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Sample records for genetic systems hiv-2

  1. A modular system to evaluate the efficacy of protease inhibitors against HIV-2.

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    Mohamed Mahdi

    Full Text Available The human immunodeficiency virus (HIV protease is a homodimeric aspartyl protease that is crucial for the viral life-cycle, cleaving proviral polyproteins, hence creating mature protein components that are required for the formation of an infectious virus. With diagnostic measures and clinically used protease inhibitors focusing on HIV-1, due to its higher virulence and prevalence, studies of the efficacy of those inhibitors on HIV-2 protease remain widely lacking. Utilizing a wild-type HIV-2 vector backbone and cloning techniques we have developed a cassette system where the efficacy of clinically used protease inhibitors can be studied for various serotypes of HIV-2 protease both in enzymatic and cell culture assays. In our experiments, optimization of the expression protocol led to a relatively stable enzyme, for cell culture assays, the efficiency of transfection and transduction capability of the modified vector was tested and was not found to differ from that of the wild-type, moreover, a 2nd generation protease inhibitor was used to demonstrate the usefulness of the system. The combination of assays performed with our cassette system is expected to provide an accurate measure of the efficacy of currently used; as well as experimental protease inhibitors on HIV-2.

  2. A modular system to evaluate the efficacy of protease inhibitors against HIV-2.

    Science.gov (United States)

    Mahdi, Mohamed; Matúz, Krisztina; Tóth, Ferenc; Tőzsér, József

    2014-01-01

    The human immunodeficiency virus (HIV) protease is a homodimeric aspartyl protease that is crucial for the viral life-cycle, cleaving proviral polyproteins, hence creating mature protein components that are required for the formation of an infectious virus. With diagnostic measures and clinically used protease inhibitors focusing on HIV-1, due to its higher virulence and prevalence, studies of the efficacy of those inhibitors on HIV-2 protease remain widely lacking. Utilizing a wild-type HIV-2 vector backbone and cloning techniques we have developed a cassette system where the efficacy of clinically used protease inhibitors can be studied for various serotypes of HIV-2 protease both in enzymatic and cell culture assays. In our experiments, optimization of the expression protocol led to a relatively stable enzyme, for cell culture assays, the efficiency of transfection and transduction capability of the modified vector was tested and was not found to differ from that of the wild-type, moreover, a 2nd generation protease inhibitor was used to demonstrate the usefulness of the system. The combination of assays performed with our cassette system is expected to provide an accurate measure of the efficacy of currently used; as well as experimental protease inhibitors on HIV-2.

  3. HIV-2 Integrase Variation in Integrase Inhibitor-Naïve Adults in Senegal, West Africa

    Science.gov (United States)

    Gottlieb, Geoffrey S.; Smith, Robert A.; Dia Badiane, Ndeye Mery; Ba, Selly; Hawes, Stephen E.; Toure, Macoumba; Starling, Alison K.; Traore, Fatou; Sall, Fatima; Cherne, Stephen L.; Stern, Joshua; Wong, Kim G.; Lu, Paul; Kim, Moon; Raugi, Dana N.; Lam, Airin; Mullins, James I.; Kiviat, Nancy B.

    2011-01-01

    Background Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. Methods We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. Results No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. Conclusion Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients. PMID:21765953

  4. HIV-2 integrase variation in integrase inhibitor-naïve adults in Senegal, West Africa.

    Directory of Open Access Journals (Sweden)

    Geoffrey S Gottlieb

    Full Text Available Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155. Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.

  5. Marburg Virus Reverse Genetics Systems

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    Kristina Maria Schmidt

    2016-06-01

    Full Text Available The highly pathogenic Marburg virus (MARV is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  6. HIV-2 infection: Where are we today?

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    Nayana A Ingole

    2013-01-01

    Full Text Available Context: The choice of antiretroviral therapy for HIV-2 differs from that for HIV-1, underscoring the importance of differentiating between the two. Aims: The current study was planned to find out the prevalence of HIV-2 infection at our center and to find out the utility of the current diagnostic algorithm in identifying the type of HIV infection. Setting and Design: Retrospective analysis in a tertiary care teaching institute over a period of three years. Materials and Methods: All patients diagnosed as HIV infected using NACO/WHO HIV testing strategy III were included in the study. They were classified as HIV-1 infected, HIV-2 infected and HIV-1 and HIV-2 co-infected based on their test results. For discordant samples, immunoblotting result from National Reference Laboratory was considered as final. Statistical Analysis Used: Comparison between HIV-1, HIV-2 and HIV-1+2 positive groups for age, gender, route of transmission was made using chi squared test. P value < 0.05 was considered as significant. Results: Of the total of 66,708 patients tested, 5,238 (7.9% were positive for HIV antibodies. 7.62%, 0.14%, 0.08% and 0.004% were HIV-1, HIV-2, HIV-1 and HIV-2 co-infected and HIV type indeterminate (HIV-1 Indeterminate, 2+ respectively. The current algorithm could not differentiate between the types of HIV infection (as HIV-1 or HIV-2 in 63 (1.2% cases. Conclusion: In areas like the Indian subcontinent, where epidemic of both HIV-1 and HIV-2 infections are ongoing, it is important to modify the current diagnostic algorithms to diagnose and confirm HIV-2 infections.

  7. Genetic manipulation system in propionibacteria.

    Science.gov (United States)

    Kiatpapan, Pornpimon; Murooka, Yoshikatsu

    2002-01-01

    Members of the genus Propionibacterium are widely used in the production of vitamin B12, tetrapyrrole compounds, and propionic acid as well as in probiotic and cheese industries. Shuttle vectors were developed in propionibacteria using replicons from endogenous plasmids in Propionibacterium and Escherichia coli and an appropriate selection marker. The efficient transformation was achieved using the shuttle vector prepared from Propionibacterium freudenreichii to overcome the high restriction modification system in propionibacteria. Expression vectors with native promoters for use in propionibacteria were also developed. Using this system, cholesterol oxidase, which is used as a diagnostic enzyme, was produced in P. freudenreichii. Genes involved in 5-aminolevulinic acid (ALA) and vitamin B12 biosynthesis in propionibacteria were isolated. ALA in propionibacteria could be synthesized via both the C4 pathway (condensation of glycine and succinyl CoA) and the C5 pathway (from glutamate). The hemA gene encoding ALA synthase from Rhodobacter spheroides, was overexpressed and ALA accumulated in P. freudenreichii. Thus, the genetic manipulation systems in propionibacteria will facilitate genetic studies of probiotics and the vitamin B12 biosynthetic pathway.

  8. HIV-2 and its neurological manifestations

    African Journals Online (AJOL)

    drugs is warranted in all such patients. Cryptococcal meningitis is an opportunistic fungal infection, the initial port of entry of which is the lungs. Patients with HIV-2 infection and cryptococcal meningitis have been described in The Gambia," Ivory Coast"2 and the. USA3' but, surprisingly, it does not appear common; no such.

  9. Evolution of genetic systems in filamentous ascomycetes

    NARCIS (Netherlands)

    Nauta, M.J.

    1994-01-01

    A great variety of genetic systems exist in filamentous ascomycetes. The transmission of genetic material does not only occur by (sexual or asexual) reproduction, but it can also follow vegetative fusion of different strains. In this thesis the evolution of this variability is studied,

  10. Amplification and cloning of near full-length HIV-2 genomes.

    Science.gov (United States)

    Gao, Feng

    2005-01-01

    The genomes of human immunodeficiency virus type 2 (HIV-2), like those of HIV-1, are not only extremely variable but are also highly recombinogenic. Determination of subtypes based on partial genomes cannot predict the subtype classification of other regions of the genome owing to the frequent occurrence of recombinant genomes among subtypes. To fully understand the genetic variation and evolution of HIV-2s, full-length viral genomes need to be obtained for genetic analysis. Full-length HIV-2 genomes can also be used as infectious clones to study viral biological characteristics and as reference sequences for phylogenetic analysis. More important, all genes in the obtained genomes can be cloned into expression vectors to produce proteins that can be used as antigens for diagnostic reagents or as immunogens for vaccine development. The long-range polymerase chain reaction technique has recently become a more preferred method than the lambda phage cloning method to obtain near-full-length HIV-2 genomes.

  11. Modeling of Nonlinear Systems using Genetic Algorithm

    Science.gov (United States)

    Hayashi, Kayoko; Yamamoto, Toru; Kawada, Kazuo

    In this paper, a newly modeling system by using Genetic Algorithm (GA) is proposed. The GA is an evolutionary computational method that simulates the mechanisms of heredity or evolution of living things, and it is utilized in optimization and in searching for optimized solutions. Most process systems have nonlinearities, so it is necessary to anticipate exactly such systems. However, it is difficult to make a suitable model for nonlinear systems, because most nonlinear systems have a complex structure. Therefore the newly proposed method of modeling for nonlinear systems uses GA. Then, according to the newly proposed scheme, the optimal structure and parameters of the nonlinear model are automatically generated.

  12. An integrated system for genetic analysis

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    Duan Xiao

    2006-04-01

    Full Text Available Abstract Background Large-scale genetic mapping projects require data management systems that can handle complex phenotypes and detect and correct high-throughput genotyping errors, yet are easy to use. Description We have developed an Integrated Genotyping System (IGS to meet this need. IGS securely stores, edits and analyses genotype and phenotype data. It stores information about DNA samples, plates, primers, markers and genotypes generated by a genotyping laboratory. Data are structured so that statistical genetic analysis of both case-control and pedigree data is straightforward. Conclusion IGS can model complex phenotypes and contain genotypes from whole genome association studies. The database makes it possible to integrate genetic analysis with data curation. The IGS web site http://bioinformatics.well.ox.ac.uk/project-igs.shtml contains further information.

  13. Study of HIV-2 primer-template initiation complex using antisense oligonucleotides

    DEFF Research Database (Denmark)

    Boulmé, F; Freund, F; Gryaznov, S

    2000-01-01

    HIV-2 reverse transcription is initiated by the retroviral DNA polymerase (reverse transcriptase) from a cellular tRNALys3 partially annealed to the primer binding site in the 5'-region of viral RNA. The HIV-2 genome has two A-rich regions upstream of the primer binding site. In contrast to HIV-1...... RNA, no direct evidence of interactions with the U-rich anticodon loop of tRNALys3 has been described to date. Here we address the question of the potential role of the interactions between these highly structured regions in the initiation of viral DNA synthesis. To evaluate this we used an antisense...... approach, first validated in our in vitro HIV-1 reverse transcription system. Annealing of the antisense oligonucleotides to the pre-primer binding site (the upstream region contiguous to the HIV-2 primer binding site) was determined in the presence of native tRNALys3 or synthetic primers. Using natural...

  14. Efficient and Robust Paramyxoviridae Reverse Genetics Systems

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    Beaty, Shannon M.; Won, Sohui T.; Hong, Patrick; Lyons, Michael; Vigant, Frederic; Freiberg, Alexander N.; tenOever, Benjamin R.; Duprex, W. Paul

    2017-01-01

    ABSTRACT The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low. We have substantially increased rescue efficiency for representative viruses from all five major Paramyxoviridae genera (from ~1 in 106-107 to ~1 in 102-103 transfected cells) by the addition of a self-cleaving hammerhead ribozyme (Hh-Rbz) sequence immediately preceding the start of the recombinant viral antigenome and the use of a codon-optimized T7 polymerase (T7opt) gene to drive paramyxovirus rescue. Here, we report a strategy for robust, reliable, and high-efficiency rescue of paramyxovirus reverse genetics systems, featuring several major improvements: (i) a vaccinia virus-free method, (ii) freedom to use any transfectable cell type for viral rescue, (iii) a single-step transfection protocol, and (iv) use of the optimal T7 promoter sequence for high transcription levels from the antigenomic plasmid without incorporation of nontemplated G residues. The robustness of our T7opt-HhRbz system also allows for greater latitude in the ratios of transfected accessory plasmids used that result in successful rescue. Thus, our system may facilitate the rescue and interrogation of the increasing number of emerging paramyxoviruses. IMPORTANCE The ability to manipulate the genome of paramyxoviruses and evaluate the effects of these changes at the phenotypic level is a powerful tool for the investigation of specific aspects of the viral life cycle and viral pathogenesis. However, reverse genetics systems for paramyxoviruses

  15. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A

    2013-01-01

    HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework o...

  16. Genetic testing by cancer site: endocrine system.

    Science.gov (United States)

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  17. Genetic Manipulation of the Endocannabinoid System.

    Science.gov (United States)

    Zimmer, Andreas

    2015-01-01

    The physiological and pathophysiological functions of the endocannabinoid system have been studied extensively using transgenic and targeted knockout mouse models. The first gene deletions of the cannabinoid CB(1) receptor were described in the late 1990s, soon followed by CB(2) and FAAH mutations in early 2000. These mouse models helped to elucidate the fundamental role of endocannabinoids as retrograde transmitters in the CNS and in the discovery of many unexpected endocannabinoid functions, for example, in the skin, bone and liver. We now have knockout mouse models for almost every receptor and enzyme of the endocannabinoid system. Conditional mutant mice were mostly developed for the CB(1) receptor, which is widely expressed on many different neurons, astrocytes and microglia, as well as on many cells outside the CNS. These mouse strains include "floxed" CB(1) alleles and mice with a conditional re-expression of CB(1). The availability of these mice made it possible to decipher the function of CB(1) in specific neuronal circuits and cell populations or to discriminate between central and peripheral effects. Many of the genetic mouse models were also used in combination with viral expression systems. The purpose of this review is to provide a comprehensive overview of the existing genetic models and to summarize some of the most important discoveries that were made with these animals.

  18. Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease.

    Science.gov (United States)

    Moreno-Moral, Aida; Pesce, Francesco; Behmoaras, Jacques; Petretto, Enrico

    2017-01-01

    Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

  19. HIV-2 diagnosis and quantification in high-risk patients

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    Kojic Erna

    2008-08-01

    Full Text Available Abstract Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML. Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States.

  20. Periodontal disease associated to systemic genetic disorders.

    Science.gov (United States)

    Nualart Grollmus, Zacy Carola; Morales Chávez, Mariana Carolina; Silvestre Donat, Francisco Javier

    2007-05-01

    A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis--in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefévre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefévre syndrome, where an established treatment protocol is available.

  1. Using Genetic Algorithms for Building Metrics of Collaborative Systems

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    Cristian CIUREA

    2011-01-01

    Full Text Available he paper objective is to reveal the importance of genetic algorithms in building robust metrics of collaborative systems. The main types of collaborative systems in economy are presented and some characteristics of genetic algorithms are described. A genetic algorithm was implemented in order to determine the local maximum and minimum points of the relative complexity function associated to a collaborative banking system. The intelligent collaborative systems based on genetic algorithms, representing the new generation of collaborative systems, are analyzed and the implementation of auto-adaptive interfaces in a banking application is described.

  2. Genetic therapy for the nervous system.

    Science.gov (United States)

    Bowers, William J; Breakefield, Xandra O; Sena-Esteves, Miguel

    2011-04-15

    Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state.

  3. Population Genetics of Identifiler System in Malaysia.

    Science.gov (United States)

    Nakamura, Yasutaka; Samejima, Michinaga; Minaguchi, Kiyoshi; Nambiar, Phrabhakaran

    2016-01-01

    Short tandem repeat (STR) polymorphisms were investigated in 341 unrelated Malay individuals (218 males and 123 females) living in or around Kuala Lumpur by using a forensic analysts kit. The following STRs were targeted: D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA. The purpose of this study was to elucidate population genetics in Malaysia and calculate statistical parameters for forensic and anthropological research. Data on these STRs in the target population were obtained and subjected to statistical analysis. Accordance with the Hardy-Weinberg equilibrium was proven for all the loci targeted. The combined power of discrimination was greater than 0.9999999999, indicating that this multiplex system is an excellent tool for forensic casework. The allele frequency in the data were weighed against that in four other local populations (Chinese, Iranian, Belgian, and African). The average coefficient of correlation was strongest in the order of Africa (0.092522), Belgium (0.264822), Iran (0.404363), and China (0.706661). These results are consistent with what is known about the anthropological history of and prehistoric human migration in the Malay region. We believe that these data offer a valuable anthropological resource, being applicable to the statistical evaluation of DNA evidence in human identification, as well as the determination of ethnicity in healthy populations.

  4. HIV-2 and its neurological manifestations | Rolfe | South African ...

    African Journals Online (AJOL)

    Diagnostic facilities necessary for the accurate diagnosis of neurological disease are not available in most of Africa and autopsy reports have been few. These constraints have restricted the information available on the pattern of neuropathology induced by HIV-2. However, it possesses neurotropic properties similar to ...

  5. Genetic fuzzy system modeling and simulation of vascular behaviour

    DEFF Research Database (Denmark)

    Tang, Jiaowei; Boonen, Harrie C.M.

    in principle for any physiological system that is characterized by auto-regulatory control and adaptation. Methods: Currently, one modeling approach is being investigated, Genetic Fuzzy System (GFS). In Genetic Fuzzy Systems, the model algorithm mimics the biologic genetic evolutionary process to learn...... and find the optimal parameters in a Fuzzy Control set that can control the fluctuation of physical features in a blood vessel, based on experimental data (training data). Our solution is to create chromosomes or individuals composed of a sequence of parameters in the fuzzy system and find the best...... chromosome or individual to define the fuzzy system. The model is implemented by combining the Matlab Genetic algorithm and Fuzzy system toolboxes, respectively. To test the performance of this method, experimental data sets about calculated pressure change in different blood vessels after several chemical...

  6. GeneNetwork: A Toolbox for Systems Genetics.

    Science.gov (United States)

    Mulligan, Megan K; Mozhui, Khyobeni; Prins, Pjotr; Williams, Robert W

    2017-01-01

    The goal of systems genetics is to understand the impact of genetic variation across all levels of biological organization, from mRNAs, proteins, and metabolites, to higher-order physiological and behavioral traits. This approach requires the accumulation and integration of many types of data, and also requires the use of many types of statistical tools to extract relevant patterns of covariation and causal relations as a function of genetics, environment, stage, and treatment. In this protocol we explain how to use the GeneNetwork web service, a powerful and free online resource for systems genetics. We provide workflows and methods to navigate massive multiscalar data sets and we explain how to use an extensive systems genetics toolkit for analysis and synthesis. Finally, we provide two detailed case studies that take advantage of human and mouse cohorts to evaluate linkage between gene variants, addiction, and aging.

  7. Seed Systems and Plant Genetic Resources for Food and Agriculture

    NARCIS (Netherlands)

    Louwaars, N.P.; Coent, le P.; Osborn, T.

    2011-01-01

    This report examines the role of seed and seed systems in the conservation and the use of plant genetic resources for food and agriculture. It focuses on developments since the publication of the first report on the State of the World’s Plant Genetic Resources for Food and Agriculture.

  8. Optimization of RAPD-PCR reaction system for genetic relationships ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-02-08

    Feb 8, 2010 ... controlling petal color may play an important role in RAPD analysis. Moreover, genetic diversities ... study showed the RAPD optimization system was suitable and RAPD molecular marker was effective and useful tool for detection of genetic relationships among camellia cultivars. Key words: Optimization ...

  9. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    Directory of Open Access Journals (Sweden)

    Didier K Ekouevi

    Full Text Available HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA.We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region.Data was merged for 1,754 patients (56% female, including 1,021 HIV-2 infected patients (551 on ART and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART. At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7 and 42.4 years, IQR (37.0-47.3 for dually seropositive patients (p = 0.048. Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C. The median CD4 count at the ART initiation is 166 cells/mm(3, IQR (83-247 among HIV-2 infected patients and 146 cells/mm(3, IQR (55-249 among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3 after 24 months on ART for HIV-2 patients and 169 cells/mm(3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3.This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  10. Profile of the HIV Epidemic in Cape Verde: Molecular Epidemiology and Drug Resistance Mutations among HIV-1 and HIV-2 Infected Patients from Distinct Islands of the Archipelago

    Science.gov (United States)

    de Pina-Araujo, Isabel Inês M.; Guimarães, Monick L.; Bello, Gonzalo; Vicente, Ana Carolina P.; Morgado, Mariza G.

    2014-01-01

    HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010–2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1–75) and 47 (IQR = 12–84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be

  11. Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

    Directory of Open Access Journals (Sweden)

    Isabel Inês M de Pina-Araujo

    Full Text Available HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM among antiretroviral therapy naïve (ARTn patients and patients under treatment (ARTexp from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections, 67% were female. The median ages were 34 (IQR = 1-75 and 47 (IQR = 12-84 for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%, CRF02_AG (30.6%, F1 (9.7%, URFs (10.4%, B (5.2%, CRF05_DF (3.0%, C (2.2%, CRF06_cpx (0.7%, CRF25_cpx (0.7% and CRF49_cpx (0.7%, whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM was observed in 3.4% (2/58 of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI, but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69 of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes and 17.6% (3/17 of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both. This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented.

  12. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

    Directory of Open Access Journals (Sweden)

    Maia Hightower

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

  13. Population mobility and the changing epidemics of HIV-2 in Portugal

    DEFF Research Database (Denmark)

    Carvalho, A C; Valadas, E; França, L

    2012-01-01

    Portugal is the European country with the highest frequency of HIV-2 infection, which is mainly concentrated in West Africa. The cumulative number of notified HIV-2 infections in Portugal was 1813 by the end of December 2008. To better characterize the dynamics of HIV-2 infection in the country...

  14. Time-Delay System Identification Using Genetic Algorithm

    DEFF Research Database (Denmark)

    Yang, Zhenyu; Seested, Glen Thane

    2013-01-01

    Due to the unknown dead-time coefficient, the time-delay system identification turns to be a non-convex optimization problem. This paper investigates the identification of a simple time-delay system, named First-Order-Plus-Dead-Time (FOPDT), by using the Genetic Algorithm (GA) technique. The qual......Due to the unknown dead-time coefficient, the time-delay system identification turns to be a non-convex optimization problem. This paper investigates the identification of a simple time-delay system, named First-Order-Plus-Dead-Time (FOPDT), by using the Genetic Algorithm (GA) technique...

  15. A yeast screening system for simultaneously monitoring multiple genetic endpoints

    International Nuclear Information System (INIS)

    Dixon, M.L.; Mortimer, R.K.

    1986-01-01

    Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)

  16. Robust reactor power control system design by genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Joon; Cho, Kyung Ho; Kim, Sin [Cheju National University, Cheju (Korea, Republic of)

    1997-12-31

    The H{sub {infinity}} robust controller for the reactor power control system is designed by use of the mixed weight sensitivity. The system is configured into the typical two-port model with which the weight functions are augmented. Since the solution depends on the weighting functions and the problem is of nonconvex, the genetic algorithm is used to determine the weighting functions. The cost function applied in the genetic algorithm permits the direct control of the power tracking performances. In addition, the actual operating constraints such as rod velocity and acceleration can be treated as design parameters. Compared with the conventional approach, the controller designed by the genetic algorithm results in the better performances with the realistic constraints. Also, it is found that the genetic algorithm could be used as an effective tool in the robust design. 4 refs., 6 figs. (Author)

  17. Structure of an HIV-2 gp120 in Complex with CD4.

    Science.gov (United States)

    Davenport, Yunji W; West, Anthony P; Bjorkman, Pamela J

    2016-02-15

    HIV-2 is a nonpandemic form of the virus causing AIDS, and the majority of HIV-2-infected patients exhibit long-term nonprogression. The HIV-1 and HIV-2 envelope glycoproteins, the sole targets of neutralizing antibodies, share 30 to 40% identity. As a first step in understanding the reduced pathogenicity of HIV-2, we solved a 3.0-Å structure of an HIV-2 gp120 bound to the host receptor CD4, which reveals structural similarity to HIV-1 gp120 despite divergence in amino acid sequence. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Recent insights into the genetic basis of systemic lupus erythematosus

    OpenAIRE

    Moser, Kathy L.; Kelly, Jennifer A.; Lessard, Christopher J.; Harley, John B.

    2009-01-01

    Genetic variation was first shown to be part of the cause of systemic lupus erythematosus (SLE or lupus) in the 1970s with associations in the human leukocyte antigen (HLA) region. Almost four decades later, and with the help of increasingly powerful genetic approaches, more than 25 genes are now known to contribute to the mechanisms that predispose individuals to lupus. Over half of these loci have been discovered in the past two years, underscoring the extraordinary success of recent genome...

  19. Computational power and generative capacity of genetic systems.

    Science.gov (United States)

    Igamberdiev, Abir U; Shklovskiy-Kordi, Nikita E

    2016-01-01

    Semiotic characteristics of genetic sequences are based on the general principles of linguistics formulated by Ferdinand de Saussure, such as the arbitrariness of sign and the linear nature of the signifier. Besides these semiotic features that are attributable to the basic structure of the genetic code, the principle of generativity of genetic language is important for understanding biological transformations. The problem of generativity in genetic systems arises to a possibility of different interpretations of genetic texts, and corresponds to what Alexander von Humboldt called "the infinite use of finite means". These interpretations appear in the individual development as the spatiotemporal sequences of realizations of different textual meanings, as well as the emergence of hyper-textual statements about the text itself, which underlies the process of biological evolution. These interpretations are accomplished at the level of the readout of genetic texts by the structures defined by Efim Liberman as "the molecular computer of cell", which includes DNA, RNA and the corresponding enzymes operating with molecular addresses. The molecular computer performs physically manifested mathematical operations and possesses both reading and writing capacities. Generativity paradoxically resides in the biological computational system as a possibility to incorporate meta-statements about the system, and thus establishes the internal capacity for its evolution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Steady-State-Preserving Simulation of Genetic Regulatory Systems

    Directory of Open Access Journals (Sweden)

    Ruqiang Zhang

    2017-01-01

    Full Text Available A novel family of exponential Runge-Kutta (expRK methods are designed incorporating the stable steady-state structure of genetic regulatory systems. A natural and convenient approach to constructing new expRK methods on the base of traditional RK methods is provided. In the numerical integration of the one-gene, two-gene, and p53-mdm2 regulatory systems, the new expRK methods are shown to be more accurate than their prototype RK methods. Moreover, for nonstiff genetic regulatory systems, the expRK methods are more efficient than some traditional exponential RK integrators in the scientific literature.

  1. The genetics of anxiety-related negative valence system traits.

    Science.gov (United States)

    Savage, Jeanne E; Sawyers, Chelsea; Roberson-Nay, Roxann; Hettema, John M

    2017-03-01

    NIMH's Research Domain Criteria (RDoC) domain of negative valence systems (NVS) captures constructs of negative affect such as fear and distress traditionally subsumed under the various internalizing disorders. Through its aims to capture dimensional measures that cut across diagnostic categories and are linked to underlying neurobiological systems, a large number of phenotypic constructs have been proposed as potential research targets. Since "genes" represent a central "unit of analysis" in the RDoC matrix, it is important for studies going forward to apply what is known about the genetics of these phenotypes as well as fill in the gaps of existing knowledge. This article reviews the extant genetic epidemiological data (twin studies, heritability) and molecular genetic association findings for a broad range of putative NVS phenotypic measures. We find that scant genetic epidemiological data is available for experimentally derived measures such as attentional bias, peripheral physiology, or brain-based measures of threat response. The molecular genetic basis of NVS phenotypes is in its infancy, since most studies have focused on a small number of candidate genes selected for putative association to anxiety disorders (ADs). Thus, more research is required to provide a firm understanding of the genetic aspects of anxiety-related NVS constructs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Immune System Model Calibration by Genetic Algorithm

    NARCIS (Netherlands)

    Presbitero, A.; Krzhizhanovskaya, V.; Mancini, E.; Brands, R.; Sloot, P.

    2016-01-01

    We aim to develop a mathematical model of the human immune system for advanced individualized healthcare where medication plan is fine-tuned to fit a patient's conditions through monitored biochemical processes. One of the challenges is calibrating model parameters to satisfy existing experimental

  3. Stabilization of Electromagnetic Suspension System Behavior by Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Abbas Najar Khoda Bakhsh

    2012-07-01

    Full Text Available Electromagnetic suspension system with a nonlinear and unstable behavior, is used in maglev trains. In this paper a linear mathematical model of system is achieved and the state feedback method is used to improve the system stability. The control coefficients are tuned by two different methods, Riccati and a new method based on Genetic algorithm. In this new proposed method, we use Genetic algorithm to achieve the optimum values of control coefficients. The results of the system simulation by Matlab indicate the effectiveness of new proposed system. When a new reference of air gap is needed or a new external force is added, the proposed system could omit the vibration and shake of the train coupe and so, passengers feel more comfortable.

  4. Periodontal disease associated to systemic genetic disorders

    OpenAIRE

    Nualart Grollmus, Zacy Carola; Morales Chávez, Mariana Carolina; Silvestre Donat, Francisco Javier

    2007-01-01

    A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role ...

  5. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Cytoplasmic genetic male sterility (CGMS) resulting from nuclear-cytoplasmic interaction has been commercially exploited for the production of F1 hybrid seed in rice. The. CGMS system involves three lines, namely a cytoplasmic male sterile (CMS) line, a maintainer line and a restorer line where restorer line (R line) ...

  6. Timing of gene expression from different genetic systems in shaping ...

    Indian Academy of Sciences (India)

    Timing of gene expression from different genetic systems in shaping leucine and isoleucine contents of rapeseed (Brassica napus L.) meal ... Department of Agronomy, Zhejiang University, Hangzhou, 310029, People's Republic of China; School of Agriculture and Food Science, Zhejiang A & F University, Lin'an, 311300, ...

  7. System control fuzzy neural sewage pumping stations using genetic algorithms

    Directory of Open Access Journals (Sweden)

    Владлен Николаевич Кузнецов

    2015-06-01

    Full Text Available It is considered the system of management of sewage pumping station with regulators based on a neuron network with fuzzy logic. Linguistic rules for the controller based on fuzzy logic, maintaining the level of effluent in the receiving tank within the prescribed limits are developed. The use of genetic algorithms for neuron network training is shown.

  8. Time-Delay System Identification Using Genetic Algorithm

    DEFF Research Database (Denmark)

    Yang, Zhenyu; Seested, Glen Thane

    2013-01-01

    problem through an identification approach using the real coded Genetic Algorithm (GA). The desired FOPDT/SOPDT model is directly identified based on the measured system's input and output data. In order to evaluate the quality and performance of this GA-based approach, the proposed method is compared...

  9. Aging and Ambiguous ROS. System Genetics Analysis.

    Science.gov (United States)

    Baranov, Vladislav S; Baranova, Elena V

    2017-01-01

    Famous Free Radical Theory (FRT) of aging, the 50th year anniversary of which is celebrated in 2015 postulates a crucial role of Reactive Oxygen Species (ROS) in aging. Still it is the most robust theory of aging as mitochondria ROS production (mtROSp) correlates well with four principal ''rules" of aging being universal, endogenous, progressive, and deleterious. Vast number of experiments in different species prove mutagenic effect of ROS and their carcinogenic properties. So far, FRT stimulates the search of new pharmaceuticals with antioxidant activity. However, some recent experimental data and clinical findings render doubt to ROS as a principal senescence drivers and come in conflict with original version of FRT. Growth stimulating effects of ROS and their modest antitumor properties support these objections. One should remember that FRT is only one of the numerous theories of aging. Molecular mechanisms of senescence involve all living systems and numerous metabolic pathways which are also variable owing to the unique properties of individual genome and unique epigenetic modulations operating throughout the lifetime thus making aging a unique private matter. Universal theory of aging that incorporates and explains all known and suggested mechanisms of aging, is illusive. However, knowledge of unique peculiarities of individual genome, its feasible editing and efficient epigenetic regulation of metabolic pathways give a chance to postpone aging and extend period of active longevity.

  10. Subcloning of HIV-2 nef genes in E. coli and immunological reactivity of expressed fusion proteins.

    Science.gov (United States)

    Ulrich, R; Siakkou, H; Mayer, J; Kienzle, N; Müller-Lantzsch, N; Krüger, D H

    1993-09-01

    The nef gene located in the 3' region of the HIV-2 genome encodes an N-terminally myristylated protein of 27-35 kD, likely to be involved in the regulation of viral transcription. The nef genes of HIV-2 isolates GH-1, ROD, ST, BEN, and D194.17 were inserted into E. coli pEX vectors and expression of Nef beta-galactosidase fusion proteins was detected in stained gels. All fusion proteins specifically reacted with a rabbit serum raised against bacterially expressed Nef from HIV-2D194.17. Sera from monkeys inoculated with HIV-2BEN or SIVMAC251 recognized the Nef proteins of only certain HIV-2 isolates. No cross-reactivity of these sera with HIV-1 Nef and of a rabbit anti-HIV-1-Nef serum with the described HIV-2 Nef fusion proteins was observed.

  11. An International Collaboration To Standardize HIV-2 Viral Load Assays: Results from the 2009 ACHIEV2E Quality Control Study▿

    OpenAIRE

    Damond, F.; Benard, A.; Balotta, Claudia; Böni, Jürg; Cotten, Matthew; Duque, Vitor; Ferns, Bridget; Garson, Jeremy; Gomes, Perpetua; Gonçalves, Fátima; Gottlieb, Geoffrey; Kupfer, Bernd; Ruelle, Jean; Rodes, Berta; Soriano, Vicente

    2011-01-01

    Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHIEV2E study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own H...

  12. Mapping genetic influences on the corticospinal motor system in humans

    DEFF Research Database (Denmark)

    Cheeran, B J; Ritter, C; Rothwell, J C

    2009-01-01

    of the contribution of single nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the corticospinal motor system is essential to the acquisition of fine manual motor skills which require a finely tuned coordination of activity in distal forelimb muscles. Here we review recent brain mapping...... degeneration. These studies underscore the potential of non-invasive brain mapping techniques to characterize the genetic influence on the human corticospinal motor system....

  13. Bacteriophage-based genetic system for selection of nonsplicing inteins.

    Science.gov (United States)

    Cann, Isaac K O; Amaya, Kensey R; Southworth, Maurice W; Perler, Francine B

    2004-05-01

    A genetic selection system that detects splicing and nonsplicing activities of inteins was developed based on the ability to rescue a T4 phage strain with a conditionally inactive DNA polymerase. This phage defect can be complemented by expression of plasmid-encoded phage RB69 DNA polymerase. Insertion of an intein gene into the active site of the RB69 DNA polymerase gene renders polymerase activity and phage viability dependent on protein splicing. The effectiveness of the system was tested by screening for thermosensitive splicing mutants. Development of genetic systems with the potential of identifying protein splicing inhibitors is a first step towards controlling proliferation of pathogenic microbes harboring inteins in essential proteins.

  14. Genetic Algorithm Based Design of Fuzzy Logic Power System Stabilizers in Multimachine Power System

    OpenAIRE

    Manisha Dubey; Aalok Dubey

    2010-01-01

    This paper presents an approach for the design of fuzzy logic power system stabilizers using genetic algorithms. In the proposed fuzzy expert system, speed deviation and its derivative have been selected as fuzzy inputs. In this approach the parameters of the fuzzy logic controllers have been tuned using genetic algorithm. Incorporation of GA in the design of fuzzy logic power system stabilizer will add an intelligent dimension to the stabilizer and significantly reduces ...

  15. Dynamic modeling of genetic networks using genetic algorithm and S-system.

    Science.gov (United States)

    Kikuchi, Shinichi; Tominaga, Daisuke; Arita, Masanori; Takahashi, Katsutoshi; Tomita, Masaru

    2003-03-22

    The modeling of system dynamics of genetic networks, metabolic networks or signal transduction cascades from time-course data is formulated as a reverse-problem. Previous studies focused on the estimation of only network structures, and they were ineffective in inferring a network structure with feedback loops. We previously proposed a method to predict not only the network structure but also its dynamics using a Genetic Algorithm (GA) and an S-system formalism. However, it could predict only a small number of parameters and could rarely obtain essential structures. In this work, we propose a unified extension of the basic method. Notable improvements are as follows: (1) an additional term in its evaluation function that aims at eliminating futile parameters; (2) a crossover method called Simplex Crossover (SPX) to improve its optimization ability; and (3) a gradual optimization strategy to increase the number of predictable parameters. The proposed method is implemented as a C program called PEACE1 (Predictor by Evolutionary Algorithms and Canonical Equations 1). Its performance was compared with the basic method. The comparison showed that: (1) the convergence rate increased about 5-fold; (2) the optimization speed was raised about 1.5-fold; and (3) the number of predictable parameters was increased about 5-fold. Moreover, we successfully inferred the dynamics of a small genetic network constructed with 60 parameters for 5 network variables and feedback loops using only time-course data of gene expression.

  16. Genetic optimization of steam multi-turbines system

    International Nuclear Information System (INIS)

    Olszewski, Pawel

    2014-01-01

    Optimization analysis of partially loaded cogeneration, multiple-stages steam turbines system was numerically investigated by using own-developed code (C++). The system can be controlled by following variables: fresh steam temperature, pressure, and flow rates through all stages in steam turbines. Five various strategies, four thermodynamics and one economical, which quantify system operation, were defined and discussed as an optimization functions. Mathematical model of steam turbines calculates steam properties according to the formulation proposed by the International Association for the Properties of Water and Steam. Genetic algorithm GENOCOP was implemented as a solving engine for non–linear problem with handling constrains. Using formulated methodology, example solution for partially loaded system, composed of five steam turbines (30 input variables) with different characteristics, was obtained for five strategies. The genetic algorithm found multiple solutions (various input parameters sets) giving similar overall results. In real application it allows for appropriate scheduling of machine operation that would affect equable time load of every system compounds. Also based on these results three strategies where chosen as the most complex: the first thermodynamic law energy and exergy efficiency maximization and total equivalent energy minimization. These strategies can be successfully used in optimization of real cogeneration applications. - Highlights: • Genetic optimization model for a set of five various steam turbines was presented. • Four various thermodynamic optimization strategies were proposed and discussed. • Operational parameters (steam pressure, temperature, flow) influence was examined. • Genetic algorithm generated optimal solutions giving the best estimators values. • It has been found that similar energy effect can be obtained for various inputs

  17. Retinal vein occlusion: genetic predisposition and systemic risk factors.

    Science.gov (United States)

    Giannaki, Kassiani; Politou, Marianna; Rouvas, Alexandros; Merkouri, Efrossyni; Travlou, Anthi; Theodosiadis, Panayiotis; Gialeraki, Argyri

    2013-04-01

    The role of systemic risk factors (age, smoking, diabetes, arterial hypertension) in the development of retinal vein occlusion (RVO) is well established. However, the association of RVO with genetic predisposition to thrombosis remains poorly understood. The aim of the study was to assess any possible additional effect of genetic predisposition to the already well known 'classical' risk factors of RVO in a cohort of elderly Greek patients. Fifty-one elderly patients with RVO and 51 healthy individuals matched for age and sex were evaluated for systemic risk factors (smoking, diabetes, dyslipidemia, arterial hypertension) and coagulation defects (lupus anticoagulant, natural inhibitors of coagulation). Additionally, genotyping was performed for mutations/polymorphisms involved in haemostasis such as: FV G1691A, FV G4070A, FIIG 20210A, MTHFR C677T and A1298C, PAI-1-675 4G/5G, F XIII exon 2G/T, EPCR A4600G and G4678C. We identified systemic risk factors in the majority of the patients Hypertension (P=0.001), dyslipidemia (P=0.029) and diabetes (P=0.01) are associated with RVO in the majority of the patients. The prevalence of prothrombotic risk factors was not significantly different in the patients with RVO compared to controls. Apart from systemic risk factors, genetic predisposition to thrombosis does not seem to have an important association with RVO in this group of elderly patients.

  18. From classical genetics to quantitative genetics to systems biology: modeling epistasis.

    Directory of Open Access Journals (Sweden)

    David L Aylor

    2008-03-01

    Full Text Available Gene expression data has been used in lieu of phenotype in both classical and quantitative genetic settings. These two disciplines have separate approaches to measuring and interpreting epistasis, which is the interaction between alleles at different loci. We propose a framework for estimating and interpreting epistasis from a classical experiment that combines the strengths of each approach. A regression analysis step accommodates the quantitative nature of expression measurements by estimating the effect of gene deletions plus any interaction. Effects are selected by significance such that a reduced model describes each expression trait. We show how the resulting models correspond to specific hierarchical relationships between two regulator genes and a target gene. These relationships are the basic units of genetic pathways and genomic system diagrams. Our approach can be extended to analyze data from a variety of experiments, multiple loci, and multiple environments.

  19. HIV-2 interaction with cell coreceptors: amino acids within the V1/V2 region of viral envelope are determinant for CCR8, CCR5 and CXCR4 usage.

    Science.gov (United States)

    Santos-Costa, Quirina; Lopes, Maria Manuel; Calado, Marta; Azevedo-Pereira, José Miguel

    2014-11-25

    Human immunodeficiency virus 1 and 2 (HIV-1 and HIV-2) use cellular receptors in distinct ways. Besides a more promiscuous usage of coreceptors by HIV-2 and a more frequent detection of CD4-independent HIV-2 isolates, we have previously identified two HIV-2 isolates (HIV-2MIC97 and HIV-2MJC97) that do not use the two major HIV coreceptors: CCR5 and CXCR4. All these features suggest that in HIV-2 the Env glycoprotein subunits may have a different structural organization enabling distinct - although probably less efficient - interactions with cellular receptors. By infectivity assays using GHOST cell line expressing CD4 and CCR8 and blocking experiments using CCR8-specific ligand, I-309, we show that efficient replication of HIV-2MIC97 and HIV-2MJC97 requires the presence of CCR8 at plasma cell membrane. Additionally, we disclosed the determinants of chemokine receptor usage at the molecular level, and deciphered the amino acids involved in the usage of CCR8 (R8 phenotype) and in the switch from CCR8 to CCR5 or to CCR5/CXCR4 usage (R5 or R5X4 phenotype). The data obtained from site-directed mutagenesis clearly indicates that the main genetic determinants of coreceptor tropism are located within the V1/V2 region of Env surface glycoprotein of these two viruses. We conclude that a viral population able to use CCR8 and unable to infect CCR5 or CXCR4-positive cells, may exist in some HIV-2 infected individuals during an undefined time period, in the course of the asymptomatic stage of infection. This suggests that in vivo alternate molecules might contribute to HIV infection of natural target cells, at least under certain circumstances. Furthermore we provide direct and unequivocal evidence that the usage of CCR8 and the switch from R8 to R5 or R5X4 phenotype is determined by amino acids located in the base and tip of V1 and V2 loops of HIV-2 Env surface glycoprotein.

  20. Efficient Feedforward Linearization Technique Using Genetic Algorithms for OFDM Systems

    Directory of Open Access Journals (Sweden)

    García Paloma

    2010-01-01

    Full Text Available Feedforward is a linearization method that simultaneously offers wide bandwidth and good intermodulation distortion suppression; so it is a good choice for Orthogonal Frequency Division Multiplexing (OFDM systems. Feedforward structure consists of two loops, being necessary an accurate adjustment between them along the time, and when temperature, environmental, or operating changes are produced. Amplitude and phase imbalances of the circuit elements in both loops produce mismatched effects that lead to degrade its performance. A method is proposed to compensate these mismatches, introducing two complex coefficients calculated by means of a genetic algorithm. A full study is carried out to choose the optimal parameters of the genetic algorithm applied to wideband systems based on OFDM technologies, which are very sensitive to nonlinear distortions. The method functionality has been verified by means of simulation.

  1. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    non-coding RNAs (ncRNAs). The integration of transcriptomics data with genomic data in a systems genetics context represents a valuable possibility to go deep into the causal and regulatory mechanisms that generate complex traits and diseases. However RNA-Seq data have to be treated carefully......Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand...... the biological mechanisms behind complex diseases or traits. In the recent past, transcriptomic studies with microarrays have been replaced with the new powerful RNA-seq technologies. This has led to detection of novel gene transcripts, novel regulatory mechanisms, allele specific gene expression and numerous...

  2. Genetic biases for showy males: are some genetic systems especially conducive to sexual selection?

    Science.gov (United States)

    Reeve, Hudson Kern; Pfennig, David W

    2003-02-04

    Male secondary sexual characters (conspicuous ornaments, signals, colors) are among nature's most striking features. Yet, it is unclear why certain groups of organisms are more likely than others to evolve these traits. One explanation for such taxonomic biases is that some genetic systems may be especially conducive to sexual selection. Here, we present theory and simulation results demonstrating that rare alleles encoding either male ornaments or female preferences for those ornaments are better protected against random loss in species with ZZZW or ZZZO sex chromosome systems (male homogamety) than in species with XXXY or XXXO systems (male heterogamety). Moreover, this protection is much stronger in diploid than haplodiploid species. We also present empirical data showing that male secondary sexual characters are better developed in diploid than haplodiploid species and in diploid species with male homogamety than in those with male heterogamety. Thus, taxonomic biases for showy males may stem from differences in sex chromosome systems.

  3. Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic tuberculosis

    DEFF Research Database (Denmark)

    Seng, R; Gustafson, P; Gomes, VF

    2002-01-01

    BACKGROUND: HIV-1 infection is associated with an increased incidence of and mortality from tuberculosis. Few community studies have examined the effect of HIV-2 on tuberculosis. METHODS: We investigated the association between HIV-1, HIV-2 and active tuberculosis in four districts (population 42...

  4. Genetic fuzzy system predicting contractile reactivity patterns of small arteries

    DEFF Research Database (Denmark)

    Tang, J; Sheykhzade, Majid; Clausen, B F

    2014-01-01

    information. We developed a genetic fuzzy system (GFS) algorithm that is capable of learning all information in time-domain physiological data. Data on isometric force development of isolated small arteries were used as a framework for developing and optimizing a GFS. GFS performance was improved by several......Monitoring of physiological surrogate end points in drug development generates dynamic time-domain data reflecting the state of the biological system. Conventional data analysis often reduces the information in these data by extracting specific data points, thereby discarding potentially useful...

  5. Plasma HIV-2 RNA According to CD4 Count Strata among HIV-2-Infected Adults in the IeDEA West Africa Collaboration

    Science.gov (United States)

    Ekouévi, Didier K.; Avettand-Fènoël, Véronique; Tchounga, Boris K.; Coffie, Patrick A.; Sawadogo, Adrien; Minta, Daouda; Minga, Albert; Eholie, Serge P.; Plantier, Jean-Christophe; Damond, Florence; Dabis, François; Rouzioux, Christine

    2015-01-01

    Background Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve. Method A cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL). Results A total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm3 and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm3 (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm3 with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm3, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL. Conclusion This study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment. PMID

  6. Optimal design of link systems using successive zooming genetic algorithm

    Science.gov (United States)

    Kwon, Young-Doo; Sohn, Chang-hyun; Kwon, Soon-Bum; Lim, Jae-gyoo

    2009-07-01

    Link-systems have been around for a long time and are still used to control motion in diverse applications such as automobiles, robots and industrial machinery. This study presents a procedure involving the use of a genetic algorithm for the optimal design of single four-bar link systems and a double four-bar link system used in diesel engine. We adopted the Successive Zooming Genetic Algorithm (SZGA), which has one of the most rapid convergence rates among global search algorithms. The results are verified by experiment and the Recurdyn dynamic motion analysis package. During the optimal design of single four-bar link systems, we found in the case of identical input/output (IO) angles that the initial and final configurations show certain symmetry. For the double link system, we introduced weighting factors for the multi-objective functions, which minimize the difference between output angles, providing balanced engine performance, as well as the difference between final output angle and the desired magnitudes of final output angle. We adopted a graphical method to select a proper ratio between the weighting factors.

  7. Computational Genetic Regulatory Networks Evolvable, Self-organizing Systems

    CERN Document Server

    Knabe, Johannes F

    2013-01-01

    Genetic Regulatory Networks (GRNs) in biological organisms are primary engines for cells to enact their engagements with environments, via incessant, continually active coupling. In differentiated multicellular organisms, tremendous complexity has arisen in the course of evolution of life on earth. Engineering and science have so far achieved no working system that can compare with this complexity, depth and scope of organization. Abstracting the dynamics of genetic regulatory control to a computational framework in which artificial GRNs in artificial simulated cells differentiate while connected in a changing topology, it is possible to apply Darwinian evolution in silico to study the capacity of such developmental/differentiated GRNs to evolve. In this volume an evolutionary GRN paradigm is investigated for its evolvability and robustness in models of biological clocks, in simple differentiated multicellularity, and in evolving artificial developing 'organisms' which grow and express an ontogeny starting fr...

  8. Spatial genetic structure of a symbiotic beetle-fungal system: toward multi-taxa integrated landscape genetics.

    Directory of Open Access Journals (Sweden)

    Patrick M A James

    Full Text Available Spatial patterns of genetic variation in interacting species can identify shared features that are important to gene flow and can elucidate co-evolutionary relationships. We assessed concordance in spatial genetic variation between the mountain pine beetle (Dendroctonus ponderosae and one of its fungal symbionts, Grosmanniaclavigera, in western Canada using neutral genetic markers. We examined how spatial heterogeneity affects genetic variation within beetles and fungi and developed a novel integrated landscape genetics approach to assess reciprocal genetic influences between species using constrained ordination. We also compared landscape genetic models built using Euclidean distances based on allele frequencies to traditional pair-wise Fst. Both beetles and fungi exhibited moderate levels of genetic structure over the total study area, low levels of structure in the south, and more pronounced fungal structure in the north. Beetle genetic variation was associated with geographic location while that of the fungus was not. Pinevolume and climate explained beetle genetic variation in the northern region of recent outbreak expansion. Reciprocal genetic relationships were only detectedin the south where there has been alonger history of beetle infestations. The Euclidean distance and Fst-based analyses resulted in similar models in the north and over the entire study area, but differences between methods in the south suggest that genetic distances measures should be selected based on ecological and evolutionary contexts. The integrated landscape genetics framework we present is powerful, general, and can be applied to other systems to quantify the biotic and abiotic determinants of spatial genetic variation within and among taxa.

  9. An integrated Korean biodiversity and genetic information retrieval system.

    Science.gov (United States)

    Lim, Jeongheui; Bhak, Jong; Oh, Hee-Mock; Kim, Chang-Bae; Park, Yong-Ha; Paek, Woon Kee

    2008-12-12

    On-line biodiversity information databases are growing quickly and being integrated into general bioinformatics systems due to the advances of fast gene sequencing technologies and the Internet. These can reduce the cost and effort of performing biodiversity surveys and genetic searches, which allows scientists to spend more time researching and less time collecting and maintaining data. This will cause an increased rate of knowledge build-up and improve conservations. The biodiversity databases in Korea have been scattered among several institutes and local natural history museums with incompatible data types. Therefore, a comprehensive database and a nation wide web portal for biodiversity information is necessary in order to integrate diverse information resources, including molecular and genomic databases. The Korean Natural History Research Information System (NARIS) was built and serviced as the central biodiversity information system to collect and integrate the biodiversity data of various institutes and natural history museums in Korea. This database aims to be an integrated resource that contains additional biological information, such as genome sequences and molecular level diversity. Currently, twelve institutes and museums in Korea are integrated by the DiGIR (Distributed Generic Information Retrieval) protocol, with Darwin Core2.0 format as its metadata standard for data exchange. Data quality control and statistical analysis functions have been implemented. In particular, integrating molecular and genetic information from the National Center for Biotechnology Information (NCBI) databases with NARIS was recently accomplished. NARIS can also be extended to accommodate other institutes abroad, and the whole system can be exported to establish local biodiversity management servers. A Korean data portal, NARIS, has been developed to efficiently manage and utilize biodiversity data, which includes genetic resources. NARIS aims to be integral in maximizing

  10. Recent insights into the genetic basis of systemic lupus erythematosus.

    Science.gov (United States)

    Moser, K L; Kelly, J A; Lessard, C J; Harley, J B

    2009-07-01

    Genetic variation was first shown to be important in systemic lupus erythematosus (SLE or lupus) in the 1970s with associations in the human leukocyte antigen region. Almost four decades later, and with the help of increasingly powerful genetic approaches, more than 25 genes are now known to contribute to the mechanisms that predispose individuals to lupus. Over half of these loci have been discovered in the past 2 years, underscoring the extraordinary success of genome-wide association approaches in SLE. Well-established risk factors include alleles in the major histocompatibility complex region (multiple genes), IRF5, ITGAM, STAT4, BLK, BANK1, PDCD1, PTPN22, TNFSF4, TNFAIP3, SPP1, some of the Fcgamma receptors, and deficiencies in several complement components, including C1q, C4 and C2. As reviewed here, many susceptibility genes fall into key pathways that are consistent with previous studies implicating immune complexes, host immune signal transduction and interferon pathways in the pathogenesis of SLE. Other loci have no known function or apparent immunological role and have the potential to reveal novel disease mechanisms. Certainly, as our understanding of the genetic etiology of SLE continues to mature, important new opportunities will emerge for developing more effective diagnostic and clinical management tools for this complex autoimmune disease.

