. Sumi

    2013-01-01

    An efficient and optimum economic operation and planning of electric power generation systems is very important. The basic requirement of power economic dispatch (ED) is to generate adequate electricity to meet load demand at the lowest possible cost under a number of constrains. Genetic Algorithms (GA) represents a class of general purpose stochastic search techniques which simulate natural inheritance by genetics. In this paper, the principles of genetics involving natural selection and evo...

  10. Load forecasting for supermarket refrigeration

    DEFF Research Database (Denmark)

    Bacher, Peder; Madsen, Henrik; Aalborg Nielsen, Henrik

    This report presents a study of models for forecasting the load for supermarket refrigeration. The data used for building the forecasting models consists of load measurements, local climate measurements and weather forecasts. The load measurements are from a supermarket located in a village...... in Denmark. The load for refrigeration is the sum of all cabinets in the supermarket, both low and medium temperature cabinets, and spans a period of one year. As input to the forecasting models the ambient temperature observed near the supermarket together with weather forecasts are used. Every hour...... the hourly load for refrigeration for the following 42 hours is forecasted. The forecast models are adaptive linear time-series models which are fitted with a computationally efficient recursive least squares scheme. The dynamic relations between the inputs and the load is modeled by simple transfer...

  11. Robust optimization for total maximum daily load allocations

    Science.gov (United States)

    Jia, Yanbing; Culver, Teresa B.

    2006-02-01

    The determination of the pollutant load distribution among different pollutant sources in a watershed is a critical step in total maximum daily load (TMDL) development. Under current TMDL practices, TMDL allocations are typically determined through a trial-and-error approach of reducing pollutant loadings until a watershed simulation model predicts that water quality standards will be met given a margin of safety. Unfortunately, many feasible combinations of load reductions and significant uncertainties may exist. Therefore it is difficult and time-consuming to compare various allocation scenarios using a trial-and-error approach. A robust optimization model is developed in this study to incorporate the uncertainty of water quality predictions and to minimize pollutant load reductions given various levels of reliability with respect to the water quality standards. The generalized likelihood uncertainty estimation approach is used to explicitly address the uncertainty of a watershed simulation model, the Hydrological Simulation Program-Fortran. The uncertainty is integrated into TMDL allocations using a robust genetic algorithm model linked with a response matrix approach. The developed robust optimization model is demonstrated using a case study based on the Moore's Creek fecal coliform TMDL study. The trade-offs between reliability levels and total load reductions of allocation scenarios are evaluated, and the optimized load reduction scenarios are compared with the scenario generated by a trial-and-error approach and approved by the U.S. Environmental Protection Agency. The results show that the optimized load reduction scenario requires 30% less load reductions than the scenario approved by the U.S. Environmental Protection Agency at the same reliability level.

  12. Load forecasting of supermarket refrigeration

    DEFF Research Database (Denmark)

    Rasmussen, Lisa Buth; Bacher, Peder; Madsen, Henrik

    2016-01-01

    This paper presents a novel study of models for forecasting the electrical load for supermarket refrigeration. The data used for building the models consists of load measurements, local climate measurements and weather forecasts. The load measurements are from a supermarket located in a village...... in Denmark. Every hour the hourly electrical load for refrigeration is forecasted for the following 42 h. The forecast models are adaptive linear time series models. The model has two regimes; one for opening hours and one for closing hours, this is modeled by a regime switching model and two different...

  13. Alaska Village Electric Load Calculator

    Energy Technology Data Exchange (ETDEWEB)

    Devine, M.; Baring-Gould, E. I.

    2004-10-01

    As part of designing a village electric power system, the present and future electric loads must be defined, including both seasonal and daily usage patterns. However, in many cases, detailed electric load information is not readily available. NREL developed the Alaska Village Electric Load Calculator to help estimate the electricity requirements in a village given basic information about the types of facilities located within the community. The purpose of this report is to explain how the load calculator was developed and to provide instructions on its use so that organizations can then use this model to calculate expected electrical energy usage.

  14. Metamaterial Loadings for Waveguide Miniaturization

    CERN Document Server

    Odabasi, H

    2013-01-01

    We show that a rectangular metallic waveguide loaded with metamaterial elements consisting of electric-field coupled (ELC) resonators placed at the side walls can operate well below the cutoff frequency of the respective unloaded waveguide. The dispersion diagrams indicate that propagating modes in ELC-loaded waveguides are of forward-type for both TE and TM modes. We also study the dispersion diagram and transmission characteristics of rectangular metallic waveguides simultaneously loaded with ELCs and split ring resonators (SRRs). Such doubly-loaded waveguides can support both forward wave and backward waves, and provide independent control of the propagation characteristics for the respective modes.