  11. CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection

    DEFF Research Database (Denmark)

    Buggert, Marcus; Frederiksen, Juliet Wairimu; Lund, Ole

    2016-01-01

    OBJECTIVE: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T...... with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of ART also to individuals with aviremic HIV-2 infection....

  12. Genetic learning in rule-based and neural systems

    Science.gov (United States)

    Smith, Robert E.

    1993-01-01

    The design of neural networks and fuzzy systems can involve complex, nonlinear, and ill-conditioned optimization problems. Often, traditional optimization schemes are inadequate or inapplicable for such tasks. Genetic Algorithms (GA's) are a class of optimization procedures whose mechanics are based on those of natural genetics. Mathematical arguments show how GAs bring substantial computational leverage to search problems, without requiring the mathematical characteristics often necessary for traditional optimization schemes (e.g., modality, continuity, availability of derivative information, etc.). GA's have proven effective in a variety of search tasks that arise in neural networks and fuzzy systems. This presentation begins by introducing the mechanism and theoretical underpinnings of GA's. GA's are then related to a class of rule-based machine learning systems called learning classifier systems (LCS's). An LCS implements a low-level production-system that uses a GA as its primary rule discovery mechanism. This presentation illustrates how, despite its rule-based framework, an LCS can be thought of as a competitive neural network. Neural network simulator code for an LCS is presented. In this context, the GA is doing more than optimizing and objective function. It is searching for an ecology of hidden nodes with limited connectivity. The GA attempts to evolve this ecology such that effective neural network performance results. The GA is particularly well adapted to this task, given its naturally-inspired basis. The LCS/neural network analogy extends itself to other, more traditional neural networks. Conclusions to the presentation discuss the implications of using GA's in ecological search problems that arise in neural and fuzzy systems.

  13. Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene.

    Science.gov (United States)

    Chintalapudi, Sumana R; Jablonski, Monica M

    2017-01-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas. We found that chromosome 1 harbors an eQTL that modulates the expression of Sncg in the mouse retina and identified Pfdn2 as the candidate upstream modulator of Sncg expression. Downregulation of Pfdn2 in enriched RGCs causes a concomitant reduction in Sncg. In this chapter, we describe our strategy and methods for identifying and confirming a genetic modulation of a glaucoma-associated gene. A similar method can be applied to other genes expressed in other tissues.

  14. Global structual optimizations of surface systems with a genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Chuang, Feng-Chuan [Iowa State Univ., Ames, IA (United States)

    2005-01-01

    Global structural optimizations with a genetic algorithm were performed for atomic cluster and surface systems including aluminum atomic clusters, Si magic clusters on the Si(111) 7 x 7 surface, silicon high-index surfaces, and Ag-induced Si(111) reconstructions. First, the global structural optimizations of neutral aluminum clusters Aln algorithm in combination with tight-binding and first-principles calculations were performed to study the structures of magic clusters on the Si(111) 7 x 7 surface. Extensive calculations show that the magic cluster observed in scanning tunneling microscopy (STM) experiments consist of eight Si atoms. Simulated STM images of the Si magic cluster exhibit a ring-like feature similar to STM experiments. Third, a genetic algorithm coupled with a highly optimized empirical potential were used to determine the lowest energy structure of high-index semiconductor surfaces. The lowest energy structures of Si(105) and Si(114) were determined successfully. The results of Si(105) and Si(114) are reported within the framework of highly optimized empirical potential and first-principles calculations. Finally, a genetic algorithm coupled with Si and Ag tight-binding potentials were used to search for Ag-induced Si(111) reconstructions at various Ag and Si coverages. The optimized structural models of √3 x √3, 3 x 1, and 5 x 2 phases were reported using first-principles calculations. A novel model is found to have lower surface energy than the proposed double-honeycomb chained (DHC) model both for Au/Si(111) 5 x 2 and Ag/Si(111) 5 x 2 systems.

  15. Genetics

    Science.gov (United States)

    ... Likelihood of getting certain diseases Mental abilities Natural talents An abnormal trait (anomaly) that is passed down ... one of them has a genetic disorder. Information Human beings have cells with 46 chromosomes . These consist ...

  16. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus.

    Science.gov (United States)

    Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C; Freedman, Barry I; Kaufman, Kenneth M; Kelly, Jennifer A; Niewold, Timothy B; Kamen, Diane L; Gilkeson, Gary S; Ziegler, Julie T; Langefeld, Carl D; Alarcón, Graciela S; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E; Kimberly, Robert P; Reveille, John D; Vilá, Luis M; Merrill, Joan T; Anaya, Juan-Manuel; James, Judith A; Pons-Estel, Bernardo A; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L; Vyse, Timothy J; Criswell, Lindsey A; Gaffney, Patrick M; Tsao, Betty P; Jacob, Chaim O; Harley, John B; Alarcón-Riquelme, Marta E; Sawalha, Amr H

    2011-10-01

    Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0 × 10(-6), OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future.

  17. Genetic Algorithm-Based Identification of Fractional-Order Systems

    Directory of Open Access Journals (Sweden)

    Shengxi Zhou

    2013-05-01

    Full Text Available Fractional calculus has become an increasingly popular tool for modeling the complex behaviors of physical systems from diverse domains. One of the key issues to apply fractional calculus to engineering problems is to achieve the parameter identification of fractional-order systems. A time-domain identification algorithm based on a genetic algorithm (GA is proposed in this paper. The multi-variable parameter identification is converted into a parameter optimization by applying GA to the identification of fractional-order systems. To evaluate the identification accuracy and stability, the time-domain output error considering the condition variation is designed as the fitness function for parameter optimization. The identification process is established under various noise levels and excitation levels. The effects of external excitation and the noise level on the identification accuracy are analyzed in detail. The simulation results show that the proposed method could identify the parameters of both commensurate rate and non-commensurate rate fractional-order systems from the data with noise. It is also observed that excitation signal is an important factor influencing the identification accuracy of fractional-order systems.

  18. Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Mohan, Chandra; Putterman, Chaim

    2015-06-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that has a broad spectrum of effects on the majority of organs, including the kidneys. Approximately 40-70% of patients with SLE will develop lupus nephritis. Renal assault during SLE is initiated by genes that breach immune tolerance and promote autoantibody production. These genes might act in concert with other genetic factors that augment innate immune signalling and IFN-I production, which in turn can generate an influx of effector leucocytes, inflammatory mediators and autoantibodies into end organs, such as the kidneys. The presence of cognate antigens in the glomerular matrix, together with intrinsic molecular abnormalities in resident renal cells, might further accentuate disease progression. This Review discusses the genetic insights and molecular mechanisms for key pathogenic contributors in SLE and lupus nephritis. We have categorized the genes identified in human studies of SLE into one of four pathogenic events that lead to lupus nephritis. We selected these categories on the basis of the cell types in which these genes are expressed, and the emerging paradigms of SLE pathogenesis arising from murine models. Deciphering the molecular basis of SLE and/or lupus nephritis in each patient will help physicians to tailor specific therapies.

  19. Laboratory diagnosis of the first cases of HIV-2 infection in Canada.

    OpenAIRE

    Neumann, P W; O'Shaughnessy, M V; Lepine, D; D'Souza, I; Major, C; McLaughlin, B

    1989-01-01

    Until recently the geographic distribution of infection due to human immunodeficiency virus type 2 (HIV-2) had excluded North America. We report the first two cases of such infection in Canada. Both people came from endemic areas of western Africa and were asymptomatic. The results of a commercial enzyme immunoassay specific for HIV-1 antibody were positive in both cases, but those of the Western blot technique were indeterminate. The Western blot technique specific for HIV-2 antibody and the...

  20. Genetic Testing in the Workplace: A Caste System for Workers?

    Science.gov (United States)

    Samuels, Sheldon W.

    1999-01-01

    "Authorized" genetic testing may be obtained from employees with coercion or threat. Unless protections are put in place, employers and health insurers will use genetic screening to hire and fire. (JOW)

  1. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  2. The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients

    Directory of Open Access Journals (Sweden)

    Novo Carlos

    2008-09-01

    Full Text Available Abstract Background This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2–4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity Results The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%, increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites. Conclusion The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size

  3. Genetic Control of Wiring Specificity in the Fly Olfactory System

    Science.gov (United States)

    Hong, Weizhe; Luo, Liqun

    2014-01-01

    Precise connections established between pre- and postsynaptic partners during development are essential for the proper function of the nervous system. The olfactory system detects a wide variety of odorants and processes the information in a precisely connected neural circuit. A common feature of the olfactory systems from insects to mammals is that the olfactory receptor neurons (ORNs) expressing the same odorant receptor make one-to-one connections with a single class of second-order olfactory projection neurons (PNs). This represents one of the most striking examples of targeting specificity in developmental neurobiology. Recent studies have uncovered central roles of transmembrane and secreted proteins in organizing this one-to-one connection specificity in the olfactory system. Here, we review recent advances in the understanding of how this wiring specificity is genetically controlled and focus on the mechanisms by which transmembrane and secreted proteins regulate different stages of the Drosophila olfactory circuit assembly in a coordinated manner. We also discuss how combinatorial coding, redundancy, and error-correcting ability could contribute to constructing a complex neural circuit in general. PMID:24395823

  4. From genetic variability to phenotypic expression of blood group systems.

    Science.gov (United States)

    Raud, L; Férec, C; Fichou, Y

    2017-11-01

    More than 300 red blood cell (RBC) antigens belonging to 36 blood group systems have been officially reported in humans by the International Society of Blood Transfusion (ISBT). Phenotypic variability is directly linked to the expression of the 41 blood group genes. The Rh blood group system, which is composed of 54 antigens, is the most complex and polymorphic system. Many rare genetic variants within the RH (RHD and RHCE) genes, involving various mutational mechanisms (single-nucleotide substitutions, short insertions/deletions, rearrangements, large deletions), have been reported in the literature and reference databases. Expression of the variants induces variable clinical outcomes depending on their nature and impact on antigen structure. Their respective molecular and cellular effects remain however poorly studied. Biological resources to conduct this research are also barely available. We have paid a specific attention to three different classes of single-nucleotide substitutions: 1/ splice site variants in the Rh, Kell, Kidd, Junior and Langereis systems by the minigene splicing assay developed locally; 2/ missense variants in the RhD protein and their effect on intermolecular interaction with its protein partner RhAG, intracellular trafficking and plasma membrane integration; and 3/ synonymous variants in the RHD gene. Overall not only this project has fundamental objectives by analyzing the functional effect of variants in order to make genotype-phenotype correlation, but the aim is also to develop/engineer molecular tools and cell models to carry out those studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Genetic Programming Based Ensemble System for Microarray Data Classification

    Directory of Open Access Journals (Sweden)

    Kun-Hong Liu

    2015-01-01

    Full Text Available Recently, more and more machine learning techniques have been applied to microarray data analysis. The aim of this study is to propose a genetic programming (GP based new ensemble system (named GPES, which can be used to effectively classify different types of cancers. Decision trees are deployed as base classifiers in this ensemble framework with three operators: Min, Max, and Average. Each individual of the GP is an ensemble system, and they become more and more accurate in the evolutionary process. The feature selection technique and balanced subsampling technique are applied to increase the diversity in each ensemble system. The final ensemble committee is selected by a forward search algorithm, which is shown to be capable of fitting data automatically. The performance of GPES is evaluated using five binary class and six multiclass microarray datasets, and results show that the algorithm can achieve better results in most cases compared with some other ensemble systems. By using elaborate base classifiers or applying other sampling techniques, the performance of GPES may be further improved.

  6. Genetically engineered biological agents in therapy for systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Elena Aleksandrovna Aseeva

    2013-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.

  7. 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...

  8. SYSGENET: a meeting report from a new European network for systems genetics

    Czech Academy of Sciences Publication Activity Database

    Schughart, K.; Forejt, Jiří

    2010-01-01

    Roč. 21, 7-8 (2010), s. 331-336 ISSN 0938-8990 R&D Projects: GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50520514 Keywords : mouse genetic reference populations * complex genetics of human disease * mouse model systems Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.771, year: 2010

  9. Genetic and physiologic dissection of the vertebrate cardiac conduction system.

    Directory of Open Access Journals (Sweden)

    Neil C Chi

    2008-05-01

    Full Text Available Vertebrate hearts depend on highly specialized cardiomyocytes that form the cardiac conduction system (CCS to coordinate chamber contraction and drive blood efficiently and unidirectionally throughout the organism. Defects in this specialized wiring system can lead to syncope and sudden cardiac death. Thus, a greater understanding of cardiac conduction development may help to prevent these devastating clinical outcomes. Utilizing a cardiac-specific fluorescent calcium indicator zebrafish transgenic line, Tg(cmlc2:gCaMP(s878, that allows for in vivo optical mapping analysis in intact animals, we identified and analyzed four distinct stages of cardiac conduction development that correspond to cellular and anatomical changes of the developing heart. Additionally, we observed that epigenetic factors, such as hemodynamic flow and contraction, regulate the fast conduction network of this specialized electrical system. To identify novel regulators of the CCS, we designed and performed a new, physiology-based, forward genetic screen and identified for the first time, to our knowledge, 17 conduction-specific mutations. Positional cloning of hobgoblin(s634 revealed that tcf2, a homeobox transcription factor gene involved in mature onset diabetes of the young and familial glomerulocystic kidney disease, also regulates conduction between the atrium and the ventricle. The combination of the Tg(cmlc2:gCaMP(s878 line/in vivo optical mapping technique and characterization of cardiac conduction mutants provides a novel multidisciplinary approach to further understand the molecular determinants of the vertebrate CCS.

  10. Improved reactor regulating system logical architecture using genetic algorithm

    Directory of Open Access Journals (Sweden)

    Hyo-Sub Shim

    2017-12-01

    Full Text Available An improved Reactor Regulating System (RRS logic architecture, which is combined with genetic algorithm (GA, is implemented in this work. It is devised to provide an optimal solution to the current RRS. The current system works desirably and has contributed to safe and stable nuclear power plant operation. However, during the ascent and descent section of the reactor power, the RRS output reveals a relatively high steady-state error, and the output also carries a considerable level of overshoot. In an attempt to consolidate conservatism and minimize the error, this work proposes to apply GA to RRS and suggests reconfiguring the system. Prior to the use of GA, reverse engineering is implemented to build a Simulink-based RRS model. Reengineering is followed to produce a newly configured RRS to generate an output that has a reduced steady-state error and diminished overshoot level. A full-scope APR1400 simulator is used to examine the dynamic behaviors of RRS and to build the RRS Simulink model.

  11. Male Circumcision and the Epidemic Emergence of HIV-2 in West Africa

    Science.gov (United States)

    Hewlett, Barry Stephen; Camacho, Ricardo Jorge

    2016-01-01

    Background Epidemic HIV-2 (groups A and B) emerged in humans circa 1930–40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985–91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread. Male circumcision (MC) is known to correlate negatively with HIV-1 prevalence in Africa, but studies examining this issue for HIV-2 are lacking. Methods We reviewed published HIV-2 serosurveys for 30 cities of all West African countries and obtained credible estimates of real prevalence through Bayesian estimation. We estimated past MC rates of 218 West African ethnic groups, based on ethnographic literature and fieldwork. We collected demographic tables specifying the ethnic partition in cities. Uncertainty was incorporated by defining plausible ranges of parameters (e.g. timing of introduction, proportion circumcised). We generated 1,000 sets of past MC rates per city using Latin Hypercube Sampling with different parameter combinations, and explored the correlation between HIV-2 prevalence and estimated MC rate (both logit-transformed) in the 1,000 replicates. Results and Conclusions Our survey reveals that, in the early 20th century, MC was far less common and geographically more variable than nowadays. HIV-2 prevalence in 1985–91 and MC rates in 1950 were negatively correlated (Spearman rho = -0.546, IQR: -0.553–-0.546, p≤0.0021). Guinea-Bissau and Côte d'Ivoire cities had markedly lower MC rates. In addition, MC was uncommon in rural southwestern Côte d'Ivoire in 1930.The differential HIV-2 spread in West Africa correlates with different historical MC rates. We suggest HIV-2 only formed early substantial foci in cities with substantial uncircumcised

  12. Phenotype prediction using regularized regression on genetic data in the DREAM5 Systems Genetics B Challenge.

    Directory of Open Access Journals (Sweden)

    Po-Ru Loh

    Full Text Available A major goal of large-scale genomics projects is to enable the use of data from high-throughput experimental methods to predict complex phenotypes such as disease susceptibility. The DREAM5 Systems Genetics B Challenge solicited algorithms to predict soybean plant resistance to the pathogen Phytophthora sojae from training sets including phenotype, genotype, and gene expression data. The challenge test set was divided into three subcategories, one requiring prediction based on only genotype data, another on only gene expression data, and the third on both genotype and gene expression data. Here we present our approach, primarily using regularized regression, which received the best-performer award for subchallenge B2 (gene expression only. We found that despite the availability of 941 genotype markers and 28,395 gene expression features, optimal models determined by cross-validation experiments typically used fewer than ten predictors, underscoring the importance of strong regularization in noisy datasets with far more features than samples. We also present substantial analysis of the training and test setup of the challenge, identifying high variance in performance on the gold standard test sets.

  13. Moving toward a system genetics view of disease.

    Science.gov (United States)

    Sieberts, Solveig K; Schadt, Eric E

    2007-07-01

    Testing hundreds of thousands of DNA markers in human, mouse, and other species for association to complex traits like disease is now a reality. However, information on how variations in DNA impact complex physiologic processes flows through transcriptional and other molecular networks. In other words, DNA variations impact complex diseases through the perturbations they cause to transcriptional and other biological networks, and these molecular phenotypes are intermediate to clinically defined disease. Because it is also now possible to monitor transcript levels in a comprehensive fashion, integrating DNA variation, transcription, and phenotypic data has the potential to enhance identification of the associations between DNA variation and diseases like obesity and diabetes, as well as characterize those parts of the molecular networks that drive these diseases. Toward that end, we review methods for integrating expression quantitative trait loci (eQTLs), gene expression, and clinical data to infer causal relationships among gene expression traits and between expression and clinical traits. We further describe methods to integrate these data in a more comprehensive manner by constructing coexpression gene networks that leverage pairwise gene interaction data to represent more general relationships. To infer gene networks that capture causal information, we describe a Bayesian algorithm that further integrates eQTLs, expression, and clinical phenotype data to reconstruct whole-gene networks capable of representing causal relationships among genes and traits in the network. These emerging network approaches, aimed at processing high-dimensional biological data by integrating data from multiple sources, represent some of the first steps in statistical genetics to identify multiple genetic perturbations that alter the states of molecular networks and that in turn push systems into disease states. Evolving statistical procedures that operate on networks will be critical

  14. Application of the genetic algorithm for optimisation of large solar hot water systems

    NARCIS (Netherlands)

    Loomans, M.G.L.C.; Visser, H.

    2002-01-01

    An implementation of the genetic algorithm in a design support tool for (large) solar hot water systems is described. The tool calculates the yield and the costs of solar hot water systems based on technical and financial data of the system components. The genetic algorithm allows for optimisation

  15. Hybrid Genetic Algorithm Optimization for Case Based Reasoning Systems

    International Nuclear Information System (INIS)

    Mohamed, A.H.

    2008-01-01

    The success of a CBR system largely depen ds on an effective retrieval of useful prior case for the problem. Nearest neighbor and induction are the main CBR retrieval algorithms. Each of them can be more suitable in different situations. Integrated the two retrieval algorithms can catch the advantages of both of them. But, they still have some limitations facing the induction retrieval algorithm when dealing with a noisy data, a large number of irrelevant features, and different types of data. This research utilizes a hybrid approach using genetic algorithms (GAs) to case-based induction retrieval of the integrated nearest neighbor - induction algorithm in an attempt to overcome these limitations and increase the overall classification accuracy. GAs can be used to optimize the search space of all the possible subsets of the features set. It can deal with the irrelevant and noisy features while still achieving a significant improvement of the retrieval accuracy. Therefore, the proposed CBR-GA introduces an effective general purpose retrieval algorithm that can improve the performance of CBR systems. It can be applied in many application areas. CBR-GA has proven its success when applied for different problems in real-life

  16. Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner.

    Science.gov (United States)

    Alford, Justine E; Marongiu, Michela; Watkins, Gemma L; Anderson, Emma C

    2016-01-01

    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release.

  17. Determinants in HIV-2 Env and tetherin required for functional interaction.

    Science.gov (United States)

    Exline, Colin M; Yang, Su Jung; Haworth, Kevin G; Rengarajan, Srinivas; Lopez, Lisa A; Droniou, Magali E; Seclen, Eduardo; Cannon, Paula M

    2015-08-07

    The interferon-inducible factor BST-2/tetherin blocks the release of nascent virions from the surface of infected cells for certain enveloped virus families. The primate lentiviruses have evolved several counteracting mechanisms which, in the case of HIV-2, is a function of its Env protein. We sought to further understand the features of the Env protein and tetherin that are important for this interaction, and to evaluate the selective pressure on HIV-2 to maintain such an activity. By examining Env mutants with changes in the ectodomain of the protein (virus ROD14) or the cytoplasmic tail (substitution Y707A) that render the proteins unable to counteract tetherin, we determined that an interaction between Env and tetherin is important for this activity. Furthermore, this Env-tetherin interaction required an alanine face in the tetherin ectodomain, although insertion of this domain into an artificial tetherin-like protein was not sufficient to confer sensitivity to the HIV-2 Env. The replication of virus carrying the ROD14 substitutions was significantly slower than the matched wild-type virus, but it acquired second-site mutations during passaging in the cytoplasmic tail of Env which restored the ability of the protein to both bind to and counteract tetherin. These results shed light on the interaction between HIV-2 and tetherin, suggesting a physical interaction that maps to the ectodomains of both proteins and indicating a strong selection pressure to maintain an anti-tetherin activity in the HIV-2 Env.

  18. National Genetic Evaluation (System of Hanwoo (Korean Native Cattle

    Directory of Open Access Journals (Sweden)

    B. Park

    2013-02-01

    practically contributed to the improvement in aspects of quality and quantity. In sum, the current selection system is good enough to accommodate circumstances where fewer sires are used on many more cows. Although progeny tests take longer and cost more, they seem to be appropriate under the circumstances of the domestic market with its higher requirement for better meat quality. Consequently, accumulative data collection, genetic evaluation model development, revision of selection indices, as well as cooperation among farms, associations, National Agricultural Cooperative Federation, universities, research institutes, and government agencies must be applied to the Hanwoo selection program. All these efforts will assist the domestic market to secure a competitive position against imported beef under Free Trade Agreement trade system and will provide farmers with higher profits as well as the public with a higher quality of beef.

  19. Optimal Sensors and Actuators Placement for Large-Scale Unstable Systems via Restricted Genetic Algorithm

    DEFF Research Database (Denmark)

    Seyyed Sakha, Masoud; Shaker, Hamid Reza

    2017-01-01

    expensive. The computational burden is significant in particular for large-scale systems. In this paper, we develop a new technique for placing sensor and actuator in large-scale systems by using Restricted Genetic Algorithm (RGA). The RGA is a kind of genetic algorithm which is developed specifically...

  20. Novel surface display system for proteins on non-genetically modified gram-positive bacteria

    NARCIS (Netherlands)

    Bosma, T; Kanninga, R; Neef, J; Audouy, SAL; van Roosmalen, ML; Steen, A; Buist, G; Kok, J; Kuipers, OP; Robillard, G; Leenhouts, K

    A novel display system is described that allows highly efficient immobilization of heterologous proteins on bacterial surfaces in applications for which the use of genetically modified bacteria is less desirable. This system is based on nonliving and non-genetically modified gram-positive bacterial

  1. Applications of Systems Genetics and Biology for Obesity Using Pig Models

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Kadarmideen, Haja N.

    2016-01-01

    approach, a branch of systems biology. In this chapter, we will describe the state of the art of genetic studies on human obesity, using pig populations. We will describe the features of using the pig as a model for human obesity and briefly discuss the genetics of obesity, and we will focus on systems......In many biomedical research areas, animals have been used as a model to increase the understanding of molecular mechanisms involved in human diseases. One of those areas is human obesity, where porcine models are increasingly used. The pig shows genetic and physiological features that are very...... similar to humans and have shown to be an excellent model for human obesity. Using pig populations, many genetic studies have been performed to unravel the genetic architecture of human obesity. Most of them are pinpointing toward single genes, but more and more studies focus on a systems genetics...

  2. Performance of 3 Rapid Tests for Discrimination Between HIV-1 and HIV-2 in Guinea-Bissau, West Africa

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Bjarnason Obinah, Magnús Pétur; Jespersen, Sanne

    2014-01-01

    As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated ...... (agreement 90.9%) and SD Bioline HIV-1/2 3.0 (agreement 84.5%). Our results underscore the need for evaluation of tests in relevant populations before implementation....

  3. Genetic evaluation of the serotonergic system in chronic fatigue syndrome.

    Science.gov (United States)

    Smith, Alicia K; Dimulescu, Irina; Falkenberg, Virginia R; Narasimhan, Supraja; Heim, Christine; Vernon, Suzanne D; Rajeevan, Mangalathu S

    2008-02-01

    Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown etiology with no known lesions, diagnostic markers or therapeutic intervention. The pathophysiology of CFS remains elusive, although abnormalities in the central nervous system (CNS) have been implicated, particularly hyperactivity of the serotonergic (5-hydroxytryptamine; 5-HT) system and hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Since alterations in 5-HT signaling can lead to physiologic and behavioral changes, a genetic evaluation of the 5-HT system was undertaken to identify serotonergic markers associated with CFS and potential mechanisms for CNS abnormality. A total of 77 polymorphisms in genes related to serotonin synthesis (TPH2), signaling (HTR1A, HTR1E, HTR2A, HTR2B, HTR2C, HTR3A, HTR3B, HTR4, HTR5A, HTR6, and HTR7), transport (SLC6A4), and catabolism (MAOA) were examined in 137 clinically evaluated subjects (40 CFS, 55 with insufficient fatigue, and 42 non-fatigued, NF, controls) derived from a population-based CFS surveillance study in Wichita, Kansas. Of the polymorphisms examined, three markers (-1438G/A, C102T, and rs1923884) all located in the 5-HT receptor subtype HTR2A were associated with CFS when compared to NF controls. Additionally, consistent associations were observed between HTR2A variants and quantitative measures of disability and fatigue in all subjects. The most compelling of these associations was with the A allele of -1438G/A (rs6311) which is suggested to have increased promoter activity in functional studies. Further, in silico analysis revealed that the -1438 A allele creates a consensus binding site for Th1/E47, a transcription factor implicated in the development of the nervous system. Electrophoretic mobility shift assay supports allele-specific binding of E47 to the A allele but not the G allele at this locus. These data indicate that sequence variation in HTR2A, potentially resulting in its enhanced activity, may be involved in the

  4. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors

    DEFF Research Database (Denmark)

    von Deimling, A; Fimmers, R; Schmidt, M C

    2000-01-01

    Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However...

  5. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    Directory of Open Access Journals (Sweden)

    Lisette J. A. Kogelman

    2014-07-01

    Full Text Available Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH and differentially wired (DW networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g. NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g. metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways

  6. Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

    DEFF Research Database (Denmark)

    Madsen, M. B.; Kogelman, L. J. A.; Kadarmideen, H. N.

    2018-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel...... the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4......) compared with the subsequent period (4-8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment. The strongest interactions in the initial SSRI treatment period involved genes encoding transcriptional factors, and in the subsequent period...

  7. Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

    National Research Council Canada - National Science Library

    Baylink, David

    2004-01-01

    The primary goal of the proposed work is to apply several state of the art molecular genetic and gene therapy technologies to address fundamental questions in bone biology with a particular emphasis on attempting: l...

  8. Systems genetic analysis of brown adipose tissue function

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Saba, L. M.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Hüttl, M.; Marková, I.; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Smith, H.; Tabakoff, B.

    2018-01-01

    Roč. 50, č. 1 (2018), s. 52-66 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * coexpression modules * quantitative trait locus * recombinant inbred strains * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Human genetics Impact factor: 3.044, year: 2016

  9. Genetic Programming for Medicinal Plant Family Identification System

    Directory of Open Access Journals (Sweden)

    Indra Laksmana

    2014-11-01

    Full Text Available Information about medicinal plants that is available in text documents is generally quite easy to access, however, one needs some efforts to use it. This research was aimed at utilizing crucial information taken from a text document to identify the family of several species of medicinal plants using a heuristic approach, i.e. genetic programming. Each of the species has its unique features. The genetic program puts the characteristics or special features of each family into a tree form. There are a number of processes involved in the investigated method, i.e. data acquisition, booleanization, grouping of training and test data, evaluation, and analysis. The genetic program uses a training process to select the best individual, initializes a generate-rule process to create several individuals and then executes a fitness evaluation. The next procedure is a genetic operation process, which consists of tournament selection to choose the best individual based on a fitness value, the crossover operation and the mutation operation. These operations have the purpose of complementing the individual. The best individual acquired is the expected solution, which is a rule for classifying medicinal plants. This process produced three rules, one for each plant family, displaying a feature structure that distinguishes each of the families from each other. The genetic program then used these rules to identify the medicinal plants, achieving an average accuracy of 86.47%.

  10. The Possibility to Use Genetic Algorithms and Fuzzy Systems in the Development of Tutorial Systems

    Directory of Open Access Journals (Sweden)

    Anca Ioana ANDREESCU

    2006-01-01

    Full Text Available In this paper we are presenting state of the art information methods and techniques that can be applied in the development of efficient tutorial systems and also the possibility to use genetic algorithms and fuzzy systems in the construction of such systems. All this topics have been studied during the development of the research project INFOSOC entitled "Tutorial System based on Eduknowledge for Work Security and Health in SMEs According to the European Union Directives" accomplished by a teaching stuff from the Academy of Economic Studies, Bucharest, in collaboration with the National Institute for Research and Development in Work Security, the National Institute for Small and Middle Enterprises and SC Q’NET International srl.

  11. DESIGN OPTIMIZATION OF MECHANICAL SYSTEMS USING GENETIC ALGORITHMS

    Directory of Open Access Journals (Sweden)

    Hamit SARUHAN

    2003-08-01

    Full Text Available This papeı- prcsents an algorithnı foı· thedesign of minimum weight of speed reducer., geartrain, subject to a specificd set of constraints. Thestudy is p rimari1y aimed to expose the potential ofgenetic algorithms, to discuss their applicationcapabilities, and to show the concept of thesealgorithms as optiınization techniques an d theirscope of application by implementing them to thespeed reducer. Results obtained for the minimum\\Veight of speed reducer are prescnted to provideinsight into the capabilities of these tecbniques.Genetic algorithms are efficient search techniqucswhich are inspircd fronı natural genetics selectionprocess to cxplore a given search space.

  12. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web ...

  13. An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

    The main theme of this paper concerns the persistent critique of Gilbert Gottlieb on developmental behavior genetics and my reactions to this critique, the latter changing from rejection to complete acceptation. Concise characterizations of developmental behavior genetics, developmental systems theory (to which Gottlieb made essential…

  14. Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

    Science.gov (United States)

    Weiss, J.; Egea-Cortines, M.

    2008-01-01

    We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

  15. Optimization of Electrical System for a Large DC Offshore Wind Farm by Genetic Algorithm

    DEFF Research Database (Denmark)

    Zhao, Menghua; Chen, Zhe; Blaabjerg, Frede

    2004-01-01

    This paper proposes an optimization platform based on Genetic Algorithm, where the main components of the electrical system of a wind farm and key technical specifications are used as input parameters and the topology of the electrical system is to be optimized for a minimum cost and high...... reliability. A method to encode and decode an electrical system is studied. The reliability evaluation for a given network is also investigated. Genetic Algorithm is implemented to find the optimum network design for a large DC wind farm. It is concluded that different topologies may cause very different cost...... and reliability, and the Genetic Algorithm is capable of finding the optimum solution....

  16. Lambda phage genetic switch as a system with critical behaviour

    Czech Academy of Sciences Publication Activity Database

    Vohradský, Jiří

    2017-01-01

    Roč. 431, OCT 27 2017 (2017), s. 32-38 ISSN 0022-5193 R&D Projects: GA MŠk(CZ) LM2015055 Institutional support: RVO:61388971 Keywords : Critical behaviour * Phage lambda * Genetic networks Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.113, year: 2016

  17. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Abstract. We studied the genetics of fertility restoration by producing three-way test cross (TWTC) hybrids involved different combi- nations of restorers, maintainers and partial restorers of rice. Pollen and spikelet fertility of 16 TWTC hybrids were studied. Six TWTC involving restorer/restorer combinations as male parents ...

  18. Inbreeding in stochastic subdivided mating systems: the genetic ...

    Indian Academy of Sciences (India)

    2015-03-03

    Mar 3, 2015 ... models have predominantly focussed on the evolution of parasite populations under strong selection or in epidemic situations, and our ... transmission dynamics and life history characteristics in parasite populations. J. Genet. .... history characteristics) on average levels of coancestry between par- asites at ...

  19. Inbreeding in stochastic subdivided mating systems: the genetic ...

    Indian Academy of Sciences (India)

    2015-03-03

    Mar 3, 2015 ... neutral and inherited in a Mendelian fashion. The parasites ... at time t was necessarily the product of the mating of indi- ..... Trends Ecol. Evol. 18, 523–530. Dye 1994 Models for investigating genetic exchange in protozoan populations. In Modelling vector-borne and other parasitic dis- eases (ed.

  20. Determining the frequency and mechanisms of HIV-1 and HIV-2 RNA copackaging by single-virion analysis

    DEFF Research Database (Denmark)

    Dilley, Kari A; Ni, Na; Nikolaitchik, Olga A

    2011-01-01

    HIV-1 and HIV-2 are derived from two distinct primate viruses and share only limited sequence identity. Despite this, HIV-1 and HIV-2 Gag polyproteins can coassemble into the same particle and their genomes can undergo recombination, albeit at an extremely low frequency, implying that HIV-1 and H...

  1. Comparison between genetic fuzzy system and neuro fuzzy system to select oil wells for hydraulic fracturing; Comparacao entre genetic fuzzy system e neuro fuzzy system para selecao de pocos de petroleo para fraturamento hidraulico

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Antonio Orestes de Salvo [PETROBRAS, Rio de Janeiro, RJ (Brazil); Ferreira Filho, Virgilio Jose Martins [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil)

    2004-07-01

    The hydraulic fracture operation is wide used to increase the oil wells production and to reduce formation damage. Reservoir studies and engineer analysis are made to select the wells for this kind of operation. As the reservoir parameters have some diffuses characteristics, Fuzzy Inference Systems (SIF) have been tested for this selection processes in the last few years. This paper compares the performance of a neuro fuzzy system and a genetic fuzzy system used for hydraulic Fracture well selection, with knowledge acquisition from an operational data base to set the SIF membership functions. The training data and the validation data used were the same for both systems. We concluded that, in despite of the genetic fuzzy system would be a younger process, it got better results than the neuro fuzzy system. Another conclusion was that, as the genetic fuzzy system can work with constraints, the membership functions setting kept the consistency of variables linguistic values. (author)

  2. The Collaborative Cross Resource for Systems Genetics Research of Infectious Diseases.

    Science.gov (United States)

    Maurizio, Paul L; Ferris, Martin T

    2017-01-01

    An increasing body of evidence highlights the role of host genetic variation in driving susceptibility to severe disease following pathogen infection. In order to fully appreciate the importance of host genetics on infection susceptibility and resulting disease, genetically variable experimental model systems should be employed. These systems allow for the identification, characterization, and mechanistic dissection of genetic variants that cause differential disease responses. Herein we discuss application of the Collaborative Cross (CC) panel of recombinant inbred strains to study viral pathogenesis, focusing on practical considerations for experimental design, assessment and analysis of disease responses within the CC, as well as some of the resources developed for the CC. Although the focus of this chapter is on viral pathogenesis, many of the methods presented within are applicable to studies of other pathogens, as well as to case-control designs in genetically diverse populations.

  3. New Highly Sensitive Real-Time PCR Assay for HIV-2 Group A and Group B DNA Quantification.

    Science.gov (United States)

    Bertine, Mélanie; Gueudin, Marie; Mélard, Adeline; Damond, Florence; Descamps, Diane; Matheron, Sophie; Collin, Fidéline; Rouzioux, Christine; Plantier, Jean-Christophe; Avettand-Fenoel, Véronique

    2017-09-01

    HIV-2 infection is characterized by a very low replication rate in most cases and low progression. This necessitates an approach to patient monitoring that differs from that for HIV-1 infection. Here, a new highly specific and sensitive method for HIV-2 DNA quantification was developed. The new test is based on quantitative real-time PCR targeting the long terminal repeat (LTR) and gag regions and using an internal control. Analytical performance was determined in three laboratories, and clinical performance was determined on blood samples from 63 patients infected with HIV-2 group A ( n = 35) or group B ( n = 28). The specificity was 100%. The 95% limit of detection was three copies/PCR and the limit of quantification was six copies/PCR. The within-run coefficients of variation were between 1.03% at 3.78 log 10 copies/PCR and 27.02% at 0.78 log 10 copies/PCR. The between-run coefficient of variation was 5.10%. Both manual and automated nucleic acid extraction methods were validated. HIV-2 DNA loads were detectable in blood cells from all 63 patients. When HIV-2 DNA was quantifiable, median loads were significantly higher in antiretroviral-treated than in naive patients and were similar for groups A and B. HIV-2 DNA load was correlated with HIV-2 RNA load ( r = 0.68; 95% confidence interval [CI], 0.4 to 0.8; P < 0.0001). Our data show that this new assay is highly sensitive and quantifies the two main HIV-2 groups, making it useful for the diagnosis of HIV-2 infection and for pathogenesis studies on HIV-2 reservoirs. Copyright © 2017 American Society for Microbiology.

  4. Genetic Variation in the Dopamine System Influences Intervention Outcome in Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Rochellys Diaz Heijtz

    2018-02-01

    Interpretation: Naturally occurring genetic variation in the dopamine system can influence treatment outcomes in children with cerebral palsy. A polygenic dopamine score might be valid for treatment outcome prediction and for designing individually tailored interventions for children with cerebral palsy.

  5. Optimization of Neuro-Fuzzy System Using Genetic Algorithm for Chromosome Classification

    Directory of Open Access Journals (Sweden)

    M. Sarosa

    2013-09-01

    Full Text Available Neuro-fuzzy system has been shown to provide a good performance on chromosome classification but does not offer a simple method to obtain the accurate parameter values required to yield the best recognition rate. This paper presents a neuro-fuzzy system where its parameters can be automatically adjusted using genetic algorithms. The approach combines the advantages of fuzzy logic theory, neural networks, and genetic algorithms. The structure consists of a four layer feed-forward neural network that uses a GBell membership function as the output function. The proposed methodology has been applied and tested on banded chromosome classification from the Copenhagen Chromosome Database. Simulation result showed that the proposed neuro-fuzzy system optimized by genetic algorithms offers advantages in setting the parameter values, improves the recognition rate significantly and decreases the training/testing time which makes genetic neuro-fuzzy system suitable for chromosome classification.

  6. Immune System and Genetics: A Different Approach to the Diversity of Antibodies

    International Nuclear Information System (INIS)

    Matta Camacho, Nubia Estela

    2011-01-01

    It is common to find in immunology or genetic books a chapter entitled immune system and genetics; this association focuses on how the generation of antibodies broke the paradigm one gene, one protein, since in this case one gene generates millions of proteins. However, the immune system has many more links to genetics and heredity. For example, any substance or compound that an organism produces is a potential antigen, when it is recognized as foreign by the immune system of another organism from the same or different species. The proteins that are potentially antigenic are encoded by the individual's genotype. The ability of the immune system to respond to antigenic proteins, as well as the type and intensity of that response, are also correlated with the organism's genotype. In addition, deficiencies in the immune response may be associated with mutations or genetic polymorphisms, which result in susceptibility to infection diseases.

  7. Genetic architecture of variation in the lateral line sensory system of threespine sticklebacks.

    Science.gov (United States)

    Wark, Abigail R; Mills, Margaret G; Dang, Lam-Ha; Chan, Yingguang Frank; Jones, Felicity C; Brady, Shannon D; Absher, Devin M; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M; Kingsley, David M; Peichel, Catherine L

    2012-09-01

    Vertebrate sensory systems have evolved remarkable diversity, but little is known about the underlying genetic mechanisms. The lateral line sensory system of aquatic vertebrates is a promising model for genetic investigations of sensory evolution because there is extensive variation within and between species, and this variation is easily quantified. In the present study, we compare the lateral line sensory system of threespine sticklebacks (Gasterosteus aculeatus) from an ancestral marine and a derived benthic lake population. We show that lab-raised individuals from these populations display differences in sensory neuromast number, neuromast patterning, and groove morphology. Using genetic linkage mapping, we identify regions of the genome that influence different aspects of lateral line morphology. Distinct loci independently affect neuromast number on different body regions, suggesting that a modular genetic structure underlies the evolution of peripheral receptor number in this sensory system. Pleiotropy and/or tight linkage are also important, as we identify a region on linkage group 21 that affects multiple aspects of lateral line morphology. Finally, we detect epistasis between a locus on linkage group 4 and a locus on linkage group 21; interactions between these loci contribute to variation in neuromast pattern. Our results reveal a complex genetic architecture underlying the evolution of the stickleback lateral line sensory system. This study further uncovers a genetic relationship between sensory morphology and non-neural traits (bony lateral plates), creating an opportunity to investigate morphological constraints on sensory evolution in a vertebrate model system.

  8. Major depletion of plasmacytoid dendritic cells in HIV-2 infection, an attenuated form of HIV disease.

    Directory of Open Access Journals (Sweden)

    Rita Cavaleiro

    2009-11-01

    Full Text Available Plasmacytoid dendritic cells (pDC provide an important link between innate and acquired immunity, mediating their action mainly through IFN-alpha production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-alpha production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-alpha inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-alpha levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of "attenuated" HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-alpha production does occur.

  9. Control of the lighting system using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Čongradac Velimir D.

    2012-01-01

    Full Text Available The manufacturing, distribution and use of electricity are of fundamental importance for the social life and they have the biggest influence on the environment associated with any human activity. The energy needed for building lighting makes up 20-40% of the total consumption. This paper displays the development of the mathematical model and genetic algorithm for the control of dimmable lighting on problems of regulating the level of internal lighting and increase of energetic efficiency using daylight. A series of experiments using the optimization algorithm on the realized model confirmed very high savings in electricity consumption.

  10. Population dynamics of HIV-2 in rural West Africa: comparison with HIV-1 and ongoing transmission at the heart of the epidemic

    NARCIS (Netherlands)

    de Silva, Thushan I.; van Tienen, Carla; Onyango, Clayton; Jabang, Abdoulie; Vincent, Tim; Loeff, Maarten F. Schim van der; Coutinho, Roel A.; Jaye, Assan; Rowland-Jones, Sarah; Whittle, Hilton; Cotten, Matthew; Hué, Stéphane

    2013-01-01

    To compare the population dynamics of HIV-2 and HIV-1, and to characterize ongoing HIV-2 transmission in rural Guinea-Bissau. Phylogenetic and phylodynamic analyses using HIV-2 gag and env, and HIV-1 env sequences, combined with epidemiological data from a community cohort. Samples were obtained

  11. Setaria viridis as a model system to advance millet genetics and genomics

    Directory of Open Access Journals (Sweden)

    Pu Huang

    2016-11-01

    Full Text Available Millet is a common name for a group of polyphyletic, small-seeded cereal crops that include pearl, finger and foxtail millet. Millet species are an important source of calories for many societies, often in developing countries. Compared to major cereal crops such as rice and maize, millets are generally better adapted to dry and hot environments. Despite their food security value, the genetic architecture of agronomically important traits in millets, including both morphological traits and climate resilience remains poorly studied. These complex traits have been challenging to dissect in large part because of the lack of sufficient genetic tools and resources. In this article, we review the phylogenetic relationship among various millet species and discuss the value of a genetic model system for millet research. We propose that a broader adoption of green foxtail (Setaria viridis as a model system for millets could greatly accelerate the pace of gene discovery in the millets, and summarize available and emerging resources in S. viridis and its domesticated relative S. italica. These resources have value in forward genetics, reverse genetics and high throughput phenotyping. We describe methods and strategies to best utilize these resources to facilitate the genetic dissection of complex traits. We envision that coupling cutting-edge technologies and the use of S. viridis for gene discovery will accelerate genetic research in millets in general. This will enable strategies and provide opportunities to increase productivity, especially in the semi-arid tropics of Asia and Africa where millets are staple food crop.

  12. Molecular genetic variability, population structure and mating system in tropical forages

    Directory of Open Access Journals (Sweden)

    Melissa Garcia

    2013-09-01

    Full Text Available Microsatellite (SSR markers were developed for the following tropical forage species, using accessions available from the plant genetic resources (PGR collections held by EMBRAPA (Brazilian Agricultural Research Corporation: Brachiaria brizantha, B. humidicola, Panicum maximum, Paspalum spp., Stylosanthes capitata, S. guianensis, S. macrocephala, Calopogonium mucunoides and Centrosema spp. The markers were used to analyze population structure and genetic diversity, evolution and origin of the genetic variability in the center of origin, mating systems and genetic resources in EMBRAPA’s germplasm bank. The results shed light on the amount of genetic variation within and between populations, revealed the need in some cases for further plant collection to adequately represent the species in PGR collections, allowed us to assemble core collections (subsets of the total collections that should contain most of the available diversity and (in the case of the legumes showed the need to avoid unwanted outcrossing when regenerating conserved material. The data will allow plant breeders to better select accessions for hybrid production, discriminate between genotypes and use marker-assisted selection in breeding programs. Our results will also underpin the construction of genetic maps, mapping of genes of agronomic interest and numerous other studies on genetic variability, population structure, gene flow and reproductive systems for the tropical forage species studied in this work.

  13. A New Selectable Marker System for Genetic Studies of Bacteria: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Parsons, D; Tolmasky, M; Chain, P; Segelke, B W

    2011-03-18

    Genetic manipulations in bacteria currently rely on the introduction of antibiotic resistance genes into a bacterial strain; for those organisms that will be used for commercial or industrial applications, the genetic cassette encoding the antibiotic resistance is sometimes removed after selection. it is clear that if alternative technologies could obviate the need to introduce antibiotic resistance into bacteria, they would most certainly become a standard tool in molecular micriobiology for commercial, industrial as well as research applications. Here, they present the development of a novel genetic engineering technology based on toxin-antitoxin systems to modify bacterial genomes without the use of antibiotic resistance in the mutagenesis process. The primary goal is to develop antibiotic-free selection for genetically altered select agent pathogens. They are adapting the toxinc-antitoxin system to enable gene replacement in select agent pathogens since the NIH restrictions introducing antibiotic resistance into select agent pathogens have hindered research with select agent pathogens.

  14. [Reverse genetics system of rotaviruses: development and application for analysis of VP4 spike protein].

    Science.gov (United States)

    Komoto, Satoshi

    2013-01-01

    The rotavirus genome is composed of 11 gene segments of double-stranded (ds)RNA. Reverse genetics is the powerful and ideal methodology for the molecular analysis of virus biology, which enables the virus genome to be artificially manipulated. Although reverse genetics systems exist for nearly all major groups of RNA viruses, development of such a system for rotaviruses is more challenging owing in part to the technical complexity of manipulation of their multi-segmented genome. A breakthrough in the field of rotavirus reverse genetics came in 2006, when we established the first reverse genetics system for rotaviruses, which is a partially plasmid-based system that permits replacement of a viral gene segment with the aid of a helper virus. Although this helper virus-driven system is technically limited and gives low levels of recombinant viruses, it allows alteration of the rotavirus genome, thus contributing to our understanding of these medically important viruses. In this review, I describe the development and application of our rotavirus reverse genetics system, and its future perspectives.

  15. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

    Science.gov (United States)

    Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

    2015-01-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  16. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    Directory of Open Access Journals (Sweden)

    Brian J Bennett

    2015-12-01

    Full Text Available Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP. The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden and human cholesteryl ester transfer protein (CETP. The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear

  17. Maximization of a nuclear system availability through maintenance scheduling optimization using a genetic algorithm

    International Nuclear Information System (INIS)

    Lapa, C.M.F.; Pereira, C.M.N.A.; Mol, A.C.D.A.

    2000-01-01

    In this paper, a method for preventive maintenance scheduling optimization of standby systems, based on genetic algorithm and probabilistic safety analysis, is described. The goal of this approach is to improve the average availability of the system through the optimization of the preventive maintenance policy. Here, the genetic modeling propitiates unconstrained optimization, allowing nonconstant intervals between maintenance, adapting them to the aging parameter of the Weibull distribution used. In order to demonstrate the effectiveness of the proposed method, it is applied to a nuclear system of a two-loop pressurized water reactor. The results, when compared with those obtained by some standard maintenance policies, reveal gains at safety level. (orig.)

  18. The quantitative basis of the Arabidopsis innate immune system to endemic pathogens depends on pathogen genetics

    DEFF Research Database (Denmark)

    Corwin, Jason A; Copeland, Daniel; Feusier, Julie

    2016-01-01

    The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used...... the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B...... shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes....

  19. Reinvestigation of a genetic-based classifier system: the effectiveness of recombination

    NARCIS (Netherlands)

    van Kampen, A. H.; Buydens, L. M.

    1997-01-01

    An empirical study for the effectiveness of recombination in a genetic-based classifier system applied to the field of ion chromatography is presented. From a comparison of the classifier system with and without crossover it followed that recombination was unable to make a significant contribution

  20. Using Genetic Algorithm and MODFLOW to Characterize Aquifer System of Northwest Florida (Published Proceedings)

    Science.gov (United States)

    By integrating Genetic Algorithm and MODFLOW2005, an optimizing tool is developed to characterize the aquifer system of Region II, Northwest Florida. The history and the newest available observation data of the aquifer system is fitted automatically by using the numerical model c...

  1. Using Genetic Algorithm and MODFLOW to Characterize Aquifer System of Northwest Florida

    Science.gov (United States)

    By integrating Genetic Algorithm and MODFLOW2005, an optimizing tool is developed to characterize the aquifer system of Region II, Northwest Florida. The history and the newest available observation data of the aquifer system is fitted automatically by using the numerical model c...

  2. Optimisation of electrical system for offshore wind farms via genetic algorithm

    DEFF Research Database (Denmark)

    Chen, Zhe; Zhao, Menghua; Blaabjerg, Frede

    2009-01-01

    An optimisation platform based on genetic algorithm (GA) is presented, where the main components of a wind farm and key technical specifications are used as input parameters and the electrical system design of the wind farm is optimised in terms of both production cost and system reliability...

  3. Contribution to Control of an Elastic Two-Mass System by Means of Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Zelmira Ferkova

    2007-01-01

    Full Text Available Oscillations of an elastic two-mass system with all known parameters may be suppressed by suitable feedback signal. An observer enables to estimate this feedback without measurement of load mechanism speed. This article contains application of genetic algorithms for identification of elastic system parameters and determination of corresponding observer feedback coefficients. Design correctness is verified by simulation.

  4. FuGeIDS: Fuzzy Genetic paradigms in Intrusion Detection Systems

    OpenAIRE

    Borgohain, Rajdeep

    2012-01-01

    With the increase in the number of security threats, Intrusion Detection Systems have evolved as a significant countermeasure against these threats. And as such, the topic of Intrusion Detection Systems has become one of the most prominent research topics in recent years. This paper gives an overview of the Intrusion Detection System and looks at two major machine learning paradigms used in Intrusion Detection System, Genetic Algorithms and Fuzzy Logic and how to apply them for intrusion dete...

  5. Genetic-neuro-fuzzy system for grading depression

    Directory of Open Access Journals (Sweden)

    Kumar Ashish

    2018-01-01

    Full Text Available Main aim of this study is to develop a software prototype tool for grading and diagnosing depression that will help general physicians for first hand applications. Identification of key symptoms responsible for depression is also another important issue considered in this study. It involves collection of data taken from patients through doctors. Due to several reasons, collection of data in Indian scenario is extremely difficult and thus this tool will be very handy and useful for general physicians working at remote locations. Also, it is possible to collect a data pool through this software model. An intelligent Neuro-Fuzzy model is developed for this purpose. Performance of the said model has been optimized through two approaches. In Approach 1, where a back-propagation algorithm has been considered and in Approach 2, Genetic Algorithm has been used. The model is trained with 78 data and validated with 10 data. Approach 2 superseded Approach 1 in terms of diagnostic accuracy. Therefore, it can be said that the soft computing-based diagnostic models could assist the doctors to make informed decisions. Data for training and validation for this purpose has been collected during 2004–2005 from a Government mental hospital in India.

  6. Population genetic structure in a social landscape: barley in a traditional Ethiopian agricultural system.

    Science.gov (United States)

    Samberg, Leah H; Fishman, Lila; Allendorf, Fred W

    2013-12-01

    Conservation strategies are increasingly driven by our understanding of the processes and patterns of gene flow across complex landscapes. The expansion of population genetic approaches into traditional agricultural systems requires understanding how social factors contribute to that landscape, and thus to gene flow. This study incorporates extensive farmer interviews and population genetic analysis of barley landraces (Hordeum vulgare) to build a holistic picture of farmer-mediated geneflow in an ancient, traditional agricultural system in the highlands of Ethiopia. We analyze barley samples at 14 microsatellite loci across sites at varying elevations and locations across a contiguous mountain range, and across farmer-identified barley types and management strategies. Genetic structure is analyzed using population-based and individual-based methods, including measures of population differentiation and genetic distance, multivariate Principal Coordinate Analysis, and Bayesian assignment tests. Phenotypic analysis links genetic patterns to traits identified by farmers. We find that differential farmer management strategies lead to markedly different patterns of population structure across elevation classes and barley types. The extent to which farmer seed management appears as a stronger determinant of spatial structure than the physical landscape highlights the need for incorporation of social, landscape, and genetic data for the design of conservation strategies in human-influenced landscapes.

  7. Fault Diagnosis of Power System Based on Improved Genetic Optimized BP-NN

    Directory of Open Access Journals (Sweden)

    Yuan Pu

    2015-01-01

    Full Text Available BP neural network (Back-Propagation Neural Network, BP-NN is one of the most widely neural network models and is applied to fault diagnosis of power system currently. BP neural network has good self-learning and adaptive ability and generalization ability, but the operation process is easy to fall into local minima. Genetic algorithm has global optimization features, and crossover is the most important operation of the Genetic Algorithm. In this paper, we can modify the crossover of traditional Genetic Algorithm, using improved genetic algorithm optimized BP neural network training initial weights and thresholds, to avoid the problem of BP neural network fall into local minima. The results of analysis by an example, the method can efficiently diagnose network fault location, and improve fault-tolerance and grid fault diagnosis effect.

  8. Developmental system at the crossroads of system theory, computer science, and genetic engineering

    CERN Document Server

    Węgrzyn, Stefan; Vidal, Pierre

    1990-01-01

    Many facts were at the origin of the present monograph. The ftrst is the beauty of maple leaves in Quebec forests in Fall. It raised the question: how does nature create and reproduce such beautiful patterns? The second was the reading of A. Lindenmayer's works on L systems. Finally came the discovery of "the secrets of DNA" together with many stimulating ex­ changes with biologists. Looking at such facts from the viewpoint of recursive numerical systems led to devise a simple model based on six elementary operations organized in a generating word, the analog of the program of a computer and of the genetic code of DNA in the cells of a living organism. It turned out that such a model, despite its simplicity, can account for a great number of properties of living organisms, e.g. their hierarchical structure, their ability to regenerate after a trauma, the possibility of cloning, their sensitivity to mutation, their growth, decay and reproduction. The model lends itself to analysis: the knowledge of the genera...

  9. System Response Analysis and Model Order Reduction, Using Conventional Method, Bond Graph Technique and Genetic Programming

    Directory of Open Access Journals (Sweden)

    Lubna Moin

    2009-04-01

    Full Text Available This research paper basically explores and compares the different modeling and analysis techniques and than it also explores the model order reduction approach and significance. The traditional modeling and simulation techniques for dynamic systems are generally adequate for single-domain systems only, but the Bond Graph technique provides new strategies for reliable solutions of multi-domain system. They are also used for analyzing linear and non linear dynamic production system, artificial intelligence, image processing, robotics and industrial automation. This paper describes a unique technique of generating the Genetic design from the tree structured transfer function obtained from Bond Graph. This research work combines bond graphs for model representation with Genetic programming for exploring different ideas on design space tree structured transfer function result from replacing typical bond graph element with their impedance equivalent specifying impedance lows for Bond Graph multiport. This tree structured form thus obtained from Bond Graph is applied for generating the Genetic Tree. Application studies will identify key issues and importance for advancing this approach towards becoming on effective and efficient design tool for synthesizing design for Electrical system. In the first phase, the system is modeled using Bond Graph technique. Its system response and transfer function with conventional and Bond Graph method is analyzed and then a approach towards model order reduction is observed. The suggested algorithm and other known modern model order reduction techniques are applied to a 11th order high pass filter [1], with different approach. The model order reduction technique developed in this paper has least reduction errors and secondly the final model retains structural information. The system response and the stability analysis of the system transfer function taken by conventional and by Bond Graph method is compared and

  10. Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates.

    Science.gov (United States)

    Chen, Chia-Yen; Shingai, Masashi; Welbourn, Sarah; Martin, Malcolm A; Borrego, Pedro; Taveira, Nuno; Strebel, Klaus

    2016-12-15

    Although HIV-2 does not encode a vpu gene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit. Lentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode a vpu gene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2

  11. 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

  12. 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...

  13. Genetics of the proteolytic system of lactic acid bacteria

    NARCIS (Netherlands)

    Kok, Jan

    1990-01-01

    The proteolytic system of lactic acid bacteria is of eminent importance for the rapid growth of these organisms in protein-rich media. The combined action of proteinases and peptidases provides the cell with small peptides and essential amino acids. The amino acids and peptides thus liberated have

  14. Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders.

    Science.gov (United States)

    Lester, Kathryn J; Coleman, Jonathan R I; Roberts, Susanna; Keers, Robert; Breen, Gerome; Bögels, Susan; Creswell, Cathy; Hudson, Jennifer L; McKinnon, Anna; Nauta, Maaike; Rapee, Ronald M; Schneider, Silvia; Silverman, Wendy K; Thastum, Mikael; Waite, Polly; Wergeland, Gro Janne H; Eley, Thalia C

    2017-03-01

    Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre- and post-treatment and during the follow-up period in the full sample and a subset with fear-based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

  15. Automatic Tuning of PID Controller for a 1-D Levitation System Using a Genetic Algorithm

    DEFF Research Database (Denmark)

    Yang, Zhenyu; Pedersen, Gerulf K.m.

    2006-01-01

    The automatic PID control design for a onedimensional magnetic levitation system is investigated. The PID controller is automatically tuned using the non-dominated sorting genetic algorithm (NSGA-II) based on a nonlinear system model. The developed controller is digitally implemented and tested....... The preliminary simulation and test results show a bright potential to use artificial intelligence methods for supporting the control design for complicated nonlinear and open-loop unstable systems....

  16. Systems Genetics and Transcriptomics of Feed Efficiency in Dairy Cattle

    DEFF Research Database (Denmark)

    Salleh, Suraya Binti Mohamad; Hoglund, J.; Løvendahl, P.

    Feed is the largest variable cost in milk production industries, thus improving feed efficiency will give better use of resources. This project works closely on definitions of feed efficiency in dairy cattle and uses advanced integrated genomics, bioinformatics and systems biology methods linking...... transcriptomics differences to important attributes or traits related to dairy cattle feed efficiency. Twenty cows (10 Jersey; 10 Holstein Friesian) will be used in the experiment. These two groups of breeds will be divided into two feed efficiency groups depending on their feed efficiency status which......-hydroxybutyrates, Triacylglyceride and urea. Feed efficiency, namely Residual Feed Intake and Kleiber Ratio based on daily feed or dry matter intake, body weight and milk production records also will be calculated. The bovine RNAseq gene expression data will be analyzed using statistical-bioinformatics and systems biology...

  17. Genetics of the proteolytic system of lactic acid bacteria

    OpenAIRE

    Kok, Jan

    1990-01-01

    The proteolytic system of lactic acid bacteria is of eminent importance for the rapid growth of these organisms in protein-rich media. The combined action of proteinases and peptidases provides the cell with small peptides and essential amino acids. The amino acids and peptides thus liberated have to be translocated across the cytoplasmic membrane. To that purpose, the cell contains specific transport proteins. The internalized peptides are further degraded to amino acids by intracellullar pe...

  18. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

    Directory of Open Access Journals (Sweden)

    Ricard Dominique

    2010-05-01

    Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given

  19. Mining Plant Genomic and Genetic Data Using the GnpIS Information System.

    Science.gov (United States)

    Adam-Blondon, A-F; Alaux, M; Durand, S; Letellier, T; Merceron, G; Mohellibi, N; Pommier, C; Steinbach, D; Alfama, F; Amselem, J; Charruaud, D; Choisne, N; Flores, R; Guerche, C; Jamilloux, V; Kimmel, E; Lapalu, N; Loaec, M; Michotey, C; Quesneville, H

    2017-01-01

    GnpIS is an information system designed to help scientists working on plants and fungi to decipher the molecular and genetic architecture of trait variations by facilitating the navigation through genetic, genomic, and phenotypic information. The purpose of the present chapter is to illustrate how users can (1) explore datasets from phenotyping experiments in order to build new datasets for studying genotype × environment interactions in traits, (2) browse into the results of other genetic analysis data such as GWAS to generate or check working hypothesis about candidate genes or to identify important alleles and germplasms for breeding programs, and (3) explore the polymorphism in specific area of the genome using InterMine, JBrowse tools embedded in the GnpIS information system.

  20. Multi-system Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

    Science.gov (United States)

    Fears, Scott C.; Service, Susan K.; Kremeyer, Barbara; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Ramirez, Margarita; Castrillón, Gabriel; Gomez-Franco, Juliana; Lopez, Maria C.; Montoya, Gabriel; Montoya, Patricia; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Ericson, Marissa; Jalbrzikowski, Maria; Luykx, Jurjen J.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier; Glahn, David C.; Ospina-Duque, Jorge; Risch, Neil; Ruiz-Linares, Andrés; Thompson, Paul M.; Cantor, Rita M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Freimer, Nelson B.; Bearden, Carrie E.

    2014-01-01

    IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), yet its pathogenesis remains poorly understood. A focus on measuring multi-system quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that impact on BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomic phenotypes that appear heritable and associated with severe bipolar disorder (BP-I), and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN Multi-generational pedigree study in two closely related, genetically isolated populations: the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). PARTICIPANTS 738 individuals, all from CVCR and ANT pedigrees, of whom 181 are affected with BP-I. MAIN OUTCOME MEASURE Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) phenotypes. RESULTS Seventy-five percent (126) of the phenotypes investigated were significantly heritable, and 31% (53) were associated with BP-I. About 1/4 of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions, and volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND

  1. Selection and genetic gain in rubber tree (Hevea populations using a mixed mating system

    Directory of Open Access Journals (Sweden)

    Costa Reginaldo Brito da

    2000-01-01

    Full Text Available The components of genetic variation and genetic gain obtained with three selection methods - individual, combined and multi-effect index selection - were compared in rubber tree [Hevea brasiliensis (Willd. ex Adr. de Juss. Muell. Arg.] progenies. The rubber tree is a cross pollinating species with a mixed reproductive system in which the self pollination rate is 22%. Twenty-two half sib progenies were planted at experimental stations at Pindorama, Votuporanga and Jaú, in São Paulo State, using a randomized and complete block design, with five replications and ten plants per plot. Dry rubber production was assessed when the plants were three years old. Based on the genetic variability of the populations, Pindorama was the best environment for the expression of variability. At the individual level, heritability was seriously affected when random progenies from an open pollinating population were considered as half sib progenies. Considerable overestimation of genetic gains occurred during individual, combined and multi-effect index selection when the rubber tree reproductive system was not considered as mixed. Selection based on the multi-effect index maximizes genetic progress and should be used more in rubber tree breeding programs.

  2. Symmetries in Genetic Systems and the Concept of Geno-Logical Coding

    Directory of Open Access Journals (Sweden)

    Sergey V. Petoukhov

    2016-12-01

    Full Text Available The genetic code of amino acid sequences in proteins does not allow understanding and modeling of inherited processes such as inborn coordinated motions of living bodies, innate principles of sensory information processing, quasi-holographic properties, etc. To be able to model these phenomena, the concept of geno-logical coding, which is connected with logical functions and Boolean algebra, is put forward. The article describes basic pieces of evidence in favor of the existence of the geno-logical code, which exists in p­arallel with the known genetic code of amino acid sequences but which serves for transferring inherited processes along chains of generations. These pieces of evidence have been received due to the analysis of symmetries in structures of molecular-genetic systems. The analysis has revealed a close connection of the genetic system with dyadic groups of binary numbers and with other mathematical objects, which are related with dyadic groups: Walsh functions (which are algebraic characters of dyadic groups, bit-reversal permutations, logical holography, etc. These results provide a new approach for mathematical modeling of genetic structures, which uses known mathematical formalisms from technological fields of noise-immunity coding of information, binary analysis, logical holography, and digital devices of artificial intellect. Some opportunities for a development of algebraic-logical biology are opened.

  3. Periodic Pattern of Genetic and Fitness Diversity during Evolution of an Artificial Cell-Like System.

    Science.gov (United States)

    Ichihashi, Norikazu; Aita, Takuyo; Motooka, Daisuke; Nakamura, Shota; Yomo, Tetsuya

    2015-12-01

    Genetic and phenotypic diversity are the basis of evolution. Despite their importance, however, little is known about how they change over the course of evolution. In this study, we analyzed the dynamics of the adaptive evolution of a simple evolvable artificial cell-like system using single-molecule real-time sequencing technology that reads an entire single artificial genome. We found that the genomic RNA population increases in fitness intermittently, correlating with a periodic pattern of genetic and fitness diversity produced by repeated diversification and domination. In the diversification phase, a genomic RNA population spreads within a genetic space by accumulating mutations until mutants with higher fitness are generated, resulting in an increase in fitness diversity. In the domination phase, the mutants with higher fitness dominate, decreasing both the fitness and genetic diversity. This study reveals the dynamic nature of genetic and fitness diversity during adaptive evolution and demonstrates the utility of a simplified artificial cell-like system to study evolution at an unprecedented resolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Development of enzymes and enzyme systems by genetic engineering to convert biomass to sugars

    Science.gov (United States)

    TITLE Development of Enzymes and Enzyme Systems by Genetic Engineering to Convert Biomass to Sugars ABSTRACT Plant cellulosic material is one of the most viable renewable resources for the world’s fuel and chemical feedstock needs. Currently ethanol derived from corn starch is the most common li...

  5. Application of genetic algorithm in electrical system optimization for offshore wind farms

    DEFF Research Database (Denmark)

    Chen, Zhe; Zhao, M.; Blaabjerg, Frede

    2008-01-01

    Genetic Algorithm (GA) has been widely used in solving optimization problem in different areas. This paper illustrates the application of GA in the electrical system design for offshore wind farms, where the main components of a wind farm and key technical specifications are used as input...

  6. A reverse genetics system for avian coronavirus infectious bronchitis virus based on targeted RNA recombination

    NARCIS (Netherlands)

    van Beurden, Steven J; Berends, Alinda J; Krämer-Kühl, Annika; Spekreijse, Dieuwertje; Chénard, Gilles; Philipp, Hans-Christian; Mundt, Egbert; Rottier, Peter J M; Verheije, M Hélène

    2017-01-01

    BACKGROUND: Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of chickens that causes severe economic losses in the poultry industry worldwide. Major advances in the study of the molecular biology of IBV have resulted from the development of reverse genetics systems for

  7. DTREEv2, a computer-based support system for the risk assessment of genetically modified plants

    NARCIS (Netherlands)

    Pertry, I.; Nothegger, C.; Sweet, J.; Kuiper, H.A.; Davies, H.; Iserentant, D.; Hull, R.; Mezzetti, B.; Messens, K.; Loose, De M.; Oliveira, de D.; Burssens, S.; Gheysen, G.; Tzotzos, G.

    2014-01-01

    Risk assessment of genetically modified organisms (GMOs) remains a contentious area and a major factor influencing the adoption of agricultural biotech. Methodologically, in many countries, risk assessment is conducted by expert committees with little or no recourse to databases and expert systems

  8. Genomic conflict in scale insects : The causes and consequences of bizarre genetic systems

    NARCIS (Netherlands)

    Ross, Laura; Pen, Ido; Shuker, David M.

    2010-01-01

    It is now clear that mechanisms of sex determination are extraordinarily labile, with considerable variation across all taxonomic levels. This variation is often expressed through differences in the genetic system (XX-XY, XX-XO, haplodiploidy, and so on). Why there is so much variation in such a

  9. Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

    NARCIS (Netherlands)

    Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N.; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J.; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population

  10. Targetable genetic features of primary testicular and primary central nervous system lymphomas

    NARCIS (Netherlands)

    Chapuy, Bjoern; Roemer, Margaretha G. M.; Stewart, Chip; Tan, Yuxiang; Abo, Ryan P.; Zhang, Liye; Dunford, Andrew J.; Meredith, David M.; Thorner, Aaron R.; Jordanova, Ekaterina S.; Liu, Gang; Feuerhake, Friedrich; Ducar, Matthew D.; Illerhaus, Gerald; Gusenleitner, Daniel; Linden, Erica A.; Sun, Heather H.; Homer, Heather; Aono, Miyuki; Pinkus, Geraldine S.; Ligon, Azra H.; Ligon, Keith L.; Ferry, Judith A.; Freeman, Gordon J.; van Hummelen, Paul; Golub, Todd R.; Getz, Gad; Rodig, Scott J.; de Jong, Daphne; Monti, Stefano; Shipp, Margaret A.

    2016-01-01

    Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic

  11. A CRISPR-Cas9 System for Genetic Engineering of Filamentous Fungi.

    Directory of Open Access Journals (Sweden)

    Christina S Nødvig

    Full Text Available The number of fully sequenced fungal genomes is rapidly increasing. Since genetic tools are poorly developed for most filamentous fungi, it is currently difficult to employ genetic engineering for understanding the biology of these fungi and to fully exploit them industrially. For that reason there is a demand for developing versatile methods that can be used to genetically manipulate non-model filamentous fungi. To facilitate this, we have developed a CRISPR-Cas9 based system adapted for use in filamentous fungi. The system is simple and versatile, as RNA guided mutagenesis can be achieved by transforming a target fungus with a single plasmid. The system currently contains four CRISPR-Cas9 vectors, which are equipped with commonly used fungal markers allowing for selection in a broad range of fungi. Moreover, we have developed a script that allows identification of protospacers that target gene homologs in multiple species to facilitate introduction of common mutations in different filamentous fungi. With these tools we have performed RNA-guided mutagenesis in six species of which one has not previously been genetically engineered. Moreover, for a wild-type Aspergillus aculeatus strain, we have used our CRISPR Cas9 system to generate a strain that contains an AACU_pyrG marker and demonstrated that the resulting strain can be used for iterative gene targeting.

  12. Seed systems for African food security: linking molecular genetic analysis and cultivator knowledge in West Africa

    NARCIS (Netherlands)

    Richards, P.; Bruin-Hoekzema, de M.; Hughes, S.G.; Kudadjie, C.Y.; Offei, S.K.; Struik, P.C.

    2009-01-01

    A challenge for African countries is how to integrate new sources of knowledge on plant genetics with knowledge from farmer practice to help improve food security. This paper considers the knowledge content of farmer seed systems in the light of a distinction drawn in artificial intelligence

  13. Genetic variations in the serotoninergic system contribute to body-mass index in Chinese adolescents.

    Directory of Open Access Journals (Sweden)

    Chunhui Chen

    Full Text Available OBJECTIVE: Obesity has become a worldwide health problem in the past decades. Human and animal studies have implicated serotonin in appetite regulation, and behavior genetic studies have shown that body mass index (BMI has a strong genetic component. However, the roles of genes related to the serotoninergic (5-hydroxytryptamine,5-HT system in obesity/BMI are not well understood, especially in Chinese subjects. SUBJECTS AND DESIGN: With a sample of 478 healthy Chinese volunteers, this study investigated the relation between BMI and genetic variations of the serotoninergic system as characterized by 136 representative polymorphisms. We used a system-level approach to identify SNPs associated with BMI, then estimated their overall contribution to BMI by multiple regression and verified it by permutation. RESULTS: We identified 12 SNPs that made statistically significant contributions to BMI. After controlling for gender and age, four of these SNPs accounted for 7.7% additional variance of BMI. Permutation analysis showed that the probability of obtaining these findings by chance was low (p = 0.015, permuted for 1000 times. CONCLUSION: These results showed that genetic variations in the serotoninergic system made a moderate contribution to individual differences in BMI among a healthy Chinese sample, suggesting that a similar approach can be used to study obesity.

  14. An international collaboration to standardize HIV-2 viral load assays: results from the 2009 ACHI(E)V(2E) quality control study.

    Science.gov (United States)

    Damond, F; Benard, A; Balotta, Claudia; Böni, Jürg; Cotten, Matthew; Duque, Vitor; Ferns, Bridget; Garson, Jeremy; Gomes, Perpetua; Gonçalves, Fátima; Gottlieb, Geoffrey; Kupfer, Bernd; Ruelle, Jean; Rodes, Berta; Soriano, Vicente; Wainberg, Mark; Taieb, Audrey; Matheron, Sophie; Chene, Genevieve; Brun-Vezinet, Francoise

    2011-10-01

    Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHI(E)V(2E) study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log(10) copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log(10) copies/ml and 3.7 log(10) copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed.

  15. Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.

    Science.gov (United States)

    Janjigian, Yelena Y; Sanchez-Vega, Francisco; Jonsson, Philip; Chatila, Walid K; Hechtman, Jaclyn F; Ku, Geoffrey Y; Riches, Jamie C; Tuvy, Yaelle; Kundra, Ritika; Bouvier, Nancy; Vakiani, Efsevia; Gao, Jianjiong; Heins, Zachary J; Gross, Benjamin E; Kelsen, David P; Zhang, Liying; Strong, Vivian E; Schattner, Mark; Gerdes, Hans; Coit, Daniel G; Bains, Manjit; Stadler, Zsofia K; Rusch, Valerie W; Jones, David R; Molena, Daniela; Shia, Jinru; Robson, Mark E; Capanu, Marinela; Middha, Sumit; Zehir, Ahmet; Hyman, David M; Scaltriti, Maurizio; Ladanyi, Marc; Rosen, Neal; Ilson, David H; Berger, Michael F; Tang, Laura; Taylor, Barry S; Solit, David B; Schultz, Nikolaus

    2018-01-01

    The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein-Barr virus-positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance. Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49-58. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Pectasides et al., p. 37 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

  16. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials.

    Science.gov (United States)

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G

    2015-01-01

    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials.

  17. Optimization of redundancy by using genetic algorithm for reliability of plant protection system

    International Nuclear Information System (INIS)

    Yoo, D. W.; Seong, S. H.; Kim, D. H.; Park, H. Y.; Gu, I. S.

    2000-01-01

    The design and development of a reliable protection system has been becoming a key issue in industry field because the reliability of system is considered as an important factor to perform the system's function successfully. Plant Protection System(PPS) guarantees the safety of plant by accident detection and control action against the transient conditions of plant. This paper presents the analysis of PPS reliability and the formal problem statement about optimal redundancy based on the reliability of PPS. And the optimization problem is solved by genetic algorithm. The genetic algorithm is a useful tool to solve the problems, in the case of large searching, complex gradient, existence local minimum. The effectiveness of the proposed optimization technique is proved by the target reliability of one channel of PPS, using the failure rate based on the MIL-HDBK-217

  18. Evolving Rule-Based Systems in two Medical Domains using Genetic Programming

    DEFF Research Database (Denmark)

    Tsakonas, A.; Dounias, G.; Jantzen, Jan

    2004-01-01

    We demonstrate, compare and discuss the application of two genetic programming methodologies for the construction of rule-based systems in two medical domains: the diagnosis of Aphasia's subtypes and the classification of Pap-Smear Test examinations. The first approach consists of a scheme...... of a standard entropy based machine learning approach and to those of a standard genetic programming symbolic expression approach. In the diagnosis of subtypes of Aphasia, two models for crisp rule-bases are presented. The first one discriminates between four major types and the second attempts...

  19. Comparison of the efficiency of different newcastle disease virus reverse genetics systems.

    Science.gov (United States)

    Liu, Haijin; de Almeida, Renata Servan; Gil, Patricia; Albina, Emmanuel

    2017-11-01

    Rescue of negative-sense single-stranded RNA viruses ((-)ssRNA virus), generally requires the handling of a large number of plasmids to provide the virus genome and essential components for gene expression and genome replication. This constraint probably renders reverse genetics of (-)ssRNA virus more complex and less efficient. Some authors have shown that the fewer the plasmids, the more efficient reverse genetics is for segmented RNA virus. However, it is not clear if the same applies for (-)ssRNA, such as Newcastle disease virus (NDV). To address this issue, six variants of NDV reverse genetic systems were established by cloning combinations of NP, P and L genes, mini-genome or full-genome in 4, 3, 2 and 1 plasmid. In terms of mini-genome and full-genome rescue, we showed that only the 2-plasmid system, assembling three support plasmids together, was able to improve the rescue efficiency over that of the conventional 4-plasmid system. These results may help establish and/or improve reverse genetics for other mononegaviruses. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sexual systems and population genetic structure in an annual plant: testing the metapopulation model.

    Science.gov (United States)

    Obbard, Darren J; Harris, Stephen A; Pannell, John R

    2006-03-01

    The need for reproductive assurance during dispersal, along with the pressure of local mate competition, means that the importance of frequent or repeated colonization is implicit in the literature on sexual system evolution. However, there have been few empirical tests of the association between colonization history and sexual system in plants, and none within a single species. Here we use patterns of genetic diversity to provide such a test in the Mercurialis annua species complex, which spans the range of systems from self-compatible monoecy through androdioecy to dioecy. This variation has been hypothesized to result from differing patterns of metapopulation turnover and recolonization. Because monoecy should be favored during colonization, androdioecy and dioecy will be maintained only in regions with low rates of local extinction and recolonization, and these differences should also be reflected in patterns of neutral genetic diversity. We show that monoecious populations of M. annua display lower within-population genetic diversity than androdioecious populations and higher genetic differentiation than dioecious and androdioecious populations, as predicted by metapopulation models. In contrast, regional diversity in M. annua appears to be primarily a product of postglacial range expansion from two refugia in the eastern and western Mediterranean Basin.

  1. Modeling the evolution of complex genetic systems: the gene network family tree.

    Science.gov (United States)

    Fierst, Janna L; Phillips, Patrick C

    2015-01-01

    In 1994 and 1996, Andreas Wagner introduced a novel model in two papers addressing the evolution of genetic regulatory networks. This work, and a suite of papers that followed using similar models, helped integrate network thinking into biology and motivate research focused on the evolution of genetic networks. The Wagner network has its mathematical roots in the Ising model, a statistical physics model describing the activity of atoms on a lattice, and in neural networks. These models have given rise to two branches of applications, one in physics and biology and one in artificial intelligence and machine learning. Here, we review development along these branches, outline similarities and differences between biological models of genetic regulatory circuits and neural circuits models used in machine learning, and identify ways in which these models can provide novel insights into biological systems. © 2014 Wiley Periodicals, Inc.

  2. A Genetic Algorithm Approach to the Optimization of a Radioactive Waste Treatment System

    International Nuclear Information System (INIS)

    Yang, Yeongjin; Lee, Kunjai; Koh, Y.; Mun, J.H.; Kim, H.S.

    1998-01-01

    This study is concerned with the applications of goal programming and genetic algorithm techniques to the analysis of management and operational problems in the radioactive waste treatment system (RWTS). A typical RWTS is modeled and solved by goal program and genetic algorithm to study and resolve the effects of conflicting objectives such as cost, limitation of released radioactivity to the environment, equipment utilization and total treatable radioactive waste volume before discharge and disposal. The developed model is validated and verified using actual data obtained from the RWTS at Kyoto University in Japan. The solution by goal programming and genetic algorithm would show the optimal operation point which is to maximize the total treatable radioactive waste volume and minimize the released radioactivity of liquid waste even under the restricted resources. The comparison of two methods shows very similar results. (author)

  3. The influence of HLA-types on disease progression among HIV-2 infected patients in Guinea-Bissau

    DEFF Research Database (Denmark)

    Thomsen, Ditte; Erikstrup, Christian; Jespersen, Sanne

    2018-01-01

    class I and II alleles that may influence the disease progression of HIV-2 infection. DESIGN: Cohort follow-up study. METHODS: We used high resolution HLA typing of DNA from 437 antiretroviral treatment naïve HIV-2 infected patients from the Bissau HIV Cohort, Guinea-Bissau, to identify HLA alleles......OBJECTIVES: HIV-2 is endemic in West Africa and is characterized by lower transmissibility due to lower viral load, and HIV-2 infected persons usually have a slower progression to AIDS. The mechanisms behind the slower disease progression are unknown. The main objective was to identify specific HLA...... with an influence on HIV-2 disease progression. The effect of HLA-type on viral load and CD4 cell count was assessed initially by ranksum-test and t-test, followed by adjusted logistic regression and multivariable linear regression analysis, respectively. RESULTS: Three alleles (HLA-B58:01, HLA-DPB110:01 and HLA...

  4. Genetic predictors of systemic sclerosis-associated interstitial lung disease: a review of recent literature.

    Science.gov (United States)

    Stock, Carmel J W; Renzoni, Elisabetta A

    2018-02-23

    The interplay between genetic and environmental factors is likely involved in the pathogenesis of systemic sclerosis (SSc). Interstitial lung disease associated in the context of SSc (SSc-ILD) is associated with significant morbidity, and is the leading cause of death in SSc. The spectrum of SSc-ILD severity is wide, ranging from patients with only limited and inherently stable pulmonary involvement, to those with extensive and progressive pulmonary fibrosis. In order to provide accurate prognostic information for patients, and to initiate appropriate monitoring and treatment regimens, the ability to identify patients at risk of developing severe ILD early in the disease course is crucial. Identification of genetic variants involved in disease pathogenesis can not only potentially provide diagnostic/prognostic markers, but can also highlight dysregulated molecular pathways for therapeutic targeting. A number of genetic associations have been established for susceptibility to SSc, but far fewer studies have investigated genetic susceptibility to SSc-ILD specifically. In this review we present a summary of the studies assessing genetic associations with SSc-ILD.

  5. Uniparental genetic systems: a male and a female perspective in the domestic cattle origin and evolution

    Directory of Open Access Journals (Sweden)

    Piera Di Lorenzo

    2016-09-01

    Full Text Available Over the last 20 years, the two uniparentally inherited marker systems, namely mitochondrial DNA and Y chromosome have been widely employed to solve questions about origin and prehistorical range expansions, demographic processes, both in humans and domestic animals. The mtDNA and the Y chromosome, with their unique patterns of inheritance, continue to be extremely important source of information. These markers played significant roles in farm animals in the evaluation of the genetic variation within- and among-breed strains and lines and have widely applied in the fields of linkage mapping, paternity tests, prediction of breeding values in genome-assisted selection, analysis of genetic diversity within breeds detection of population admixture, assessment of inbreeding and relationships between breeds, and assignment of individuals to their breed of origin. This approach offers a unique opportunity to save genetic resources and achieving improved productivity. In the past years, significant progress was achieved in reconstructing detailed cattle phylogenies; many studies indicated multiple parental sources and several levels of phylogeographic structuring. More detailed researches are still in progress in order to provide a more comprehensive picture of such extant variability. This paper is focused on reviewing the use of the two uniparental markers as valuable tool for the characterization of cattle genetic diversity. Furthermore, their implications in animal breeding, management and genetic resources conservation are also reported.

  6. A robust genetic system for producing heterodimeric native and mutant cytochrome bc(1).

    Science.gov (United States)

    Khalfaoui-Hassani, Bahia; Lanciano, Pascal; Daldal, Fevzi

    2013-10-15

    The ubihydroquinone:cytochrome c oxidoreductase, or cytochrome bc1, is central to the production of ATP by oxidative phosphorylation and photophosphorylation in many organisms. Its three-dimensional structure depicts it as a homodimer with each monomer composed of the Fe-S protein, cytochrome b, and cytochrome c1 subunits. Recent genetic approaches successfully produced heterodimeric variants of this enzyme, providing insights into its mechanism of function. However, these experimental setups are inherently prone to genetic rearrangements as they carry repeated copies of cytochrome bc1 structural genes. Duplications present on a single replicon (one-plasmid system) or a double replicon (two-plasmid system) could yield heterogeneous populations via homologous recombination or other genetic events at different frequencies, especially under selective growth conditions. In this work, we assessed the origins and frequencies of genetic variations encountered in these systems and describe an improved variant of the two-plasmid system. We found that use of a recombination-deficient background (recA) minimizes spontaneous formation of co-integrant plasmids and renders the homologous recombination within the cytochrome b gene copies inconsequential. On the basis of the data, we conclude that both the newly improved RecA-deficient and the previously used RecA-proficient two-plasmid systems reliably produce native and mutant heterodimeric cytochrome bc1 variants. The two-plasmid system developed here might contribute to the study of "mitochondrial heteroplasmy"-like heterogeneous states in model bacteria (e.g., Rhodobacter species) suitable for bioenergetics studies. In the following paper (DOI 10.1021/bi400561e), we describe the use of the two-plasmid system to produce and characterize, in membranes and in purified states, an active heterodimeric cytochrome bc1 variant with unusual intermonomer electron transfer properties.

  7. Population Genetics and Genetic Variability ofBulinus globosus (Gastropoda: Planorbidae) From the Two Main River Systems in Zimbabwe

    DEFF Research Database (Denmark)

    Mukaratirwa, S.; Siegismund, Hans Redlef; Kristensen, Thomas K.

    1996-01-01

    Bullnus globosus is the only known vector of Schistosoma haematoblum in Zimbabwe. The population genetic structure of this vector snail from the two main river drainage systems, represented by 27 localities, was determined from starch gel lsoenzyme electrophoretic data. Out of 11 enzyme systems s...

  8. Genetic Scheduling and Reinforcement Learning in Multirobot Systems for Intelligent Warehouses

    Directory of Open Access Journals (Sweden)

    Jiajia Dou

    2015-01-01

    Full Text Available A new hybrid solution is presented to improve the efficiency of intelligent warehouses with multirobot systems, where the genetic algorithm (GA based task scheduling is combined with reinforcement learning (RL based path planning for mobile robots. Reinforcement learning is an effective approach to search for a collision-free path in unknown dynamic environments. Genetic algorithm is a simple but splendid evolutionary search method that provides very good solutions for task allocation. In order to achieve higher efficiency of the intelligent warehouse system, we design a new solution by combining these two techniques and provide an effective and alternative way compared with other state-of-the-art methods. Simulation results demonstrate the effectiveness of the proposed approach regarding the optimization of travel time and overall efficiency of the intelligent warehouse system.

  9. Optimal Design of Pumped Pipeline Systems Using Genetic Algorithm and Mathematical Optimization

    Directory of Open Access Journals (Sweden)

    Mohammadhadi Afshar

    2007-12-01

    Full Text Available In recent years, much attention has been paid to the optimal design of pipeline systems. In this study, the problem of pipeline system optimal design has been solved through genetic algorithm and mathematical optimization. Pipe diameters and their thicknesses are considered as decision variables to be designed in a manner that water column separation and excessive pressures are avoided in the event of pump failure. Capabilities of the genetic algorithm and the mathematical programming method are compared for the problem under consideration. For simulation of transient streams, explicit characteristic method is used in which devices such as pumps are defined as boundary conditions of the equations defining the hydraulic behavior of pipe segments. The problem of optimal design of pipeline systems is a constrained problem which is converted to an unconstrained optimization problem using an external penalty function approach. The efficiency of the proposed approaches is verified in one example and the results are presented.

  10. Reconstructing genetic mating systems in the absence of parental information in colonially breeding waterbirds

    Directory of Open Access Journals (Sweden)

    Mussi Gonçalves Priscila F

    2011-07-01

    Full Text Available Abstract Background DNA-based studies have demonstrated that avian genetic mating systems vary widely, with many species deviating from long-assumed monogamy by practicing extra-pair paternity and conspecific brood parasitism. Colonially breeding waterbirds provide interesting models in which to investigate this question because they show nesting habits proposed to promote alternative reproductive strategies. However, little is known about the genetic mating systems of this group of birds, mainly due to difficulties in obtaining genetic data from incubating adults at nests that are necessary for conducting conventional parentage studies. Here, we inferred kinship patterns among offspring in broods of three co-distributed waterbird species, Wood Stork (Mycteria americana, Roseate Spoonbill (Platalea ajaja and Great Egret (Ardea alba egretta, to investigate genetic mating system in the absence of parental data. Results Multi-step analyses combining estimates of relatedness coefficients, formulation of relationship-hypotheses, significance testing of alternative hypotheses, and maximum-likelihood sibship reconstruction techniques revealed evidence that alternative reproductive strategies may be present in natural populations of Wood Storks and Roseate Spoonbills, whereas relatedness of co-nestlings diagnosed in the Great Egrets did not deviate from a hypothesis of genetic monogamy. Specifically, under this analytical framework, inferred kinship relationships revealed that Great Egret nests contained full-sibling nestlings (100%, with the Roseate Spoonbill (RS and Wood Stork (WS exhibiting proportions of half-siblings (RS: 5% and/or unrelated nestlings (RS: 24%; WS: 70%, patterns consistent with extra-pair paternity and conspecific brood parasitism, respectively. Conclusions We provide evidence that genetic monogamy occurs in Brazilian natural breeding colonies of the Great Egret, but is not the sole reproductive strategy employed by the Wood Stork

  11. Genetic coding and united-hypercomplex systems in the models of algebraic biology.

    Science.gov (United States)

    Petoukhov, Sergey V

    2017-08-01

    Structured alphabets of DNA and RNA in their matrix form of representations are connected with Walsh functions and a new type of systems of multidimensional numbers. This type generalizes systems of complex numbers and hypercomplex numbers, which serve as the basis of mathematical natural sciences and many technologies. The new systems of multi-dimensional numbers have interesting mathematical properties and are called in a general case as "systems of united-hypercomplex numbers" (or briefly "U-hypercomplex numbers"). They can be widely used in models of multi-parametrical systems in the field of algebraic biology, artificial life, devices of biological inspired artificial intelligence, etc. In particular, an application of U-hypercomplex numbers reveals hidden properties of genetic alphabets under cyclic permutations in their doublets and triplets. A special attention is devoted to the author's hypothesis about a multi-linguistic in DNA-sequences in a relation with an ensemble of U-numerical sub-alphabets. Genetic multi-linguistic is considered as an important factor to provide noise-immunity properties of the multi-channel genetic coding. Our results attest to the conformity of the algebraic properties of the U-numerical systems with phenomenological properties of the DNA-alphabets and with the complementary device of the double DNA-helix. It seems that in the modeling field of algebraic biology the genetic-informational organization of living bodies can be considered as a set of united-hypercomplex numbers in some association with the famous slogan of Pythagoras "the numbers rule the world". Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Deciphering genetic diversity and inheritance of tomato fruit weight and composition through a systems biology approach.

    Science.gov (United States)

    Pascual, Laura; Xu, Jiaxin; Biais, Benoît; Maucourt, Mickaël; Ballias, Patricia; Bernillon, Stéphane; Deborde, Catherine; Jacob, Daniel; Desgroux, Aurore; Faurobert, Mireille; Bouchet, Jean-Paul; Gibon, Yves; Moing, Annick; Causse, Mathilde

    2013-12-01

    Integrative systems biology proposes new approaches to decipher the variation of phenotypic traits. In an effort to link the genetic variation and the physiological and molecular bases of fruit composition, the proteome (424 protein spots), metabolome (26 compounds), enzymatic profile (26 enzymes), and phenotypes of eight tomato accessions, covering the genetic diversity of the species, and four of their F1 hybrids, were characterized at two fruit developmental stages (cell expansion and orange-red). The contents of metabolites varied among the genetic backgrounds, while enzyme profiles were less variable, particularly at the cell expansion stage. Frequent genotype by stage interactions suggested that the trends observed for one accession at a physiological level may change in another accession. In agreement with this, the inheritance modes varied between crosses and stages. Although additivity was predominant, 40% of the traits were non-additively inherited. Relationships among traits revealed associations between different levels of expression and provided information on several key proteins. Notably, the role of frucktokinase, invertase, and cysteine synthase in the variation of metabolites was highlighted. Several stress-related proteins also appeared related to fruit weight differences. These key proteins might be targets for improving metabolite contents of the fruit. This systems biology approach provides better understanding of networks controlling the genetic variation of tomato fruit composition. In addition, the wide data sets generated provide an ideal framework to develop innovative integrated hypothesis and will be highly valuable for the research community.

  13. The Interplay between Forest Management Practices, Genetic Monitoring, and Other Long-Term Monitoring Systems

    Directory of Open Access Journals (Sweden)

    Darius Kavaliauskas

    2018-03-01

    Full Text Available The conservation and sustainable use of forests and forest genetic resources (FGR is a challenging task for scientists and foresters. Forest management practices can affect diversity on various levels: genetic, species, and ecosystem. Understanding past natural disturbance dynamics and their level of dependence on human disturbances and management practices is essential for the conservation and management of FGR, especially in the light of climate change. In this review, forest management practices and their impact on genetic composition are reviewed, synthesized, and interpreted in the light of existing national and international forest monitoring schemes and concepts from various European projects. There is a clear need and mandate for forest genetic monitoring (FGM, while the requirements thereof lack complementarity with existing forest monitoring. Due to certain obstacles (e.g., the lack of unified FGM implementation procedures across the countries, high implementation costs, large number of indicators and verifiers for FGM proposed in the past, merging FGM with existing forest monitoring is complicated. Nevertheless, FGM is of paramount importance for forestry and the natural environment in the future, regardless of the presence or existence of other monitoring systems, as it provides information no other monitoring system can yield. FGM can provide information related to adaptive and neutral genetic diversity changes over time, on a species and/or on a population basis and can serve as an early warning system for the detection of potentially harmful changes of forest adaptability. In addition, FGM offers knowledge on the adaptive potential of forests under the changing environment, which is important for the long-term conservation of FGR.

  14. Trends of HIV-1, HIV-2 and dual infection in women attending outpatient clinics in Senegal, 1990–2009

    Science.gov (United States)

    Heitzinger, K; Sow, P S; Badiane, N M Dia; Gottlieb, G S; N’Doye, I; Toure, M; Kiviat, N B; Hawes, S E

    2013-01-01

    Summary We assessed trends in the relative prevalences of HIV-1, HIV-2 and dual HIV-1/HIV-2 infection in 10,321 women attending outpatient clinics in Senegal between 1990 and 2009. The relative prevalence of HIV-1 (defined as the proportion of seropositive subjects having HIV-1) rose sharply from 38% in 1990 until 1993 (P Senegal. From 1993 to 2009, the relative prevalence of HIV-1 increased at a slower rate, while the relative prevalences of HIV-2 and dual infection decreased. These results confirm trends in HIV prevalence observed in other West African populations and provide a critical update on HIV transmission risk among women in Senegal. PMID:23104745

  15. HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community.

    Directory of Open Access Journals (Sweden)

    Carla van Tienen

    Full Text Available Survival of people with HIV-2 and HTLV-1 infection is better than that of HIV-1 infected people, but long-term follow-up data are rare. We compared mortality rates of HIV-1, HIV-2, and HTLV-1 infected subjects with those of retrovirus-uninfected people in a rural community in Guinea-Bissau.In 1990, 1997 and 2007, adult residents (aged ≥15 years were interviewed, a blood sample was drawn and retroviral status was determined. An annual census was used to ascertain the vital status of all subjects. Cox regression analysis was used to estimate mortality hazard ratios (HR, comparing retrovirus-infected versus uninfected people.A total of 5376 subjects were included; 197 with HIV-1, 424 with HIV-2 and 325 with HTLV-1 infection. The median follow-up time was 10.9 years (range 0.0-20.3. The crude mortality rates were 9.6 per 100 person-years of observation (95% confidence interval 7.1-12.9 for HIV-1, 4.1 (3.4-5.0 for HIV-2, 3.6 (2.9-4.6 for HTLV-1, and 1.6 (1.5-1.8 for retrovirus-negative subjects. The HR comparing the mortality rate of infected to that of uninfected subjects varied significantly with age. The adjusted HR for HIV-1 infection varied from 4.0 in the oldest age group (≥60 years to 12.7 in the youngest (15-29 years. The HR for HIV-2 infection varied from 1.2 (oldest to 9.1 (youngest, and for HTLV-1 infection from 1.2 (oldest to 3.8 (youngest.HTLV-1 infection is associated with significantly increased mortality. The mortality rate of HIV-2 infection, although lower than that of HIV-1 infection, is also increased, especially among young people.

  16. Identification of Host Micro RNAs That Differentiate HIV-1 and HIV-2 Infection Using Genome Expression Profiling Techniques

    Directory of Open Access Journals (Sweden)

    Krishnakumar Devadas

    2016-05-01

    Full Text Available While human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2 share many similar traits, major differences in pathogenesis and clinical outcomes exist between the two viruses. The differential expression of host factors like microRNAs (miRNAs in response to HIV-1 and HIV-2 infections are thought to influence the clinical outcomes presented by the two viruses. MicroRNAs are small non-coding RNA molecules which function in transcriptional and post-transcriptional regulation of gene expression. MiRNAs play a critical role in many key biological processes and could serve as putative biomarker(s for infection. Identification of miRNAs that modulate viral life cycle, disease progression, and cellular responses to infection with HIV-1 and HIV-2 could reveal important insights into viral pathogenesis and provide new tools that could serve as prognostic markers and targets for therapeutic intervention. The aim of this study was to elucidate the differential expression profiles of host miRNAs in cells infected with HIV-1 and HIV-2 in order to identify potential differences in virus-host interactions between HIV-1 and HIV-2. Differential expression of host miRNA expression profiles was analyzed using the miRNA profiling polymerase chain reaction (PCR arrays. Differentially expressed miRNAs were identified and their putative functional targets identified. The results indicate that hsa-miR 541-3p, hsa-miR 518f-3p, and hsa-miR 195-3p were consistently up-regulated only in HIV-1 infected cells. The expression of hsa-miR 1225-5p, hsa-miR 18a* and hsa-miR 335 were down modulated in HIV-1 and HIV-2 infected cells. Putative functional targets of these miRNAs include genes involved in signal transduction, metabolism, development and cell death.

  17. Study of the HIV-2 Env cytoplasmic tail variability and its impact on Tat, Rev and Nef.

    Science.gov (United States)

    Bakouche, Nordine; Vandenbroucke, Anne-Thérèse; Goubau, Patrick; Ruelle, Jean

    2013-01-01

    The HIV-2 env's 3' end encodes the cytoplasmic tail (CT) of the Env protein. This genomic region also encodes the rev, Tat and Nef protein in overlapping reading frames. We studied the variability in the CT coding region in 46 clinical specimens and in 2 reference strains by sequencing and by culturing. The aims were to analyse the variability of Env CT and the evolution of proteins expressed from overlapping coding sequences. A 70% reduction of the length of the CT region affected the HIV-2 ROD and EHO strains in vitro due to a premature stop codon in the env gene. In clinical samples this wasn't observed, but the CT length varied due to insertions and deletions. We noted 3 conserved and 3 variable regions in the CT. The conserved regions were those containing residues involved in Env endocytosis, the potential HIV-2 CT region implicated in the NF-kB activation and the potential end of the lentiviral lytic peptide one. The variable regions were the potential HIV-2 Kennedy region, the potential lentiviral lytic peptide two and the beginning of the potential lentiviral lytic peptide one. A very hydrophobic region was coded downstream of the premature stop codon observed in vitro, suggesting a membrane spanning region. Interestingly, the nucleotides that are responsible for the variability of the CT don't impact rev and Nef. However, in the Kennedy-like coding region variability resulted only from nucleotide changes that impacted Env and Tat together. The HIV-2 Env, Tat and Rev C-terminal part are subject to major length variations in both clinical samples and cultured strains. The HIV-2 Env CT contains variable and conserved regions. These regions don't affect the rev and Nef amino acids composition which evolves independently. In contrast, Tat co-evolves with the Env CT.

  18. Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau

    DEFF Research Database (Denmark)

    Sørensen, Allan; Jespersen, Sanne; Katzenstein, Terese L

    2016-01-01

    HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Methods: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Sim~ao Mendes in Guinea......-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Results: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive...

  19. Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal cardiac arrhythmias.

    Science.gov (United States)

    Koizumi, Akiko; Sasano, Tetsuo; Kimura, Wataru; Miyamoto, Yoshihiro; Aiba, Takeshi; Ishikawa, Taisuke; Nogami, Akihiko; Fukamizu, Seiji; Sakurada, Harumizu; Takahashi, Yoshihide; Nakamura, Hiroaki; Ishikura, Tomoyuki; Koseki, Haruhiko; Arimura, Takuro; Kimura, Akinori; Hirao, Kenzo; Isobe, Mitsuaki; Shimizu, Wataru; Miura, Naoyuki; Furukawa, Tetsushi

    2016-05-07

    Ventricular fibrillation (VF), the main cause of sudden cardiac death (SCD), occurs most frequently in the acute phase of myocardial infarction: a certain fraction of VF, however, develops in an apparently healthy heart, referred as idiopathic VF. The contribution of perturbation in the fast conduction system in the ventricle, the His-Purkinje system, for idiopathic VF has been implicated, but the underlying mechanism remains unknown. Irx3/IRX3 encodes a transcription factor specifically expressed in the His-Purkinje system in the heart. Genetic deletion of Irx3 provides a mouse model of ventricular fast conduction disturbance without anatomical or contraction abnormalities. The aim of this study was to examine the link between perturbed His-Purkinje system and idiopathic VF in Irx3-null mice, and to search for IRX3 genetic defects in idiopathic VF patients in human. Telemetry electrocardiogram recording showed that Irx3-deleted mice developed frequent ventricular tachyarrhythmias mostly at night. Ventricular tachyarrhythmias were enhanced by exercise and sympathetic nerve activation. In human, the sequence analysis of IRX3 exons in 130 probands of idiopathic VF without SCN5A mutations revealed two novel IRX3 mutations, 1262G>C (R421P) and 1453C>A (P485T). Ventricular fibrillation associated with physical activities in both probands with IRX3 mutations. In HL-1 cells and neonatal mouse ventricular myocytes, IRX3 transfection up-regulated SCN5A and connexin-40 mRNA, which was attenuated by IRX3 mutations. IRX3 genetic defects and resultant functional perturbation in the His-Purkinje system are novel genetic risk factors of idiopathic VF, and would improve risk stratification and preventive therapy for SCD in otherwise healthy hearts. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  20. Unfolding neutron spectra obtained from BS–TLD system using genetic algorithm

    International Nuclear Information System (INIS)

    Santos, J.A.L.; Silva, E.R.; Ferreira, T.A.E; Vilela, E.C.