  15. A genetical approach to deep venous thrombosis

    National Research Council Canada - National Science Library

    Celal Yavuz

    2012-01-01

    ... theresearcher’s enquiry to investigating the basis of organismalthrombotic predisposition. The common prothromboticgenetic mutations include factor V Leiden, factor IIG20210 A, plasminogen activator inhibitor-1, prothrombinA20210, and factor XIII - VIII...

  16. electrical load survey electrical load survey and forecast

    African Journals Online (AJOL)

    eobe

    paper reports the results of electrical load demand and forecast for Elebu rural community located in Kwara State,. Nigeria. The expected peak ... Keywords: hybrid system, renewable energy, optimization, electrical energy, load survey and forecasts. 1. ..... vehicle renewable energy, Monaco, March 26-29,. 2009, pp. 1-9.

  17. [Genetic amniocentesis].

    Science.gov (United States)

    Violante Díaz, M; Carrillo Hinojosa, M; García Necoechea, M P; Escobedo Aguirre, F; Lowenberg Favela, E; Ahued Ahued, J R

    1989-04-01

    179 patients were studied by genetic amniocentesis (GA) in sessions of 3 punctures each. This was done in order to follow a prenatal diagnosis (PD) program and study amniotic fluid at the Hospital Regional 20 de Novembre (ISSSTE) between May 1983 and December 1987. The parameters taken were: age, indications, number of sessions, number punctures, echosonographic studies for gestational age, placental insertion, punction site, amniotic fluid volume, blood contamination, failures and handling of the patient. A low incidence of abortion is reported. We don't have cases of dripping of amniotic fluid or transvaginal haemorrhage. Multiple insertion of the needle and placental or vessel lesions of the cord, as causes of a fetal death are still argued if we have in mind avoiding chances; we didn't have those complications in our cases. The percent is low if there are not previous spontaneous abortions. 79% of the amniotic fluid samples were sent between the 15th and 17th weeks of pregnancy. For alpha fetus protein determination 12 and for biochemical studies 1, specially for beta-galactosidase level. This was done at the Biomedical Investigation Institute of the National Autonomous University of Mexico (in parents with generalized gangliosidosis GM1). Even though results were good, the technique has still risks and complications. An ultrasonic study of the procedures made by physicians with trustable experience is needed. Our country has the need to create more Prenatal Genetic Diagnosis Centers.

  18. Crane-Load Contact Sensor

    Science.gov (United States)

    Youngquist, Robert; Mata, Carlos; Cox, Robert

    2005-01-01

    An electronic instrument has been developed as a prototype of a portable crane-load contact sensor. Such a sensor could be helpful in an application in which the load rests on a base in a horizontal position determined by vertical alignment pins (see Figure 1). If the crane is not positioned to lift the load precisely vertically, then the load can be expected to swing once it has been lifted clear of the pins. If the load is especially heavy, large, and/or fragile, it could hurt workers and/or damage itself and nearby objects. By indicating whether the load remains in contact with the pins when it has been lifted a fraction of the length of the pins, the crane-load contact sensor helps the crane operator determine whether it is safe to lift the load clear of the pins: If there is contact, then the load is resting against the sides of the pins and, hence, it may not be safe to lift; if contact is occasionally broken, then the load is probably not resting against the pins, so it should be safe to lift. It is assumed that the load and base, or at least the pins and the surfaces of the alignment holes in the load, are electrically conductive, so the instrument can use electrical contact to indicate mechanical contact. However, DC resistance cannot be used as an indicator of contact for the following reasons: The load and the base are both electrically grounded through cables (the load is grounded through the lifting cable of the crane) to prevent discharge of static electricity. In other words, the DC resistance between the load and the pins is always low, as though they were always in direct contact. Therefore, instead of DC resistance, the instrument utilizes the AC electrical impedance between the pins and the load. The signal frequency used in the measurement is high enough (.1 MHz) that the impedance contributed by the cables and the electrical ground network of the building in which the crane and the base are situated is significantly greater than the contact

  19. Probabilistic Load Models for Simulating the Impact of Load Management

    DEFF Research Database (Denmark)

    Chen, Peiyuan; Bak-Jensen, Birgitte; Chen, Zhe

    2009-01-01

    to simulate the impact of load management. The joint-normal model is superior in modeling the tail region of the hourly load distribution and implementing the change of hourly standard deviation. Whereas the AR(12) model requires much less parameter and is superior in modeling the autocorrelation......This paper analyzes a distribution system load time series through autocorrelation coefficient, power spectral density, probabilistic distribution and quantile value. Two probabilistic load models, i.e. the joint-normal model and the autoregressive model of order 12 (AR(12)), are proposed....... It is concluded that the AR(12) model is favored with limited measurement data and that the joint-normal model may provide better results with a large data set. Both models can be applied in general to model load time series and used in time-sequential simulation of distribution system planning....

  20. 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