    2012-01-01

    Due to the variability of neutron spectrum within the same environment, it is essential that the spectral distribution as a function of energy should be characterized. The precise information allows radiological quantities establishment related to that spectrum, but it is necessary that a spectrometric system covers a large interval of energy and an unfolding process is appropriate. This paper proposes use of a technique of Artificial Intelligence (AI) called genetic algorithm (GA), which uses bio-inspired mathematical models with the implementation of a specific matrix to unfolding data obtained from a combination of TLDs embedded in a BS system to characterize the neutron spectrum as a function of energy. The results obtained with this method were in accordance with reference spectra, thus enabling this technique to unfold neutron spectra with the BS–TLD system. - Highlights: ► The unfolding code used the artificial intelligence technique called genetic algorithms. ► A response matrix specific to the unfolding data obtained with the BS–TLD system is used by the AGLN. ► The observed results demonstrate the potential use of genetic algorithms in solving complex nuclear problems.

  1. Construction and characterisation of a complete reverse genetics system of dengue virus type 3

    Directory of Open Access Journals (Sweden)

    Jefferson Jose da Silva Santos

    2013-12-01

    Full Text Available Dengue virulence and fitness are important factors that determine disease outcome. However, dengue virus (DENV molecular biology and pathogenesis are not completely elucidated. New insights on those mechanisms have been facilitated by the development of reverse genetic systems in the past decades. Unfortunately, instability of flavivirus genomes cloned in Escherichia coli has been a major problem in these systems. Here, we describe the development of a complete reverse genetics system, based on the construction of an infectious clone and replicon for a low passage DENV-3 genotype III of a clinical isolate. Both constructs were assembled into a newly designed yeast- E. coli shuttle vector by homologous recombination technique and propagated in yeast to prevent any possible genome instability in E. coli . RNA transcripts derived from the infectious clone are infectious upon transfection into BHK-21 cells even after repeated passages of the plasmid in yeast. Transcript-derived DENV-3 exhibited growth kinetics, focus formation size comparable to original DENV-3 in mosquito C6/36 cell culture. In vitro characterisation of DENV-3 replicon confirmed its identity and ability to replicate transiently in BHK-21 cells. The reverse genetics system reported here is a valuable tool that will facilitate further molecular studies in DENV replication, virus attenuation and pathogenesis.

  2. Molecular Detection of Bladder Cancer by Fluorescence Microsatellite Analysis and an Automated Genetic Analyzing System

    Directory of Open Access Journals (Sweden)

    Sarel Halachmi

    2007-01-01

    Full Text Available To investigate the ability of an automated fluorescent analyzing system to detect microsatellite alterations, in patients with bladder cancer. We investigated 11 with pathology proven bladder Transitional Cell Carcinoma (TCC for microsatellite alterations in blood, urine, and tumor biopsies. DNA was prepared by standard methods from blood, urine and resected tumor specimens, and was used for microsatellite analysis. After the primers were fluorescent labeled, amplification of the DNA was performed with PCR. The PCR products were placed into the automated genetic analyser (ABI Prism 310, Perkin Elmer, USA and were subjected to fluorescent scanning with argon ion laser beams. The fluorescent signal intensity measured by the genetic analyzer measured the product size in terms of base pairs. We found loss of heterozygocity (LOH or microsatellite alterations (a loss or gain of nucleotides, which alter the original normal locus size in all the patients by using fluorescent microsatellite analysis and an automated analyzing system. In each case the genetic changes found in urine samples were identical to those found in the resected tumor sample. The studies demonstrated the ability to detect bladder tumor non-invasively by fluorescent microsatellite analysis of urine samples. Our study supports the worldwide trend for the search of non-invasive methods to detect bladder cancer. We have overcome major obstacles that prevented the clinical use of an experimental system. With our new tested system microsatellite analysis can be done cheaper, faster, easier and with higher scientific accuracy.

  3. The genetic algorithm for the nonlinear programming of water pollution control system

    Energy Technology Data Exchange (ETDEWEB)

    Wei, J.; Zhang, J. [China University of Geosciences (China)

    1999-08-01

    In the programming of water pollution control system the combined method of optimization with simulation is used generally. It is not only laborious in calculation, but also the global optimum of the obtained solution is guaranteed difficult. In this paper, the genetic algorithm (GA) used in the nonlinear programming of water pollution control system is given, by which the preferred conception for the programming of waste water system is found in once-through operation. It is more succinct than the conventional method and the global optimum of the obtained solution could be ensured. 6 refs., 4 figs., 3 tabs.

  4. Application of genetic algorithms to the maintenance scheduling optimization in a nuclear system basing on reliability

    International Nuclear Information System (INIS)

    Lapa, Celso M. Franklin; Pereira, Claudio M.N.A.; Mol, Antonio C. de Abreu

    1999-01-01

    This paper presents a solution based on genetic algorithm and probabilistic safety analysis that can be applied in the optimization of the preventive maintenance politic of nuclear power plant safety systems. The goal of this approach is to improve the average availability of the system through the optimization of the preventive maintenance scheduling politic. The auxiliary feed water system of a two loops pressurized water reactor is used as a sample case, in order to demonstrate the effectiveness of the proposed method. The results, when compared to those obtained by some standard maintenance politics, reveal quantitative gains and operational safety levels. (author)

  5. Research on central heating system control strategy based on genetic algorithm

    Science.gov (United States)

    Ding, Sa; Yang, Jianhua; Lu, Wei; Duan, Zhipeng

    2017-03-01

    The central heating is a major way of warming in northeast China in winter, however, the traditional heating method is inefficient, intensifying the energy consumption. How to improve the heating efficiency and reduce energy waste attracts more and more attentions in our country. In this paper, the mathematical model of heat transfer station temperature control system was established based on the structure of central heating system. The feedforward-feedback control strategy was used to overcome temperature fluctuations caused by the pressurized heating exchange system. The genetic algorithm was used to optimize the parameters of PID controller and simulation results demonstrated that central heating temperature achieved well control effect and meet stabilization requirements.

  6. Stochastic resonances in a distributed genetic broadcasting system: the NFκB/IκB paradigm.

    Science.gov (United States)

    Wang, Zhipeng; Potoyan, Davit A; Wolynes, Peter G

    2018-01-01

    Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites. Taking the genetic regulatory network of NF κ B as an exemplary system we explore the impact of having numerous distributed sites on the stochastic dynamics of oscillatory broadcasting genetic networks pointing out how resonances in binding cycles control the network's specificity and performance. We also show that active kinetic regulation of binding and unbinding through molecular stripping of DNA bound transcription factors can lead to a higher coherence of gene-co-expression and synchronous clearance. © 2018 The Author(s).

  7. Synthetic biology with artificially expanded genetic information systems. From personalized medicine to extraterrestrial life.

    Science.gov (United States)

    Benner, Steven A; Hutter, Daniel; Sismour, A Michael

    2003-01-01

    Over 15 years ago, the Benner group noticed that the DNA alphabet need not be limited to the four standard nucleotides known in natural DNA. Rather, twelve nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are possible within the geometry of the Watson-Crick pair (Fig. 1). Synthesis and studies on these compounds have brought us to the threshold of a synthetic biology, an artificial chemical system that does basic processes needed for life (in particular, Darwinian evolution), but with unnatural chemical structures. At the same time, the artificial genetic information systems (AEGIS) that we have developed have been used in FDA-approved commercial tests for managing HIV and hepatitis C infections in individual patients, and in a tool that seeks the virus for severe acute respiratory syndrome (SARS). AEGIS also supports the next generation of robotic probes to search for genetic molecules on Mars, Europa, and elsewhere where NASA probes will travel.

  8. Y-chromosomal insights into the genetic impact of the caste system in India.

    Science.gov (United States)

    Zerjal, Tatiana; Pandya, Arpita; Thangaraj, Kumarasamy; Ling, Edmund Y S; Kearley, Jennifer; Bertoneri, Stefania; Paracchini, Silvia; Singh, Lalji; Tyler-Smith, Chris

    2007-03-01

    The caste system has persisted in Indian Hindu society for around 3,500 years. Like the Y chromosome, caste is defined at birth, and males cannot change their caste. In order to investigate the genetic consequences of this system, we have analysed male-lineage variation in a sample of 227 Indian men of known caste, 141 from the Jaunpur district of Uttar Pradesh and 86 from the rest of India. We typed 131 Y-chromosomal binary markers and 16 microsatellites. We find striking evidence for male substructure: in particular, Brahmins and Kshatriyas (but not other castes) from Jaunpur each show low diversity and the predominance of a single distinct cluster of haplotypes. These findings confirm the genetic isolation and drift within the Jaunpur upper castes, which are likely to result from founder effects and social factors. In the other castes, there may be either larger effective population sizes, or less strict isolation, or both.

  9. Transgene-based, female-specific lethality system for genetic sexing of the silkworm, Bombyx mori.

    Science.gov (United States)

    Tan, Anjiang; Fu, Guoliang; Jin, Li; Guo, Qiuhong; Li, Zhiqian; Niu, Baolong; Meng, Zhiqi; Morrison, Neil I; Alphey, Luke; Huang, Yongping

    2013-04-23

    Transgene-based genetic sexing methods are being developed for insects of agricultural and public health importance. Male-only rearing has long been sought in sericulture because males show superior economic characteristics, such as better fitness, lower food consumption, and higher silk yield. Here we report the establishment of a transgene-based genetic sexing system for the silkworm, Bombyx mori. We developed a construct in which a positive feedback loop regulated by sex-specific alternative splicing leads to high-level expression of the tetracycline-repressible transactivator in females only. Transgenic animals show female-specific lethality during embryonic and early larval stages, leading to male-only cocoons. This transgene-based female-specific lethal system not only has wide application in sericulture, but also has great potential in lepidopteran pest control.

  10. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation.

    NARCIS (Netherlands)

    Guryev, V.; Cuppen, E.

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental

  11. Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation

    NARCIS (Netherlands)

    Guryev, Victor; Cuppen, Edwin

    2009-01-01

    Rapid advances in DNA sequencing improve existing techniques and enable new approaches in genetics and functional genomics, bringing about unprecedented coverage, resolution and sensitivity. Enhanced toolsets can facilitate the untangling of connections between genomic variation, environmental

  12. Predictive Control of Hydronic Floor Heating Systems using Neural Networks and Genetic Algorithms

    DEFF Research Database (Denmark)

    Vinther, Kasper; Green, Torben; Østergaard, Søren

    2017-01-01

    This paper presents the use a neural network and a micro genetic algorithm to optimize future set-points in existing hydronic floor heating systems for improved energy efficiency. The neural network can be trained to predict the impact of changes in set-points on future room temperatures. Additio...... space is not guaranteed. Evaluation of the performance of multiple neural networks is performed, using different levels of information, and optimization results are presented on a detailed house simulation model....

  13. Altered balance of main vasopressor and vasodepressor systems in rats with genetic hypertension and hypertriglyceridaemia

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Dobešová, Zdenka; Zicha, Josef

    2002-01-01

    Roč. 102, č. 3 (2002), s. 269-277 ISSN 0143-5221 R&D Projects: GA AV ČR IAA7011711; GA AV ČR IAA7011805; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : Prague hereditary hypertriglyceridaemic rats * sympathetic nervous system Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.941, year: 2002

  14. Adaptation of Mamdani Fuzzy Inference System Using Neuro - Genetic Approach for Tactical Air Combat Decision Support System

    OpenAIRE

    Tran, Cong; Jain, Lakhmi; Abraham, Ajith

    2004-01-01

    Normally a decision support system is build to solve problem where multi-criteria decisions are involved. The knowledge base is the vital part of the decision support containing the information or data that is used in decision-making process. This is the field where engineers and scientists have applied several intelligent techniques and heuristics to obtain optimal decisions from imprecise information. In this paper, we present a hybrid neuro-genetic learning approach for the adaptation a Ma...

  15. Design of the Fuzzy Control Systems Based on Genetic Algorithm for Intelligent Robots

    Directory of Open Access Journals (Sweden)

    Gyula Mester

    2014-07-01

    Full Text Available This paper gives the structure optimization of fuzzy control systems based on genetic algorithm in the MATLAB environment. The genetic algorithm is a powerful tool for structure optimization of the fuzzy controllers, therefore, in this paper, integration and synthesis of fuzzy logic and genetic algorithm has been proposed. The genetic algorithms are applied for fuzzy rules set, scaling factors and membership functions optimization. The fuzzy control structure initial consist of the 3 membership functions and 9 rules and after the optimization it is enough for the 4 DOF SCARA Robot control to compensate for structured and unstructured uncertainty. Fuzzy controller with the generalized bell membership functions can provide better dynamic performance of the robot then with the triangular membership functions. The proposed joint-space controller is computationally simple and had adaptability to a sudden change in the dynamics of the robot. Results of the computer simulation applied to the 4 DOF SCARA Robot show the validity of the proposed method.

  16. Targetable genetic features of primary testicular and primary central nervous system lymphomas.

    Science.gov (United States)

    Chapuy, Bjoern; Roemer, Margaretha G M; Stewart, Chip; Tan, Yuxiang; Abo, Ryan P; Zhang, Liye; Dunford, Andrew J; Meredith, David M; Thorner, Aaron R; Jordanova, Ekaterina S; Liu, Gang; Feuerhake, Friedrich; Ducar, Matthew D; Illerhaus, Gerald; Gusenleitner, Daniel; Linden, Erica A; Sun, Heather H; Homer, Heather; Aono, Miyuki; Pinkus, Geraldine S; Ligon, Azra H; Ligon, Keith L; Ferry, Judith A; Freeman, Gordon J; van Hummelen, Paul; Golub, Todd R; Getz, Gad; Rodig, Scott J; de Jong, Daphne; Monti, Stefano; Shipp, Margaret A

    2016-02-18

    Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL. © 2016 by The American Society of Hematology.

  17. Dual-reporter surrogate systems for efficient enrichment of genetically modified cells.

    Science.gov (United States)

    Ren, Chonghua; Xu, Kun; Liu, Zhongtian; Shen, Juncen; Han, Furong; Chen, Zhilong; Zhang, Zhiying

    2015-07-01

    Isolation of genetically modified cells generated by designed nucleases are challenging, since they are often phenotypically indistinguishable from their parental cells. To efficiently enrich genetically modified cells, we developed two dual-reporter surrogate systems, namely NHEJ-RPG and SSA-RPG based on NHEJ and SSA repair mechanisms, respectively. Repair and enrichment efficiencies of these two systems were compared using different nucleases. In both CRISPR-Cas9- and ZFNs-induced DSB repair studies, we found that the efficiency and sensitivity of the SSA-RPG reporter with direct repeat length more than 200 bp were much higher than the NHEJ-RPG reporter. By utilizing the SSA-RPG reporter, we achieved the enrichment for indels in several endogenous loci with 6.3- to 34.8-fold of non-selected cells. Thus, the highly sensitive SSA-RPG reporter can be used for activity validation of designed nucleases and efficient enrichment of genetically modified cells. Besides, our systems offer alternative enrichment choices either by puromycin selection or FACS.

  18. Evaluation of a 13-loci STR multiplex system for Cannabis sativa genetic identification.

    Science.gov (United States)

    Houston, Rachel; Birck, Matthew; Hughes-Stamm, Sheree; Gangitano, David

    2016-05-01

    Marijuana (Cannabis sativa) is the most commonly used illicit substance in the USA. The development of a validated method using Cannabis short tandem repeats (STRs) could aid in the individualization of samples as well as serve as an intelligence tool to link multiple cases. For this purpose, a modified 13-loci STR multiplex method was optimized and evaluated according to ISFG and SWGDAM guidelines. A real-time PCR quantification method for C. sativa was developed and validated, and a sequenced allelic ladder was also designed to accurately genotype 199 C. sativa samples from 11 U.S. Customs and Border Protection seizures. Distinguishable DNA profiles were generated from 127 samples that yielded full STR profiles. Four duplicate genotypes within seizures were found. The combined power of discrimination of this multilocus system is 1 in 70 million. The sensitivity of the multiplex STR system is 0.25 ng of template DNA. None of the 13 STR markers cross-reacted with any of the studied species, except for Humulus lupulus (hops) which generated unspecific peaks. Phylogenetic analysis and case-to-case pairwise comparison of 11 cases using F st as genetic distance revealed the genetic association of four groups of cases. Moreover, due to their genetic similarity, a subset of samples (N = 97) was found to form a homogeneous population in Hardy-Weinberg and linkage equilibrium. The results of this research demonstrate the applicability of this 13-loci STR system in associating Cannabis cases for intelligence purposes.

  19. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates.

    Science.gov (United States)

    Visseaux, Benoit; Charpentier, Charlotte; Collin, Gilles; Bertine, Mélanie; Peytavin, Gilles; Damond, Florence; Matheron, Sophie; Lefebvre, Eric; Brun-Vézinet, Françoise; Descamps, Diane

    2015-01-01

    Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 antagonist that has completed Phase 2b development in HIV-1 infection. Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3) cell lines. Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI) of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively). The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively. In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted.

  20. PID-Controller Tuning Optimization with Genetic Algorithms in Servo Systems

    Directory of Open Access Journals (Sweden)

    Arturo Y. Jaen-Cuellar

    2013-09-01

    Full Text Available Performance improvement is the main goal of the study of PID control and much research has been conducted for this purpose. The PID filter is implemented in almost all industrial processes because of its well-known beneficial features. In general, the whole system's performance strongly depends on the controller's efficiency and hence the tuning process plays a key role in the system's behaviour. In this work, the servo systems will be analysed, specifically the positioning control systems. Among the existent tuning methods, the Gain-Phase Margin method based on Frequency Response analysis is the most adequate for controller tuning in positioning control systems. Nevertheless, this method can be improved by integrating an optimization technique. The novelty of this work is the development of a new methodology for PID control tuning by coupling the Gain-Phase Margin method with the Genetic Algorithms in which the micro-population concept and adaptive mutation probability are applied. Simulations using a positioning system model in MATLAB and experimental tests in two CNC machines and an industrial robot are carried out in order to show the effectiveness of the proposal. The obtained results are compared with both the classical Gain-Phase Margin tuning and with a recent PID controller optimization using Genetic Algorithms based on real codification. The three methodologies are implemented using software.

  1. The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics.

    Science.gov (United States)

    Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Subedy, Anushriya; Eshbaugh, Robert; Palmer, Christine; Maloof, Julin; Kliebenstein, Daniel J

    2016-02-01

    The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes.

  2. The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics.

    Directory of Open Access Journals (Sweden)

    Jason A Corwin

    2016-02-01

    Full Text Available The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs and nucleotide-binding site leucine-rich repeat proteins (NLRs, were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60% when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen

  3. Interspecific sex in grass smuts and the genetic diversity of their pheromone-receptor system.

    Directory of Open Access Journals (Sweden)

    Ronny Kellner

    2011-12-01

    Full Text Available The grass smuts comprise a speciose group of biotrophic plant parasites, so-called Ustilaginaceae, which are specifically adapted to hosts of sweet grasses, the Poaceae family. Mating takes a central role in their life cycle, as it initiates parasitism by a morphological and physiological transition from saprobic yeast cells to pathogenic filaments. As in other fungi, sexual identity is determined by specific genomic regions encoding allelic variants of a pheromone-receptor (PR system and heterodimerising transcription factors. Both operate in a biphasic mating process that starts with PR-triggered recognition, directed growth of conjugation hyphae, and plasmogamy of compatible mating partners. So far, studies on the PR system of grass smuts revealed diverse interspecific compatibility and mating type determination. However, many questions concerning the specificity and evolutionary origin of the PR system remain unanswered. Combining comparative genetics and biological approaches, we report on the specificity of the PR system and its genetic diversity in 10 species spanning about 100 million years of mating type evolution. We show that three highly syntenic PR alleles are prevalent among members of the Ustilaginaceae, favouring a triallelic determination as the plesiomorphic characteristic of this group. Furthermore, the analysis of PR loci revealed increased genetic diversity of single PR locus genes compared to genes of flanking regions. Performing interspecies sex tests, we detected a high potential for hybridisation that is directly linked to pheromone signalling as known from intraspecies sex. Although the PR system seems to be optimised for intraspecific compatibility, the observed functional plasticity of the PR system increases the potential for interspecific sex, which might allow the hybrid-based genesis of newly combined host specificities.

  4. Multi-heuristic dynamic task allocation using genetic algorithms in a heterogeneous distributed system

    Science.gov (United States)

    Page, Andrew J.; Keane, Thomas M.; Naughton, Thomas J.

    2010-01-01

    We present a multi-heuristic evolutionary task allocation algorithm to dynamically map tasks to processors in a heterogeneous distributed system. It utilizes a genetic algorithm, combined with eight common heuristics, in an effort to minimize the total execution time. It operates on batches of unmapped tasks and can preemptively remap tasks to processors. The algorithm has been implemented on a Java distributed system and evaluated with a set of six problems from the areas of bioinformatics, biomedical engineering, computer science and cryptography. Experiments using up to 150 heterogeneous processors show that the algorithm achieves better efficiency than other state-of-the-art heuristic algorithms. PMID:20862190

  5. Prediksi Jumlah Kunjungan Pasien Rawat Jalan Menggunakan Metode Genetic Fuzzy Systems Studi Kasus : Rumah Sakit Usada Sidoarjo

    Directory of Open Access Journals (Sweden)

    Lia Farihul Mubin

    2012-09-01

    Full Text Available Rumah sakit adalah institusi pelayanan kesehatan yang menyelenggarakan pelayanan kesehatan perorangan secara paripurna yang menyediakan pelayanan rawat jalan, rawat inap dan gawat darurat. Rawat jalan merupakan proses bisnis utama dari rumah sakit Usada Sidoarjo, namun ketersediaan sumber daya pada unit rawat jalan tidak sebanding dengan jumlah pasien yang harus dilayani. Apabila kunjungan pasien rawat jalan dapat diramalkan secara akurat dapat membantu organisasi dalam pengambilan keputusan dan perencanaan sumber daya dimasa depan. Dalam penelitian ini, metode Genetic Fuzzy System (GFS dipilih untuk melakukan peramalan jumlah kunjungan pasien rawat jalan. Kelebihan Genetic Fuzzy System dibandingkan dengan metode time series tradisional adalah metode time series tradisional membutuhkan lebih banyak data historikal dan data harus mematuhi distribusi normal. Metode Genetic Fuzzy System ini menggunakan  jenis Mamdani fuzzy rule based system dan menggunakan algoritma genetika untuk mengembangkan pengetahuan dasar sistem fuzzy. Penelitian menggunakan Genetic Fuzzy Systems memberikan hasil MAPE sebesar 12,125 %

  6. Growth performance of three pejerrey genetic groups in intensive culture system

    Directory of Open Access Journals (Sweden)

    Rafael Aldrighi Tavares

    2014-10-01

    Full Text Available This study examined the growth performance of Odontesthes bonariensis, O. humensis and hybrid (O. bonariensis X O. humensis in intensive culture system for a period of 180 days, using the body weight (W, total length (Lt, condition factor (CF, allometric coefficient (b, specific growth rate (SGR and estimates of body weight and maximum total length (Wmax, Ltmax as indicators. Fish were randomly selected from three genetic groups (Bonariensis, Humensis and Hybrid, divided into water recirculation system consisting of 12 tanks (50 L. 12 measurements of body weight and total length (0, 2, 7, 14, 21, 30, 45, 60, 75, 90, 120, 180 days were taken by means of a random sample of 10 subjects per replicate. All genetic groups grew in weight and length over the period analyzed, being influenced by the genetics of each species. O. bonariensis showed the best performance in growth and hybrid fish showed intermediate growth and estimated maximum body weight exceeding the pure species. Based on these results, it would be helpful the selective breeding and formation of domesticated strains.

  7. Ruminant Nutrition Symposium: a systems approach to integrating genetics, nutrition, and metabolic efficiency in dairy cattle.

    Science.gov (United States)

    McNamara, J P

    2012-06-01

    The role of the dairy cow is to help provide high-quality protein and other nutrients for humans. We must select and manage cows with the goal of reaching the greatest possible efficiency for any given environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still quite large. In part this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as biological research findings show more specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact by endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and proper animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes during the transition period. Using existing metabolic models, we can design experiments specifically to integrate new data from transcriptional arrays into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and large advances in efficiency and show directly how this can be applied on the farms.

  8. Genetic Algorithm Based Simulated Annealing Method for Solving Unit Commitment Problem in Utility System

    Science.gov (United States)

    Rajan, C. Christober Asir

    2010-10-01

    The objective of this paper is to find the generation scheduling such that the total operating cost can be minimized, when subjected to a variety of constraints. This also means that it is desirable to find the optimal generating unit commitment in the power system for the next H hours. Genetic Algorithms (GA's) are general-purpose optimization techniques based on principles inspired from the biological evolution using metaphors of mechanisms such as neural section, genetic recombination and survival of the fittest. In this, the unit commitment schedule is coded as a string of symbols. An initial population of parent solutions is generated at random. Here, each schedule is formed by committing all the units according to their initial status ("flat start"). Here the parents are obtained from a pre-defined set of solution's i.e. each and every solution is adjusted to meet the requirements. Then, a random recommitment is carried out with respect to the unit's minimum down times. And SA improves the status. A 66-bus utility power system with twelve generating units in India demonstrates the effectiveness of the proposed approach. Numerical results are shown comparing the cost solutions and computation time obtained by using the Genetic Algorithm method and other conventional methods.

  9. Genetic risk and longitudinal disease activity in systemic lupus erythematosus using targeted maximum likelihood estimation.

    Science.gov (United States)

    Gianfrancesco, M A; Balzer, L; Taylor, K E; Trupin, L; Nititham, J; Seldin, M F; Singer, A W; Criswell, L A; Barcellos, L F

    2016-09-01

    Systemic lupus erythematous (SLE) is a chronic autoimmune disease associated with genetic and environmental risk factors. However, the extent to which genetic risk is causally associated with disease activity is unknown. We utilized longitudinal-targeted maximum likelihood estimation to estimate the causal association between a genetic risk score (GRS) comprising 41 established SLE variants and clinically important disease activity as measured by the validated Systemic Lupus Activity Questionnaire (SLAQ) in a multiethnic cohort of 942 individuals with SLE. We did not find evidence of a clinically important SLAQ score difference (>4.0) for individuals with a high GRS compared with those with a low GRS across nine time points after controlling for sex, ancestry, renal status, dialysis, disease duration, treatment, depression, smoking and education, as well as time-dependent confounding of missing visits. Individual single-nucleotide polymorphism (SNP) analyses revealed that 12 of the 41 variants were significantly associated with clinically relevant changes in SLAQ scores across time points eight and nine after controlling for multiple testing. Results based on sophisticated causal modeling of longitudinal data in a large patient cohort suggest that individual SLE risk variants may influence disease activity over time. Our findings also emphasize a role for other biological or environmental factors.

  10. Atypical presentations of genital herpes simplex virus in HIV-1 and HIV-2 effectively treated by imiquimod.

    Science.gov (United States)

    McKendry, Anna; Narayana, Srinivasulu; Browne, Rita

    2015-05-01

    Atypical presentations of genital herpes simplex virus have been described in HIV. We report two cases with hypertrophic presentations which were effectively treated with imiquimod, one of which is the first reported case occurring in a patient with HIV-2. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  11. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

    DEFF Research Database (Denmark)

    Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

    2017-01-01

    excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2......Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations......, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were...

  12. Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic

    NARCIS (Netherlands)

    Martinez-Steele, Euridice; Awasana, Akum Aveika; Corrah, Tumani; Sabally, Saihou; van der Sande, Marianne; Jaye, Assan; Togun, Toyin; Sarge-Njie, Ramu; McConkey, Samuel J.; Whittle, Hilton; Schim van der Loeff, Maarten F.

    2007-01-01

    Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections. To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and

  13. Serum capacity to inhibit reverse transcriptase in vitro distinguishes HIV-1 infection from HIV-2 or SIV infection

    NARCIS (Netherlands)

    Wolfs, T. F.; Geelen, J. L.; Schellekens, H.; Barin, F.; Dekker, J. T.; Goudsmit, J.

    1989-01-01

    The inhibition of HIV-1 and SIV reverse transcriptase by human and rhesus macaque serum positive for HIV-1 or HIV-2/SIV antibodies was studied. The domain to which reverse transcriptase-inhibiting antibodies were elicited appeared to be highly antigenic. A total of 67% (48 of 72) of individuals had

  14. Network reconfiguration for loss reduction in electrical distribution system using genetic algorithm

    International Nuclear Information System (INIS)

    Adail, A.S.A.A.

    2012-01-01

    Distribution system is a critical links between the utility and the nuclear installation. During feeding electricity to that installation there are power losses. The quality of the network depends on the reduction of these losses. Distribution system which feeds the nuclear installation must have a higher quality power. For example, in Inshas site, electrical power is supplied to it from two incoming feeders (one from new abu-zabal substation and the other from old abu-zabal substation). Each feeder is designed to carry the full load, while the operator preferred to connect with a new abu-zabal substation, which has a good power quality. Bad power quality affects directly the nuclear reactor and has a negative impact on the installed sensitive equipment's of the operation. The thesis is Studying the electrical losses in a distribution system (causes and effected factors), feeder reconfiguration methods, and applying of genetic algorithm in an electric distribution power system. In the end, this study proposes an optimization technique based on genetic algorithms for distribution network reconfiguration to reduce the network losses to minimum. The proposed method is applied to IEEE test network; that contain 3 feeders and 16 nodes. The technique is applied through two groups, distribution have general loads, and nuclear loads. In the groups the technique applied to seven cases at normal operation state, system fault condition as well as different loads conditions. Simulated results are drawn to show the accuracy of the technique.

  15. Causation of nervous system tumors in children: insights from traditional and genetically engineered animal models

    International Nuclear Information System (INIS)

    Rice, Jerry M.

    2004-01-01

    Pediatric neurogenic tumors include primitive neuroectodermal tumors (PNETs), especially medulloblastoma; ependymomas and choroid plexus papillomas; astrocytomas; retinoblastoma; and sympathetic neuroblastoma. Meningiomas and nerve sheath tumors, although uncommon in childhood, are also significant because they can result from exposures of children to ionizing radiation. Specific chromosomal loci and specific genes are related to each of these tumor types. Virtually all these genes appear to act as tumor suppressor genes, which are inactivated in tumor cells by mutations or by chromosomal loss. In genetically engineered mice, some genes that are clearly associated with specific human tumors (e.g., RB1 in retinoblastoma and NF2 in meningiomas and schwannomas) have no such effect. Other genetic constructs in mice involving the genes p53, ptc1, and Nf1 have produced tumors remarkably similar to some of the human pediatric neoplasms. Some of these tumors become clinically apparent after only a few weeks, while the mice are still juveniles, especially when two or more tumor suppressor genes are inactivated in the same genetic construct. Conversely, at least one genetic pathway in rodents involving point mutation in the coding region of a transforming gene (neu in malignant schwannomas) does not appear to operate in any human tumors. The nervous system is markedly susceptible to experimental carcinogenesis during early life in rodents, dogs, primates, and other nonhuman species, and there is no obvious reason why this generalization should not also apply to humans. However, except for therapeutic ionizing radiation, no physical, chemical, or biological cause of human pediatric nervous system tumors is known. The failure of experimental transplacental carcinogenesis to mirror human pediatric experience more closely may reflect the need for multiple mutational events in target cells, and for experimental carcinogens that are capable of causing the full spectrum of

  16. Genetic algorithm based optimization on modeling and design of hybrid renewable energy systems

    International Nuclear Information System (INIS)

    Ismail, M.S.; Moghavvemi, M.; Mahlia, T.M.I.

    2014-01-01

    Highlights: • Solar data was analyzed in the location under consideration. • A program was developed to simulate operation of the PV hybrid system. • Genetic algorithm was used to optimize the sizes of the hybrid system components. • The costs of the pollutant emissions were considered in the optimization. • It is cost effective to power houses in remote areas with such hybrid systems. - Abstract: A sizing optimization of a hybrid system consisting of photovoltaic (PV) panels, a backup source (microturbine or diesel), and a battery system minimizes the cost of energy production (COE), and a complete design of this optimized system supplying a small community with power in the Palestinian Territories is presented in this paper. A scenario that depends on a standalone PV, and another one that depends on a backup source alone were analyzed in this study. The optimization was achieved via the usage of genetic algorithm. The objective function minimizes the COE while covering the load demand with a specified value for the loss of load probability (LLP). The global warming emissions costs have been taken into account in this optimization analysis. Solar radiation data is firstly analyzed, and the tilt angle of the PV panels is then optimized. It was discovered that powering a small rural community using this hybrid system is cost-effective and extremely beneficial when compared to extending the utility grid to supply these remote areas, or just using conventional sources for this purpose. This hybrid system decreases both operating costs and the emission of pollutants. The hybrid system that realized these optimization purposes is the one constructed from a combination of these sources

  17. Development of Web-Based Menu Planning Support System and its Solution Using Genetic Algorithm

    Science.gov (United States)

    Kashima, Tomoko; Matsumoto, Shimpei; Ishii, Hiroaki

    2009-10-01

    Recently lifestyle-related diseases have become an object of public concern, while at the same time people are being more health conscious. As an essential factor for causing the lifestyle-related diseases, we assume that the knowledge circulation on dietary habits is still insufficient. This paper focuses on everyday meals close to our life and proposes a well-balanced menu planning system as a preventive measure of lifestyle-related diseases. The system is developed by using a Web-based frontend and it provides multi-user services and menu information sharing capabilities like social networking services (SNS). The system is implemented on a Web server running Apache (HTTP server software), MySQL (database management system), and PHP (scripting language for dynamic Web pages). For the menu planning, a genetic algorithm is applied by understanding this problem as multidimensional 0-1 integer programming.

  18. A CRISPR-Cas9 System for Genetic Engineering of Filamentous Fungi

    DEFF Research Database (Denmark)

    Nødvig, Christina Spuur; Nielsen, Jakob Blæsbjerg; Kogle, Martin Engelhard

    2015-01-01

    there is a demand for developing versatile methods that can be used to genetically manipulate non-model filamentous fungi. To facilitate this, we have developed a CRISPR-Cas9 based system adapted for use in filamentous fungi. The system is simple and versatile, as RNA guided mutagenesis can be achieved...... by transforming a target fungus with a single plasmid. The system currently contains four CRISPR- Cas9 vectors, which are equipped with commonly used fungal markers allowing for selection in a broad range of fungi. Moreover, we have developed a script that allows identification of protospacers that target gene...... used our CRISPR Cas9 system to generate a strain that contains an AACU_pyrG marker and demonstrated that the resulting strain can be used for iterative gene targeting....

  19. Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.

    Science.gov (United States)

    Johnson-Tesch, Benjamin A; Gawande, Rakhee S; Zhang, Lei; MacMillan, Margaret L; Nascene, David R

    2017-06-01

    Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (Pcentral nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

  20. Accurate episomal HIV 2-LTR circles quantification using optimized DNA isolation and droplet digital PCR.

    Science.gov (United States)

    Malatinkova, Eva; Kiselinova, Maja; Bonczkowski, Pawel; Trypsteen, Wim; Messiaen, Peter; Vermeire, Jolien; Verhasselt, Bruno; Vervisch, Karen; Vandekerckhove, Linos; De Spiegelaere, Ward

    2014-01-01

    In HIV-infected patients on combination antiretroviral therapy (cART), the detection of episomal HIV 2-LTR circles is a potential marker for ongoing viral replication. Quantification of 2-LTR circles is based on quantitative PCR or more recently on digital PCR assessment, but is hampered due to its low abundance. Sample pre-PCR processing is a critical step for 2-LTR circles quantification, which has not yet been sufficiently evaluated in patient derived samples. We compared two sample processing procedures to more accurately quantify 2-LTR circles using droplet digital PCR (ddPCR). Episomal HIV 2-LTR circles were either isolated by genomic DNA isolation or by a modified plasmid DNA isolation, to separate the small episomal circular DNA from chromosomal DNA. This was performed in a dilution series of HIV-infected cells and HIV-1 infected patient derived samples (n=59). Samples for the plasmid DNA isolation method were spiked with an internal control plasmid. Genomic DNA isolation enables robust 2-LTR circles quantification. However, in the lower ranges of detection, PCR inhibition caused by high genomic DNA load substantially limits the amount of sample input and this impacts sensitivity and accuracy. Moreover, total genomic DNA isolation resulted in a lower recovery of 2-LTR templates per isolate, further reducing its sensitivity. The modified plasmid DNA isolation with a spiked reference for normalization was more accurate in these low ranges compared to genomic DNA isolation. A linear correlation of both methods was observed in the dilution series (R2=0.974) and in the patient derived samples with 2-LTR numbers above 10 copies per million peripheral blood mononuclear cells (PBMCs), (R2=0.671). Furthermore, Bland-Altman analysis revealed an average agreement between the methods within the 27 samples in which 2-LTR circles were detectable with both methods (bias: 0.3875±1.2657 log10). 2-LTR circles quantification in HIV-infected patients proved to be more

  1. Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

    Science.gov (United States)

    Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N.; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J.; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10−4), oral ulcers (P = 6.9×10−4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested. PMID:22194982

  2. Double genetically modified symbiotic system for improved Cu phytostabilization in legume roots.

    Science.gov (United States)

    Pérez-Palacios, Patricia; Romero-Aguilar, Asunción; Delgadillo, Julián; Doukkali, Bouchra; Caviedes, Miguel A; Rodríguez-Llorente, Ignacio D; Pajuelo, Eloísa

    2017-06-01

    Excess copper (Cu) in soils has deleterious effects on plant growth and can pose a risk to human health. In the last decade, legume-rhizobium symbioses became attractive biotechnological tools for metal phytostabilization. For this technique being useful, metal-tolerant symbionts are required, which can be generated through genetic manipulation.In this work, a double symbiotic system was engineered for Cu phytostabilization: On the one hand, composite Medicago truncatula plants expressing the metallothionein gene mt4a from Arabidopsis thaliana in roots were obtained to improve plant Cu tolerance. On the other hand, a genetically modified Ensifer medicae strain, expressing copper resistance genes copAB from Pseudomonas fluorescens driven by a nodulation promoter, nifHp, was used for plant inoculation. Our results indicated that expression of mt4a in composite plants ameliorated plant growth and nodulation and enhanced Cu tolerance. Lower levels of ROS-scavenging enzymes and of thiobarbituric acid reactive substances (TBARS), such as malondialdehyde (a marker of lipid peroxidation), suggested reduced oxidative stress. Furthermore, inoculation with the genetically modified Ensifer further improved root Cu accumulation without altering metal loading to shoots, leading to diminished values of metal translocation from roots to shoots. The double modified partnership is proposed as a suitable tool for Cu rhizo-phytostabilization.

  3. Association of systemic lupus erythematosus clinical features with European population genetic substructure.

    Directory of Open Access Journals (Sweden)

    Elisa Alonso-Perez

    Full Text Available Systemic Lupus Erythematosus (SLE is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10(-4, oral ulcers (P = 6.9×10(-4 and photosensitivity (P = 0.002. Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested.

  4. Association of systemic lupus erythematosus clinical features with European population genetic substructure.

    Science.gov (United States)

    Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J; Gomez-Reino, Juan J; Gonzalez, Antonio

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10(-4)), oral ulcers (P = 6.9×10(-4)) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested.

  5. Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune System.

    Directory of Open Access Journals (Sweden)

    Yael Steuerman

    2016-04-01

    Full Text Available Sequence variation can affect the physiological state of the immune system. Major experimental efforts targeted at understanding the genetic control of the abundance of immune cell subpopulations. However, these studies are typically focused on a limited number of immune cell types, mainly due to the use of relatively low throughput cell-sorting technologies. Here we present an algorithm that can reveal the genetic basis of inter-individual variation in the abundance of immune cell types using only gene expression and genotyping measurements as input. Our algorithm predicts the abundance of immune cell subpopulations based on the RNA levels of informative marker genes within a complex tissue, and then provides the genetic control on these predicted immune traits as output. A key feature of the approach is the integration of predictions from various sets of marker genes and refinement of these sets to avoid spurious signals. Our evaluation of both synthetic and real biological data shows the significant benefits of the new approach. Our method, VoCAL, is implemented in the freely available R package ComICS.

  6. Males and females contribute unequally to offspring genetic diversity in the polygynandrous mating system of wild boar.

    Directory of Open Access Journals (Sweden)

    Javier Pérez-González

    Full Text Available The maintenance of genetic diversity across generations depends on both the number of reproducing males and females. Variance in reproductive success, multiple paternity and litter size can all affect the relative contributions of male and female parents to genetic variation of progeny. The mating system of the wild boar (Sus scrofa has been described as polygynous, although evidence of multiple paternity in litters has been found. Using 14 microsatellite markers, we evaluated the contribution of males and females to genetic variation in the next generation in independent wild boar populations from the Iberian Peninsula and Hungary. Genetic contributions of males and females were obtained by distinguishing the paternal and maternal genetic component inherited by the progeny. We found that the paternally inherited genetic component of progeny was more diverse than the maternally inherited component. Simulations showed that this finding might be due to a sampling bias. However, after controlling for the bias by fitting both the genetic diversity in the adult population and the number of reproductive individuals in the models, paternally inherited genotypes remained more diverse than those inherited maternally. Our results suggest new insights into how promiscuous mating systems can help maintain genetic variation.

  7. Seeding-inspired chemotaxis genetic algorithm for the inference of biological systems.

    Science.gov (United States)

    Wu, Shinq-Jen; Wu, Cheng-Tao

    2014-09-18

    A large challenge in the post-genomic era is to obtain the quantitatively dynamic interactive information of the important constitutes of underlying systems. The S-system is a dynamic and structurally rich model that determines the net strength of interactions between genes and/or proteins. Good generation characteristics without the need for prior information have allowed S-systems to become one of the most promising canonical models. Various evolutionary computation technologies have recently been developed for the identification of system parameters and skeletal-network structures. However, the gaps between the truncated and preserved terms remain too small. Additionally, current research methods fail to identify the structures of high dimensional systems (e.g., 30 genes with 1800 connections). Optimization technologies should converge fast and have the ability to adaptively adjust the search. In this study, we propose a seeding-inspired chemotaxis genetic algorithm (SCGA) that can force evolution to adjust the population movement to identify a favorable location. The seeding-inspired training strategy is a method to achieve optimal results with limited resources. SCGA introduces seeding-inspired genetic operations to allow a population to possess competitive power (exploitation and exploration) and a winner-chemotaxis-induced population migration to force a population to repeatedly tumble away from an attractor and swim toward another attractor. SCGA was tested on several canonical biological systems. SCGA not only learned the correct structure within only one to three pruning steps but also ensures pruning safety. The values of the truncated terms were all smaller than 10 -14 , even for a thirty-gene system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Optimization of fog inlet air cooling system for combined cycle power plants using genetic algorithm

    International Nuclear Information System (INIS)

    Ehyaei, Mehdi A.; Tahani, Mojtaba; Ahmadi, Pouria; Esfandiari, Mohammad

    2015-01-01

    In this research paper, a comprehensive thermodynamic modeling of a combined cycle power plant is first conducted and the effects of gas turbine inlet fogging system on the first and second law efficiencies and net power outputs of combined cycle power plants are investigated. The combined cycle power plant (CCPP) considered for this study consist of a double pressure heat recovery steam generator (HRSG) to utilize the energy of exhaust leaving the gas turbine and produce superheated steam to generate electricity in the Rankine cycle. In order to enhance understanding of this research and come up with optimum performance assessment of the plant, a complete optimization is using a genetic algorithm conducted. In order to achieve this goal, a new objective function is defined for the system optimization including social cost of air pollution for the power generation systems. The objective function is based on the first law efficiency, energy cost and the external social cost of air pollution for an operational system. It is concluded that using inlet air cooling system for the CCPP system and its optimization results in an increase in the average output power, first and second law efficiencies by 17.24%, 3.6% and 3.5%, respectively, for three warm months of year. - Highlights: • To model the combined cycle power plant equipped with fog inlet air cooling method. • To conduct both exergy and economic analyses for better understanding. • To conduct a complete optimization using a genetic algorithm to determine the optimal design parameters of the system

  9. Exergoeconomic analysis and optimization of an Integrated Solar Combined Cycle System (ISCCS) using genetic algorithm

    International Nuclear Information System (INIS)

    Baghernejad, A.; Yaghoubi, M.

    2011-01-01

    Research highlights: → We applied thermoeconomic concept for optimization of an Integrated Solar Combined Cycle System (ISCCS) using genetic algorithm. → Optimization process improves the total performance of the system in a way that the objective function is decreased by 10.98%, the exergetic efficiency of the system is increased from about 43.79% to 46.8% and the rate of fuel cost is decreased by 7.23%. → Cost of electricity produced by steam turbine and gas turbine in the optimum design condition of the ISCCS are about 7.1% and 1.17% lower with respect to the base case. → Increasing solar field operation periods from 1000 to 2000 hours per year reduces the unit cost of electricity produced by steam turbine about 14%. → The unit cost of electricity has a linear and remarkable increase with fuel cost. Also by increasing the system construction period from 3 to 6 years, the unit cost of electricity produced by steam turbine increased about 13%. -- Abstract: In this study, thermoeconomic concept is applied using genetic algorithm for optimization of an Integrated Solar Combined Cycle System (ISCCS) that produces 400 MW of electricity. Attempt is made to minimize objective function including investment cost of equipments and cost of exergy destruction. Optimization process carried out by using exergoeconomic principles and genetic algorithm. The developed code first validated with a thermal system and good comparison is observed. Then the analysis is made for the ISCCS, and it shows that objective function for the optimum operation reduced by about 11%. Also cost of electricity produced by steam turbine and gas turbine in the optimum design of the ISCCS are about 7.1% and 1.17% lower with respect to the base case. These objectives are achieved with 13.3% increase in capital investment. Finally, sensitivity analysis is carried out to study the effect of changes in the unit cost of electricity for the system important parameters such as interest rate, plant

  10. Genetic prion disease: no role for the immune system in disease pathogenesis?

    Science.gov (United States)

    Friedman-Levi, Yael; Binyamin, Orli; Frid, Kati; Ovadia, Haim; Gabizon, Ruth

    2014-08-01

    Prion diseases, which can manifest by transmissible, sporadic or genetic etiologies, share several common features, such as a fatal neurodegenerative outcome and the aberrant accumulation of proteinase K (PK)-resistant PrP forms in the CNS. In infectious prion diseases, such as scrapie in mice, prions first replicate in immune organs, then invade the CNS via ascending peripheral tracts, finally causing death. Accelerated neuroinvasion and death occurs when activated prion-infected immune cells infiltrate into the CNS, as is the case for scrapie-infected mice induced for experimental autoimmune encephalomyelitis (EAE), a CNS inflammatory insult. To establish whether the immune system plays such a central role also in genetic prion diseases, we induced EAE in TgMHu2ME199K mice, a line mimicking for late onset genetic Creutzfeldt Jacob disease (gCJD), a human prion disease. We show here that EAE induction of TgMHu2ME199K mice neither accelerated nor aggravated prion disease manifestation. Concomitantly, we present evidence that PK-resistant PrP forms were absent from CNS immune infiltrates, and most surprisingly also from lymph nodes and spleens of TgMHu2ME199K mice at all ages and stages of disease. These results imply that the mechanism of genetic prion disease differs widely from that of the infectious presentation, and that the conversion of mutant PrPs into PK resistant forms occurs mostly/only in the CNS. If the absence of pathogenic PrP forms form immune organs is also true for gCJD patients, it may suggest their blood is devoid of prion infectivity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Genetic patterns in European geometrid moths revealed by the Barcode Index Number (BIN system.

    Directory of Open Access Journals (Sweden)

    Axel Hausmann

    Full Text Available BACKGROUND: The geometrid moths of Europe are one of the best investigated insect groups in traditional taxonomy making them an ideal model group to test the accuracy of the Barcode Index Number (BIN system of BOLD (Barcode of Life Datasystems, a method that supports automated, rapid species delineation and identification. METHODOLOGY/PRINCIPAL FINDINGS: This study provides a DNA barcode library for 219 of the 249 European geometrid moth species (88% in five selected subfamilies. The data set includes COI sequences for 2130 specimens. Most species (93% were found to possess diagnostic barcode sequences at the European level while only three species pairs (3% were genetically indistinguishable in areas of sympatry. As a consequence, 97% of the European species we examined were unequivocally discriminated by barcodes within their natural areas of distribution. We found a 1:1 correspondence between BINs and traditionally recognized species for 67% of these species. Another 17% of the species (15 pairs, three triads shared BINs, while specimens from the remaining species (18% were divided among two or more BINs. Five of these species are mixtures, both sharing and splitting BINs. For 82% of the species with two or more BINs, the genetic splits involved allopatric populations, many of which have previously been hypothesized to represent distinct species or subspecies. CONCLUSIONS/SIGNIFICANCE: This study confirms the effectiveness of DNA barcoding as a tool for species identification and illustrates the potential of the BIN system to characterize formal genetic units independently of an existing classification. This suggests the system can be used to efficiently assess the biodiversity of large, poorly known assemblages of organisms. For the moths examined in this study, cases of discordance between traditionally recognized species and BINs arose from several causes including overlooked species, synonymy, and cases where DNA barcodes revealed

  12. Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders

    Science.gov (United States)

    Coleman, Jonathan R. I.; Roberts, Susanna; Keers, Robert; Breen, Gerome; Bögels, Susan; Creswell, Cathy; Hudson, Jennifer L.; McKinnon, Anna; Nauta, Maaike; Rapee, Ronald M.; Schneider, Silvia; Silverman, Wendy K.; Thastum, Mikael; Waite, Polly; Wergeland, Gro Janne H.; Eley, Thalia C.

    2016-01-01

    Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re‐emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre‐ and post‐treatment and during the follow‐up period in the full sample and a subset with fear‐based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow‐up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear‐based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27346075

  13. Optimization of cascade hydropower system operation by genetic algorithm to maximize clean energy output

    Directory of Open Access Journals (Sweden)

    Aida Tayebiyan

    2016-06-01

    Full Text Available Background: Several reservoir systems have been constructed for hydropower generation around the world. Hydropower offers an economical source of electricity with reduce carbon emissions. Therefore, it is such a clean and renewable source of energy. Reservoirs that generate hydropower are typically operated with the goal of maximizing energy revenue. Yet, reservoir systems are inefficiently operated and manage according to policies determined at the construction time. It is worth noting that with little enhancement in operation of reservoir system, there could be an increase in efficiency of the scheme for many consumers. Methods: This research develops simulation-optimization models that reflect discrete hedging policy (DHP to manage and operate hydropower reservoir system and analyse it in both single and multireservoir system. Accordingly, three operational models (2 single reservoir systems and 1 multi-reservoir system were constructed and optimized by genetic algorithm (GA. Maximizing the total power generation in horizontal time is chosen as an objective function in order to improve the functional efficiency in hydropower production with consideration to operational and physical limitations. The constructed models, which is a cascade hydropower reservoirs system have been tested and evaluated in the Cameron Highland and Batang Padang in Malaysia. Results: According to the given results, usage of DHP for hydropower reservoir system operation could increase the power generation output to nearly 13% in the studied reservoir system compared to present operating policy (TNB operation. This substantial increase in power production will enhance economic development. Moreover, the given results of single and multi-reservoir systems affirmed that hedging policy could manage the single system much better than operation of the multi-reservoir system. Conclusion: It can be summarized that DHP is an efficient and feasible policy, which could be used

  14. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    DEFF Research Database (Denmark)

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

    2012-01-01

    gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c). We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion......, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification...

  15. Safety passive system in designing reduced scale of a PWR by genetic algorithm

    International Nuclear Information System (INIS)

    Cunha, Joao J. da; Alvim, Antonio Carlos M.; Lapa, Celso Marcelo Franklin

    2005-01-01

    This paper presents the concept 'Designing by Genetic Algorithms (DbyGA)' applied on a new reduced scale system problem. The designing problem of a passive safety thermal-hydraulic system, considering dimensional and operational constraints, has been solved. Take account the passive safety characteristics of the last nuclear reactor generation, a PWR core under natural circulation is used in order to demonstrate the methodology applicability. The results revealed that some solutions (reduced scale system DbyGA) are capable of reproducing, both accurately and simultaneously, many of the physical phenomena that occur in real scale and operating conditions. However the results showed, in the non-trivial flow patterns simulation case study, some deficiencies in the DbyGA approach. These aspects revel important methodological possibilities to DbyGA performance improvement. (author)

  16. Multi-Objective Optimization Design for a Hybrid Energy System Using the Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Myeong Jin Ko

    2015-04-01

    Full Text Available To secure a stable energy supply and bring renewable energy to buildings within a reasonable cost range, a hybrid energy system (HES that integrates both fossil fuel energy systems (FFESs and new and renewable energy systems (NRESs needs to be designed and applied. This paper presents a methodology to optimize a HES consisting of three types of NRESs and six types of FFESs while simultaneously minimizing life cycle cost (LCC, maximizing penetration of renewable energy and minimizing annual greenhouse gas (GHG emissions. An elitist non-dominated sorting genetic algorithm is utilized for multi-objective optimization. As an example, we have designed the optimal configuration and sizing for a HES in an elementary school. The evolution of Pareto-optimal solutions according to the variation in the economic, technical and environmental objective functions through generations is discussed. The pair wise trade-offs among the three objectives are also examined.

  17. Antiviral activities of extracts of Euphorbia hirta L. against HIV-1, HIV-2 and SIVmac251.

    Science.gov (United States)

    Gyuris, Agnes; Szlávik, László; Minárovits, János; Vasas, Andrea; Molnár, Joseph; Hohmann, Judit

    2009-01-01

    The antiretroviral activities of extracts of Euphorbia hirta were investigated in vitro on the MT4 human T lymphocyte cell line. The cytotoxicities of the extracts were tested by means of the MTT cell proliferation assay, and then the direct effects of the aqueous extract on HIV-1, HIV-2 and SIV(mac251) reverse transcriptase (RT) activity were determined. A dose-dependent inhibition of RT activity was observed for all three viruses. The HIV-1 inhibitory potency of E. hirta was studied further, and the activities of the aqueous and 50% methanolic extracts were compared. The 50% methanolic extract was found to exert a higher antiretroviral effect than that of the aqueous extract. The 50% MeOH extract was subjected to liquid-liquid partition with dichloromethane, ethyl acetate and water. Only the remaining aqueous phase exhibited significant antiviral activity; all the lipophilic extracts appeared to be inactive. After removal of the tannins from the aqueous extract, the viral replication inhibitory effect was markedly decreased, and it was therefore concluded that tannins are most probably responsible for the high antiretroviral activity.

  18. Genetic evaluation of the mating system in the blue-and-yellow macaw (Ara ararauna, Aves, Psittacidae by DNA fingerprinting

    Directory of Open Access Journals (Sweden)

    Renato Caparroz

    2011-01-01

    Full Text Available More than 90% of birds are socially monogamous, although genetic studies indicate that many are often not sexually monogamous. In the present study, DNA fingerprinting was used to estimate the genetic relationships between nestlings belonging to the same broods to evaluate the mating system in the socially monogamous macaw, Ara ararauna. We found that in 10 of 11 broods investigated, the nestlings showed genetic similarity levels congruent with values expected among full-sibs, suggesting that they shared the same parents. However, in one brood, the low genetic similarity observed between nestlings could be a result of intraspecific brood parasitism, intraspecific nest competition or extra-pair paternity. These results, along with available behavioral and life-history data, imply that the blue-and-yellow macaw is not only socially, but also genetically monogamous. However, the occurrence of eventual cases of extra-pair paternity cannot be excluded.

  19. Felling-system and regeneration of pine forests on ecological-genetic-geographical basis

    Directory of Open Access Journals (Sweden)

    S. N. Sannikov

    2015-12-01

    Full Text Available A conception of the adaptation of Scots pine populations to the natural regeneration on open sites with the mosaic retained stand and mineralized soil surface on the basis of the ecological-genetic-geographical investigations in the forests of the Russia and the theory of petropsammofitness-pyrofitness (Sannikov S. N., 1983 has been substantiated. The methods of clear cuts with the seeding from surrounding forest, seed curtains and sufficiently extent of the substrate preparation for the pine selfsown have been selected and elaborated as a main organization principle of the system «felling-regeneration» in the plains pine forests of the forest zone. High regeneration efficiency of this system with the application of original aggregate for the optimal mineralization of the soil substrate (with its synchronous loosing has been shown on the example of dominating pine forest types in the subzone for-forest-steppe of the Western Siberia. The silvicultural-ecological and reproductive-genetic advantages of retaining seed curtains instead of separate seed trees have been substantiated. The basic parameters of the system «felling-regeneration», which guarantee a sufficient success of the following pine regeneration in the for-forest-steppe subzone, have been determined with the help of the methods of the mathematical imitation modeling of the pine selfsown density depending on the area and localization of seed curtains, surrounding forest and the extent of the substrate mineralization. The zonal differentiated system of the fellings and measures for the regeneration optimization in the climatically substituting pine forest types in the Western Siberia has been elaborated according to the parameters, studied earlier, on the ecological-genetic-geographical basis. The principles of this system in forest zone come to the clear strip-fellings with insemination of cuts from the seed curtains and forest walls, and to the hollow-fellings with the

  20. Bayesian network reconstruction using systems genetics data: comparison of MCMC methods.

    Science.gov (United States)

    Tasaki, Shinya; Sauerwine, Ben; Hoff, Bruce; Toyoshiba, Hiroyoshi; Gaiteri, Chris; Chaibub Neto, Elias

    2015-04-01

    Reconstructing biological networks using high-throughput technologies has the potential to produce condition-specific interactomes. But are these reconstructed networks a reliable source of biological interactions? Do some network inference methods offer dramatically improved performance on certain types of networks? To facilitate the use of network inference methods in systems biology, we report a large-scale simulation study comparing the ability of Markov chain Monte Carlo (MCMC) samplers to reverse engineer Bayesian networks. The MCMC samplers we investigated included foundational and state-of-the-art Metropolis-Hastings and Gibbs sampling approaches, as well as novel samplers we have designed. To enable a comprehensive comparison, we simulated gene expression and genetics data from known network structures under a range of biologically plausible scenarios. We examine the overall quality of network inference via different methods, as well as how their performance is affected by network characteristics. Our simulations reveal that network size, edge density, and strength of gene-to-gene signaling are major parameters that differentiate the performance of various samplers. Specifically, more recent samplers including our novel methods outperform traditional samplers for highly interconnected large networks with strong gene-to-gene signaling. Our newly developed samplers show comparable or superior performance to the top existing methods. Moreover, this performance gain is strongest in networks with biologically oriented topology, which indicates that our novel samplers are suitable for inferring biological networks. The performance of MCMC samplers in this simulation framework can guide the choice of methods for network reconstruction using systems genetics data. Copyright © 2015 by the Genetics Society of America.

  1. Constructing a fuzzy rule-based system using the ILFN network and Genetic Algorithm.

    Science.gov (United States)

    Yen, G G; Meesad, P

    2001-10-01

    In this paper, a method for automatic construction of a fuzzy rule-based system from numerical data using the Incremental Learning Fuzzy Neural (ILFN) network and the Genetic Algorithm is presented. The ILFN network was developed for pattern classification applications. The ILFN network, which employed fuzzy sets and neural network theory, equips with a fast, one-pass, on-line, and incremental learning algorithm. After trained, the ILFN network stored numerical knowledge in hidden units, which can then be directly interpreted into if then rule bases. However, the rules extracted from the ILFN network are not in an optimized fuzzy linguistic form. In this paper, a knowledge base for fuzzy expert system is extracted from the hidden units of the ILFN classifier. A genetic algorithm is then invoked, in an iterative manner, to reduce number of rules and select only discriminate features from input patterns needed to provide a fuzzy rule-based system. Three computer simulations using a simulated 2-D 3-class data, the well-known Fisher's Iris data set, and the Wisconsin breast cancer data set were performed. The fuzzy rule-based system derived from the proposed method achieved 100% and 97.33% correct classification on the 75 patterns for training set and 75 patterns for test set, respectively. For the Wisconsin breast cancer data set, using 400 patterns for training and 299 patterns for testing, the derived fuzzy rule-based system achieved 99.5% and 98.33% correct classification on the training set and the test set, respectively.

  2. A Double-Deck Elevator Group Supervisory Control System with Destination Floor Guidance System Using Genetic Network Programming

    Science.gov (United States)

    Yu, Lu; Zhou, Jin; Mabu, Shingo; Hirasawa, Kotaro; Hu, Jinglu; Markon, Sandor

    The Elevator Group Supervisory Control Systems (EGSCS) are the control systems that systematically manage three or more elevators in order to efficiently transport the passengers in buildings. Double-deck elevators, where two elevators are connected with each other, serve passengers at two consecutive floors simultaneously. Double-deck Elevator systems (DDES) become more complex in their behavior than conventional single-deck elevator systems (SDES). Recently, Artificial Intelligence (AI) technology has been used in such complex systems. Genetic Network Programming (GNP), a graph-based evolutionary method, has been applied to EGSCS and its advantages are shown in some papers. GNP can obtain the strategy of a new hall call assignment to the optimal elevator when it performs crossover and mutation operations to judgment nodes and processing nodes. Meanwhile, Destination Floor Guidance System (DFGS) is installed in DDES, so that passengers can also input their destinations at elevator halls. In this paper, we have applied GNP to DDES and compared DFGS with normal systems. The waiting time and traveling time of DFGS are all improved because of getting more information from DFGS. The simulations showed the effectiveness of the double-deck elevators with DFGS in different building traffics.

  3. Control of type III protein secretion using a minimal genetic system.

    Science.gov (United States)

    Song, Miryoung; Sukovich, David J; Ciccarelli, Luciano; Mayr, Julia; Fernandez-Rodriguez, Jesus; Mirsky, Ethan A; Tucker, Alex C; Gordon, D Benjamin; Marlovits, Thomas C; Voigt, Christopher A

    2017-05-09

    Gram-negative bacteria secrete proteins using a type III secretion system (T3SS), which functions as a needle-like molecular machine. The many proteins involved in T3SS construction are tightly regulated due to its role in pathogenesis and motility. Here, starting with the 35 kb Salmonella pathogenicity island 1 (SPI-1), we eliminated internal regulation and simplified the genetics by removing or recoding genes, scrambling gene order and replacing all non-coding DNA with synthetic genetic parts. This process results in a 16 kb cluster that shares no sequence identity, regulation or organizational principles with SPI-1. Building this simplified system led to the discovery of essential roles for an internal start site (SpaO) and small RNA (InvR). Further, it can be controlled using synthetic regulatory circuits, including under SPI-1 repressing conditions. This work reveals an incredible post-transcriptional robustness in T3SS assembly and aids its control as a tool in biotechnology.

  4. Sugarcane production under smallholder farming systems: Farmers preferred traits, constraints and genetic resources

    Directory of Open Access Journals (Sweden)

    Esayas Tena

    2016-05-01

    Full Text Available Smallholder sugarcane production sector is under researched and underdeveloped with limited industrial link and support. The objectives of this study were to assess the current state of sugarcane production, farmers’ perceived production constraints and preferred traits, and to collect germplasm grown by smallholder farmers in southern Ethiopia for strategic breeding and conservation. The study was conducted across 16 administrative zones, 28 districts and 56 peasant associations involving 560 smallholder sugarcane growers in southern Ethiopia using a participatory rural appraisal (PRA approach. Sugarcane genetic resources were collected through structured sampling. Findings from this study indicated that monocropping was identified as the predominant sugarcane farming system. Respondent farmers prioritized drought tolerance (21%, increased cane yield (20%, early maturity (18%, marketability (17%, and high biomass (14% as the top preferred traits of sugarcane. Ninety diverse sugarcane landraces were collected from homesteads of smallholder farmers. Findings from this study would serve as baseline information towards sugarcane research and development emphasising the constraints and preferences of smallholder sugarcane growers in Ethiopia or similar agro-ecologies. This is the first study to report farmers preferred traits and constraints, and genetic resources of sugarcane under smallholder farming systems in Ethiopia.

  5. A genetic-based neuro-fuzzy approach for modeling and control of dynamical systems.

    Science.gov (United States)

    Farag, W A; Quintana, V H; Lambert-Torres, G

    1998-01-01

    Linguistic modeling of complex irregular systems constitutes the heart of many control and decision making systems, and fuzzy logic represents one of the most effective algorithms to build such linguistic models. In this paper, a linguistic (qualitative) modeling approach is proposed. The approach combines the merits of the fuzzy logic theory, neural networks, and genetic algorithms (GA's). The proposed model is presented in a fuzzy-neural network (FNN) form which can handle both quantitative (numerical) and qualitative (linguistic) knowledge. The learning algorithm of an FNN is composed of three phases. The first phase is used to find the initial membership functions of the fuzzy model. In the second phase, a new algorithm is developed and used to extract the linguistic-fuzzy rules. In the third phase, a multiresolutional dynamic genetic algorithm (MRD-GA) is proposed and used for optimized tuning of membership functions of the proposed model. Two well-known benchmarks are used to evaluate the performance of the proposed modeling approach, and compare it with other modeling approaches.

  6. Optimization of spatial light distribution through genetic algorithms for vision systems applied to quality control

    International Nuclear Information System (INIS)

    Castellini, P; Cecchini, S; Stroppa, L; Paone, N

    2015-01-01

    The paper presents an adaptive illumination system for image quality enhancement in vision-based quality control systems. In particular, a spatial modulation of illumination intensity is proposed in order to improve image quality, thus compensating for different target scattering properties, local reflections and fluctuations of ambient light. The desired spatial modulation of illumination is obtained by a digital light projector, used to illuminate the scene with an arbitrary spatial distribution of light intensity, designed to improve feature extraction in the region of interest. The spatial distribution of illumination is optimized by running a genetic algorithm. An image quality estimator is used to close the feedback loop and to stop iterations once the desired image quality is reached. The technique proves particularly valuable for optimizing the spatial illumination distribution in the region of interest, with the remarkable capability of the genetic algorithm to adapt the light distribution to very different target reflectivity and ambient conditions. The final objective of the proposed technique is the improvement of the matching score in the recognition of parts through matching algorithms, hence of the diagnosis of machine vision-based quality inspections. The procedure has been validated both by a numerical model and by an experimental test, referring to a significant problem of quality control for the washing machine manufacturing industry: the recognition of a metallic clamp. Its applicability to other domains is also presented, specifically for the visual inspection of shoes with retro-reflective tape and T-shirts with paillettes. (paper)

  7. Apparatus, System and Method for Fast Detection of Genetic Information by PCR in an Interchangeable Chip

    KAUST Repository

    Wen, Weijia

    2011-03-03

    A polymerase chain reaction (PCR) device for fast amplification and detection of DNA includes an interchangeable PCR chamber, a temperature control component, and an optical detection system. The DNA amplification is performed on an interchangeable chip with volumes as small as 1.25 µl, while the heating and cooling rate may be as fast as 12.7 °C/second ensuring that the total time needed of only 25 minutes to complete the 35 cycle PCR amplification. The PCR may be performed according to a two-temperature approach for denaturing and annealing (Td and Ta) of DNA with the PCR chip, with which the amplification of male-specific SRY gene marker by utilizing raw saliva may be achieved. The genetic identification may be in-situ detected after PCR by the optical detection system.

  8. Genetic and epigenetic control of gene expression by CRISPR–Cas systems

    Science.gov (United States)

    Lo, Albert; Qi, Lei

    2017-01-01

    The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems has revolutionized the way researchers edit genomes. Engineering of catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas]) combined with transcriptional repressors, activators, or epigenetic modifiers enable sequence-specific regulation of gene expression and chromatin state. These CRISPR–Cas-based technologies have contributed to the rapid development of disease models and functional genomics screening approaches, which can facilitate genetic target identification and drug discovery. In this short review, we will cover recent advances of CRISPR–dCas9 systems and their use for transcriptional repression and activation, epigenome editing, and engineered synthetic circuits for complex control of the mammalian genome. PMID:28649363

  9. Optimization of Electrical System for Offshore Wind Farms via a Genetic Algorithm Approach

    DEFF Research Database (Denmark)

    Zhao, Menghua

    Offshore wind farms seem to be more attractive than onshore farms. However, offshore wind farms cost more money than onshore wind farms in both installation and maintenance. Due to the fast development of power electronics, more kinds of configurations of offshore wind farm are possible, which lead...... to very different costs, system reliability, power quality, and power losses etc. Therefore, the optimization of electrical system design for offshore wind farms becomes more and more necessary. There are two tasks in this project: 1) the first one is to construct an algorithm for finding the capacity......, and the LTC limitation of transformers, the power generation limits and the voltage operation range are considered as the constraints. The optimization method combined with probabilistic analysis is used to obtain the capacity of a given wind farm site. The OES-OWF is approached by Genetic Algorithm (GA...

  10. Application of genetic algorithms to integrated optimization of safety system availability

    International Nuclear Information System (INIS)

    Damaso, Vinicius Correa; Pereira, Claudio M.N.A.; Melo, Paulo F.F. Frutuoso e

    2005-01-01

    Experience gained on systems design, operation, and maintenance, with the increasing degree of complexity, and the growth of computational processing capacity, makes it possible the development of integrated optimization techniques, which take into account the interaction of all involved phases in systems operation. However, such a broad approach, which describes in an integrated way, the involved factors, from the conception of the structure to maintenance policies, makes the problem more complex. Generally, the original problem is cast into a simpler one, by imposing some degree of linearity, which allows for a more conventional treatment. The effect of this linear approach is a sensible increase in the number of variables and constraints to be treated. Another shortcoming is related to the fact that as long as the description of some parameters is allowed to undergo modifications, the resulting model becomes less realistic. This paper presents an integrated optimization method of system performance based on genetic algorithms. The aim is to maximize the benefits from operating a simplified system, where different features, like the structure itself, its design, reliability, redundancy allocation, test and maintenance actions scheduling, and costs, are simultaneously taken into account in an integrated way. The availability model treats the original problem without performing any transformation. The set of solutions generated allows a decision-making support for which budgetary and safety constraints must be considered. The results show that the integrated approach used for optimizing the system is much more convenient and should be applied to more complex systems. (author)

  11. Impact of HIV-1, HIV-2, and HIV-1+2 dual infection on the outcome of tuberculosis.

    Science.gov (United States)

    Wejse, C; Patsche, C B; Kühle, A; Bamba, F J V; Mendes, M S; Lemvik, G; Gomes, V F; Rudolf, F

    2015-03-01

    HIV-1 infection has been shown to impact the outcome of patients with tuberculosis (TB), but data regarding the impact of HIV-2 on TB outcomes are limited. The aim of this study was to assess the impact of HIV types on mortality among TB patients in Guinea-Bissau and to examine the predictive ability of the TBscoreII, a clinical score used to assess disease severity. In a prospective follow-up study, we examined the prevalence of HIV-1, HIV-2, and HIV-1+2 co-infection in TB patients in Guinea-Bissau, and the impact on outcomes at 12 months of follow-up. We included all adult TB patients in an observational TB cohort at the Bandim Health Project (BHP) in Guinea-Bissau between 2003 and 2013 and assessed survival status at 12 months after the start of treatment. A total 1312 patients were included; 499 (38%) were female (male/female ratio 1.6). Three hundred and seventy-nine patients were HIV-infected: 241 had HIV-1, 93 had HIV-2, and 45 were HIV-1+2 dual infected. The HIV type-associated risk of TB was 6-fold higher for HIV-1, 7-fold higher for HIV-1+2 dual infection, and 2-fold higher for HIV-2 compared with the HIV-uninfected. Of the patients included, 144 (11%) died, 62 (12%) among females and 82 (9%) among males (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.64-1.30; p=0.596). Compared to male patients, female patients were younger (1 year younger, 95% CI 0.5-2; p=0.04), reported a longer duration of symptoms (14 days longer, 95% CI 4-25; p=0.003), and had a higher TBscoreII (0.5 points more, 95% CI 0.3-0.7; pHIV-infected (36% vs. 25%; pHIV infection increased the mortality risk, with HIV-1 infection displaying the highest HR (5.0, 95% CI 3.5-7.1), followed by HIV-1+2 (HR 4.2, 95% CI 2.2-7.8) and HIV-2 (HR 2.1, 95% CI 1.2-3.8). A TBscoreII ≥4 was associated with increased mortality (HR 2.2, 95% CI 1.5-3.1). Significantly increased HRs were found for signs of wasting; a BMI HIV type-associated risk of TB was much higher for HIV-1 patients and higher but

  12. Testing a model for the genetic structure of personality: a comparison of the personality systems of Cloninger and Eysenck.

    Science.gov (United States)

    Heath, A C; Cloninger, C R; Martin, N G

    1994-04-01

    Genetic analysis of data from 2,680 adult Australian twin pairs demonstrated significant genetic contributions to variation in scores on the Harm Avoidance, Novelty Seeking, and Reward Dependence scales of Cloninger's Tridimensional Personality Questionnaire (TPQ), accounting for between 54% and 61% of the stable variation in these traits. Multivariate genetic triangular decomposition models were fitted to determine the extent to which the TPQ assesses the same dimensions of heritable variation as the revised Eysenck Personality Questionnaire. These analyses demonstrated that the personality systems of Eysenck and Cloninger are not simply alternative descriptions of the same dimensions of personality, but rather each provide incomplete descriptions of the structure of heritable personality differences.

  13. Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

    Energy Technology Data Exchange (ETDEWEB)

    Johnson-Tesch, Benjamin A. [University of Minnesota, Department of Radiology, Minneapolis, MN (United States); Gawande, Rakhee S.; Nascene, David R. [University of Minnesota, Department of Radiology, Neuroradiology Section, Minneapolis, MN (United States); Zhang, Lei [University of Minnesota, Biostatistical Design and Analysis Centre, Minneapolis, MN (United States); MacMillan, Margaret L. [University of Minnesota, Blood and Marrow Transplant Program, Department of Pediatrics, Minneapolis, MN (United States)

    2017-06-15

    Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations. (orig.)

  14. Genetic reporter system for positioning of proteins at the bacterial pole.

    Science.gov (United States)

    Fixen, Kathryn R; Janakiraman, Anuradha; Garrity, Sean; Slade, Daniel J; Gray, Andrew N; Karahan, Nilay; Hochschild, Ann; Goldberg, Marcia B

    2012-01-01

    Spatial organization within bacteria is fundamental to many cellular processes, although the basic mechanisms underlying localization of proteins to specific sites within bacteria are poorly understood. The study of protein positioning has been limited by a paucity of methods that allow rapid large-scale screening for mutants in which protein positioning is altered. We developed a genetic reporter system for protein localization to the pole within the bacterial cytoplasm that allows saturation screening for mutants in Escherichia coli in which protein localization is altered. Utilizing this system, we identify proteins required for proper positioning of the Shigella autotransporter IcsA. Autotransporters, widely distributed bacterial virulence proteins, are secreted at the bacterial pole. We show that the conserved cell division protein FtsQ is required for localization of IcsA and other autotransporters to the pole. We demonstrate further that this system can be applied to the study of proteins other than autotransporters that display polar positioning within bacterial cells. Many proteins localize to specific sites within bacterial cells, and localization to these sites is frequently critical to proper protein function. The mechanisms that underlie protein localization are incompletely understood, in part because of the paucity of methods that allow saturation screening for mutants in which protein localization is altered. We developed a genetic reporter assay that enables screening of bacterial populations for changes in localization of proteins to the bacterial pole, and we demonstrate the utility of the system in identifying factors required for proper localization of the polar Shigella autotransporter protein IcsA. Using this method, we identify the conserved cell division protein FtsQ as being required for positioning of IcsA to the bacterial pole. We demonstrate further that the requirement for FtsQ for polar positioning applies to other autotransporters

  15. Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

    International Nuclear Information System (INIS)

    Johnson-Tesch, Benjamin A.; Gawande, Rakhee S.; Nascene, David R.; Zhang, Lei; MacMillan, Margaret L.

    2017-01-01

    Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations. (orig.)

  16. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    OpenAIRE

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-01-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tes...

  17. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy.

    Directory of Open Access Journals (Sweden)

    Ammar Al-Chalabi

    Full Text Available BACKGROUND: Multiple system atrophy (MSA is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. Pathogenic mechanisms remain obscure but the neuropathological hallmark is the presence of alpha-synuclein-immunoreactive glial cytoplasmic inclusions. Genetic variants of the alpha-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson's disease has identified association of a SNP in SNCA with MSA. METHODOLOGY/FINDINGS: We evaluated 32 SNPs in the SNCA gene in a European population of 239 cases and 617 controls recruited as part of the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS study. We used 161 independently collected samples for replication. Two SNCA SNPs showed association with MSA: rs3822086 (P = 0.0044, and rs3775444 (P = 0.012, although only the first survived correction for multiple testing. In the MSA-C subgroup the association strengthened despite more than halving the number of cases: rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3-3.6; rs3775444 P = 0.0017, OR 4.386 (95% CI 1.6-11.7. A 7-SNP haplotype incorporating three SNPs either side of rs3822086 strengthened the association with MSA-C further (best haplotype, P = 8.7 x 10(-4. The association with rs3822086 was replicated in the independent samples (P = 0.035. CONCLUSIONS/SIGNIFICANCE: We report a genetic association between MSA and alpha-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00211224.

  18. Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel.

    Science.gov (United States)

    Dickson, Price E; Miller, Mellessa M; Calton, Michele A; Bubier, Jason A; Cook, Melloni N; Goldowitz, Daniel; Chesler, Elissa J; Mittleman, Guy

    2016-02-01

    Cocaine addiction is a major public health problem with a substantial genetic basis for which the biological mechanisms remain largely unknown. Systems genetics is a powerful method for discovering novel mechanisms underlying complex traits, and intravenous drug self-administration (IVSA) is the gold standard for assessing volitional drug use in preclinical studies. We have integrated these approaches to identify novel genes and networks underlying cocaine use in mice. Mice from 39 BXD strains acquired cocaine IVSA (0.56 mg/kg/infusion). Mice from 29 BXD strains completed a full dose-response curve (0.032-1.8 mg/kg/infusion). We identified independent genetic correlations between cocaine IVSA and measures of environmental exploration and cocaine sensitization. We identified genome-wide significant quantitative trait loci (QTL) on chromosomes 7 and 11 associated with shifts in the dose-response curve and on chromosome 16 associated with sessions to acquire cocaine IVSA. Using publicly available gene expression data from the nucleus accumbens, midbrain, and prefrontal cortex of drug-naïve mice, we identified Aplp1 and Cyfip2 as positional candidates underlying the behavioral QTL on chromosomes 7 and 11, respectively. A genome-wide significant trans-eQTL linking Fam53b (a GWAS candidate for human cocaine dependence) on chromosome 7 to the cocaine IVSA behavioral QTL on chromosome 11 was identified in the midbrain; Fam53b and Cyfip2 were co-expressed genome-wide significantly in the midbrain. This finding indicates that cocaine IVSA studies using mice can identify genes involved in human cocaine use. These data provide novel candidate genes underlying cocaine IVSA in mice and suggest mechanisms driving human cocaine use.

  19. An improved Agrobacterium-mediated transformation system for the functional genetic analysis of Penicillium marneffei.

    Science.gov (United States)

    Kummasook, Aksarakorn; Cooper, Chester R; Vanittanakom, Nongnuch

    2010-12-01

    We have developed an improved Agrobacterium-mediated transformation (AMT) system for the functional genetic analysis of Penicillium marneffei, a thermally dimorphic, human pathogenic fungus. Our AMT protocol included the use of conidia or pre-germinated conidia of P. marneffei as the host recipient for T-DNA from Agrobacterium tumefaciens and co-cultivation at 28°C for 36 hours. Bleomycin-resistant transformants were selected as yeast-like colonies following incubation at 37°C. The efficiency of transformation was approximately 123 ± 3.27 and 239 ± 13.12 transformants per plate when using 5 × 10(4) conidia and pre-germinated conidia as starting materials, respectively. Southern blot analysis demonstrated that 95% of transformants contained single copies of T-DNA. Inverse PCR was employed for identifying flanking sequences at the T-DNA insertion sites. Analysis of these sequences indicated that integration occurred as random recombination events. Among the mutants isolated were previously described stuA and gasC defective strains. These AMT-derived mutants possessed single T-DNA integrations within their particular coding sequences. In addition, other morphological and pigmentation mutants possessing a variety of gene-specific defects were isolated, including two mutants having T-DNA integrations within putative promoter regions. One of the latter integration events was accompanied by the deletion of the entire corresponding gene. Collectively, these results indicated that AMT could be used for large-scale, functional genetic analyses in P. marneffei. Such analyses can potentially facilitate the identification of those genetic elements related to morphogenesis, as well as pathogenesis in this medically important fungus.

  20. Selection of security system design via games of imperfect information and multi-objective genetic algorithm

    International Nuclear Information System (INIS)

    Lins, Isis Didier; Rêgo, Leandro Chaves; Moura, Márcio das Chagas

    2013-01-01

    This work analyzes the strategic interaction between a defender and an intelligent attacker by means of a game and reliability framework involving a multi-objective approach and imperfect information so as to support decision-makers in choosing efficiently designed security systems. A multi-objective genetic algorithm is used to determine the optimal security system's configurations representing the tradeoff between the probability of a successful defense and the acquisition and operational costs. Games with imperfect information are considered, in which the attacker has limited knowledge about the actual security system. The types of security alternatives are readily observable, but the number of redundancies actually implemented in each security subsystem is not known. The proposed methodology is applied to an illustrative example considering power transmission lines in the Northeast of Brazil, which are often targets for attackers who aims at selling the aluminum conductors. The empirical results show that the framework succeeds in handling this sort of strategic interaction. -- Highlights: ► Security components must have feasible costs and must be reliable. ► The optimal design of security systems considers a multi-objective approach. ► Games of imperfect information enable the choice of non-dominated configurations. ► MOGA, reliability and games support the entire defender's decision process. ► The selection of effective security systems may discourage attacker's actions

  1. A two-layer genetic algorithm for the design of reliable cellular manufacturing systems

    Directory of Open Access Journals (Sweden)

    Hassan Rezazadeh

    2017-06-01

    Full Text Available This study presents a new mathematical model for the design of reliable cellular manufacturing systems, which leads to reduced manufacturing costs, improved product quality and improved total reliability of the manufacturing system. This model is expected to provide a more noticeable improvement in time and solution quality in comparison with other existing models. Each part to be manufactured may select each of the predefined manufacturing routes, such that the total reliability of the system is increased. On the other hand, the model adopts to categorize the machines to determine the manufacturing cells (cell formation and reduce the transportation costs. Thereby, both criteria of system reliability and manufacturing costs will be simultaneously improved. Due to the complexity of cell formation problems, a two-layer genetic algorithm is applied on the problem in order to achieve near optimal solutions. Furthermore, the performance of the proposed algorithm is shown for solving some computational experiments. Finally, the results of a practical study for designing a cellular manufacturing system as a case study in Iranian Diesel Engine Manufacturing Co., Tabriz, Iran are present.

  2. MolabIS--an integrated information system for storing and managing molecular genetics data.

    Science.gov (United States)

    Truong, Cong V C; Groeneveld, Linn F; Morgenstern, Burkhard; Groeneveld, Eildert

    2011-10-31

    Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org.

  3. Genetic variation of the ghrelin signalling system in individuals with amphetamine dependence.

    Directory of Open Access Journals (Sweden)

    Petra Suchankova

    Full Text Available The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL as well as GHS-R1A (GHSR genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n = 104 and controls from the general population (n = 310. A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (pc  = 0.02. A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (pc  = 0.03. The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders.

  4. A Comparative Study of Probability Collectives Based Multi-agent Systems and Genetic Algorithms

    Science.gov (United States)

    Huang, Chien-Feng; Wolpert, David H.; Bieniawski, Stefan; Strauss, Charles E. M.

    2005-01-01

    We compare Genetic Algorithms (GA's) with Probability Collectives (PC), a new framework for distributed optimization and control. In contrast to GA's, PC-based methods do not update populations of solutions. Instead they update an explicitly parameterized probability distribution p over the space of solutions. That updating of p arises as the optimization of a functional of p. The functional is chosen so that any p that optimizes it should be p peaked about good solutions. The PC approach works in both continuous and discrete problems. It does not suffer from the resolution limitation of the finite bit length encoding of parameters into GA alleles. It also has deep connections with both game theory and statistical physics. We review the PC approach using its motivation as the information theoretic formulation of bounded rationality for multi-agent systems. It is then compared with GA's on a diverse set of problems. To handle high dimensional surfaces, in the PC method investigated here p is restricted to a product distribution. Each distribution in that product is controlled by a separate agent. The test functions were selected for their difficulty using either traditional gradient descent or genetic algorithms. On those functions the PC-based approach significantly outperforms traditional GA's in both rate of descent, trapping in false minima, and long term optimization.

  5. Systems Genetics Implicates Cytoskeletal Genes in Oocyte Control of Cloned Embryo Quality

    Science.gov (United States)

    Cheng, Yong; Gaughan, John; Midic, Uros; Han, Zhiming; Liang, Cheng-Guang; Patel, Bela G.; Latham, Keith E.

    2013-01-01

    Cloning by somatic cell nuclear transfer is an important technology, but remains limited due to poor rates of success. Identifying genes supporting clone development would enhance our understanding of basic embryology, improve applications of the technology, support greater understanding of establishing pluripotent stem cells, and provide new insight into clinically important determinants of oocyte quality. For the first time, a systems genetics approach was taken to discover genes contributing to the ability of an oocyte to support early cloned embryo development. This identified a primary locus on mouse chromosome 17 and potential loci on chromosomes 1 and 4. A combination of oocyte transcriptome profiling data, expression correlation analysis, and functional and network analyses yielded a short list of likely candidate genes in two categories. The major category—including two genes with the strongest genetic associations with the traits (Epb4.1l3 and Dlgap1)—encodes proteins associated with the subcortical cytoskeleton and other cytoskeletal elements such as the spindle. The second category encodes chromatin and transcription regulators (Runx1t1, Smchd1, and Chd7). Smchd1 promotes X chromosome inactivation, whereas Chd7 regulates expression of pluripotency genes. Runx1t1 has not been associated with these processes, but acts as a transcriptional repressor. The finding that cytoskeleton-associated proteins may be key determinants of early clone development highlights potential roles for cytoplasmic components of the oocyte in supporting nuclear reprogramming. The transcriptional regulators identified may contribute to the overall process as downstream effectors. PMID:23307892

  6. Functional relevance for associations between genetic variants and systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Fei-Yan Deng

    Full Text Available Systemic lupus erythematosus (SLE is a serious prototype autoimmune disease characterized by chronic inflammation, auto-antibody production and multi-organ damage. Recent association studies have identified a long list of loci that were associated with SLE with relatively high statistical power. However, most of them only established the statistical associations of genetic markers and SLE at the DNA level without supporting evidence of functional relevance. Here, using publically available datasets, we performed integrative analyses (gene relationship across implicated loci analysis, differential gene expression analysis and functional annotation clustering analysis and combined with expression quantitative trait loci (eQTLs results to dissect functional mechanisms underlying the associations for SLE. We found that 14 SNPs, which were significantly associated with SLE in previous studies, have cis-regulation effects on four eQTL genes (HLA-DQA1, HLA-DQB1, HLA-DQB2, and IRF5 that were also differentially expressed in SLE-related cell groups. The functional evidence, taken together, suggested the functional mechanisms underlying the associations of 14 SNPs and SLE. The study may serve as an example of mining publically available datasets and results in validation of significant disease-association results. Utilization of public data resources for integrative analyses may provide novel insights into the molecular genetic mechanisms underlying human diseases.

  7. Networks in Coronary Heart Disease Genetics As a Step towards Systems Epidemiology.

    Science.gov (United States)

    Drenos, Fotios; Grossi, Enzo; Buscema, Massimo; Humphries, Steve E

    2015-01-01

    We present the use of innovative machine learning techniques in the understanding of Coronary Heart Disease (CHD) through intermediate traits, as an example of the use of this class of methods as a first step towards a systems epidemiology approach of complex diseases genetics. Using a sample of 252 middle-aged men, of which 102 had a CHD event in 10 years follow-up, we applied machine learning algorithms for the selection of CHD intermediate phenotypes, established markers, risk factors, and their previously associated genetic polymorphisms, and constructed a map of relationships between the selected variables. Of the 52 variables considered, 42 were retained after selection of the most informative variables for CHD. The constructed map suggests that most selected variables were related to CHD in a context dependent manner while only a small number of variables were related to a specific outcome. We also observed that loss of complexity in the network was linked to a future CHD event. We propose that novel, non-linear, and integrative epidemiological approaches are required to combine all available information, in order to truly translate the new advances in medical sciences to gains in preventive measures and patients care.

  8. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...... of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment...

  9. The role of endosymbionts in the evolution of haploid-male genetic systems in scale insects (Coccoidea)

    NARCIS (Netherlands)

    Ross, Laura; Shuker, David M.; Normark, Benjamin B.; Pen, Ido

    There is an extraordinary diversity in genetic systems across species, but this variation remains poorly understood. In part, this is because the mechanisms responsible for transitions between systems are often unknown. A recent hypothesis has suggested that conflict between hosts and endosymbiotic

  10. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

    Science.gov (United States)

    Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

    2015-01-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  11. Plant traits correlated with generation time directly affect inbreeding depression and mating system and indirectly genetic structure

    Directory of Open Access Journals (Sweden)

    Hardy Olivier J

    2009-07-01

    Full Text Available Abstract Background Understanding the mechanisms that control species genetic structure has always been a major objective in evolutionary studies. The association between genetic structure and species attributes has received special attention. As species attributes are highly taxonomically constrained, phylogenetically controlled methods are necessary to infer causal relationships. In plants, a previous study controlling for phylogenetic signal has demonstrated that Wright's FST, a measure of genetic differentiation among populations, is best predicted by the mating system (outcrossing, mixed-mating or selfing and that plant traits such as perenniality and growth form have only an indirect influence on FST via their association with the mating system. The objective of this study is to further outline the determinants of plant genetic structure by distinguishing the effects of mating system on gene flow and on genetic drift. The association of biparental inbreeding and inbreeding depression with population genetic structure, mating system and plant traits are also investigated. Results Based on data from 263 plant species for which estimates of FST, inbreeding (FIS and outcrossing rate (tm are available, we confirm that mating system is the main influencing factor of FST. Moreover, using an alternative measure of FST unaffected by the impact of inbreeding on effective population size, we show that the influence of tm on FST is due to its impact on gene flow (reduced pollen flow under selfing and on genetic drift (higher drift under selfing due to inbreeding. Plant traits, in particular perenniality, influence FST mostly via their effect on the mating system but also via their association with the magnitude of selection against inbred individuals: the mean inbreeding depression increases from short-lived herbaceous to long-lived herbaceous and then to woody species. The influence of perenniality on mating system does not seem to be related to

  12. A multi-phase genetic algorithm for the efficient management of multi-chiller systems

    International Nuclear Information System (INIS)

    Beghi, Alessandro; Cecchinato, Luca; Rampazzo, Mirco

    2011-01-01

    In HVAC plants of medium-high cooling capacity, multiple-chiller systems are often employed. In such systems, chillers are independent of each other to provide standby capacity, operational flexibility, and less disruption maintenance. However, the problem of efficiently managing multiple-chiller systems is complex in many respects. In particular, the electrical energy consumption in the chiller plant markedly increases if the chillers are managed improperly, therefore significant energy savings can be achieved by optimizing the chiller operations of HVAC systems. In this paper an unified method for Multi-Chiller Management optimization is presented, that deals simultaneously with the Optimal Chiller Loading and Optimal Chiller Sequencing problems. The main objective is that of reducing both power consumption and operative costs. The approach is based on a cooling load estimation algorithm, and the optimization step is performed by means of a multi-phase genetic algorithm, that provides an efficient and suitable approach to solve this kind of complex multi-objective optimization problem. The performance of the algorithm is evaluated by resorting to a dynamic simulation environment developed in Matlab/Simulink TM , where the plant dynamics are accurately described. It is shown that the proposed algorithm gives superior performance with respect to standard approaches, in terms of both energy performance and load profile tracking.

  13. Toward a workable biosafety system for regulating genetically modified organisms in Ethiopia: balancing conservation and competitiveness.

    Science.gov (United States)

    Abraham, Adane

    2013-01-01

    On September 9, 2009, Ethiopia enacted a highly restrictive biosafety law firmly based on precautionary principles as a foundation for its GMO regulation system. Its drafting process, led by the country's Environmental Protection Authority, was judged as biased, focusing only on protecting the environment from perceived risks, giving little attention to potential benefits of GMOs. Many of its provisions are very stringent, exceeding those of Cartagena Protocol on Biosafety, while others cannot be fulfilled by applicants, collectively rendering the emerged biosafety system unworkable. These provisions include requirements for advance informed agreement and rigorous socioeconomic assessment in risk evaluation for all GMO transactions, including contained research use-which requires the head of the competent national authority of the exporting country to take full responsibility for GMO-related information provided-and stringent labeling, insurance and monitoring requirements for all GMO activities. Furthermore, there is no provision to establish an independent national biosafety decision-making body(ies). As a result, foreign technology owners that provide highly demanded technologies like Bt cotton declined to work with Ethiopia. There is a fear that the emerged biosafety system might also continue to suppress domestic genetic engineering research and development. Thus, to benefit from GMOs, Ethiopia has to revise its biosafety system, primarily by making changes to some provisions of the law in a way that balances its diverse interests of conserving biodiversity, protecting the environment and enhancing competition in agricultural and other economic sectors.

  14. GoldenBraid: an iterative cloning system for standardized assembly of reusable genetic modules.

    Directory of Open Access Journals (Sweden)

    Alejandro Sarrion-Perdigones

    Full Text Available Synthetic Biology requires efficient and versatile DNA assembly systems to facilitate the building of new genetic modules/pathways from basic DNA parts in a standardized way. Here we present GoldenBraid (GB, a standardized assembly system based on type IIS restriction enzymes that allows the indefinite growth of reusable gene modules made of standardized DNA pieces. The GB system consists of a set of four destination plasmids (pDGBs designed to incorporate multipartite assemblies made of standard DNA parts and to combine them binarily to build increasingly complex multigene constructs. The relative position of type IIS restriction sites inside pDGB vectors introduces a double loop ("braid" topology in the cloning strategy that allows the indefinite growth of composite parts through the succession of iterative assembling steps, while the overall simplicity of the system is maintained. We propose the use of GoldenBraid as an assembly standard for Plant Synthetic Biology. For this purpose we have GB-adapted a set of binary plasmids for A. tumefaciens-mediated plant transformation. Fast GB-engineering of several multigene T-DNAs, including two alternative modules made of five reusable devices each, and comprising a total of 19 basic parts are also described.

  15. An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Karsten Tillack

    Full Text Available The brain dopaminergic (DA system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson's disease (PD and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification.Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA or the reverse tetracycline-regulated transactivator (rtTA under control of the tyrosine hydroxylase (TH promoter, TH-tTA (tet-OFF and TH-rtTA (tet-ON mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time.These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases.

  16. An intelligent system for lung cancer diagnosis using a new genetic algorithm based feature selection method.

    Science.gov (United States)

    Lu, Chunhong; Zhu, Zhaomin; Gu, Xiaofeng

    2014-09-01

    In this paper, we develop a novel feature selection algorithm based on the genetic algorithm (GA) using a specifically devised trace-based separability criterion. According to the scores of class separability and variable separability, this criterion measures the significance of feature subset, independent of any specific classification. In addition, a mutual information matrix between variables is used as features for classification, and no prior knowledge about the cardinality of feature subset is required. Experiments are performed by using a standard lung cancer dataset. The obtained solutions are verified with three different classifiers, including the support vector machine (SVM), the back-propagation neural network (BPNN), and the K-nearest neighbor (KNN), and compared with those obtained by the whole feature set, the F-score and the correlation-based feature selection methods. The comparison results show that the proposed intelligent system has a good diagnosis performance and can be used as a promising tool for lung cancer diagnosis.

  17. Population genetic studies in the Balkans. II. DNA-STR-systems.

    Science.gov (United States)

    Huckenbeck, W; Scheil, H G; Schmidt, H D; Efremovska, L; Xirotiris, N

    2001-09-01

    Within a study of the genetics of Southeastern European populations four DNA-STR-systems (D21S11, FGA, TH01, VWA) were examined in seven samples (samples of three Aromuns and four other Balkan populations). The results have been compared to data from four samples from literature (Austrians, Germans, Hungarians, Slovenians). The results show three clusters: a) the Aromuns from Albania (Andon Poci) and Macedonia (Stip region), b) the Romanian Aromuns (Kogalniceanu), Romanians (Constanta, Ploiesti) and Albanians (Tirana) und c) the data from literature. A sample of Northeastern Greece clearly differs from these three clusters. Including seven serum protein polymorphisms (without the populations from literature) results in two clusters: a) the three Aromun populations and b) Albanians and Romanians. Again the sample of Northeastern Greece clearly differs from these clusters.

  18. Unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma.

    Science.gov (United States)

    Hirao, Ichiro; Kimoto, Michiko

    2012-01-01

    Toward the expansion of the genetic alphabet of DNA, several artificial third base pairs (unnatural base pairs) have been created. Synthetic DNAs containing the unnatural base pairs can be amplified faithfully by PCR, along with the natural A-T and G-C pairs, and transcribed into RNA. The unnatural base pair systems now have high potential to open the door to next generation biotechnology. The creation of unnatural base pairs is a consequence of repeating "proof of concept" experiments. In the process, initially designed base pairs were modified to address their weak points. Some of them were artificially evolved to ones with higher efficiency and selectivity in polymerase reactions, while others were eliminated from the analysis. Here, we describe the process of unnatural base pair development, as well as the tests of their applications.

  19. [Genetic diversity and mating system Pinus brutia var. Stankewiczii sukacz. in small localities of Sudak (Crimea)].

    Science.gov (United States)

    Korshikov, I I; Kalafat, L A; Milchevskaya, Ya G

    2015-01-01

    A comparative analysis of genetic variation at 12 polymorphic isozyme loci, and the mating system has been carried out in mature trees and their seed progeny in three small localities of Pinus brutia var. stankewiczii Sukacz. near the town of Sudak--settlement of Novyi Svet in the Crimea. We found that embryos maintain the same allelic diversity as mother plants but their observed heterozygosity is lower on the average by 37.4%. The significant deviation of genotype distribution from the theoretically expected ratios caused by the deficiency of heterozygotes was observed at 8 out of 12 loci. Multilocus estimate of outcrossing rate (t(m)) in populations varied from 68.9 to 94.9% making on the average 80.7%.

  20. Optimization of distribution piping network in district cooling system using genetic algorithm with local search

    International Nuclear Information System (INIS)

    Chan, Apple L.S.; Hanby, Vic I.; Chow, T.T.

    2007-01-01

    A district cooling system is a sustainable means of distribution of cooling energy through mass production. A cooling medium like chilled water is generated at a central refrigeration plant and supplied to serve a group of consumer buildings through a piping network. Because of the substantial capital investment involved, an optimal design of the distribution piping configuration is one of the crucial factors for successful implementation of the district cooling scheme. In the present study, genetic algorithm (GA) incorporated with local search techniques was developed to find the optimal/near optimal configuration of the piping network in a hypothetical site. The effect of local search, mutation rate and frequency of local search on the performance of the GA in terms of both solution quality and computation time were investigated and presented in this paper

  1. Towards a formal design model based on a genetic design model system

    DEFF Research Database (Denmark)

    Storga, Mario; Andreasen, Mogens Myrup; Marjanovic, Dorian

    2005-01-01

    developed by N.H. Mortensen was chosen. In order to achieve the useful formalization of the GDMS structure we have followed modelling procedure on the four levels: epistemological, generic, domain and project level. As an epistemological foundation, The Suggested Upper Merged Ontology (SUMO) proposed....... In this article, we briefly summarize our experience of converting informal definitions of the concepts from the product development domain based on the existing theoretical background into formal design model. As a main data source for extracting the content of a design ontology, Genetic Design Model System...... by IEEE, provides us definitions for the most general and universal concepts, that we used in our research for derivation of terms definitions and axioms in the Design Ontology. The Design Ontology was evaluated using the OntoEdit® ontology engineering environment, on a real product example, and based...

  2. A high-throughput multiplex genetic detection system for Helicobacter pylori identification, virulence and resistance analysis.

    Science.gov (United States)

    Hu, Binjie; Zhao, Fuju; Wang, Shiwen; Olszewski, Michal A; Bian, Haipeng; Wu, Yong; Kong, Mimi; Xu, Lingli; Miao, Yingxin; Fang, Yi; Yang, Changqing; Zhao, Hu; Zhang, Yanmei

    2016-10-01

    We established a high-throughput multiplex genetic detection system (HMGS) for identification of Helicobacter pylori with concomitant analysis of virulence and drug resistance. Confirmed 132 H. pylori cultures from gastric biopsies were screened by 20-gene site-HMGS, sequencing and E-test. HMGS was highly sensitive and specific for H. pylori identification. Concordance rate between HMGS and sequencing averaged 94.5% (virulence genes) and 97.3% (resistance genes). Observed resistance rates to four mainstream antibiotics were high, except for amoxicillin. Significant association between virulence genotype and risks for specific gastrointestinal diseases was found for five genes. Metronidazole resistance in peptic ulcer patients was significantly higher. HMGS is an effective method for H. pylori identification and analysis of virulence and drug resistance.

  3. Application of Genetic Algorithm and Particle Swarm Optimization techniques for improved image steganography systems

    Science.gov (United States)

    Jude Hemanth, Duraisamy; Umamaheswari, Subramaniyan; Popescu, Daniela Elena; Naaji, Antoanela

    2016-01-01

    Image steganography is one of the ever growing computational approaches which has found its application in many fields. The frequency domain techniques are highly preferred for image steganography applications. However, there are significant drawbacks associated with these techniques. In transform based approaches, the secret data is embedded in random manner in the transform coefficients of the cover image. These transform coefficients may not be optimal in terms of the stego image quality and embedding capacity. In this work, the application of Genetic Algorithm (GA) and Particle Swarm Optimization (PSO) have been explored in the context of determining the optimal coefficients in these transforms. Frequency domain transforms such as Bandelet Transform (BT) and Finite Ridgelet Transform (FRIT) are used in combination with GA and PSO to improve the efficiency of the image steganography system.

  4. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Zhernakova, Daria V.; Westra, Harm-Jan

    2015-01-01

    . The eQTL mapping resulted in 987 cis-eQTLs and 73 trans-eQTLs (false discovery rate metabolic pathways. We reduced the eQTL search space by focusing on differentially expressed and co-expressed genes and disease-associated single nucleotide...... the transcriptome, and may reveal novel genes affecting complex diseases. Integration of genomic and transcriptomic variation (expression quantitative trait loci [eQTL] mapping) has identified causal variants that affect complex diseases. We integrated transcriptomic data from adipose tissue and genomic data from...... a porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. METHODS: Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential...

  5. Identification and characterization of HIV-2 strains obtained from asymptomatic patients that do not use CCR5 or CXCR4 coreceptors

    International Nuclear Information System (INIS)

    Azevedo-Pereira, J.M.; Santos-Costa, Q.; Mansinho, K.; Moniz-Pereira, J.

    2003-01-01

    In vivo, human immunodeficiency virus type 2 (HIV-2) infection reveals several unique characteristics when compared to HIV-1 infection, the most remarkable of which is the extraordinarily long asymptomatic period. Here we describe two HIV-2 primary isolates, obtained from asymptomatic individuals, which do not infect any coreceptor-expressing cell lines tested. In those cells, we show that the absence of replication is directly related to cell entry events. Furthermore, productive infection observed in peripheral blood mononuclear cells (PBMC) was not inhibited by natural ligands and monoclonal antibodies directed to CCR5 and CXCR4. Finally, viral entry efficiency and viral progeny production of these viruses are markedly impaired in PBMC, indicating a reduced replicative fitness of both viruses. In conclusion, our data suggest that in some HIV-2 asymptomatic individuals, the circulating viruses are unable to use the major coreceptors to infect PBMC. This fact should have important implications in HIV-2 pathogenesis and transmission

  6. Genetic and biochemical changes of the serotonergic system in migraine pathobiology.

    Science.gov (United States)

    Gasparini, Claudia Francesca; Smith, Robert Anthony; Griffiths, Lyn Robyn

    2017-12-01

    Migraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the family in addition to the sufferer, particularly as it affects three times more women than men and is most prevalent between the ages of 25 and 45, the years of child rearing. Migraine typically occurs in individuals with a genetic predisposition and is aggravated by specific environmental triggers. Attempts to study the biochemistry of migraine began as early as the 1960s and were primarily directed at serotonin metabolism after an increase of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin was observed in urine of migraineurs. Genetic and biochemical studies have primarily focused on the neurotransmitter serotonin, considering receptor binding, transport and synthesis of serotonin and have investigated serotonergic mediators including enzymes, receptors as well as intermediary metabolites. These studies have been mainly assayed in blood, CSF and urine as the most accessible fluids. More recently PET imaging technology integrated with a metabolomics and a systems biology platform are being applied to study serotonergic biology. The general trend observed is that migraine patients have alterations of neurotransmitter metabolism detected in biological fluids with different biochemistry from controls, however the interpretation of the biological significance of these peripheral changes is unresolved. In this review we present the biology of the serotonergic system and metabolic routes for serotonin and discuss results of biochemical studies with regard to alterations in serotonin in brain, cerebrospinal fluid, saliva, platelets, plasma and urine of migraine patients.

  7. System network planning expansion using mathematical programming, genetic algorithms and tabu search

    Energy Technology Data Exchange (ETDEWEB)

    Sadegheih, A. [Department of Industrial Engineering, University of Yazd, P.O. Box 89195-741, Yazd (Iran); Drake, P.R. [E-Business and Operations Management Division, University of Liverpool Management School, University of Liverpool, Liverpool (United Kingdom)

    2008-06-15

    In this paper, system network planning expansion is formulated for mixed integer programming, a genetic algorithm (GA) and tabu search (TS). Compared with other optimization methods, GAs are suitable for traversing large search spaces, since they can do this relatively rapidly and because the use of mutation diverts the method away from local minima, which will tend to become more common as the search space increases in size. GA's give an excellent trade off between solution quality and computing time and flexibility for taking into account specific constraints in real situations. TS has emerged as a new, highly efficient, search paradigm for finding quality solutions to combinatorial problems. It is characterized by gathering knowledge during the search and subsequently profiting from this knowledge. The attractiveness of the technique comes from its ability to escape local optimality. The cost function of this problem consists of the capital investment cost in discrete form, the cost of transmission losses and the power generation costs. The DC load flow equations for the network are embedded in the constraints of the mathematical model to avoid sub-optimal solutions that can arise if the enforcement of such constraints is done in an indirect way. The solution of the model gives the best line additions and also provides information regarding the optimal generation at each generation point. This method of solution is demonstrated on the expansion of a 10 bus bar system to 18 bus bars. Finally, a steady-state genetic algorithm is employed rather than generational replacement, also uniform crossover is used. (author)

  8. Genetic Algorithm-Based Model Order Reduction of Aeroservoelastic Systems with Consistant States

    Science.gov (United States)

    Zhu, Jin; Wang, Yi; Pant, Kapil; Suh, Peter M.; Brenner, Martin J.

    2017-01-01

    This paper presents a model order reduction framework to construct linear parameter-varying reduced-order models of flexible aircraft for aeroservoelasticity analysis and control synthesis in broad two-dimensional flight parameter space. Genetic algorithms are used to automatically determine physical states for reduction and to generate reduced-order models at grid points within parameter space while minimizing the trial-and-error process. In addition, balanced truncation for unstable systems is used in conjunction with the congruence transformation technique to achieve locally optimal realization and weak fulfillment of state consistency across the entire parameter space. Therefore, aeroservoelasticity reduced-order models at any flight condition can be obtained simply through model interpolation. The methodology is applied to the pitch-plant model of the X-56A Multi-Use Technology Testbed currently being tested at NASA Armstrong Flight Research Center for flutter suppression and gust load alleviation. The present studies indicate that the reduced-order model with more than 12× reduction in the number of states relative to the original model is able to accurately predict system response among all input-output channels. The genetic-algorithm-guided approach exceeds manual and empirical state selection in terms of efficiency and accuracy. The interpolated aeroservoelasticity reduced order models exhibit smooth pole transition and continuously varying gains along a set of prescribed flight conditions, which verifies consistent state representation obtained by congruence transformation. The present model order reduction framework can be used by control engineers for robust aeroservoelasticity controller synthesis and novel vehicle design.

  9. Associations of renin-angiotensin system genetic polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Griessenauer, Christoph J; Tubbs, R Shane; Foreman, Paul M; Chua, Michelle H; Vyas, Nilesh A; Lipsky, Robert H; Lin, Mingkuan; Iyer, Ramaswamy; Haridas, Rishikesh; Walters, Beverly C; Chaudry, Salman; Malieva, Aisana; Wilkins, Samantha; Harrigan, Mark R; Fisher, Winfield S; Shoja, Mohammadali M

    2017-05-01

    OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin Angiotensin System (CARAS) study prospectively evaluated associations of common RAS polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensin converting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5'exonuclease genotyping assays and pyrosequencing. Analysis of associations of RAS polymorphisms and clinical course after aSAH were performed. RESULTS A total of 166 patients were screened, and 149 aSAH patients were included for analysis. A recessive effect of allele I (insertion) of the ACE I/D (insertion/deletion) polymorphism was identified for Hunt and Hess grade in all patients (OR 2.76, 95% CI 1.17-6.50; p = 0.0206) with subsequent poor functional outcome. There was a similar effect on delayed cerebral ischemia (DCI) in patients 55 years or younger (OR 3.63, 95% CI 1.04-12.7; p = 0.0439). In patients older than 55 years, there was a recessive effect of allele A of the angiotensin II receptor Type 2 (AT2) A/C single nucleotide polymorphism (SNP) on DCI (OR 4.70, 95% CI 1.43-15.4; p = 0.0111). CONCLUSIONS Both the ACE I/D polymorphism and the AT2 A/C single nucleotide polymorphism were associated with an age-dependent risk of delayed cerebral ischemia, whereas only the ACE I/D polymorphism was associated with poor clinical grade at presentation. Further studies are required to elucidate the relevant pathophysiology and its potential implication in the treatment of patients with aSAH.

  10. System network planning expansion using mathematical programming, genetic algorithms and tabu search

    International Nuclear Information System (INIS)

    Sadegheih, A.; Drake, P.R.

    2008-01-01

    In this paper, system network planning expansion is formulated for mixed integer programming, a genetic algorithm (GA) and tabu search (TS). Compared with other optimization methods, GAs are suitable for traversing large search spaces, since they can do this relatively rapidly and because the use of mutation diverts the method away from local minima, which will tend to become more common as the search space increases in size. GA's give an excellent trade off between solution quality and computing time and flexibility for taking into account specific constraints in real situations. TS has emerged as a new, highly efficient, search paradigm for finding quality solutions to combinatorial problems. It is characterized by gathering knowledge during the search and subsequently profiting from this knowledge. The attractiveness of the technique comes from its ability to escape local optimality. The cost function of this problem consists of the capital investment cost in discrete form, the cost of transmission losses and the power generation costs. The DC load flow equations for the network are embedded in the constraints of the mathematical model to avoid sub-optimal solutions that can arise if the enforcement of such constraints is done in an indirect way. The solution of the model gives the best line additions and also provides information regarding the optimal generation at each generation point. This method of solution is demonstrated on the expansion of a 10 bus bar system to 18 bus bars. Finally, a steady-state genetic algorithm is employed rather than generational replacement, also uniform crossover is used

  11. The effectiveness of argumentation in tutorial dialogues with an Intelligent Tutoring System for genetic risk of breast cancer

    Science.gov (United States)

    Cedillos-Whynott, Elizabeth M.; Wolfe, Christopher R.; Widmer, Colin L.; Brust-Renck, Priscila G.; Weil, Audrey; Reyna, Valerie F.

    2017-01-01

    BRCA Gist is an Intelligent Tutoring System that helps women understand issues related to genetic testing and breast cancer risk. In two laboratory experiments and a field experiment with community and web-based samples, an avatar asked 120 participants to produce arguments for and against genetic testing for breast cancer risk. Two raters assessed the number of argumentation elements (claim, reason, backing, etc.) found in response to prompts soliciting arguments for and against genetic testing for breast cancer risk (IRR=.85). When asked to argue for genetic testing, 53.3 % failed to meet the minimum operational definition of making an argument, a claim supported by one or more reasons. When asked to argue against genetic testing, 59.3 % failed to do so. Of those who failed to generate arguments most simply listed disconnected reasons. However, participants who provided arguments against testing (40.7 %) performed significantly higher on a posttest of declarative knowledge. In each study we found positive correlations between the quality of arguments against genetic testing (i.e., number of argumentation elements) and genetic risk categorization scores. Although most interactions did not contain two or more argument elements, when more elements of arguments were included in the argument against genetic testing interaction, participants had greater learning outcomes. Apparently, many participants lack skills in making coherent arguments. These results suggest an association between argumentation ability (knowing how to make complex arguments) and subsequent learning. Better education in developing arguments may be necessary for people to learn from generating arguments within Intelligent Tutoring Systems and other settings. PMID:26511370

  12. The influence of health care policies and health care system distrust on willingness to undergo genetic testing.

    Science.gov (United States)

    Armstrong, Katrina; Putt, Mary; Halbert, Chanita Hughes; Grande, David; Schwartz, Jerome Sanford; Liao, Kaijun; Marcus, Noora; Demeter, Mirar Bristol; Shea, Judy

    2012-05-01

    As the potential role of genetic testing in disease prevention and management grows, so does concern about differences in uptake of genetic testing across social and racial groups. Characteristics of how genetic tests are delivered may influence willingness to undergo testing and, if they affect population subgroups differently, alter disparities in testing. Conjoint analysis study of the effect of 3 characteristics of genetic test delivery (ie, attributes) on willingness to undergo genetic testing for cancer risk. Data were collected using a random digit dialing survey of 128 African American and 209 white individuals living in the United States. Measures included conjoint scenarios, the Revised Health Care System Distrust Scale (including the values and competence subscales), health insurance coverage, and sociodemographic characteristics. The 3 attributes studied were disclosure of test results to the health insurer, provision of the test by a specialist or primary care doctor, and race-specific or race-neutral marketing. In adjusted analyses, disclosure of test results to insurers, having to get the test from a specialist, and race-specific marketing were all inversely associated with willingness to undergo the genetic test, with the greatest effect for the disclosure attribute. Racial differences in willingness to undergo testing were not statistically significant (P=0.07) and the effect of the attributes on willingness to undergo testing did not vary by patient race. However, the decrease in willingness to undergo testing with insurance disclosure was greater among individuals with high values distrust (P=0.03), and the decrease in willingness to undergo testing from specialist access was smaller among individuals with high competence distrust (P=0.03). Several potentially modifiable characteristics of how genetic tests are delivered are associated with willingness to undergo testing. The effect of 2 of these characteristics vary according to the level of

  13. The Genetic Determinism of Biochemical Systems Polymorphous From the Blood Serum in Pigs

    Directory of Open Access Journals (Sweden)

    Nicoleta Işfan

    2010-05-01

    Full Text Available The study of genetic markers and identification of new markers make the subject of an increasing number of research projects in various fields such as genetics of immunology, biochemical genetics, molecular genetics, quantitative genetics and the genetic amelioration of animals. The information provided by electrophoresis graphs has been used to determine the frequency of various categories of alleles (for the loci of pre-albumin, transferines and serum amylases, the frequency of various phenotypes and the genetic structure for each and every locus and, simultaneously, for the loci being studied. The discussion over the varieties of serum proteins was carried on for the purpose of using them as genetic markers, in order to appreciate the levels of genetic unity or diversity within the stock of swine that has been studied. A pair of simple alleles has been determined for each of the three loci. When the three loci were studied simultaneously, out of the 27 possible combinations, only 15 have been found. The sample studied has found to be genetically balanced for every of the three loci. However, when the simultaneous study has been applied, the same sample has not been found genetically balanced.

  14. Genetic algorithms for the optimization of pipeline systems for liquid distribution (2)

    International Nuclear Information System (INIS)

    Narvaez, Paulo Cesar; Galeano, Haiver

    2004-01-01

    This is the second of two articles presenting a Genetic Algorithm (GA) to obtain an optimal design, from an economical and operational point of view, of a pipeline system for the distribution of liquids, based on criteria such as complying with the laws of preservation of mass and energy, volume of flow requirements in the points of consumption where pressure is known, restriction in pressure value in those points of the system where it is unknown as well as in the velocity which must be under the erosion limit. In this article the traditional techniques for designing a GA in this type of problems are combined with some ideas that have not been applied to this field previously. The proposed GA allows for the sizing of liquid distribution systems that include pipelines, nodes for consumption and provision, tanks, pumping equipment, nozzles, control valves and accessories. The first article of this series (Galeano, 2003), presents the different formulations found in literature for the design of networks through optimization techniques and formulates mathematically, the optimization problem. In this article, the characteristics of the GA are specified and it is applied to solve the Alperovits and Shamir (1977) network and for a fireproof network, which allowed testing some of the characteristics of the model that are not found in the literature, such as the possibility of including pumping equipment, aspersion nozzles and accessories. In addition, the contribution of the components and sensitivity are analyzed in order to investigate some characteristics and parameters of the implemented GA

  15. Development of a recombinant DNA assay system for the detection of genetic change in astronauts' cells

    International Nuclear Information System (INIS)

    Atchley, S.V.; Chen, D.J.C.; Strniste, G.F.; Walters, R.A.; Moyzis, R.K.

    1984-01-01

    We are developing a new recombinant DNA system for the detection and measurement of genetic change in humans caused by exposure to low level ionizing radiation. A unique feature of the method is the use of cloned repetitive DNA probes to assay human DNA for structural changes during or after irradiation. Repetitive sequences exist in different families. Collectively they constitute over 25% of the DNA in a human cell. Repeat families have between 10 and 500,000 members. We have constructed repetitive DNA sequence libraries using recombinant DNA techniques. From these libraries we have isolated and characterized individual repeats comprising 75 to 90% of the mass of human repetitive DNA. Repeats used in our assay system exist in tandem arrays in the genome. Perturbation of these sequences in a cell, followed by detection with a repeat probe, produces a new, multimeric ''ladder'' pattern on an autoradiogram. The repeat probe used in our initial study is complementary to 1% of human DNA. Therefore, the sensitivity of this method is several orders of magnitude better than existing assays. Preliminary evidence from human skin cells exposed to acute, low-dose x-ray treatments indicates that DNA is affected at a dose as low as 5R. The radiation doses used in this system are well within the range of doses received by astronauts during spaceflight missions. Due to its small material requirements, this technique could easily be adapted for use in space. 16 refs., 1 fig

  16. GLOBAL DESIGN OPTIMIZATION OF A REFRIGERATION SYSTEM USING A GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    L. Govindarajan

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: The optimal design of industrial three-stage refrigeration systems to minimize total production cost has been effectively implemented using an genetic algorithm (GA, which is an efficient alternative for conventional search algorithms. In this article the global optimum design parameters of a refrigeration system obtained by using GA is compared with the Nelder-Mead simplex search algorithm. The results prove that global design optimization using GA is more robust and simple, as it requires no initial guess values of design variables. Hence the proposed technique is well suited for designing a variety of industrially important systems.

    AFRIKAANSE OPSOMMING: Die optimum ontwerp van 'n driestadium-vriessisteem om totale produksiekoste te beperk, word doeltreffend met behulp van 'n genetiese algoritme (GA as alternatief vir konvensionele soekalgoritmes in werking gestel. Die navorsing is daarop toegespits om die globale optimum ontwerpparameters van die GA met die Nelder-Mead Simpleks-soekalgoritme te vergelyk. Die resultate toon dat die GA se globale optimum ontwerp robuust en eenvoudig is aangesien geskatte aanvangswaardes vir ontwerpveranderlikes nie benodig word nie. Derhalwe is die GA-tegniek besonder geskik vir die ontwerp van nywerheidsisteme van uiteenlopende aard.

  17. An Improved Genetic Algorithm for Optimal Stationary Energy Storage System Locating and Sizing

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2014-10-01

    Full Text Available The application of a stationary ultra-capacitor energy storage system (ESS in urban rail transit allows for the recuperation of vehicle braking energy for increasing energy savings as well as for a better vehicle voltage profile. This paper aims to obtain the best energy savings and voltage profile by optimizing the location and size of ultra-capacitors. This paper firstly raises the optimization objective functions from the perspectives of energy savings, regenerative braking cancellation and installation cost, respectively. Then, proper mathematical models of the DC (direct current traction power supply system are established to simulate the electrical load-flow of the traction supply network, and the optimization objections are evaluated in the example of a Chinese metro line. Ultimately, a methodology for optimal ultra-capacitor energy storage system locating and sizing is put forward based on the improved genetic algorithm. The optimized result shows that certain preferable and compromised schemes of ESSs’ location and size can be obtained, acting as a compromise between satisfying better energy savings, voltage profile and lower installation cost.

  18. Optimal Design of Gravity Pipeline Systems Using Genetic Algorithm and Mathematical Optimization

    Directory of Open Access Journals (Sweden)

    maryam rohani

    2015-03-01

    Full Text Available In recent years, the optimal design of pipeline systems has become increasingly important in the water industry. In this study, the two methods of genetic algorithm and mathematical optimization were employed for the optimal design of pipeline systems with the objective of avoiding the water hammer effect caused by valve closure. The problem of optimal design of a pipeline system is a constrained one which should be converted to an unconstrained optimization problem using an external penalty function approach in the mathematical programming method. The quality of the optimal solution greatly depends on the value of the penalty factor that is calculated by the iterative method during the optimization procedure such that the computational effort is simultaneously minimized. The results obtained were used to compare the GA and mathematical optimization methods employed to determine their efficiency and capabilities for the problem under consideration. It was found that the mathematical optimization method exhibited a slightly better performance compared to the GA method.

  19. Optimization of steel casting feeding system based on BP neural network and genetic algorithm

    Directory of Open Access Journals (Sweden)

    Xue-dan Gong

    2016-05-01

    Full Text Available The trial-and-error method is widely used for the current optimization of the steel casting feeding system, which is highly random, subjective and thus inefficient. In the present work, both the theoretical and the experimental research on the modeling and optimization methods of the process are studied. An approximate alternative model is established based on the Back Propagation (BP neural network and experimental design. The process parameters of the feeding system are taken as the input, the volumes of shrinkage cavities and porosities calculated by simulation are simultaneously taken as the output. Thus, a mathematical model is established by the BP neural network to combine the input variables with the output response. Then, this model is optimized by the nonlinear optimization function of the genetic algorithm. Finally, a feeding system optimization of a steel traveling wheel is conducted. No shrinkage cavities and porosities are induced through the optimization. Compared to the initial design scheme, the process yield is increased by 4.1% and the volume of the riser is decreased by 5.48×106 mm3.

  20. Selection of an effective microsatellite marker system for genetic control and analysis of gerbil populations in China.

    Science.gov (United States)

    Du, X Y; Li, W; Sa, X Y; Li, C L; Lu, J; Wang, Y Z; Chen, Z W

    2015-09-21

    Although gerbils have been widely used in many areas of biological research over many years, there is currently no effective genetic quality control system available. In the present study, we sought to establish a microsatellite marker system for quality control and conducted an optimized analysis of 137 microsatellite loci in two laboratory gerbil populations and one wild population. Independent sample t-tests on the mean effective allele number, mean of Shannon's information index, and mean HE suggested that 28 of the 137 microsatellite markers were informative for gerbil genetic control. Analysis of 4 laboratory gerbil populations and 1 wild population using the 28 microsatellite loci indicated that allele numbers varied from 1.9639 (Guangzhou, GZ) to 6.6071 (North-West wild, NW). The average of HO versus HE was 0.6236/0.3802, 0.6671/0.4159, 0.4185/0.3464, 0.4592/0.3821, and 0.3972/0.4167 for the Beijing, NW, Hangzhou, Dalian, and GZ populations, respectively. The GZ population showed the greatest differentiation, having higher RST and Nei's standard genetic distances. An AMO-VA revealed high genetic differentiation among the five populations (FST = 0.296). The microsatellite system established here is effective and will be important in future studies for genetic quality control and monitoring of gerbil breeds.

  1. Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back

    Science.gov (United States)

    Makarova, Kira S.

    2017-01-01

    Abstract The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci. Second, a large subset of type III CRISPR-Cas systems recruited a reverse transcriptase from a Group II intron, providing for spacer acquisition from RNA. Third, effector nucleases of Class 2 CRISPR-Cas systems that are responsible for the recognition and cleavage of the target DNA were derived from transposon-encoded TnpB nucleases, most likely, on several independent occasions. Fourth, accessory nucleases in some variants of types I and III toxin and type VI effectors RNases appear to be ultimately derived from toxin nucleases of microbial toxin–antitoxin modules. Fifth, the opposite direction of evolution is manifested in the recruitment of CRISPR-Cas systems by a distinct family of Tn7-like transposons that probably exploit the capacity of CRISPR-Cas to recognize unique DNA sites to facilitate transposition as well as by bacteriophages that employ them to cope with host defense. Additionally, individual Cas proteins, such as the Cas4 nuclease, were recruited by bacteriophages and transposons. The two-sided evolutionary connection between CRISPR-Cas and MGE fits the “guns for hire” paradigm whereby homologous enzymatic machineries, in particular nucleases, are shuttled between MGE and defense systems and are used alternately as means of offense or defense. PMID:28985291

  2. Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene.

    Directory of Open Access Journals (Sweden)

    Lina-Marcela Diaz-Gallo

    Full Text Available The ubiquitin associated and Src-homology 3 (SH3 domain containing A (UBASH3a is a suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis. The aim of the present study was to determine whether the UBASH3a gene influence the susceptibility to systemic lupus erythematosus (SLE in Caucasian populations. We evaluated five UBASH3a polymorphisms (rs2277798, rs2277800, rs9976767, rs13048049 and rs17114930, using TaqMan® allelic discrimination assays, in a discovery cohort that included 906 SLE patients and 1165 healthy controls from Spain. The SNPs that exhibit statistical significance difference were evaluated in a German replication cohort of 360 SLE patients and 379 healthy controls. The case-control analysis in the Spanish population showed a significant association between the rs9976767 and SLE (Pc = 9.9E-03 OR = 1.21 95%CI = 1.07-1.37 and a trend of association for the rs2277798 analysis (P = 0.09 OR = 0.9 95%CI = 0.79-1.02. The replication in a German cohort and the meta-analysis confirmed that the rs9976767 (Pc = 0.02; Pc = 2.4E-04, for German cohort and meta-analysis, respectively and rs2277798 (Pc = 0.013; Pc = 4.7E-03, for German cohort and meta-analysis, respectively UBASH3a variants are susceptibility factors for SLE. Finally, a conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs9976767 polymorphism. Our results suggest that UBASH3a gene plays a role in the susceptibility to SLE. Moreover, our study indicates that UBASH3a can be considered as a common genetic factor in autoimmune diseases.

  3. Management of Uncertainty by Statistical Process Control and a Genetic Tuned Fuzzy System

    Directory of Open Access Journals (Sweden)

    Stephan Birle

    2016-01-01

    Full Text Available In food industry, bioprocesses like fermentation often are a crucial part of the manufacturing process and decisive for the final product quality. In general, they are characterized by highly nonlinear dynamics and uncertainties that make it difficult to control these processes by the use of traditional control techniques. In this context, fuzzy logic controllers offer quite a straightforward way to control processes that are affected by nonlinear behavior and uncertain process knowledge. However, in order to maintain process safety and product quality it is necessary to specify the controller performance and to tune the controller parameters. In this work, an approach is presented to establish an intelligent control system for oxidoreductive yeast propagation as a representative process biased by the aforementioned uncertainties. The presented approach is based on statistical process control and fuzzy logic feedback control. As the cognitive uncertainty among different experts about the limits that define the control performance as still acceptable may differ a lot, a data-driven design method is performed. Based upon a historic data pool statistical process corridors are derived for the controller inputs control error and change in control error. This approach follows the hypothesis that if the control performance criteria stay within predefined statistical boundaries, the final process state meets the required quality definition. In order to keep the process on its optimal growth trajectory (model based reference trajectory a fuzzy logic controller is used that alternates the process temperature. Additionally, in order to stay within the process corridors, a genetic algorithm was applied to tune the input and output fuzzy sets of a preliminarily parameterized fuzzy controller. The presented experimental results show that the genetic tuned fuzzy controller is able to keep the process within its allowed limits. The average absolute error to the

  4. Development and application of genetic sexing systems for the Mediterranean fruit fly based on a temperature sensitive lethal mutation

    International Nuclear Information System (INIS)

    Franz, G.; Willhoeft, U.; Kerremans, P.; Hendrichs, J.; Rendon, P.

    1997-01-01

    The present status in genetic sexing for the Mediterranean fruit fly is discussed. This includes the selection of the appropriate sexing gene (which determines the feasibility and practical applicability of the sexing system) as well as the selection of the appropriate Y-autosome translocation (which determines the stability of the sexing system). A temperature sensitive lethal mutation is used to eliminate females during the egg stage. This mutation in combination with new Y-autosome translocations allowed the construction of a genetic sexing strain, named VIENNA-42, that is stable enough for large scale mass rearing. Also described are the analysis of this strain under field cage and field conditions and, in preparation for large scale tests in Guatemala, the outcrossing of VIENNA-42 with genetic material from the target area. (author)

  5. Genetic characterization of the inducible SOS-like system of Bacillus subtilis

    Energy Technology Data Exchange (ETDEWEB)

    Love, P.E.; Yasbin, R.E.

    1984-12-01

    The SOS-like system of Bacillus subtilis consists of several coordinately induced phenomena which are expressed after cellular insult such as DNA damage of inhibition of DNA replication. Mutagenesis of the bacterial chromosomes and the development of maintenance of competence also appear to be involved in the SOS-like response in this bacterium. The genetic characterization of the SOS-like system has involved an analysis of (i) the effects of various DNA repair mutations on the expression of inducible phenomena and (ii) the tsi-23 mutation, which renders host strains thermally inducible for each of the SOS-like functions. Bacterial filamentation was unaffected by any of the DNA repair mutations studied. In contrast, the induction of prophage after thermal or UV pretreatment was abolished in strains carrying the recE4, recA1, recB2, or recG13 mutation. The Weigle reactivation of UV-damaged bacteriophage was also inhibited by the recE4, recA1, recB2, or recG13 mutation, whereas levels of Weigle reactivation were lower in strains which carried the uvrA42, polA5, or rec-961 mutation than in the DNA repair-proficient strain. Strains which carried the recE4 mutation were incapable of chromosomal DNA-mediated transformation, and the frequency of this event was decreased in strains carrying recA1, recB2, or tsi-23 mutation. Plasmid DNA transformation efficiency was decreased only in strains carrying the tsi-23 mutation in addition to the recE4, recA1, or recB2 mutation. The results indicate that the SOS-like system of B. subtilis is regulated at different levels by two or more gene products. In this report, the current data regarding the genetic regulation of inducible phenomena are summarized, and a model is proposed to explain the mechanism of SOS-like induction in B. subtillis. 50 references, 3 figures, 6 tables.

  6. Practicability of comprehensive care in clinical genetics in the brazilian unified health system: expanding the debate

    OpenAIRE

    Lopes-Júnior, Luís Carlos; Flória-Santos, Milena; Ferraz, Victor Evangelista de Faria; Villa, Tereza Cristina Scatena; Palha, Pedro Fredemir; Bomfim, Emiliana de Omena; Abrahão, Camila Aparecida; Silva, Sara da

    2014-01-01

    This article aims to highlight the discussions on the National Policy for Comprehensive Care in Clinical Genetics and reflect on its pending regulation when genomic discoveries change the model of health care. Nine of the ten causes of morbidity and mortality worldwide presents genetic/genomic predisposition. Based on strategic planning, this Policy proposes the organization of a network of referral services and specialized centers in genetics, with capacity to meet the needs of the populatio...

  7. Dobzhansky-Muller and Wolbachia-Induced Incompatibilities in a Diploid Genetic System

    OpenAIRE

    Telschow, Arndt; Hilgenboecker, Kirsten; Hammerstein, Peter; Werren, John H.

    2014-01-01

    Genetic incompatibilities are supposed to play an important role in speciation. A general (theoretical) problem is to explain the persistence of genetic diversity after secondary contact. Previous theoretical work has pointed out that Dobzhansky-Muller incompatibilities (DMI) are not stable in the face of migration unless local selection acts on the alleles involved in incompatibility. With local selection, genetic variability exists up to a critical migration rate but is lost when migration ...

  8. A drug-sensitive genetic network masks fungi from the immune system.

    Directory of Open Access Journals (Sweden)

    Robert T Wheeler

    2006-04-01

    Full Text Available Fungal pathogens can be recognized by the immune system via their beta-glucan, a potent proinflammatory molecule that is present at high levels but is predominantly buried beneath a mannoprotein coat and invisible to the host. To investigate the nature and significance of "masking" this molecule, we characterized the mechanism of masking and consequences of unmasking for immune recognition. We found that the underlying beta-glucan in the cell wall of Candida albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin, causing the exposed fungi to elicit a stronger immune response. Using a library of bakers' yeast (Saccharomyces cerevisiae mutants, we uncovered a conserved genetic network that is required for concealing beta-glucan from the immune system and limiting the host response. Perturbation of parts of this network in the pathogen C. albicans caused unmasking of its beta-glucan, leading to increased beta-glucan receptor-dependent elicitation of key proinflammatory cytokines from primary mouse macrophages. By creating an anti-inflammatory barrier to mask beta-glucan, opportunistic fungi may promote commensal colonization and have an increased propensity for causing disease. Targeting the widely conserved gene network required for creating and maintaining this barrier may lead to novel broad-spectrum antimycotics.

  9. Genetic selection system allowing monitoring of myofibrillogenesis in living cardiomyocytes derived from mouse embryonic stem cells

    Directory of Open Access Journals (Sweden)

    R Bugorsky

    2009-08-01

    Full Text Available Embryonic stem (ES cell-derived cardiomyocytes recapitulate cardiomyogenesis in vitro and are a potential source of cells for cardiac repair. However, this requires enrichment of mixed populations of differentiating ES cells into cardiomyocytes. Toward this goal, we have generated bicistronic vectors that express both the blasticidin S deaminase (bsd gene and a fusion protein consisting of either myosin light chain (MLC-3f or human a-actinin 2A and enhanced green fluorescent protein (EGFP under the transcriptional control of the a-cardiac myosin heavy chain (a-MHC promoter. Insertion of the DNase I-hypersensitive site (HS-2 element from the b-globin locus control region, which has been shown to reduce transgene silencing in other cell systems, upstream of the transgene promoter enhanced MLC3f-EGFP gene expression levels in mouse ES cell lines. The a-MHC-a- actinin-EGFP, but not the a-MHC-MLC3f-EGFP, construct resulted in the correct incorporation of the newly synthesized fusion protein at the Z-band of the sarcomeres in ES cellderived cardiomyocytes. Exposure of embryoid bodies to blasticidin S selected for a relatively pure population of cardiomyocytes within 3 days. Myofibrillogenesis could be monitored by fluorescence microscopy in living cells due to sarcomeric epitope tagging. Therefore, this genetic system permits the rapid selection of a relatively pure population of developing cardiomyocytes from a heterogeneous population of differentiating ES cells, simultaneously allowing monitoring of early myofibrillogenesis in the selected myocytes.

  10. Procedure to select test organisms for environmental risk assessment of genetically modified crops in aquatic systems.

    Science.gov (United States)

    Hilbeck, Angelika; Bundschuh, Rebecca; Bundschuh, Mirco; Hofmann, Frieder; Oehen, Bernadette; Otto, Mathias; Schulz, Ralf; Trtikova, Miluse

    2017-11-01

    For a long time, the environmental risk assessment (ERA) of genetically modified (GM) crops focused mainly on terrestrial ecosystems. This changed when it was scientifically established that aquatic ecosystems are exposed to GM crop residues that may negatively affect aquatic species. To assist the risk assessment process, we present a tool to identify ecologically relevant species usable in tiered testing prior to authorization or for biological monitoring in the field. The tool is derived from a selection procedure for terrestrial ecosystems with substantial but necessary changes to adequately consider the differences in the type of ecosystems. By using available information from the Water Framework Directive (2000/60/EC), the procedure can draw upon existing biological data on aquatic systems. The proposed procedure for aquatic ecosystems was tested for the first time during an expert workshop in 2013, using the cultivation of Bacillus thuringiensis (Bt) maize as the GM crop and 1 stream type as the receiving environment in the model system. During this workshop, species executing important ecological functions in aquatic environments were identified in a stepwise procedure according to predefined ecological criteria. By doing so, we demonstrated that the procedure is practicable with regard to its goal: From the initial long list of 141 potentially exposed aquatic species, 7 species and 1 genus were identified as the most suitable candidates for nontarget testing programs. Integr Environ Assess Manag 2017;13:974-979. © 2017 SETAC. © 2017 SETAC.

  11. Unfolding neutron spectra with BS-TLD system using genetic algorithms

    International Nuclear Information System (INIS)

    Santos, Joelan A.L.; Silva, Everton R.; Vilela, Eudice C.

    2011-01-01

    Due to the variability of neutron spectrum within the same environment, it is essential that the spectral distribution as function of energy to be characterized. To perform this task, the neutron spectrometer has a primary role in determining the neutron flux (Φ E (E)). Precise information allows radiological quantities establishment related to that spectrum but it is necessary, however, a series of steps with a spectrometric system that can cover a large interval of energy and whose answer is isotropic. The most widely used for accomplishing this task is the spectrometric Bonner spheres system. One of the biggest problems related to neutron spectrometry is the process of data analysis, known as unfolding. Most of the work undertaken to implement new techniques of this process, using data obtained with the scintillator 6 LiI(I). However, characteristics related to the dead time make it not be so effective when used in high flow neutron fields. An alternative to this problem is the use of thermoluminescent detectors (TLD), but the codes used do not provide a more specific response matrix to unfolding the information obtained through these materials, which makes the development of a specific response matrix important to adequately characterize the response obtained by them. This paper proposes using a technique of artificial intelligence called genetic algorithm, which uses bio-inspired mathematical models and through the implementation of a specific matrix to unfolding data obtained from a combination of TLDs embedded in a system of Bonner spheres, such as thermal neutron detectors, to characterize the neutron spectrum as a function of energy. The results obtained with this method were in accordance with reference spectra, thus enables of this technique to unfolding neutrons spectra with BS-TLD system. (author)

  12. Copy number ratios determined by two digital polymerase chain reaction systems in genetically modified grains

    Science.gov (United States)

    Pérez Urquiza, M.; Acatzi Silva, A. I.

    2014-02-01

    Three certified reference materials produced from powdered seeds to measure the copy number ratio sequences of p35S/hmgA in maize containing MON 810 event, p35S/Le1 in soybeans containing GTS 40-3-2 event and DREB1A/acc1 in wheat were produced according to the ISO Guides 34 and 35. In this paper, we report digital polymerase chain reaction (dPCR) protocols, performance parameters and results of copy number ratio content of genetically modified organisms (GMOs) in these materials using two new dPCR systems to detect and quantify molecular deoxyribonucleic acid: the BioMark® (Fluidigm) and the OpenArray® (Life Technologies) systems. These technologies were implemented at the National Institute of Metrology in Mexico (CENAM) and in the Reference Center for GMO Detection from the Ministry of Agriculture (CNRDOGM), respectively. The main advantage of this technique against the more-used quantitative polymerase chain reaction (qPCR) is that it generates an absolute number of target molecules in the sample, without reference to standards or an endogenous control, which is very useful when not much information is available for new developments or there are no standard reference materials in the market as in the wheat case presented, or when it was not possible to test the purity of seeds as in the maize case presented here. Both systems reported enhanced productivity, increased reliability and reduced instrument footprint. In this paper, the performance parameters and uncertainty of measurement obtained with both systems are presented and compared.

  13. Unfolding neutron spectra with BS-TLD system using genetic algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Joelan A.L., E-mail: jasantos@cnen.gov.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Silva, Everton R. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Centro de Informatica; Ferreira, Tiago A.E. [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Dept. de Estatistica e Informatica; Fonseca, Evaldo S. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Vilela, Eudice C., E-mail: ecvilela@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    Due to the variability of neutron spectrum within the same environment, it is essential that the spectral distribution as function of energy to be characterized. To perform this task, the neutron spectrometer has a primary role in determining the neutron flux ({Phi}{sub E}(E)). Precise information allows radiological quantities establishment related to that spectrum but it is necessary, however, a series of steps with a spectrometric system that can cover a large interval of energy and whose answer is isotropic. The most widely used for accomplishing this task is the spectrometric Bonner spheres system. One of the biggest problems related to neutron spectrometry is the process of data analysis, known as unfolding. Most of the work undertaken to implement new techniques of this process, using data obtained with the scintillator {sup 6}LiI(I). However, characteristics related to the dead time make it not be so effective when used in high flow neutron fields. An alternative to this problem is the use of thermoluminescent detectors (TLD), but the codes used do not provide a more specific response matrix to unfolding the information obtained through these materials, which makes the development of a specific response matrix important to adequately characterize the response obtained by them. This paper proposes using a technique of artificial intelligence called genetic algorithm, which uses bio-inspired mathematical models and through the implementation of a specific matrix to unfolding data obtained from a combination of TLDs embedded in a system of Bonner spheres, such as thermal neutron detectors, to characterize the neutron spectrum as a function of energy. The results obtained with this method were in accordance with reference spectra, thus enables of this technique to unfolding neutrons spectra with BS-TLD system. (author)

  14. Structural basis of HIV-1 and HIV-2 protease inhibition by a monoclonal antibody

    Czech Academy of Sciences Publication Activity Database

    Řezáčová, Pavlína; Lescar, J.; Brynda, Jiří; Fábry, Milan; Hořejší, Magdalena; Sedláček, Juraj; Bentley, G.

    2001-01-01

    Roč. 9, č. 10 (2001), s. 887-895 ISSN 0969-2126 R&D Projects: GA AV ČR IAA5052502; GA ČR GV203/98/K023 Keywords : single-chain Fv * cross-reactivity * HIV protease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.975, year: 2001

  15. Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Dhamrait, Sukhbir S.; Sethi, Amar A

    2008-01-01

    BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system are sim...

  16. Fuzzy Logic, Neural Networks, Genetic Algorithms: Views of Three Artificial Intelligence Concepts Used in Modeling Scientific Systems

    Science.gov (United States)

    Sunal, Cynthia Szymanski; Karr, Charles L.; Sunal, Dennis W.

    2003-01-01

    Students' conceptions of three major artificial intelligence concepts used in the modeling of systems in science, fuzzy logic, neural networks, and genetic algorithms were investigated before and after a higher education science course. Students initially explored their prior ideas related to the three concepts through active tasks. Then,…

  17. Typing of 48 autosomal SNPs and amelogenin with GenPlex SNP genotyping system in forensic genetics

    DEFF Research Database (Denmark)

    Tomas Mas, Carmen; Stangegaard, Michael; Børsting, Claus

    2008-01-01

    with amelogenin and 48 of the 52 SNPs used in the 52 SNP-plex assay developed by the SNPforID consortium. The system requires equipment that is usually found in forensic genetic laboratories. The use of a robot for performance of the pipetting steps is highly recommendable. A total of 286 individuals from Denmark...

  18. Biomedical visual data analysis to build an intelligent diagnostic decision support system in medical genetics.

    Science.gov (United States)

    Kuru, Kaya; Niranjan, Mahesan; Tunca, Yusuf; Osvank, Erhan; Azim, Tayyaba

    2014-10-01

    In general, medical geneticists aim to pre-diagnose underlying syndromes based on facial features before performing cytological or molecular analyses where a genotype-phenotype interrelation is possible. However, determining correct genotype-phenotype interrelationships among many syndromes is tedious and labor-intensive, especially for extremely rare syndromes. Thus, a computer-aided system for pre-diagnosis can facilitate effective and efficient decision support, particularly when few similar cases are available, or in remote rural districts where diagnostic knowledge of syndromes is not readily available. The proposed methodology, visual diagnostic decision support system (visual diagnostic DSS), employs machine learning (ML) algorithms and digital image processing techniques in a hybrid approach for automated diagnosis in medical genetics. This approach uses facial features in reference images of disorders to identify visual genotype-phenotype interrelationships. Our statistical method describes facial image data as principal component features and diagnoses syndromes using these features. The proposed system was trained using a real dataset of previously published face images of subjects with syndromes, which provided accurate diagnostic information. The method was tested using a leave-one-out cross-validation scheme with 15 different syndromes, each of comprised 5-9 cases, i.e., 92 cases in total. An accuracy rate of 83% was achieved using this automated diagnosis technique, which was statistically significant (p<0.01). Furthermore, the sensitivity and specificity values were 0.857 and 0.870, respectively. Our results show that the accurate classification of syndromes is feasible using ML techniques. Thus, a large number of syndromes with characteristic facial anomaly patterns could be diagnosed with similar diagnostic DSSs to that described in the present study, i.e., visual diagnostic DSS, thereby demonstrating the benefits of using hybrid image processing

  19. Optimal power system generation scheduling by multi-objective genetic algorithms with preferences

    International Nuclear Information System (INIS)

    Zio, E.; Baraldi, P.; Pedroni, N.

    2009-01-01

    Power system generation scheduling is an important issue both from the economical and environmental safety viewpoints. The scheduling involves decisions with regards to the units start-up and shut-down times and to the assignment of the load demands to the committed generating units for minimizing the system operation costs and the emission of atmospheric pollutants. As many other real-world engineering problems, power system generation scheduling involves multiple, conflicting optimization criteria for which there exists no single best solution with respect to all criteria considered. Multi-objective optimization algorithms, based on the principle of Pareto optimality, can then be designed to search for the set of nondominated scheduling solutions from which the decision-maker (DM) must a posteriori choose the preferred alternative. On the other hand, often, information is available a priori regarding the preference values of the DM with respect to the objectives. When possible, it is important to exploit this information during the search so as to focus it on the region of preference of the Pareto-optimal set. In this paper, ways are explored to use this preference information for driving a multi-objective genetic algorithm towards the preferential region of the Pareto-optimal front. Two methods are considered: the first one extends the concept of Pareto dominance by biasing the chromosome replacement step of the algorithm by means of numerical weights that express the DM' s preferences; the second one drives the search algorithm by changing the shape of the dominance region according to linear trade-off functions specified by the DM. The effectiveness of the proposed approaches is first compared on a case study of literature. Then, a nonlinear, constrained, two-objective power generation scheduling problem is effectively tackled

  20. Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice.

    Science.gov (United States)

    Galeano, Mariarosaria; Polito, Francesca; Bitto, Alessandra; Irrera, Natasha; Campo, Giuseppe M; Avenoso, Angela; Calò, Margherita; Lo Cascio, Patrizia; Minutoli, Letteria; Barone, Mauro; Squadrito, Francesco; Altavilla, Domenica

    2011-07-01

    Hyaluronic acid (HA), an essential component of the extracellular matrix, is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and is involved in wound healing. Although numerous pieces of evidence demonstrate beneficial effects in promoting wound healing in diabetes, a systemic approach has never been tested. We used an incisional wound healing model in genetically diabetic mice to test the effects of systemic injection of HA. Diabetic (n=56) and normoglycemic (n=56) mice were subjected to incision and randomized (8 groups of 7 animals each) to receive HA at different doses, 7.5, 15 and 30mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12days. At the end of the experiment animals were sacrificed and skin wounds were excised for histological, biochemical and molecular analysis. Histology revealed that the most effective dose to improve wound repair and angiogenesis in diabetic mice was 30mg/kg. Furthermore HA injection (30mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-β and transglutaminase-II and restored the altered expression of cyclin B1/Cdc2 complex. Evaluation of skin from diabetic animals injected with HA revealed also an increase in HA content, suggesting that systemic injection may be able to restore the reduced intracellular HA pool of diabetic mice. Finally HA markedly improved skin mechanical properties. These promising results, if confirmed in a clinical setting, may improve the care and management of diabetic patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. A high-throughput cloning system for reverse genetics in Trypanosoma cruzi.

    Science.gov (United States)

    Batista, Michel; Marchini, Fabricio K; Celedon, Paola A F; Fragoso, Stenio P; Probst, Christian M; Preti, Henrique; Ozaki, Luiz S; Buck, Gregory A; Goldenberg, Samuel; Krieger, Marco A

    2010-10-13

    The three trypanosomatids pathogenic to men, Trypanosoma cruzi, Trypanosoma brucei and Leishmania major, are etiological agents of Chagas disease, African sleeping sickness and cutaneous leishmaniasis, respectively. The complete sequencing of these trypanosomatid genomes represented a breakthrough in the understanding of these organisms. Genome sequencing is a step towards solving the parasite biology puzzle, as there are a high percentage of genes encoding proteins without functional annotation. Also, technical limitations in protein expression in heterologous systems reinforce the evident need for the development of a high-throughput reverse genetics platform. Ideally, such platform would lead to efficient cloning and compatibility with various approaches. Thus, we aimed to construct a highly efficient cloning platform compatible with plasmid vectors that are suitable for various approaches. We constructed a platform with a flexible structure allowing the exchange of various elements, such as promoters, fusion tags, intergenic regions or resistance markers. This platform is based on Gateway® technology, to ensure a fast and efficient cloning system. We obtained plasmid vectors carrying genes for fluorescent proteins (green, cyan or yellow), and sequences for the c-myc epitope, and tandem affinity purification or polyhistidine tags. The vectors were verified by successful subcellular localization of two previously characterized proteins (TcRab7 and PAR 2) and a putative centrin. For the tandem affinity purification tag, the purification of two protein complexes (ribosome and proteasome) was performed. We constructed plasmids with an efficient cloning system and suitable for use across various applications, such as protein localization and co-localization, protein partner identification and protein expression. This platform also allows vector customization, as the vectors were constructed to enable easy exchange of its elements. The development of this high

  2. A high-throughput cloning system for reverse genetics in Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Ozaki Luiz S

    2010-10-01

    Full Text Available Abstract Background The three trypanosomatids pathogenic to men, Trypanosoma cruzi, Trypanosoma brucei and Leishmania major, are etiological agents of Chagas disease, African sleeping sickness and cutaneous leishmaniasis, respectively. The complete sequencing of these trypanosomatid genomes represented a breakthrough in the understanding of these organisms. Genome sequencing is a step towards solving the parasite biology puzzle, as there are a high percentage of genes encoding proteins without functional annotation. Also, technical limitations in protein expression in heterologous systems reinforce the evident need for the development of a high-throughput reverse genetics platform. Ideally, such platform would lead to efficient cloning and compatibility with various approaches. Thus, we aimed to construct a highly efficient cloning platform compatible with plasmid vectors that are suitable for various approaches. Results We constructed a platform with a flexible structure allowing the exchange of various elements, such as promoters, fusion tags, intergenic regions or resistance markers. This platform is based on Gateway® technology, to ensure a fast and efficient cloning system. We obtained plasmid vectors carrying genes for fluorescent proteins (green, cyan or yellow, and sequences for the c-myc epitope, and tandem affinity purification or polyhistidine tags. The vectors were verified by successful subcellular localization of two previously characterized proteins (TcRab7 and PAR 2 and a putative centrin. For the tandem affinity purification tag, the purification of two protein complexes (ribosome and proteasome was performed. Conclusions We constructed plasmids with an efficient cloning system and suitable for use across various applications, such as protein localization and co-localization, protein partner identification and protein expression. This platform also allows vector customization, as the vectors were constructed to enable easy

  3. Optimised operation of an off-grid hybrid wind-diesel-battery system using genetic algorithm

    International Nuclear Information System (INIS)

    Gan, Leong Kit; Shek, Jonathan K.H.; Mueller, Markus A.

    2016-01-01

    Highlights: • Diesel generator’s operation is optimised in a hybrid wind-diesel-battery system. • Optimisation is performed using wind speed and load demand forecasts. • The objective is to maximise wind energy utilisation with limited battery storage. • Physical modelling approach (Simscape) is used to verify mathematical model. • Sensitivity analyses are performed with synthesised wind and load forecast errors. - Abstract: In an off-grid hybrid wind-diesel-battery system, the diesel generator is often not utilised efficiently, therefore compromising its lifetime. In particular, the general rule of thumb of running the diesel generator at more than 40% of its rated capacity is often unmet. This is due to the variation in power demand and wind speed which needs to be supplied by the diesel generator. In addition, the frequent start-stop of the diesel generator leads to additional mechanical wear and fuel wastage. This research paper proposes a novel control algorithm which optimises the operation of a diesel generator, using genetic algorithm. With a given day-ahead forecast of local renewable energy resource and load demand, it is possible to optimise the operation of a diesel generator, subjected to other pre-defined constraints. Thus, the utilisation of the renewable energy sources to supply electricity can be maximised. Usually, the optimisation studies of a hybrid system are being conducted through simple analytical modelling, coupled with a selected optimisation algorithm to seek the optimised solution. The obtained solution is not verified using a more realistic system model, for instance the physical modelling approach. This often led to the question of the applicability of such optimised operation being used in reality. In order to take a step further, model-based design using Simulink is employed in this research to perform a comparison through a physical modelling approach. The Simulink model has the capability to incorporate the electrical

  4. Development of an improved genetic algorithm and its application in the optimal design of ship nuclear power system

    International Nuclear Information System (INIS)

    Jia Baoshan; Yu Jiyang; You Songbo

    2005-01-01

    This article focuses on the development of an improved genetic algorithm and its application in the optimal design of the ship nuclear reactor system, whose goal is to find a combination of system parameter values that minimize the mass or volume of the system given the power capacity requirement and safety criteria. An improved genetic algorithm (IGA) was developed using an 'average fitness value' grouping + 'specified survival probability' rank selection method and a 'separate-recombine' duplication operator. Combining with a simulated annealing algorithm (SAA) that continues the local search after the IGA reaches a satisfactory point, the algorithm gave satisfactory optimization results from both search efficiency and accuracy perspectives. This IGA-SAA algorithm successfully solved the design optimization problem of ship nuclear power system. It is an advanced and efficient methodology that can be applied to the similar optimization problems in other areas. (authors)

  5. Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

    Czech Academy of Sciences Publication Activity Database

    Alonso-Perez, E.; Suarez-Gestal, M.; Calaza, M.; Witte, T.; Papasteriades, Ch.; Marchini, M.; Migliaresi, S.; Kovacs, A.; Ordi-Ros, J.; Bijl, M.; Santos, M.J.; Růžičková, Šárka; Pullmann, R.; Carreira, P.; Skopouli, F.N.; D'Alfonso, S.; Sebastiani, G.D.; Suarez, A.; Blanco, F.J.; Gomez-Reino, J.J.; Gonzalez, A.

    2012-01-01

    Roč. 6, č. 12 (2012), e29033 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50520701 Keywords : erythematosus * genetic factors * genotype phenotype correlation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  6. The Relationship between Mating System and Genetic Diversity in Diploid Sexual Populations of Cyrtomium falcatum in Japan.

    Directory of Open Access Journals (Sweden)

    Ryosuke Imai

    Full Text Available The impact of variation in mating system on genetic diversity is a well-debated topic in evolutionary biology. The diploid sexual race of Cyrtomium falcatum (Japanese holly fern shows mating system variation, i.e., it displays two different types of sexual expression (gametangia formation in gametophytes: mixed (M type and separate (S type. We examined whether there is variation in the selfing rate among populations of this species, and evaluated the relationship between mating system, genetic diversity and effective population size using microsatellites. In this study, we developed eight new microsatellite markers and evaluated genetic diversity and structure of seven populations (four M-type and three S-type. Past effective population sizes (Ne were inferred using Approximate Bayesian computation (ABC. The values of fixation index (FIS, allelic richness (AR and gene diversity (h differed significantly between the M-type (FIS: 0.626, AR: 1.999, h: 0.152 and the S-type (FIS: 0.208, AR: 2.718, h: 0.367 populations (when admixed individuals were removed from two populations. Although evidence of past bottleneck events was detected in all populations by ABC, the current Ne of the M-type populations was about a third of that of the S-type populations. These results suggest that the M-type populations have experienced more frequent bottlenecks, which could be related to their higher colonization ability via gametophytic selfing. Although high population differentiation among populations was detected (FST = 0.581, F'ST = 0.739, there was no clear genetic differentiation between the M- and S-types. Instead, significant isolation by distance was detected among all populations. These results suggest that mating system variation in this species is generated by the selection for single spore colonization during local extinction and recolonization events and there is no genetic structure due to mating system.

  7. The Relationship between Mating System and Genetic Diversity in Diploid Sexual Populations of Cyrtomium falcatum in Japan.

    Science.gov (United States)

    Imai, Ryosuke; Tsuda, Yoshiaki; Matsumoto, Sadamu; Ebihara, Atsushi; Watano, Yasuyuki

    2016-01-01

    The impact of variation in mating system on genetic diversity is a well-debated topic in evolutionary biology. The diploid sexual race of Cyrtomium falcatum (Japanese holly fern) shows mating system variation, i.e., it displays two different types of sexual expression (gametangia formation) in gametophytes: mixed (M) type and separate (S) type. We examined whether there is variation in the selfing rate among populations of this species, and evaluated the relationship between mating system, genetic diversity and effective population size using microsatellites. In this study, we developed eight new microsatellite markers and evaluated genetic diversity and structure of seven populations (four M-type and three S-type). Past effective population sizes (Ne) were inferred using Approximate Bayesian computation (ABC). The values of fixation index (FIS), allelic richness (AR) and gene diversity (h) differed significantly between the M-type (FIS: 0.626, AR: 1.999, h: 0.152) and the S-type (FIS: 0.208, AR: 2.718, h: 0.367) populations (when admixed individuals were removed from two populations). Although evidence of past bottleneck events was detected in all populations by ABC, the current Ne of the M-type populations was about a third of that of the S-type populations. These results suggest that the M-type populations have experienced more frequent bottlenecks, which could be related to their higher colonization ability via gametophytic selfing. Although high population differentiation among populations was detected (FST = 0.581, F'ST = 0.739), there was no clear genetic differentiation between the M- and S-types. Instead, significant isolation by distance was detected among all populations. These results suggest that mating system variation in this species is generated by the selection for single spore colonization during local extinction and recolonization events and there is no genetic structure due to mating system.

  8. Application of Genetic Control with Adaptive Scaling Scheme to Signal Acquisition in Global Navigation Satellite System Receiver

    Directory of Open Access Journals (Sweden)

    Ho-Nien Shou

    2012-02-01

    Full Text Available This paper presents a genetic-based control scheme that not only utilizes evolutionary characteristics to find the signal acquisition parameters, but also employs an adaptive scheme to control the search space and avoid the genetic control converging to local optimal value so as to acquire the desired signal precisely and rapidly. Simulations and experiment results show that the proposed method can improve the precision of signal parameters and take less signal acquisition time than traditional serial search methods for global navigation satellite system (GNSS signals.

  9. Systems genetics and genome-wide association approaches for analysis of feed intake, feed efficiency, and performance in beef cattle

    DEFF Research Database (Denmark)

    Santana, M. H. A.; Freua, M. C.; Do, D. N.

    2016-01-01

    Feed intake, feed efficiency, and weight gain are important economic traits of beef cattle in feed lots. In the present study, we investigated the physiological processes underlying such traits from the point of view of systems genetics. Firstly, using data from 1334 Nellore (Bos indicus) cattle......, were annotated and the biological processes underlying the traits were inferred from Database for Annotation, Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results indicated several putative genomic regions associated with the target...... genetics approach used in this study revealed novel pathways related to feed efficiency traits in beef cattle....

  10. A filter rearing system for mass reared genetic sexing strains of Mediterranean fruit fly (Diptera: Tephritidae)

    International Nuclear Information System (INIS)

    Fisher, Kingsley; Caceres, Carlos

    2000-01-01

    The Mediterranean fruit fly (Medfly), Ceratitis capitata (Wied.), is arguably the world's most widespread pest of fresh fruit production. With mounting controversy over using chemicals against insect pests, the sterile insect technique (SIT) has become increasingly more important as a successful technology in controlling or eradicating many insect pests. However, the wider adoption of SIT for Medflies has been hindered by damage to fruit from sterile female stings (Hendrichs et al. 1995). Moreover, the release of sterile females in SIT for Medflies is not efficacious (Hendrichs et al. 1995), a point validated in the field in Hawaii (McInnis et al. 1994) and Guatemala (Rendon, personal communication). Hendrichs et al. (1995) list many other advantages for releasing only male Medflies including improved economy, increased safety and improved field monitoring. Genetic systems for the separation of sexes have been developed for Medflies (Franz and Kerremans 1994, Willhoeft et al. 1996) and they allow for large-scale releases of only males. Genetic sexing strains (GSS), as they are known, are based upon selectable characters linked to the male sex by using a Y-autosome translocation (Franz et al. 1996). There are two types of GSS used in mass rearing. First, strains based upon a recessive mutation (wp) change the pupal colour from brown to white. In these strains, females emerge from white pupae and males from brown pupae. A machine is used to sort the pupae based upon colour. First described by Robinson and Van Heemert (1982), the most recent strain, SEIB 6-96 based upon the T(Y;5) 2-22 translocation, is relatively stable in small scale rearing (Franz et al. 1994). Second are the temperature sensitive lethal strains (wp/tsl) which carry a temperature sensitive lethal (tsl) mutation in addition to wp. In tsl strains, female embryos are killed by exposing eggs to a 3 C temperature during development (Franz et al. 1996). Male embryos are not temperature sensitive and

  11. Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks

    Directory of Open Access Journals (Sweden)

    Zarnescu Daniela C

    2008-11-01

    Full Text Available Abstract Background In Drosophila, the genes sticky and dFmr1 have both been shown to regulate cytoskeletal dynamics and chromatin structure. These genes also genetically interact with Argonaute family microRNA regulators. Furthermore, in mammalian systems, both genes have been implicated in neuronal development. Given these genetic and functional similarities, we tested Drosophila sticky and dFmr1 for a genetic interaction and measured whole genome expression in both mutants to assess similarities in gene regulation. Results We found that sticky mutations can dominantly suppress a dFmr1 gain-of-function phenotype in the developing eye, while phenotypes produced by RNAi knock-down of sticky were enhanced by dFmr1 RNAi and a dFmr1 loss-of-function mutation. We also identified a large number of transcripts that were misexpressed in both mutants suggesting that sticky and dFmr1 gene products similarly regulate gene expression. By integrating gene expression data with a protein-protein interaction network, we found that mutations in sticky and dFmr1 resulted in misexpression of common gene networks, and consequently predicted additional specific phenotypes previously not known to be associated with either gene. Further phenotypic analyses validated these predictions. Conclusion These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes.

  12. Elevator Group Supervisory Control System Using Genetic Network Programming with Macro Nodes and Reinforcement Learning

    Science.gov (United States)

    Zhou, Jin; Yu, Lu; Mabu, Shingo; Hirasawa, Kotaro; Hu, Jinglu; Markon, Sandor

    Elevator Group Supervisory Control System (EGSCS) is a very large scale stochastic dynamic optimization problem. Due to its vast state space, significant uncertainty and numerous resource constraints such as finite car capacities and registered hall/car calls, it is hard to manage EGSCS using conventional control methods. Recently, many solutions for EGSCS using Artificial Intelligence (AI) technologies have been reported. Genetic Network Programming (GNP), which is proposed as a new evolutionary computation method several years ago, is also proved to be efficient when applied to EGSCS problem. In this paper, we propose an extended algorithm for EGSCS by introducing Reinforcement Learning (RL) into GNP framework, and an improvement of the EGSCS' performances is expected since the efficiency of GNP with RL has been clarified in some other studies like tile-world problem. Simulation tests using traffic flows in a typical office building have been made, and the results show an actual improvement of the EGSCS' performances comparing to the algorithms using original GNP and conventional control methods. Furthermore, as a further study, an importance weight optimization algorithm is employed based on GNP with RL and its efficiency is also verified with the better performances.

  13. Genetic-algorithm-based multiple regression with fuzzy inference system for detection of nocturnal hypoglycemic episodes.

    Science.gov (United States)

    Ling, Steve S H; Nguyen, Hung T

    2011-03-01

    Hypoglycemia or low blood glucose is dangerous and can result in unconsciousness, seizures, and even death. It is a common and serious side effect of insulin therapy in patients with diabetes. Hypoglycemic monitor is a noninvasive monitor that measures some physiological parameters continuously to provide detection of hypoglycemic episodes in type 1 diabetes mellitus patients (T1DM). Based on heart rate (HR), corrected QT interval of the ECG signal, change of HR, and the change of corrected QT interval, we develop a genetic algorithm (GA)-based multiple regression with fuzzy inference system (FIS) to classify the presence of hypoglycemic episodes. GA is used to find the optimal fuzzy rules and membership functions of FIS and the model parameters of regression method. From a clinical study of 16 children with T1DM, natural occurrence of nocturnal hypoglycemic episodes is associated with HRs and corrected QT intervals. The overall data were organized into a training set (eight patients) and a testing set (another eight patients) randomly selected. The results show that the proposed algorithm performs a good sensitivity with an acceptable specificity.

  14. Multiple system atrophy: genetic risks and alpha-synuclein mutations [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Heather T Whittaker

    2017-11-01

    Full Text Available Multiple system atrophy (MSA is one of the few neurodegenerative disorders where we have a significant understanding of the clinical and pathological manifestations but where the aetiology remains almost completely unknown. Research to overcome this hurdle is gaining momentum through international research collaboration and a series of genetic and molecular discoveries in the last few years, which have advanced our knowledge of this rare synucleinopathy. In MSA, the discovery of α-synuclein pathology and glial cytoplasmic inclusions remain the most significant findings. Families with certain types of α-synuclein mutations develop diseases that mimic MSA, and the spectrum of clinical and pathological features in these families suggests a spectrum of severity, from late-onset Parkinson’s disease to MSA. Nonetheless, controversies persist, such as the role of common α-synuclein variants in MSA and whether this disorder shares a common mechanism of spreading pathology with other protein misfolding neurodegenerative diseases. Here, we review these issues, specifically focusing on α-synuclein mutations.

  15. The impact of genetic susceptibility to systemic lupus erythematosus on placental malaria in mice.

    Directory of Open Access Journals (Sweden)

    Michael Waisberg

    Full Text Available Severe malaria, including cerebral malaria (CM and placental malaria (PM, have been recognized to have many of the features of uncontrolled inflammation. We recently showed that in mice genetic susceptibility to the lethal inflammatory autoimmune disease, systemic lupus erythematosus (SLE, conferred resistance to CM. Protection appeared to be mediated by immune mechanisms that allowed SLE-prone mice, prior to the onset of overt SLE symptoms, to better control their inflammatory response to Plasmodium infection. Here we extend these findings to ask does SLE susceptibility have 1 a cost to reproductive fitness and/or 2 an effect on PM in mice? The rates of conception for WT and SLE susceptible (SLE(s mice were similar as were the number and viability of fetuses in pregnant WT and SLE(s mice indicating that SLE susceptibility does not have a reproductive cost. We found that Plasmodium chabaudi AS (Pc infection disrupted early stages of pregnancy before the placenta was completely formed resulting in massive decidual necrosis 8 days after conception. Pc-infected pregnant SLE(s mice had significantly more fetuses (∼1.8 fold but SLE did not significantly affect fetal viability in infected animals. This was despite the fact that Pc-infected pregnant SLE(s mice had more severe symptoms of malaria as compared to Pc-infected pregnant WT mice. Thus, although SLE susceptibility was not protective in PM in mice it also did not have a negative impact on reproductive fitness.

  16. Genetic fate-mapping of tyrosine hydroxylase-expressing cells in the enteric nervous system.

    Science.gov (United States)

    Obermayr, F; Stamp, L A; Anderson, C R; Young, H M

    2013-04-01

    During development of the enteric nervous system, a subpopulation of enteric neuron precursors transiently expresses catecholaminergic properties. The progeny of these transiently catecholaminergic (TC) cells have not been fully characterized. We combined in vivo Cre-lox-based genetic fate-mapping with phenotypic analysis to fate-map enteric neuron subtypes arising from tyrosine hydroxylase (TH)-expressing cells. Less than 3% of the total (Hu(+) ) neurons in the myenteric plexus of the small intestine of adult mice are generated from transiently TH-expressing cells. Around 50% of the neurons generated from transiently TH-expressing cells are calbindin neurons, but their progeny also include calretinin, neurofilament-M, and serotonin neurons. However, only 30% of the serotonin neurons and small subpopulations (cells; only 0.2% of nitric oxide synthase neurons arise from TH-expressing cells. Transiently, catecholaminergic cells give rise to subpopulations of multiple enteric neuron subtypes, but the majority of each of the neuron subtypes arises from non-TC cells. © 2013 Blackwell Publishing Ltd.

  17. Improved Multiuser Detectors Employing Genetic Algorithms in a Space-Time Block Coded System

    Directory of Open Access Journals (Sweden)

    Du Yinggang

    2004-01-01

    Full Text Available Enhanced genetic algorithms (GA applied in space-time block coded (STBC multiuser detection (MUD systems in Rayleigh flat-fading channels are reported in this paper. Firstly, an improved objective function, which is designed to help speed up the search for the optimal solution, is introduced. Secondly, a decorrelating detector (DD and a minimum mean square error (MMSE detector have been added to the GA STBC MUD receiver to create the seed chromosome in the initial population. This operation has improved the receiver performance further because some signal information has been intentionally embedded in the initial population. Simulation results show that the receiver employing the improved objective function and the DD or MMSE detector can converge faster with the same bit error rate (BER performance than the receiver with the initial population chosen randomly. The total signal-to-noise ratio (SNR improvement contributed by these two modifications can reach 4 dB. Hence the proposed GA receiver is a promising solution of the STBC MUD problem.

  18. Genetic algorithms for the synthesis optimization of a set of irredundant diagnostic tests in the intelligent system

    Directory of Open Access Journals (Sweden)

    Anna E. Yankovskaya

    2001-12-01

    Full Text Available Method of the synthesis optimization of a set of irredundant diagnostic tests with genetic algorithms used to solve problems of large dimension is suggested. The idea of creating the irredundant partial implication matrix sectionalized by classification mechanisms lies in the base; creating a set of irredundant diagnostic tests is based on revealing certain kinds of regularities with the use of genetic transformations. All the obligatory and non-informative features are not used in genetic transformations. Procedures of selection able-to-compete individuals from populations, decision making concerning the object under examination of each able-to-compete individual from populations, and organizing of voting on the set of these individuals are suggested. In order to solve these problems the intelligent system is used.

  19. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility.

    Science.gov (United States)

    Chintalapudi, Sumana R; Maria, Doaa; Di Wang, Xiang; Bailey, Jessica N Cooke; Hysi, Pirro G; Wiggs, Janey L; Williams, Robert W; Jablonski, Monica M

    2017-11-24

    Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.

  20. Assessment of genetic diversity among Indian potato (Solanum tuberosum L.) collection using microsatellite and retrotransposon based marker systems.

    Science.gov (United States)

    Sharma, Vishakha; Nandineni, Madhusudan R

    2014-04-01

    Potato (Solanum tuberosum) is an important non-cereal crop throughout the world and is highly recommended for ensuring global food security. Owing to the complexities in genetics and inheritance pattern of potato, the conventional method of cross breeding for developing improved varieties has been difficult. Identification and tagging of desirable traits with informative molecular markers would aid in the development of improved varieties. Insertional polymorphism of copia-like and gypsy-like long terminal repeat retrotransposons (RTN) were investigated among 47 potato varieties from India using Inter-Retrotransposon Amplified Polymorphism (IRAP) and Retrotransposon Microsatellite Amplified Polymorphism (REMAP) marker techniques and were compared with the DNA profiles obtained with simple sequence repeats (SSRs). The genetic polymorphism, efficiency of polymorphism and effectiveness of marker systems were evaluated to assess the extent of genetic diversity among Indian potato varieties. A total of 139 polymorphic SSR alleles, 270 IRAP and 98 REMAP polymorphic bands, showing polymorphism of 100%, 87.9% and 68.5%, respectively, were used for detailed characterization of the genetic relationships among potato varieties by using cluster analysis and principal coordinate analysis (PCoA). IRAP analysis resulted in the highest number of polymorphic bands with an average of 15 polymorphic bands per assay unit when compared to the other two marker systems. Based on pair-wise comparison, the genetic similarity was calculated using Dice similarity coefficient. The SSRs showed a wide range in genetic similarity values (0.485-0.971) as compared to IRAP (0.69-0.911) and REMAP (0.713-0.947). A Mantel's matrix correspondence test showed a high positive correlation (r=0.6) between IRAP and REMAP, an intermediate value (r=0.58) for IRAP and SSR and the lowest value (r=0.17) for SSR and REMAP. Statistically significant cophenetic correlation coefficient values, of 0.961, 0.941 and 0

  1. Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Manzi Susan

    2011-01-01

    Full Text Available Abstract Background Low serum paraoxonase (PON activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE. Our prior studies have shown that the PON1/rs662 (p.Gln192Arg, PON1/rs854560 (p.Leu55Met, PON3/rs17884563 and PON3/rs740264 SNPs (single nucleotide polymorphisms significantly affect serum PON activity. Since PON1, PON2 and PON3 share high degree of structural and functional properties, in this study, we examined the role of PON2 genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample. Methods PON2 SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen PON2 SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP or TaqMan allelic discrimination methods. Results Our pair-wise linkage disequilibrium (LD analysis, using an r2 cutoff of 0.7, identified 14 PON2 tagSNPs that captured all 19 PON2 variants in our sample, 12 of which were not in high LD with known PON1 and PON3 SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five PON2 SNPs [rs6954345 (p.Ser311Cys, rs13306702, rs987539, rs11982486, and rs4729189; P = 0.005 to 2.1 × 10-6] that were significantly associated with PON activity. We found no association of PON2 SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183 and immunologic disorder (rs11981433 in SLE patients (P = 0.013 to 0.042. Conclusions Our data indicate that PON2 genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.

  2. A reliability model of the Angra 1 power system by the device of stages optimized by genetic algorithms

    International Nuclear Information System (INIS)

    Crossetti, Patricia Guimaraes

    2006-01-01

    This thesis proposes a probabilistic model to perform the reliability analysis of nuclear power plant systems under aging. This work analyses the Angra 1 power system. Systems subject to aging consist of components whose failure rates are not all constant, thus generating Non-Markovian models. Genetic algorithms were used for optimizing the application of the device of stages. Two approaches were used in the optimization, MCEF and MCEV. The results obtained for the Angra 1 power system show that the probability of a station blackout is negligible. (author)

  3. Likelihood for transcriptions in a genetic regulatory system under asymmetric stable Lévy noise

    Science.gov (United States)

    Wang, Hui; Cheng, Xiujun; Duan, Jinqiao; Kurths, Jürgen; Li, Xiaofan

    2018-01-01

    This work is devoted to investigating the evolution of concentration in a genetic regulation system, when the synthesis reaction rate is under additive and multiplicative asymmetric stable Lévy fluctuations. By focusing on the impact of skewness (i.e., non-symmetry) in the probability distributions of noise, we find that via examining the mean first exit time (MFET) and the first escape probability (FEP), the asymmetric fluctuations, interacting with nonlinearity in the system, lead to peculiar likelihood for transcription. This includes, in the additive noise case, realizing higher likelihood of transcription for larger positive skewness (i.e., asymmetry) index β, causing a stochastic bifurcation at the non-Gaussianity index value α = 1 (i.e., it is a separating point or line for the likelihood for transcription), and achieving a turning point at the threshold value β≈-0.5 (i.e., beyond which the likelihood for transcription suddenly reversed for α values). The stochastic bifurcation and turning point phenomena do not occur in the symmetric noise case (β = 0). While in the multiplicative noise case, non-Gaussianity index value α = 1 is a separating point or line for both the MFET and the FEP. We also investigate the noise enhanced stability phenomenon. Additionally, we are able to specify the regions in the whole parameter space for the asymmetric noise, in which we attain desired likelihood for transcription. We have conducted a series of numerical experiments in "regulating" the likelihood of gene transcription by tuning asymmetric stable Lévy noise indexes. This work offers insights for possible ways of achieving gene regulation in experimental research.

  4. Complex Patterns of Protease Inhibitor Resistance among Antiretroviral Treatment-Experienced HIV-2 Patients from Senegal: Implications for Second-Line Therapy

    Science.gov (United States)

    Smith, Robert A.; Ba, Selly; Toure, Macoumba; Traore, Fatou; Sall, Fatima; Pan, Charlotte; Blankenship, Lindsey; Montano, Alexandra; Olson, Julia; Dia Badiane, Ndeye Mery; Mullins, James I.; Kiviat, Nancy B.; Hawes, Stephen E.; Sow, Papa Salif; Gottlieb, Geoffrey S.

    2013-01-01

    Protease inhibitor (PI)-based antiretroviral therapy (ART) can effectively suppress HIV-2 plasma load and increase CD4 counts; however, not all PIs are equally active against HIV-2, and few data exist to support second-line therapy decisions. To identify therapeutic options for HIV-2 patients failing ART, we evaluated the frequency of PI resistance-associated amino acid changes in HIV-2 sequences from a cohort of 43 Senegalese individuals receiving unboosted indinavir (n = 18 subjects)-, lopinavir/ritonavir (n = 4)-, or indinavir and then lopinavir/ritonavir (n = 21)-containing ART. Common protease substitutions included V10I, V47A, I54M, V71I, I82F, I84V, L90M, and L99F, and most patients harbored viruses containing multiple changes. Based on genotypic data, we constructed a panel of 15 site-directed mutants of HIV-2ROD9 containing single- or multiple-treatment-associated amino acid changes in the protease-encoding region of pol. We then quantified the susceptibilities of the mutants to the HIV-2 “active” PIs saquinavir, lopinavir, and darunavir using a single-cycle assay. Relative to wild-type HIV-2, the V47A mutant was resistant to lopinavir (6.3-fold increase in the mean 50% effective concentration [EC50]), the I54M variant was resistant to darunavir and lopinavir (6.2- and 2.7-fold increases, respectively), and the L90M mutant was resistant to saquinavir (3.6-fold increase). In addition, the triple mutant that included I54M plus I84V plus L90M was resistant to all three PIs (31-, 10-, and 3.8-fold increases in the mean EC50 for darunavir, saquinavir, and lopinavir, respectively). Taken together, our data demonstrate that PI-treated HIV-2 patients frequently harbor viruses that exhibit complex patterns of PI cross-resistance. These findings suggest that sequential PI-based regimens for HIV-2 treatment may be ineffective. PMID:23571535

  5. Lv4 Is a Capsid-Specific Antiviral Activity in Human Blood Cells That Restricts Viruses of the SIVMAC/SIVSM/HIV-2 Lineage Prior to Integration.

    Science.gov (United States)

    Pizzato, Massimo; McCauley, Sean Matthew; Neagu, Martha R; Pertel, Thomas; Firrito, Claudia; Ziglio, Serena; Dauphin, Ann; Zufferey, Madeleine; Berthoux, Lionel; Luban, Jeremy

    2015-07-01

    HIV-2 and SIVMAC are AIDS-causing, zoonotic lentiviruses that jumped to humans and rhesus macaques, respectively, from SIVSM-bearing sooty mangabey monkeys. Cross-species transmission events such as these sometimes necessitate virus adaptation to species-specific, host restriction factors such as TRIM5. Here, a new human restriction activity is described that blocks viruses of the SIVSM/SIVMAC/HIV-2 lineage. Human T, B, and myeloid cell lines, peripheral blood mononuclear cells and dendritic cells were 4 to >100-fold less transducible by VSV G-pseudotyped SIVMAC, HIV-2, or SIVSM than by HIV-1. In contrast, transduction of six epithelial cell lines was equivalent to that by HIV-1. Substitution of HIV-1 CA with the SIVMAC or HIV-2 CA was sufficient to reduce HIV-1 transduction to the level of the respective vectors. Among such CA chimeras there was a general trend such that CAs from epidemic HIV-2 Group A and B isolates were the most infectious on human T cells, CA from a 1° sooty mangabey isolate was the least infectious, and non-epidemic HIV-2 Group D, E, F, and G CAs were in the middle. The CA-specific decrease in infectivity was observed with either HIV-1, HIV-2, ecotropic MLV, or ALV Env pseudotypes, indicating that it was independent of the virus entry pathway. As2O3, a drug that suppresses TRIM5-mediated restriction, increased human blood cell transduction by SIVMAC but not by HIV-1. Nonetheless, elimination of TRIM5 restriction activity did not rescue SIVMAC transduction. Also, in contrast to TRIM5-mediated restriction, the SIVMAC CA-specific block occurred after completion of reverse transcription and the formation of 2-LTR circles, but before establishment of the provirus. Transduction efficiency in heterokaryons generated by fusing epithelial cells with T cells resembled that in the T cells, indicative of a dominant-acting SIVMAC restriction activity in the latter. These results suggest that the nucleus of human blood cells possesses a restriction factor

  6. An investigation of the genetic toxicology of irradiated foodstuffs using short-term systems

    International Nuclear Information System (INIS)

    Phillips, B.J.; Kranz, E.; Elias, P.S.; Muenzner, R.

    1980-01-01

    The genetic toxicology of irradiated foodstuffs has been investigated by the use of a battery of short-term tests for genetic damage. Appropriate methods are discussed for the preparation of food samples for testing by techniques involving micro-organisms and mammalian cells in culture. A new method of sample preparation by enzymatic digestion in vitro is described and its use in the testing of three irradiated foodstuffs by the Salmonella typhimurium reverse mutation test is reported. The results of the mutation tests provide further evidence of the lack of genetic toxicity of irradiated foods. (author)

  7. Genetic Analysis of the Pathogenic Molecular Sub-phenotype Interferon Alpha Identifies Multiple Novel Loci Involved in Systemic Lupus Erythematosus

    Science.gov (United States)

    Kariuki, Silvia N.; Ghodke-Puranik, Yogita; Dorschner, Jessica M.; Chrabot, Beverly S.; Kelly, Jennifer A.; Tsao, Betty P.; Kimberly, Robert P.; Alarcón-Riquelme, Marta E.; Jacob, Chaim O.; Criswell, Lindsey A.; Sivils, Kathy L.; Langefeld, Carl D.; Harley, John B.; Skol, Andrew D.; Niewold, Timothy B.

    2014-01-01

    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. 40–50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs. low IFN-α in over 1550 SLE cases, including GWAS and replication cohorts. In meta-analysis, the top associations in European ancestry were PRKG1 rs7897633 (PMeta=2.75 × 10−8) and PNP rs1049564 (PMeta=1.24 × 10−7). We also found evidence for cross-ancestral background associations with the ANKRD44 and PLEKHF2 loci. These loci have not been previously identified in case-control SLE genetic studies. Bioinformatic analyses implicated these loci functionally in dendritic cells and natural killer cells, both of which are involved in IFN-α production in SLE. As case-control studies of heterogeneous diseases reach a limit of feasibility with respect to subject number and detectable effect size, the study of informative pathogenic subphenotypes becomes an attractive strategy for genetic discovery in complex disease. PMID:25338677

  8. Family system characteristics and psychological adjustment to cancer susceptibility genetic testing : a prospective study

    NARCIS (Netherlands)

    van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Brocker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; Van Gool, A. R.; Klijn, J. G. M.; Tibben, A.

    This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis

  9. The Genetics of Biofuel Traits in Panicum Grasses: Developing a Model System with Diploid Panicum Hallii

    Energy Technology Data Exchange (ETDEWEB)

    Juenger, Thomas [Univ. of Texas, Austin, TX (United States). Dept. of Integrative Biology; Wolfrum, Ed [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-07-31

    Our DOE funded project focused on characterizing natural variation in C4 perennial grasses including switchgrass (Panicum virgatum) and Hall’s panicgrass (Panicum hallii). The main theme of our project was to better understand traits linked with plant performance and that impact the utility of plant biomass as a biofuel feedstock. In addition, our project developed tools and resources for studying genetic variation in Panicum hallii. Our project successfully screened both Panicum virgatum and Panicum hallii diverse natural collections for a host of phenotypes, developed genetic mapping populations for both species, completed genetic mapping for biofuel related traits, and helped in the development of genomic resources of Panicum hallii. Together, these studies have improved our understanding of the role of genetic and environmental factors in impacting plant performance. This information, along with new tools, will help foster the improvement of perennial grasses for feedstock applications.

  10. Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study

    Czech Academy of Sciences Publication Activity Database

    Suarez-Gestal, M.; Calaza, M.; Endreffy, E.; Pullmann, R.; Ordi-Ros, J.; Sebastiani, D.G.; Růžičková, Šárka; Santos, J.M.; Papasteriades, C.; Marchini, M.; Skopouli, F.N.; Suarez, A.; Blanco, F.J.; D'Alfonso, S.; Bijl, M.; Carreira, P.; Witte, T.; Migliaresi, S.; Gomez-Reino, J.J.; Gonzalez, A.

    2009-01-01

    Roč. 11, č. 3 (2009), R69 ISSN 1478-6362 Keywords : Single nucleotide polymorphism susceptibility * sytemic lupus erythematosus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.271, year: 2009

  11. Metabolite Profiling of Maize Grain: Differentiation due to Genetics, Environment and Input System

    OpenAIRE

    Röhlig, Richard M.

    2011-01-01

    A metabolite profiling approach for maize (Zea mays) based on gas chromatography/mass spectrometry was applied to the simultaneous detection, identification and quantification of a broad spectrum of non-polar (fatty acid methyl esters, free fatty acids, fatty alcohols, sterols, hydrocarbons) and polar (sugars, sugar alcohols, organic and inorganic acids, amino acids, amines) constituents. The non-targeted method allowed the investigation of the influence of genetics (cultivar, genetic modific...

  12. An investigation of the genetic toxicology of irradiated foodstuffs using short-term test systems

    International Nuclear Information System (INIS)

    Phillips, B.J.; Kranz, E.; Elias, P.S.

    1980-01-01

    As part of a programme of short-term tests used to detect possible genetic toxicity in irradiated foodstuffs, cultured Chinese hamster ovary cells were exposed to extracts and digests of irradiated and unirradiated dates, fish and chicken and subjected to tests for cytotoxicity, sister chromatid exchange induction and mutation to thioguanine resistance. The results showed no evidence of genetic toxicity induced in food by irradiation. The general applicability of cell culture tests to the detection of mutagens in food is discussed. (author)

  13. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  14. The role of genetic variants in genes regulating the oxytocin-vasopressin neurohumoral system in childhood-onset aggression.

    Science.gov (United States)

    Malik, Ayesha I; Zai, Clement C; Berall, Laura; Abu, Zihad; Din, Farah; Nowrouzi, Behdin; Chen, Sheng; Beitchman, Joseph H

    2014-10-01

    The genetic etiology of aggressive behaviors remains elusive, but growing evidence suggests that they are heritable, and certain genetic variants have been implicated as contributing factors. The oxytocin-vasopressin (OXT-AVP) neurohumoral system has recently been implicated in social behaviors. Oxytocin, especially, has been linked to prosocial behaviors such as trust and social bonds. Hence, the aim of this study was to determine whether genes regulating this system were also associated with childhood-onset aggressive behaviors. Our sample included 182 White children showing extreme, persistent, and pervasive aggressive behavior. These cases were matched with 182 White controls on the basis of sex and age. We used PCR to determine the genotype for 28 single nucleotide polymorphisms within eight genes regulating the OXT-AVP system, including CD38 polymorphisms. Genotypic analyses were carried out using STATA, whereas differences in haplotypic and allelic frequencies were analyzed using Unphased. None of the results reached significance after correction for multiple testing. However, nominally significant allelic effects were observed for OXTR rs6770632T (P=0.028) and AVPR1A rs11174811G (P=0.040) in females, and OXTR rs237898A (P=0.006), rs237902C (P=0.007), and AVP rs3761249A (P=0.008) in males. Genetic variants regulating the OXT-AVP system may be associated with childhood-onset aggression.

  15. Genetically-encoded tools for cAMP probing and modulation in living systems.

    Directory of Open Access Journals (Sweden)

    Valeriy M Paramonov

    2015-09-01

    Full Text Available Intracellular 3'-5'-cyclic adenosine monophosphate (cAMP is one of the principal second messengers downstream of a manifold of signal transduction pathways, including the ones triggered by G protein-coupled receptors. Not surprisingly, biochemical assays for cAMP have been instrumental for basic research and drug discovery for decades, providing insights into cellular physiology and guiding pharmaceutical industry. However, despite impressive track record, the majority of conventional biochemical tools for cAMP probing share the same fundamental shortcoming - all the measurements require sample disruption for cAMP liberation. This common bottleneck, together with inherently low spatial resolution of measurements (as cAMP is typically analyzed in lysates of thousands of cells, underpin the ensuing limitations of the conventional cAMP assays: 1 genuine kinetic measurements of cAMP levels over time in a single given sample are unfeasible; 2 inability to obtain precise information on cAMP spatial distribution and transfer at subcellular levels, let alone the attempts to pinpoint dynamic interactions of cAMP and its effectors. At the same time, tremendous progress in synthetic biology over the recent years culminated in drastic refinement of our toolbox, allowing us not only to bypass the limitations of conventional assays, but to put intracellular cAMP life-span under tight control – something, that seemed scarcely attainable before. In this review article we discuss the main classes of modern genetically-encoded tools tailored for cAMP probing and modulation in living systems. We examine the capabilities and weaknesses of these different tools in the context of their operational characteristics and applicability to various experimental set-ups involving living cells, providing the guidance for rational selection of the best tools for particular needs.

  16. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.

    Science.gov (United States)

    Taylor, Kimberly E; Remmers, Elaine F; Lee, Annette T; Ortmann, Ward A; Plenge, Robert M; Tian, Chao; Chung, Sharon A; Nititham, Joanne; Hom, Geoffrey; Kao, Amy H; Demirci, F Yesim; Kamboh, M Ilyas; Petri, Michelle; Manzi, Susan; Kastner, Daniel L; Seldin, Michael F; Gregersen, Peter K; Behrens, Timothy W; Criswell, Lindsey A

    2008-05-30

    Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2) = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16)). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, poral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.

  17. A study on maintenance reliability allocation of urban transit brake system using hybrid neuro-genetic technique

    International Nuclear Information System (INIS)

    Bae, Chul Ho; Kim, Hyun Jun; Lee, Jung Hwan; Suh, Myung Won; Chu, Yul

    2007-01-01

    For reasonable establishing of maintenance strategies, safety security and cost limitation must be considered at the same time. In this paper, the concept of system reliability introduces and optimizes as the key of reasonable maintenance strategies. This study aims at optimizing component's reliability that satisfies the target reliability of brake system in the urban transit. First of all, constructed reliability evaluation system is used to predict and analyze reliability. This data is used for the optimization. To identify component reliability in a system, a method is presented in this paper which uses hybrid neuro-genetic technique. Feed-forward multi-layer neural networks trained by back propagation are used to find out the relationship between component reliability (input) and system reliability (output) of a structural system. The inverse problem can be formulated by using neural network. Genetic algorithm is used to find the minimum square error. Finally, this paper presents reasonable maintenance cycle of urban transit brake system by using optimal system reliability

  18. Multi-objective optimization of the control strategy of electric vehicle electro-hydraulic composite braking system with genetic algorithm

    OpenAIRE

    Zhang Fengjiao; Wei Minxiang

    2015-01-01

    Optimization of the control strategy plays an important role in improving the performance of electric vehicles. In order to improve the braking stability and recover the braking energy, a multi-objective genetic algorithm is applied to optimize the key parameters in the control strategy of electric vehicle electro-hydraulic composite braking system. Various limitations are considered in the optimization process, and the optimization results are verified by a software simulation platform of el...

  19. Genetic variation in cultivars of diploid ryegrass,Lolium perenne andL. multiflorum, at five enzyme systems

    DEFF Research Database (Denmark)

    Østergaard, H.; Nielsen, Gretha; Johansen, H.

    1985-01-01

    Samples of .apprx. 100 plants from each of 22 populations of L. perenne representing 15 cultivars, and from 13 populations of L. multiflorum representing 6 cultivars were scored for isozyme variants in 5 enzyme systems: PGI, GOT, ACP, PGM and 6-PGD [phosphoglucoisomerase, glutamate oxaloacetate...... transaminase, acid phosphatase, phosphoglucomutase, 6-phosphogluconate dehydrogenase]. From the individual banding patterns a genetic interpretation of the variation was formulated and population studies of the resulting 6 polymorphic enzyme loci were performed. No strong indications of partial selfing...

  20. Three genetic systems controlling growth, development and productivity of rice (Oryza sativa L.): a reevaluation of the 'Green Revolution'.

    Science.gov (United States)

    Zhang, Fan; Jiang, Yun-Zhu; Yu, Si-Bin; Ali, J; Paterson, A H; Khush, G S; Xu, Jian-Long; Gao, Yong-Ming; Fu, Bin-Ying; Lafitte, R; Li, Zhi-Kang

    2013-04-01

    The Green Revolution (GR-I) included worldwide adoption of semi-dwarf rice cultivars (SRCs) with mutant alleles at GA20ox2 or SD1 encoding gibberellin 20-oxidase. Two series of experiments were conducted to characterize the pleiotropic effects of SD1 and its relationships with large numbers of QTLs affecting rice growth, development and productivity. The pleiotropic effects of SD1 in the IR64 genetic background for increased height, root length/mass and grain weight, and for reduced spikelet fertility and delayed heading were first demonstrated using large populations derived from near isogenic IR64 lines of SD1. In the second set of experiments, QTLs controlling nine growth and yield traits were characterized using a new molecular quantitative genetics model and the phenotypic data of the well-known IR64/Azucena DH population evaluated across 11 environments, which revealed three genetic systems: the SD1-mediated, SD1-repressed and SD1-independent pathways that control rice growth, development and productivity. The SD1-mediated system comprised 43 functional genetic units (FGUs) controlled by GA. The SD1-repressed system was the alternative one comprising 38 FGUs that were only expressed in the mutant sd1 backgrounds. The SD1-independent one comprised 64 FGUs that were independent of SD1. GR-I resulted from the overall differences between the former two systems in the three aspects: (1) trait/environment-specific contributions; (2) distribution of favorable alleles for increased productivity in the parents; and (3) different responses to (fertilizer) inputs. Our results suggest that at 71.4 % of the detected loci, a QTL resulted from the difference between a functional allele and a loss-of-function mutant, whereas at the remaining 28.6 % of loci, from two functional alleles with differentiated effects. Our results suggest two general strategies to achieve GR-II (1) by further exploiting the genetic potential of the SD1-repressed and SD1-independent pathways and (2

  1. Powertrain Matching and Optimization of Dual-Motor Hybrid Driving System for Electric Vehicle Based on Quantum Genetic Intelligent Algorithm

    Directory of Open Access Journals (Sweden)

    Yong Wang

    2014-01-01

    Full Text Available In order to increase the driving range and improve the overall performance of all-electric vehicles, a new dual-motor hybrid driving system with two power sources was proposed. This system achieved torque-speed coupling between the two power sources and greatly improved the high performance working range of the motors; at the same time, continuously variable transmission (CVT was achieved to efficiently increase the driving range. The power system parameters were determined using the “global optimization method”; thus, the vehicle’s dynamics and economy were used as the optimization indexes. Based on preliminary matches, quantum genetic algorithm was introduced to optimize the matching in the dual-motor hybrid power system. Backward simulation was performed on the combined simulation platform of Matlab/Simulink and AVL-Cruise to optimize, simulate, and verify the system parameters of the transmission system. Results showed that quantum genetic algorithms exhibited good global optimization capability and convergence in dealing with multiobjective and multiparameter optimization. The dual-motor hybrid-driving system for electric cars satisfied the dynamic performance and economy requirements of design, efficiently increasing the driving range of the car, having high performance, and reducing energy consumption of 15.6% compared with the conventional electric vehicle with single-speed reducers.

  2. Genetically predicted testosterone and systemic inflammation in men: a separate-sample Mendelian randomization analysis in older Chinese men.

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    Full Text Available Observationally, testosterone is negatively associated with systemic inflammation, but this association is open to both residual confounding and reverse causality. Large-scale randomized controlled trials (RCTs, assessing exogenous effects, are presently unavailable. We examined the association of endogenous testosterone with well-established systemic inflammatory markers (white blood cell, granulocyte, lymphocyte and high-sensitivity C-reactive protein (hsCRP using a separate-sample Mendelian randomization analysis to minimize reverse causality.A genetic prediction rule for serum testosterone was developed in 289 young Chinese men with mean age of 21.0, using selected testosterone-related SNPs (rs10046, rs1008805 and rs1256031. Multivariable linear regression was used to examine the association of genetically predicted serum testosterone with inflammatory markers among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study.Genetically predicted testosterone was unrelated to white blood cell count (-0.01 109/L per nmol/L testosterone, 95% confidence interval (CI -0.05 to 0.04, granulocyte count (-0.02 109/L, 95% CI -0.06 to 0.02, lymphocyte count (0.005 109/L, 95% CI -0.01 to 0.02 and hsCRP (-0.05 mg/L, 95% CI -0.15 to 0.06.Our findings did not corroborate any anti-inflammatory effects of testosterone or corresponding potentially protective effects of testosterone on chronic diseases resulting from reduced low-grade systemic inflammation.

  3. Genetics on the Fly: A Primer on the Drosophila Model System

    Science.gov (United States)

    Hales, Karen G.; Korey, Christopher A.; Larracuente, Amanda M.; Roberts, David M.

    2015-01-01

    Fruit flies of the genus Drosophila have been an attractive and effective genetic model organism since Thomas Hunt Morgan and colleagues made seminal discoveries with them a century ago. Work with Drosophila has enabled dramatic advances in cell and developmental biology, neurobiology and behavior, molecular biology, evolutionary and population genetics, and other fields. With more tissue types and observable behaviors than in other short-generation model organisms, and with vast genome data available for many species within the genus, the fly’s tractable complexity will continue to enable exciting opportunities to explore mechanisms of complex developmental programs, behaviors, and broader evolutionary questions. This primer describes the organism’s natural history, the features of sequenced genomes within the genus, the wide range of available genetic tools and online resources, the types of biological questions Drosophila can help address, and historical milestones. PMID:26564900

  4. Optimization and Improvement in Robot-Based Assembly Line System by Hybrid Genetic Algorithm

    Science.gov (United States)

    Lin, Lin; Gen, Mitsuo; Gao, Jie

    In the real world, there are a lot of scenes from which the product is made by using the robot, which needs different assembly times to perform a given task, because of its capabilities and specialization. For a robotic assembly line balancing (rALB) problem, a set of tasks have to be assigned to stations, and each station needs to select one robot to process the assigned tasks. In this paper, we propose a hybrid genetic algorithm (hGA) for solving this problem. In the hGA, we use new representation method. Advanced genetic operators adapted to the specific chromosome structure and the characteristics of the rALB problem are used. In order to strengthen the search ability, a local search procedure is integrated under the framework the genetic algorithm. Some practical test instances demonstrate the effectiveness and efficiency of the proposed algorithm.

  5. Influence of ethnolinguistic diversity on the sorghum genetic patterns in subsistence farming systems in eastern Kenya.

    Directory of Open Access Journals (Sweden)

    Vanesse Labeyrie

    Full Text Available Understanding the effects of actions undertaken by human societies on crop evolution processes is a major challenge for the conservation of genetic resources. This study investigated the mechanisms whereby social boundaries associated with patterns of ethnolinguistic diversity have influenced the on-farm distribution of sorghum diversity. Social boundaries limit the diffusion of planting material, practices and knowledge, thus shaping crop diversity in situ. To assess the effect of social boundaries, this study was conducted in the contact zone between the Chuka, Mbeere and Tharaka ethnolinguistic groups in eastern Kenya. Sorghum varieties were inventoried and samples collected in 130 households. In all, 297 individual plants derived from seeds collected under sixteen variety names were characterized using a set of 18 SSR molecular markers and 15 morphological descriptors. The genetic structure was investigated using both a Bayesian assignment method and distance-based clustering. Principal Coordinates Analysis was used to describe the structure of the morphological diversity of the panicles. The distribution of the varieties and the main genetic clusters across ethnolinguistic groups was described using a non-parametric MANOVA and pairwise Fisher tests. The spatial distribution of landrace names and the overall genetic spatial patterns were significantly correlated with ethnolinguistic partition. However, the genetic structure inferred from molecular makers did not discriminate the short-cycle landraces despite their morphological distinctness. The cases of two improved varieties highlighted possible fates of improved materials. The most recent one was often given the name of local landraces. The second one, that was introduced a dozen years ago, displays traces of admixture with local landraces with differential intensity among ethnic groups. The patterns of congruence or discordance between the nomenclature of farmers' varieties and the

  6. Biological effect of the irradiation of various origins on the genetic systems of plants

    International Nuclear Information System (INIS)

    Akhundova, N.I.

    2002-01-01

    Full text: Results of the irradiation of seeds of the maize breed named 'Absheronskaya mestnaya' by a flow of neutrons are being presented in this work. The dosage of the irradiation totaled to 10 krad. Emergence of low-height fast-ripening plants named 'neutron dwarf plants' has been identified. The research of posterity has showed that yet in the 2nd and 3rd generations the forms that differ from the original ones by a number of morphological signs have emerged. They were two times lower than the original form and with a smaller area of leaves. The tallest 'dwarf' was 110 cm long and the lowest was only 65 cm long. The quantity of the changed forms far exceeded the percentage of the natural mutants emergence. Low-height 'dwarfs' which are stable for blowing of the wind represent interest for the Absheron peninsular since winds are very common there. These 'dwarf plants' represent a scientific and theoretical interest as well. Along with the morphological differences, a biochemical variability has been revealed with the 'neutron dwarfs'. Two-time decrease of the amino acids content has been noted due to the effect of the irradiation. This process is expressed as in two-time decrease of the amino acids sum and so in each of these amino acids separately. The content of lysine, threonin, valine, methionine and leucine amino acids decreases by two times. The content of isoleucine and histidine amino acids decreases by three times while the amount of phenylalanine and tyrosine amino acids decreases by half. The decrease of lysine and methionine synthesis testifies to the decrease of the activity of poly ferment systems and slowing down of the metabolism processes. This results in appearance of the undersized plants of maize. The decrease of the content of the proline, alanine and tyrosine 'stressed' amino acids states reduction of their adaptation potential. Fields of different origin - physical and biological affect the genetic apparatus of the plant cell as well

  7. Circadian Differences in the Contribution of the Brain Renin-Angiotensin System in Genetically Hypertensive Mice

    Directory of Open Access Journals (Sweden)

    Kristy L. Jackson

    2018-03-01

    Full Text Available Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS and reactive oxygen species (ROS reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle. The aim of the present study was to determine whether central AT1 receptor stimulation and the associated ROS signaling contribute to hypertension in BPH/2J mice in a circadian dependent manner.Methods: Blood pressure (BP was measured in BPH/2J and normotensive BPN/3J mice (n = 7–8 via pre-implanted telemetry devices. Acute intracerebroventricular (ICV microinjections of AT1 receptor antagonist, candesartan, and the superoxide dismutase (SOD mimetic, tempol, were administered during the dark and light period of the 24 h light cycle via a pre-implanted ICV guide cannula. In separate mice, the BP effect of ICV infusion of the AT1 receptor antagonist losartan for 7 days was compared with subcutaneous infusion to determine the contribution of the central RAS to hypertension in BPH/2J mice.Results: Candesartan administered ICV during the dark period induced depressor responses which were 40% smaller in BPH/2J than BPN/3J mice (Pstrain < 0.05, suggesting AT1 receptor stimulation may contribute less to BP maintenance in BPH/2J mice. During the light period candesartan had minimal effect on BP in either strain. ICV tempol had comparable effects on BP between strains during the light and dark period (Pstrain > 0.08, suggesting ROS signaling is also not contributing to the hypertension in BPH/2J mice. Chronic ICV administration of losartan (22 nmol/h had minimal effect on BPN/3J mice. By contrast in BPH/2J mice, both ICV and subcutaneously administered

  8. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Kimberly E Taylor

    2008-05-01

    Full Text Available Systemic lupus erythematosus (SLE is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398 and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2 = 0.94 to 0.99 were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16. This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19, nephritis (MAF = 34.3%, OR = 1.80, p<10(-11, and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13. An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10(-4 in the homogeneous subset of subjects. In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.

  9. Virus genetic variations and evade from immune system, the present influenza challenges: review article

    Directory of Open Access Journals (Sweden)

    Shahla Shahsavandi

    2015-10-01

    Full Text Available The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to

  10. Genetic variability in elite barley genotypes based on the agro-morphological characteristics evaluated under irrigated system

    Directory of Open Access Journals (Sweden)

    Renato Fernando Amabile

    Full Text Available ABSTRACT Recently, researches have shown that the Brazilian savannah has a great potential to supply the demand for barley grains. The purpose of this study was to assess the genetic variability in 39 elite barley (Hordeum vulgare L. genotypes based on the agro-morphological traits of a crop irrigated in the savannah system. An irrigation experiment in the design of complete randomized block with four replicates was conducted at Federal District - Brazil. The evaluated traits were: distance from the last knot to the rachis, distance from the flag leaf to rachis, spike length, number of grains by ear, flag leaf area, plant height, silking, lodging, grain yield, thousand-seed weight, protein content and grain commercial classification. After using analysis of variance the means were used to estimate the genetic dissimilarity among all genotypes pairs based on the Mahalanobis’ generalized distance. Cluster analysis using genetic distance matrix was performed having Unweighted Pair Group Method using Arithmetic Means method (UPGMA as the criteria. Highly significant differences were found among the genotypes for all traits evaluated. The high coefficient of genetic variation indicates the possibility of having genetic gains for all traits. The traits that most contributed to the variability were the flag leaf area and silking, while the protein content and lodging were the traits that contributed the least. Based on the cluster analysis, at least three major groups of similarity were found. There was a clustering trend of two and six-rowed materials. The most divergent genotypes were PFC 2005123, Antártica-1, Nandi and FM 404.

  11. Genetic algorithm to optimize two-echelon inventory control system for perishable goods in terms of active packaging

    Directory of Open Access Journals (Sweden)

    Babak Yousefi Yegane

    2012-01-01

    Full Text Available This paper considers an inventory control policy for a two-echelon inventory control system with one supplier-one buyer. We consider the case of deteriorating items which lead to shortage in supply chain. Therefore, it is necessary to decrease the deterioration rate by adding some specification to the packaging of these items that is known as active packaging. Although this packaging can reduce the deteriorating rate of products, but may be increases the cost of both supplier and buyer. Because of the complexity of the mathematical model, a genetic algorithm has been developed to determine the best policy of this inventory control system.

  12. Calibration of the computer model describing flows in the water supply system; example of the application of a genetic algorithm

    Science.gov (United States)

    Orłowska-Szostak, Maria; Orłowski, Ryszard

    2017-11-01

    The paper discusses some relevant aspects of the calibration of a computer model describing flows in the water supply system. The authors described an exemplary water supply system and used it as a practical illustration of calibration. A range of measures was discussed and applied, which improve the convergence and effective use of calculations in the calibration process and also the effect of such calibration which is the validity of the results obtained. Drawing up results of performed measurements, i.e. estimating pipe roughnesses, the authors performed using the genetic algorithm implementation of which is a software developed by Resan Labs company from Brazil.

  13. A multi-objective genetic approach to domestic load scheduling in an energy management system

    International Nuclear Information System (INIS)

    Soares, Ana; Antunes, Carlos Henggeler; Oliveira, Carlos; Gomes, Álvaro

    2014-01-01

    In this paper a multi-objective genetic algorithm is used to solve a multi-objective model to optimize the time allocation of domestic loads within a planning period of 36 h, in a smart grid context. The management of controllable domestic loads is aimed at minimizing the electricity bill and the end-user’s dissatisfaction concerning two different aspects: the preferred time slots for load operation and the risk of interruption of the energy supply. The genetic algorithm is similar to the Elitist NSGA-II (Nondominated Sorting Genetic Algorithm II), in which some changes have been introduced to adapt it to the physical characteristics of the load scheduling problem and improve usability of results. The mathematical model explicitly considers economical, technical, quality of service and comfort aspects. Illustrative results are presented and the characteristics of different solutions are analyzed. - Highlights: • A genetic algorithm similar to the NSGA-II is used to solve a multi-objective model. • The optimized time allocation of domestic loads in a smart grid context is achieved. • A variable preference profile for the operation of the managed loads is included. • A safety margin is used to account for the quality of the energy services provided. • A non-dominated front with the solutions in the two-objective space is obtained

  14. Genetic differentiation of Agrostis capillaris in a grassland system with stable heterogeneity due to terricolous ants

    Czech Academy of Sciences Publication Activity Database

    Rothanzl, J.; Kotoučová, M.; Hrabinová, I.; Plačková, Ivana; Herben, Tomáš

    2007-01-01

    Roč. 95, č. 1 (2007), s. 197-207 ISSN 0022-0477 R&D Projects: GA ČR GA206/06/0098 Institutional research plan: CEZ:AV0Z60050516 Keywords : clonal growth * functional differentiation * genetic variation * isozyme markers Subject RIV: EF - Botanics Impact factor: 4.422, year: 2007

  15. Genetic diversity and dispersal of Phragmites australis in a small river system

    Czech Academy of Sciences Publication Activity Database

    Fér, T.; Hroudová, Zdenka

    2009-01-01

    Roč. 90, č. 2 (2009), s. 165-171 ISSN 0304-3770 R&D Projects: GA AV ČR KJB6111304 Institutional research plan: CEZ:AV0Z60050516 Keywords : genetic variation * long-distance dispersal * spatial autocorrelation Subject RIV: EF - Botanics Impact factor: 1.697, year: 2009

  16. Genetic structure of Polytrichum formosum in relation to the breeding system as revealed by microsatellites

    NARCIS (Netherlands)

    Van der Velde, M; Van de Zande, L; Bijlsma, R

    Microsatellite variation was determined for three Danish and three Dutch populations of the haploid moss species Polytrichum formosum to gain insight into the relative importance of sexual vs. asexual reproduction for the amount and structure of genetic variation. In general, low levels of

  17. Genetic bottlenecks in agroforestry systems: results of tree nursery surveys in East Africa

    NARCIS (Netherlands)

    Lengkeek, A.G.; Jaenicke, H.; Dawson, I.K.

    2005-01-01

    Seedlings sourced through tree nurseries are expected to form an important component of future tree cover on farms. As such, the genetic composition of nursery seedlings is expected to impact on the productivity and sustainability of agroforestry ecosystems. By surveying current practices of nursery

  18. Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

    NARCIS (Netherlands)

    Rietschel, Liz; Streit, Fabian; Zhu, Gu; McAloney, Kerrie; Frank, Josef; Couvy-Duchesne, Baptiste; Witt, Stephanie H; Binz, Tina M; McGrath, John; Hickie, Ian B; Hansell, Narelle K; Wright, Margaret J; Gillespie, Nathan A; Forstner, Andreas J; Schulze, Thomas G; Wüst, Stefan; Nöthen, Markus M; Baumgartner, Markus R; Walker, Brian R; Crawford, Andrew A; Colodro-Conde, Lucía; Medland, Sarah E; Martin, Nicholas G; Rietschel, Marcella; Abdellaoui, A.; de Geus, Eco; Hottenga, J.J.; Mbarek, H.; Middeldorp, C.M.; Willemsen, Gonneke; Boomsma, D.I.

    2017-01-01

    Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors.

  19. A genetic algorithm solution to the design of slat-type shading system

    Energy Technology Data Exchange (ETDEWEB)

    Tsangrassoulis, A. [Architectural Department, School of Engineering, University of Thessaly, 38334 Volos (Greece); Bourdakis, V. [Department of Planning and Regional Development, School of Engineering, University of Thessaly, 38334 Volos (Greece); Geros, V.; Santamouris, M. [Group of Building Environmental Studies, University of Athens, Building Physics 5, 15784, Athens (Greece)

    2006-11-15

    This article presents a technique for the design of slat-type blinds based on the their relative light intensity distribution under a uniform light source. The technique offers a new approach using a genetic algorithm in order to evolve the design according to a set of parameters. (author)

  20. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    NARCIS (Netherlands)

    Kogelman, Lisette J. A.; Zhernakova, Daria V.; Westra, Harm-Jan; Cirera, Susanna; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N.

    2015-01-01

    Background: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about the

  1. Short-Term Memories in "Drosophila" Are Governed by General and Specific Genetic Systems

    Science.gov (United States)

    Zars, Troy

    2010-01-01

    In a dynamic environment, there is an adaptive value in the ability of animals to acquire and express memories. That both simple and complex animals can learn is therefore not surprising. How animals have solved this problem genetically and anatomically probably lies somewhere in a range between a single molecular/anatomical mechanism that applies…

  2. Parallel island genetic algorithm applied to a nuclear power plant auxiliary feedwater system surveillance tests policy optimization

    International Nuclear Information System (INIS)

    Pereira, Claudio M.N.A.; Lapa, Celso M.F.

    2003-01-01

    In this work, we focus the application of an Island Genetic Algorithm (IGA), a coarse-grained parallel genetic algorithm (PGA) model, to a Nuclear Power Plant (NPP) Auxiliary Feedwater System (AFWS) surveillance tests policy optimization. Here, the main objective is to outline, by means of comparisons, the advantages of the IGA over the simple (non-parallel) genetic algorithm (GA), which has been successfully applied in the solution of such kind of problem. The goal of the optimization is to maximize the system's average availability for a given period of time, considering realistic features such as: i) aging effects on standby components during the tests; ii) revealing failures in the tests implies on corrective maintenance, increasing outage times; iii) components have distinct test parameters (outage time, aging factors, etc.) and iv) tests are not necessarily periodic. In our experiments, which were made in a cluster comprised by 8 1-GHz personal computers, we could clearly observe gains not only in the computational time, which reduced linearly with the number of computers, but in the optimization outcome

  3. Optimization of linear consecutive-k-out-of-n system with a Birnbaum importance-based genetic algorithm

    International Nuclear Information System (INIS)

    Cai, Zhiqiang; Si, Shubin; Sun, Shudong; Li, Caitao

    2016-01-01

    The optimization of linear consecutive-k-out-of-n (Lin/Con/k/n) is to find an optimal component arrangement where n components are assigned to n positions to maximize the system reliability. With the interchangeability of components in practical systems, the optimization of Lin/Con/k/n systems is becoming widely applied in engineering practice, which is also a typical component assignment problem concerned by many researchers. This paper proposes a Birnbaum importance-based genetic algorithm (BIGA) to search the near global optimal solution for Lin/Con/k/n systems. First, the operation procedures and corresponding execution methods of BIGA are described in detail. Then, comprehensive simulation experiments are implemented on both small and large systems to evaluate the performance of the BIGA by comparing with the Birnbaum importance-based two-stage approach and Birnbaum importance-based genetic local search algorithm. Thirdly, further experiments are provided to discuss the applicability of BIGA for Lin/Con/k/n system with different k and n. Finally, the case study on oil transportation system is implemented to demonstrate the application of BIGA in the optimization of Lin/Con/k/n system. - Highlights: • BIGA integrates BI and GA to solve the Lin/Con/k/n systems optimization problems. • The experiment results show that the BIGA performs well in most conditions. • Suggestions are given for the application of BIGA and BITA with different k and n. • The application procedure of BIGA is demonstrated by the oil transportation system.

  4. Indoor high precision three-dimensional positioning system based on visible light communication using modified genetic algorithm

    Science.gov (United States)

    Chen, Hao; Guan, Weipeng; Li, Simin; Wu, Yuxiang

    2018-04-01

    To improve the precision of indoor positioning and actualize three-dimensional positioning, a reversed indoor positioning system based on visible light communication (VLC) using genetic algorithm (GA) is proposed. In order to solve the problem of interference between signal sources, CDMA modulation is used. Each light-emitting diode (LED) in the system broadcasts a unique identity (ID) code using CDMA modulation. Receiver receives mixed signal from every LED reference point, by the orthogonality of spreading code in CDMA modulation, ID information and intensity attenuation information from every LED can be obtained. According to positioning principle of received signal strength (RSS), the coordinate of the receiver can be determined. Due to system noise and imperfection of device utilized in the system, distance between receiver and transmitters will deviate from the real value resulting in positioning error. By introducing error correction factors to global parallel search of genetic algorithm, coordinates of the receiver in three-dimensional space can be determined precisely. Both simulation results and experimental results show that in practical application scenarios, the proposed positioning system can realize high precision positioning service.

  5. An Improved Clustering Method for Detection System of Public Security Events Based on Genetic Algorithm and Semisupervised Learning

    Directory of Open Access Journals (Sweden)

    Heng Wang

    2017-01-01

    Full Text Available The occurrence of series of events is always associated with the news report, social network, and Internet media. In this paper, a detecting system for public security events is designed, which carries out clustering operation to cluster relevant text data, in order to benefit relevant departments by evaluation and handling. Firstly, texts are mapped into three-dimensional space using the vector space model. Then, to overcome the shortcoming of the traditional clustering algorithm, an improved fuzzy c-means (FCM algorithm based on adaptive genetic algorithm and semisupervised learning is proposed. In the proposed algorithm, adaptive genetic algorithm is employed to select optimal initial clustering centers. Meanwhile, motivated by semisupervised learning, guiding effect of prior knowledge is used to accelerate iterative process. Finally, simulation experiments are conducted from two aspects of qualitative analysis and quantitative analysis, which demonstrate that the proposed algorithm performs excellently in improving clustering centers, clustering results, and consuming time.

  6. Rapid analysis of genetically modified organisms by in-house developed capillary electrophoresis chip and laser-induced fluorescence system.

    Science.gov (United States)

    Obeid, Pierre J; Christopoulos, Theodore K; Ioannou, Penelope C

    2004-03-01

    A microfabricated, inexpensive, reusable glass capillary electrophoresis chip and a laser-induced fluorescence system were developed in-house for the rapid DNA-based analysis of genetically modified organisms (GMOs). The 35S promoter sequence of cauliflower mosaic virus and the terminator of the nopaline synthase (NOS) gene from Agrobacterium tumefaciens were both detected since they are present in most genetically modified organisms. The detection of genetically modified soybean in the presence of unaltered soybean was chosen as a model. Lectin, a plant-specific gene, was also detected for confirmation of the integrity of extracted DNA. The chip was composed of two glass plates, each 25 x 76 mm, thermally bonded together to form a closed structure. Photomasks with cross-topology were prepared rapidly by using polymeric material instead of chrome plates. The widths of the injection and separation channels were 30 and 70 microm, respectively, the effective separation length 4.5 cm. The glass slide was etched to a depth of 30 microm for both the injection and separation channel. The cost of the chip was less than 1 $ and required 2 days for photomask preparation and microfabrication. The separation and detection of polymerase chain reaction-amplified NOS, 35S, and lectin sequences (180, 195, and 181 bp, respectively) was completed in less than 60 s. As low as 0.1% GMO content was detectable by the proposed system after 35 and 40 amplification cycles for 35S and NOS, respectively, using 25 ng of extracted DNA as starting material. This corresponds to only 20 genome copies of genetically modified soybean.

  7. Automatic Laser Pointer Detection Algorithm for Environment Control Device Systems Based on Template Matching and Genetic Tuning of Fuzzy Rule-Based Systems

    Directory of Open Access Journals (Sweden)

    F.

    2012-04-01

    Full Text Available In this paper we propose a new approach for laser-based environment device control systems based on the automatic design of a Fuzzy Rule-Based System for laser pointer detection. The idea is to improve the success rate of the previous approaches decreasing as much as possible the false offs and increasing the success rate in images with laser spot, i.e., the detection of a false laser spot (since this could lead to dangerous situations. To this end, we propose to analyze both, the morphology and color of a laser spot image together, thus developing a new robust algorithm. Genetic Fuzzy Systems have also been employed to improve the laser spot system detection by means of a fine tuning of the involved membership functions thus reducing the system false offs, which is the main objective in this problem. The system presented in this paper, makes use of a Fuzzy Rule-Based System adjusted by a Genetic Algorithm, which, based on laser morphology and color analysis, shows a better success rate than previous approaches.

  8. Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C M; Nielsen, C

    1989-01-01

    The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba...

  9. Serial CD4 and CD8 T-lymphocyte counts and associated mortality in an HIV-2-infected population in Guinea-Bissau

    DEFF Research Database (Denmark)

    Lisse, I M; Poulsen, A G; Aaby, P

    1996-01-01

    In an urban community in Guinea-Bissau, we followed a cohort of human immunodeficiency virus type 2 (HIV-2) seropositive individuals (N = 47) and seronegative controls (N = 82). T-lymphocyte subset determinations were done in 1988, 1990, and 1992. Serial determinations of CD4 percentages, CD8 per...

  10. Desktop Genetics.

    Science.gov (United States)

    Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward

    2016-11-01

    Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learning techniques can transform this information into a cognitive therapeutic development tool that will revolutionize medicine.

  11. Managing genetic tests, surveillance, and preventive medicine under a public health insurance system.

    Science.gov (United States)

    Filipova-Neumann, Lilia; Hoy, Michael

    2014-03-01

    There is a prospect in the medium to long term future of substantial advancements in the understanding of the relationship between disease and genetics. We consider the implications of increased information from genetic tests about predisposition to diseases from the perspective of managing health care provision under a public health insurance scheme. In particular, we consider how such information may potentially improve the targeting of medical surveillance (or prevention) activities to improve the chances of early detection of disease onset. We show that the moral hazard implications inherent in surveillance and prevention decisions that are chosen to be privately rather than socially optimal may be exacerbated by increased information about person-specific predisposition to disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Specialized Genetic Recombination Systems in Bacteria: Their Involvement in Gene Expression and Evolution,

    Science.gov (United States)

    1980-01-01

    Z operons , mainly the lactose and tryptophan regions, has resulted in the following generalizations: (1) Mu- induced mutations are strongly polar...G., Ghosal, D., Saedler, H.: Tn 951: a new transposon carrying a lactose operon . Mol. Gen. Genet. 160, 215-224 (1978) Cornelis, G., Ghosal, D...78 (1979) Malanny, N.H. : Seone properties of insertion. mutations in the operon . In: The Lactose Operon (eds. J.R. Beckwith, D. ’/ipser) , pp. 359

  13. Usher's Syndrome Type II: A Comparative Study of Genetic Mutations and Vestibular System Evaluation.

    Science.gov (United States)

    Magliulo, Giuseppe; Iannella, Giannicola; Gagliardi, Silvia; Iozzo, Nicola; Plateroti, Rocco; Mariottini, Alessandro; Torricelli, Francesca

    2017-11-01

    Objective Usher's syndrome type II (USH2) is characterized by moderate to profound congenital hearing loss, later onset of retinitis pigmentosa, and normal vestibular function. Recently, a study investigating the vestibular function of USH2 patients demonstrated a pathologic response to vestibular tests. In this cross-sectional study we performed vestibular tests of a group patients with genetic diagnosis of USH2 syndrome to demonstrate if vestibular damage is present in USH2 patients. Study Design Cross-sectional study. Setting Tertiary referral center. Subjects and Methods Mutated genes of 7 patients with a clinical diagnosis of USH2 were evaluated. Vestibular function was investigated by audiometry, Fitzgerald-Hallpike caloric vestibular testing, cervical vestibular evoked myogenic potentials (C-VEMPs), ocular vestibular evoked myogenic potentials (O-VEMPs), and video head impulse test (v-HIT). Results Genetic tests confirmed the USH2 diagnosis in 5 of 7 patients examined, with 1 patient reporting a unique mutation on genetic tests. Four (80%) of the 5 patients with a genetic diagnosis of USH2 showed pathological O-VEMPs. Two patients (40%) reported bilateral absent or abnormal values of C-VEMPs. The superior semicircular canal presented a significant deficit in 2 (40%) patients. The same 2 cases showed a pathologic response of the v-HIT of the horizontal semicircular canal. Finally, the posterior semicircular canal presented a significant deficit in 4 (40.0%) patients. Conclusion A vestibular evaluation with vestibular evoked myogenic potentials and v-HIT seems to identify latent damage to the vestibular receptors of USH2 patients.

  14. Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system.

    Science.gov (United States)

    Inda, M M; Perot, C; Guillaud-Bataille, M; Danglot, G; Rey, J A; Bello, M J; Fan, X; Eberhart, C; Zazpe, I; Portillo, E; Tuñón, T; Martínez-Peñuela, J M; Bernheim, A; Castresana, J S

    2005-12-01

    Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB. We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB. Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.

  15. Dobzhansky-muller and wolbachia-induced incompatibilities in a diploid genetic system.

    Directory of Open Access Journals (Sweden)

    Arndt Telschow

    Full Text Available Genetic incompatibilities are supposed to play an important role in speciation. A general (theoretical problem is to explain the persistence of genetic diversity after secondary contact. Previous theoretical work has pointed out that Dobzhansky-Muller incompatibilities (DMI are not stable in the face of migration unless local selection acts on the alleles involved in incompatibility. With local selection, genetic variability exists up to a critical migration rate but is lost when migration exceeds this threshold value. Here, we investigate the effect of intracellular bacteria Wolbachia on the stability of hybrid zones formed after the Dobzhansky Muller model. Wolbachia are known to cause a cytoplasmic incompatibility (CI within and between species. Incorporating intracellular bacteria Wolbachia can lead to a significant increase of critical migration rates and maintenance of divergence, primarily because Wolbachia-induced incompatibility acts to reduce frequencies of F1 hybrids. Wolbachia infect up to two-thirds of all insect species and it is therefore likely that CI co-occurs with DMI in nature. The results indicate that both isolating mechanisms strengthen each other and under some circumstances act synergistically. Thus they can drive speciation processes more forcefully than either when acting alone.

  16. Dobzhansky-muller and wolbachia-induced incompatibilities in a diploid genetic system.

    Science.gov (United States)

    Telschow, Arndt; Hilgenboecker, Kirsten; Hammerstein, Peter; Werren, John H

    2014-01-01

    Genetic incompatibilities are supposed to play an important role in speciation. A general (theoretical) problem is to explain the persistence of genetic diversity after secondary contact. Previous theoretical work has pointed out that Dobzhansky-Muller incompatibilities (DMI) are not stable in the face of migration unless local selection acts on the alleles involved in incompatibility. With local selection, genetic variability exists up to a critical migration rate but is lost when migration exceeds this threshold value. Here, we investigate the effect of intracellular bacteria Wolbachia on the stability of hybrid zones formed after the Dobzhansky Muller model. Wolbachia are known to cause a cytoplasmic incompatibility (CI) within and between species. Incorporating intracellular bacteria Wolbachia can lead to a significant increase of critical migration rates and maintenance of divergence, primarily because Wolbachia-induced incompatibility acts to reduce frequencies of F1 hybrids. Wolbachia infect up to two-thirds of all insect species and it is therefore likely that CI co-occurs with DMI in nature. The results indicate that both isolating mechanisms strengthen each other and under some circumstances act synergistically. Thus they can drive speciation processes more forcefully than either when acting alone.

  17. Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism.

    Science.gov (United States)

    Dufrasne, François E; Lombard, Catherine; Goubau, Patrick; Ruelle, Jean

    2016-10-14

    BST-2 or tetherin is a host cell restriction factor that prevents the budding of enveloped viruses at the cell surface, thus impairing the viral spread. Several countermeasures to evade this antiviral factor have been positively selected in retroviruses: the human immunodeficiency virus type 2 (HIV-2) relies on the envelope glycoprotein (Env) to overcome BST-2 restriction. The Env gp36 ectodomain seems involved in this anti-tetherin activity, however residues and regions interacting with BST-2 are not clearly defined. Among 32 HIV-2 ROD Env mutants tested, we demonstrated that the asparagine residue at position 659 located in the gp36 ectodomain is mandatory to exert the anti-tetherin function. Viral release assays in cell lines expressing BST-2 showed a loss of viral release ability for the HIV-2 N659D mutant virus compared to the HIV-2 wild type virus. In bst-2 inactivated H9 cells, those differences were lost. Subtilisin treatment of infected cells demonstrated that the N659D mutant was more tethered at the cell surface. Förster resonance energy transfer (FRET) experiments confirmed a direct molecular link between Env and BST-2 and highlighted an inability of the mutant to bind BST-2. We also tested a virus presenting a truncation of 109 amino acids at the C-terminal part of Env, a cytoplasmic tail partial deletion that is spontaneously selected in vitro. Interestingly, viral release assays and FRET experiments indicated that a full Env cytoplasmic tail was essential in BST-2 antagonism. In HIV-2 infected cells, an efficient Env-mediated antagonism of BST-2 is operated through an intermolecular link involving the asparagine 659 residue as well as the C-terminal part of the cytoplasmic tail.

  18. [Development of an antigen 'sandwich' enzyme immunoassay for the detection of antibodies against HIV-2 by using a biotinylated synthetic peptide of gp36 protein].

    Science.gov (United States)

    Delahanty-Fernández, Aurora; Bequer-Ariza, Dunia Clara; Hernández-Marín, Milenen; Zulueta-Rodríguez, Orlando; Pozo-Peña, Lilliam; Hernández-Spengler, Idialis; Ramos-Martínez, Grisell; Valdespino-Díaz, Marcos Antonio; Ventura-Paz, Julio

    2015-01-01

    Among the several existing methods for the detection of antibodies to HIV, the 'sandwich' ELISA is currently the most used. This study aims to assess a biotinylated monomeric synthetic peptide of the glycoprotein trans-membrane gp36 from HIV-2, in a sandwich assay, for the detection of antibodies against this HIV-2 protein. To perform the assay, plates coated with recombinant protein gp36 at 0.5μg/mL and synthetic peptide gp36(5) at 1μg/mL were used. The concentration of the biotinylated synthetic peptide (gp36(5)-B) used was 0.1μg/mL prepared with a Tris-BSA-NaCl buffer solution and the Streptavidin- Alkaline Phosphatase conjugate diluted 1:30000 prepared with a PBS-Sucrose-BSA solution. Positive serum samples to antibodies against HIV-1 and HIV-2 viruses (88 and 34, respectively) were tested, with 483 negative samples from blood donors and 96 serum samples to assess the analytical specificity. All the samples were tested using the UMELISA HIV 1+2 RECOMBINANT assay, and all positives were confirmed using a DAHIV-BLOT assay. Thirty four samples with antibodies against HIV-2 were assessed as positive for both coating variants. The highest specificity was obtained with the variant using the synthetic peptide gp36(5) in its coating. The antigen 'sandwich' assay developed by using gp36(5)-B enables the detection of antibodies against gp36 protein of HIV-2. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Maintenance of adaptive differentiation by Wolbachia induced bidirectional cytoplasmic incompatibility: the importance of sib-mating and genetic systems.

    Science.gov (United States)

    Branca, Antoine; Vavre, Fabrice; Silvain, Jean-François; Dupas, Stéphane

    2009-08-04

    Bacteria of the genus Wolbachia are reproductive parasites widespread among arthropods. The most common effect arising from the presence of Wolbachia in a population is Cytoplasmic Incompatibility (CI), whereby postmating reproductive isolation occurs in crosses between an infected male and an uninfected female, or when a male is infected with a different strain of Wolbachia to that of the female (bidirectional CI). Previous theoretical models have demonstrated that bidirectional CI can contribute to the genetic divergence of populations in haploid and diploid organisms. However, haplodiploid organisms were not considered in these models even though they include Nasonia parasitoid wasps - the best example of the implication of Wolbachia in ongoing speciation. Moreover, previous work did not investigate inbreeding mating systems, which are frequently observed in arthropod species. We developed a stochastic two-island model which simulated three genetic scenarios, diploidy, haploidy, and haplodiploidy, with two CI phenotypes being considered for the latter: (1) male development of female progeny; and (2) mortality of fertilized eggs. We also investigated the effect of varying the proportion of sib mating. In the model each allopatric population was initially fixed for a single allele at a nuclear locus under positive selection and infected with one strain of Wolbachia. Each simulation presupposed that the two populations were fixed for a different allele and a different strain of Wolbachia. The degree of genetic differentiation observed in the locus under selection due to bidirectional CI was much lower for the two haplodiploid phenotypes than for either diploids or haploids. Furthermore, we demonstrated that sib-mating may compensate for the lower efficiency of bidirectional CI in haplodiploids by maintaining genetic divergence. Our model suggests that maintenance of genetic differentiation facilitated by Wolbachia is more likely to occur in diploids and haploids

  20. Maintenance of adaptive differentiation by Wolbachia induced bidirectional cytoplasmic incompatibility: the importance of sib-mating and genetic systems

    Directory of Open Access Journals (Sweden)

    Branca Antoine

    2009-08-01

    Full Text Available Abstract Background Bacteria of the genus Wolbachia are reproductive parasites widespread among arthropods. The most common effect arising from the presence of Wolbachia in a population is Cytoplasmic Incompatibility (CI, whereby postmating reproductive isolation occurs in crosses between an infected male and an uninfected female, or when a male is infected with a different strain of Wolbachia to that of the female (bidirectional CI. Previous theoretical models have demonstrated that bidirectional CI can contribute to the genetic divergence of populations in haploid and diploid organisms. However, haplodiploid organisms were not considered in these models even though they include Nasonia parasitoid wasps – the best example of the implication of Wolbachia in ongoing speciation. Moreover, previous work did not investigate inbreeding mating systems, which are frequently observed in arthropod species. Results We developed a stochastic two-island model which simulated three genetic scenarios, diploidy, haploidy, and haplodiploidy, with two CI phenotypes being considered for the latter: (1 male development of female progeny; and (2 mortality of fertilized eggs. We also investigated the effect of varying the proportion of sib mating. In the model each allopatric population was initially fixed for a single allele at a nuclear locus under positive selection and infected with one strain of Wolbachia. Each simulation presupposed that the two populations were fixed for a different allele and a different strain of Wolbachia. The degree of genetic differentiation observed in the locus under selection due to bidirectional CI was much lower for the two haplodiploid phenotypes than for either diploids or haploids. Furthermore, we demonstrated that sib-mating may compensate for the lower efficiency of bidirectional CI in haplodiploids by maintaining genetic divergence. Conclusion Our model suggests that maintenance of genetic differentiation facilitated by

  1. Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry

    Science.gov (United States)

    Ho, Vincy Wing Sze; Wong, Ming-Kin; An, Xiaomeng; Guan, Daogang; Shao, Jiaofang; Ng, Hon Chun Kaoru; Ren, Xiaoliang; He, Kan; Liao, Jinyue; Ang, Yingjin; Chen, Long; Huang, Xiaotai; Yan, Bin; Xia, Yiji; Chan, Leanne Lai Hang; Chow, King Lau; Yan, Hong; Zhao, Zhongying

    2015-01-01

    Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems-level genetic architecture coordinating division timing, we performed a high-content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild-type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time-lapse imaging followed by computer-aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development. PMID:26063786

  2. Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry.

    Science.gov (United States)

    Ho, Vincy Wing Sze; Wong, Ming-Kin; An, Xiaomeng; Guan, Daogang; Shao, Jiaofang; Ng, Hon Chun Kaoru; Ren, Xiaoliang; He, Kan; Liao, Jinyue; Ang, Yingjin; Chen, Long; Huang, Xiaotai; Yan, Bin; Xia, Yiji; Chan, Leanne Lai Hang; Chow, King Lau; Yan, Hong; Zhao, Zhongying

    2015-06-10

    Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems-level genetic architecture coordinating division timing, we performed a high-content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild-type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time-lapse imaging followed by computer-aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  3. Determination of interrill soil erodibility coefficient based on Fuzzy and Fuzzy-Genetic Systems

    Directory of Open Access Journals (Sweden)

    Habib Palizvan Zand

    2017-02-01

    Full Text Available Introduction: Although the fuzzy logic science has been used successfully in various sudies of hydrology and soil erosion, but in literature review no article was found about its performance for estimating of interrill erodibility. On the other hand, studies indicate that genetic algorithm techniques can be used in fuzzy models and finding the appropriate membership functions for linguistic variables and fuzzy rules. So this study was conducted to develop the fuzzy and fuzzy–genetics models and investigation of their performance in the estimation of soil interrill erodibility factor (Ki. Materials and Methods: For this reason 36 soil samples with different physical and chemical properties were collected from west of Azerbaijan province . soilsamples were also taken from the Ap or A horizon of each soil profile. The samples were air-dried , sieved and Some soil characteristics such as soil texture, organic matter (OM, cation exchange capacity (CEC, sodium adsorption ratio (SAR, EC and pH were determined by the standard laboratory methods. Aggregates size distributions (ASD were determined by the wet-sieving method and fractal dimension of soil aggregates (Dn was also calculated. In order to determination of soil interrill erodibility, the flume experiment performed by packing soil a depth of 0.09-m in 0.5 × 1.0 m. soil was saturated from the base and adjusted to 9% slope and was subjected to at least 90 min rainfall . Rainfall intensity treatments were 20, 37 and 47 mm h-1. During each rainfall event, runoff was collected manually in different time intervals, being less than 60 s at the beginning, up to 15 min near the end of the test. At the end of the experiment, the volumes of runoff samples and the mass of sediment load at each time interval were measured. Finally interrill erodibility values were calculated using Kinnell (11 Equation. Then by statistical analyses Dn and sand percent of the soils were selected as input variables and Ki as

  4. Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.

    Science.gov (United States)

    Castillejo-López, Casimiro; Delgado-Vega, Angélica M; Wojcik, Jerome; Kozyrev, Sergey V; Thavathiru, Elangovan; Wu, Ying-Yu; Sánchez, Elena; Pöllmann, David; López-Egido, Juan R; Fineschi, Serena; Domínguez, Nicolás; Lu, Rufei; James, Judith A; Merrill, Joan T; Kelly, Jennifer A; Kaufman, Kenneth M; Moser, Kathy L; Gilkeson, Gary; Frostegård, Johan; Pons-Estel, Bernardo A; D'Alfonso, Sandra; Witte, Torsten; Callejas, José Luis; Harley, John B; Gaffney, Patrick M; Martin, Javier; Guthridge, Joel M; Alarcón-Riquelme, Marta E

    2012-01-01

    Altered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis. The GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.

  5. Population Genetic Structure and Reproductive Strategy of the Introduced Grass Centotheca lappacea in Tropical Land-Use Systems in Sumatra.

    Science.gov (United States)

    Hodač, Ladislav; Ulum, Fuad Bahrul; Opfermann, Nicole; Breidenbach, Natalie; Hojsgaard, Diego; Tjitrosoedirdjo, Sri Sudarmiyati; Vornam, Barbara; Finkeldey, Reiner; Hörandl, Elvira

    2016-01-01

    Intensive transformation of lowland rainforest into oil palm and rubber monocultures is the most common land-use practice in Sumatra (Indonesia), accompanied by invasion of weeds. In the Jambi province, Centotheca lappacea is one of the most abundant alien grass species in plantations and in jungle rubber (an extensively used agroforest), but largely missing in natural rainforests. Here, we investigated putative genetic differentiation and signatures for adaptation in the introduced area. We studied reproductive mode and ploidy level as putative factors for invasiveness of the species. We sampled 19 populations in oil palm and rubber monocultures and in jungle rubber in two regions (Bukit Duabelas and Harapan). Amplified fragment length polymorphisms (AFLP) revealed a high diversity of individual genotypes and only a weak differentiation among populations (FST = 0.173) and between the two regions (FST = 0.065). There was no significant genetic differentiation between the three land-use systems. The metapopulation of C. lappacea consists of five genetic partitions with high levels of admixture; all partitions appeared in both regions, but with different proportions. Within the Bukit Duabelas region we observed significant isolation-by-distance. Nine AFLP loci (5.3% of all loci) were under natural diversifying selection. All studied populations of C. lappacea were diploid, outcrossing and self-incompatible, without any hints of apomixis. The estimated residence time of c. 100 years coincides with the onset of rubber and oil palm planting in Sumatra. In the colonization process, the species is already in a phase of establishment, which may be enhanced by efficient selection acting on a highly diverse gene pool. In the land-use systems, seed dispersal might be enhanced by adhesive spikelets. At present, the abundance of established populations in intensively managed land-use systems might provide opportunities for rapid dispersal of C. lappacea across rural landscapes

  6. Forecasting the EMU inflation rate: Linear econometric vs. non-linear computational models using genetic neural fuzzy systems

    DEFF Research Database (Denmark)

    Kooths, Stefan; Mitze, Timo Friedel; Ringhut, Eric

    2004-01-01

    to a battery of parametric and non-parametric test statistics to measure their performance in one- and four-step ahead forecasts of quarterly data. Using genetic-neural fuzzy systems we find the computational approach superior to some degree and show how to combine both techniques successfully.......This paper compares the predictive power of linear econometric and non-linear computational models for forecasting the inflation rate in the European Monetary Union (EMU). Various models of both types are developed using different monetary and real activity indicators. They are compared according...

  7. On the vulnerability of iris-based systems to a software attack based on a genetic algorithm

    OpenAIRE

    Gómez-Barrero, Marta; Galbally Herrero, Javier; Tomé González, Pedro; Fiérrez, Julián

    2012-01-01

    The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-33275-3_14 Proceedings of 17th Iberoamerican Congress, CIARP 2012, Buenos Aires, Argentina The vulnerabilities of a standard iris verification system to a novel indirect attack based on a binary genetic algorithm are studied. The experiments are carried out on the iris subcorpus of the publicly available BioSecure DB. The attack has shown a remarkable performance, thus proving the lack of robustness o...

  8. A Combined Methodology of Adaptive Neuro-Fuzzy Inference System and Genetic Algorithm for Short-term Energy Forecasting

    Directory of Open Access Journals (Sweden)

    KAMPOUROPOULOS, K.

    2014-02-01

    Full Text Available This document presents an energy forecast methodology using Adaptive Neuro-Fuzzy Inference System (ANFIS and Genetic Algorithms (GA. The GA has been used for the selection of the training inputs of the ANFIS in order to minimize the training result error. The presented algorithm has been installed and it is being operating in an automotive manufacturing plant. It periodically communicates with the plant to obtain new information and update the database in order to improve its training results. Finally the obtained results of the algorithm are used in order to provide a short-term load forecasting for the different modeled consumption processes.

  9. Genetic Diversity in Relict and Fragmented Populations of Ulmus glabra Hudson in the Central System of the Iberian Peninsula

    Directory of Open Access Journals (Sweden)

    María Martín del Puerto

    2017-04-01

    Full Text Available Ulmus glabra Hudson, or Wych elm, occurs as fragmented and relict natural populations in the Central System, which acts as a refugium in the Iberian Peninsula. Considering the importance of the Central System populations of U. glabra, the main objective was to assess their genetic diversity using nuclear microsatellite markers. A total of 360 different genotypes were detected in the 427 U. glabra individuals analyzed. Wych elm populations showed a highly significant genetic differentiation (24%; p = 0.0001. Of the 22 populations studied, population of Rozas de Puerto Real (ROZ showed the highest values of effective number of alleles (2.803, mean Shannon’s diversity (1.047 and expected heterozygosity (0.590. Populations of ROZ and Mombeltrán (MOM showed the highest values of observed heterozygosity (0.838 and 0.709, respectively, and highly negative values for inbreeding coefficient (−0.412 and −0.575, respectively. Also, most of putative hybrids (50 of 55 were observed in these two populations. Demographic analysis revealed signals for recent (four populations and ancestral (fifteen populations bottlenecks. Fragmented populations with diminishing number of individuals, along with anthropogenic intervention and Dutch elm disease (DED, are the main threats to U. glabra populations. From a future perspective, the information generated can be considered in the formulation of conservation strategies for U. glabra populations in the Central System.

  10. Genetic analysis of eight population groups living in Taiwan using a 13 X-chromosomal STR loci multiplex system.

    Science.gov (United States)

    Hwa, Hsiao-Lin; Lee, James Chun-I; Chang, Yih-Yuan; Yin, Hsiang-Yi; Chen, Ya-Hui; Tseng, Li-Hui; Su, Yi-Ning; Ko, Tsang-Ming

    2011-01-01

    A 13 X-chromosomal short tandem repeat (STR) multiplex system (DXS6807, DXS8378, DSX9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7424, DXS101, GATA172D05, HPRTB, DXS8377, and DXS7423) was tested on 1,037 DNA samples from eight population groups currently living in Taiwan. Different distributions of the allelic frequencies in different populations were presented. DXS8377 and DXS101 were the two most polymorphic loci in these eight populations, whereas DXS7423 was the least informative marker in most of the populations studied. The genetic distances between the populations and the constructed phylogenetic tree revealed a long genetic distance between Asian and Caucasian populations as well as isolation of the Tao population. The phylogenetic tree grouped populations into clusters compatible with their ethnogeographic relationships. This 13 X-chromosomal short tandem repeat multiplex system offers a considerable number of polymorphic patterns in different populations. This system can be useful in forensic identification casework and ethnogeographic research.

  11. Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus

    Science.gov (United States)

    Park, Joo Youn; Moon, Bo Youn; Park, Juw Won; Thornton, Justin A.; Park, Yong Ho; Seo, Keun Seok

    2017-01-01

    Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus. PMID:28322317

  12. Potential large animal models for gene therapy of human genetic diseases of immune and blood cell systems.

    Science.gov (United States)

    Bauer, Thomas R; Adler, Rima L; Hickstein, Dennis D

    2009-01-01

    Genetic mutations involving the cellular components of the hematopoietic system--red blood cells, white blood cells, and platelets--manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy before their use in humans with the corresponding disease.

  13. Fault Diagnosis System of Induction Motors Based on Neural Network and Genetic Algorithm Using Stator Current Signals

    Directory of Open Access Journals (Sweden)

    Tian Han

    2006-01-01

    Full Text Available This paper proposes an online fault diagnosis system for induction motors through the combination of discrete wavelet transform (DWT, feature extraction, genetic algorithm (GA, and neural network (ANN techniques. The wavelet transform improves the signal-to-noise ratio during a preprocessing. Features are extracted from motor stator current, while reducing data transfers and making online application available. GA is used to select the most significant features from the whole feature database and optimize the ANN structure parameter. Optimized ANN is trained and tested by the selected features of the measurement data of stator current. The combination of advanced techniques reduces the learning time and increases the diagnosis accuracy. The efficiency of the proposed system is demonstrated through motor faults of electrical and mechanical origins on the induction motors. The results of the test indicate that the proposed system is promising for the real-time application.

  14. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age

  15. Genetic differentiation of sockeye salmon subpopulations from a geologically young Alaskan lake system

    Science.gov (United States)

    Burger, C.V.; Spearman, William J.; Cronin, M.A.

    1997-01-01

    The Tustumena lake drainage in southcentral Alaska is glacially turbid and geologically young (salmon Oncorhynchus nerka at Tustumena Lake, based on the distribution and timing of spawners. The subpopulations included early-run salmon that spawned in six clearwater tributaries of the lake (mid August), lake shoreline spawners (late August), and late-run fish that spawned in the lake's outlet, the Kasilof River (late September). Our objective was to determine the degree of genetic differentiation among these subpopulations based on restriction enzyme analyses of the cytochrome b gene of mitochondrial DNA and analyses of four polymorphic allozyme loci. Mitochondrial DNA haplotype frequencies for outlet-spawning sockeye salmon differed significantly from those of all other subpopulations. The most common (36%) haplotype in the outlet subpopulation did not occur elsewhere, thus suggesting little or no gene flow between outlet spawners and other spatially close subpopulations at Tustumena Lake. Allele frequencies at two allozyme loci also indicated a degree of differentiation of the outlet subpopulation from the shoreline and tributary subpopulations. Allele frequencies for three tributary subpopulations were temporally stable over approximately 20 years (based on a comparison to previously published results) despite initiation of a hatchery program in two of the tributaries during the intervening period. Collectively, our results are consistent with the hypothesis that significant genetic differentiation has occurred within the Tustumena Lake drainage since deglaciation approximately 2,000 years ago.

  16. Genetic Variation in the Natriuretic Peptide System, Circulating Natriuretic Peptide Levels, and Blood Pressure

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen L; Nielsen, Søren J; Torp-Pedersen, Christian

    2012-01-01

    -h ambulatory BP measurements (ABPMs) will influence the effect of NP gene variations on BP levels.MethodsWe used rs632793 at the NPPB (NP precursor B) locus to investigate the relationship between genetically determined serum N-terminal pro-brain NP (NT-proBNP) concentrations and BP levels...... determined by both 24-h ABPMs and OBPMs in a population consisting of 1,397 generally healthy individuals taking no BP-lowering drugs.Resultsrs632793 was significantly correlated with serum Nt-proBNP levels (r = 0.10, P = 0.0003), and participants with the A:A genotype had lower serum Nt-proBNP levels than......). Office BP decreased across the genotypes from A:A to G:G, but the differences did not reach statistical significance (P = 0.12).ConclusionsThis study suggests that 24-h ABPMs is a better method than OBPMs to detect significant differences in BP levels related to genetic variance and provides further...

  17. Genetic marking and characterization of Tac2-expressing neurons in the central and peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Mar Lynn

    2012-01-01

    Full Text Available Abstract Background The neurocircuits that process somatic sensory information in the dorsal horn of the spinal cord are still poorly understood, with one reason being the lack of Cre lines for genetically marking or manipulating selective subpopulations of dorsal horn neurons. Here we describe Tac2-Cre mice that were generated to express the Cre recombinase gene from the Tac2 locus. Tachykinin 2 (Tac2 encodes a neurotransmitter, neurokinin B (NKB. Results By crossing Tac2-Cre mice with ROSA26-tdTomato reporter mice, we directly visualized Tac2 lineage neurons in the dorsal root ganglia, the dorsal horn of the spinal cord, and many parts of the brain including the olfactory bulb, cerebral cortex, amygdala, hippocampus, habenula, hypothalamus, and cerebellum. This Tac2-Cre allele itself was a null allele for the Tac2 gene. Behavioral analyses showed that Tac2 homozygous null mice responded normally to a series of algogenic (pain-inducing and pruritic (itch-inducing stimuli. Conclusions Tac2-Cre mice are a useful tool to mark specific subsets of neurons in the sensory ganglia, the dorsal spinal cord, and the brain. These mice can also be used for future genetic manipulations to study the functions of Tac2-expressing neurons or the functions of genes expressed in these neurons.

  18. QTL mapping with different genetic systems for nine non-essential amino acids of cottonseeds.

    Science.gov (United States)

    Liu, Haiying; Quampah, Alfred; Chen, Jinhong; Li, Jinrong; Huang, Zhuangrong; He, Qiuling; Shi, Chunhai; Zhu, Shuijin

    2017-06-01

    Amino acid is an important nutrient resource for both human and animals. Using a set of 188 RILs population derived from an elite hybrid cross of upland cotton cultivars 'HS46' × 'MARCABUCAG8US-1-88' and their immortal F 2 (IF 2 ) with reciprocal backcrosses BC 1 F 1 and BC 2 F 1 (BC) populations in two environments, the QTLs located on the embryo genome and maternal plant genome for nine amino acids of cottonseed were studied across environments. The QTL Network-CL-2.0-seed software was used to analyze the QTLs and their genetic effects for nine amino acids. A total of 56 QTLs for nine amino acids were detected in both populations, with many having over 5% of phenotypic variation. Ten of the total QTLs could be simultaneously found in the IF 2 and BC populations. For most QTLs, the genetic effects from embryo genome were more important than those from maternal plant genome for the performance of nine amino acids. Significant embryo additive main effects and maternal additive main effect with their environment interaction effects from many QTLs were also found in present experiment. Some QTLs with larger phenotypic variation were important for improving the amino-acid contents in cottonseeds.

  19. Conserved genetic pathways controlling the development of the diffuse endocrine system in vertebrates and Drosophila.

    Science.gov (United States)

    Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina L

    2010-05-01

    The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. Copyright 2009. Published by Elsevier Inc.

  20. Development of a system for genetic manipulation of the facultative methanotroph Methylocella silvestris BL2.

    Science.gov (United States)

    Crombie, Andrew; Murrell, J Colin

    2011-01-01

    An understanding of the metabolism and metabolic regulation of the facultative methanotroph Methylocella silvestris BL2 is required to understand its role in methane oxidation in the environment, and methods for genetics manipulation are essential tools in these investigations. In addition, the ability to engineer the metabolic capabilities of M. silvestris may well have useful biotechnological applications. We describe a simple and effective method of genetic manipulation for this organism which relies on the electroporation of a linear DNA fragment to introduce chromosomal gene deletions. In a two-step procedure, the gene of interest is first replaced with an antibiotic-resistance cassette which is subsequently removed, resulting in an unmarked gene deletion. This method is illustrated by the deletion of isocitrate lyase, which abolished growth on one-carbon and severely disabled growth on two-carbon compounds. Subsequent complementation with the wild-type gene and promoter restored growth, demonstrating stable transcription from the broad-host-range plasmid employed. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Genetic polymorphisms in the cytokine and chemokine system: their possible importance in allogeneic stem cell transplantation.

    Science.gov (United States)

    Loeffler, Juergen; Ok, Michael; Morton, Oliver C; Mezger, Markus; Einsele, Hermann

    2010-01-01

    Chemokines represent central players of the innate and adaptive immunity and are involved in the regulation of inflammatory events occurring during infectious complications or during graft vs. host disease (GvHD). Patients after allogeneic stem cell transplantation (alloSCT) are at a high risk for the development of acute GvHD or to suffer from fungal infections. Susceptibility to fungal infections and the course of GvHD can be genetically influenced by single nucleotide polymorphisms (SNPs), which regulate expression or biological activity of chemokines, and therefore have an impact on the outcome of invasive aspergillosis and GvHD. High lightened studies of abetting factors for GvHD revealed SNPs in TNFA, IL-6, IL-10, INF-γ, CCL2, CCL5 (RANTES), IL-1Ra, IL-23R, IL-7Ralpha, IL-10RB, and CCR9 genes as prevalent considerable. Furthermore, additional SNPs were described to be significantly associated with fungal infections (Aspergillus fumigatus, Candida albicans), including markers in CCL3, CCL4, CCL20, CXCL2, CXCL8, CXCL10, CCR1, and CCR2. This review summarizes the current knowledge about the growing number of genetic markers in chemokine genes and their relevance for patients after alloSCT.

  2. QTL mapping based on different genetic systems for essential amino acid contents in cottonseeds in different environments.

    Science.gov (United States)

    Liu, Haiying; Quampah, Alfred; Chen, Jinhong; Li, Jinrong; Huang, Zhuangrong; He, Qiuling; Zhu, Shuijin; Shi, Chunhai

    2013-01-01

    Cottonseeds are rich in various essential amino acids. However, the inheritance of them at molecular level are still not defined across various genetic systems. In the present study, using a newly developed mapping model that can analyze the embryo and maternal main effects as well as QTL × environment interaction effects on quantitative quality trait loci (QTLs) in cottonseeds, a study on QTL located in the tetraploid embryo and tetraploid maternal plant genomes for essential amino acid contents in cottonseeds under different environments was carried out, using the immortal F2 (IF2) populations from a set of 188 recombinant inbred lines derived from an intraspecific hybrid cross of two upland cotton germplasms HS46 and MARKCBUCAG8US-1-88 as experimental materials. The results showed a total of 35 QTLs associated with these quality traits in cottonseeds. Nineteen QTLs were subsequently mapped on chromosome 5, 6 and 8 in sub-A genome and chromosome 15, 18, 22 and 23 in sub-D genome. Eighteen QTLs were also found having QTL × environment (QE) interaction effects. The genetic main effects from QTLs located on chromosomes in the embryo and maternal plant genomes and their QE effects in different environments were all important for these essential amino acids in cottonseeds. The results suggested that the influence of environmental factors on the expression of some QTLs located in different genetic systems should be considered when improving for these amino acids. This study can serve as the foundation for the improvement of these essential amino acids in cottonseeds.

  3. Reverse Genetics System Demonstrates that Rotavirus Nonstructural Protein NSP6 Is Not Essential for Viral Replication in Cell Culture.

    Science.gov (United States)

    Komoto, Satoshi; Kanai, Yuta; Fukuda, Saori; Kugita, Masanori; Kawagishi, Takahiro; Ito, Naoto; Sugiyama, Makoto; Matsuura, Yoshiharu; Kobayashi, Takeshi; Taniguchi, Koki

    2017-11-01

    The use of overlapping open reading frames (ORFs) to synthesize more than one unique protein from a single mRNA has been described for several viruses. Segment 11 of the rotavirus genome encodes two nonstructural proteins, NSP5 and NSP6. The NSP6 ORF is present in the vast majority of rotavirus strains, and therefore the NSP6 protein would be expected to have a function in viral replication. However, there is no direct evidence of its function or requirement in the viral replication cycle yet. Here, taking advantage of a recently established plasmid-only-based reverse genetics system that allows rescue of recombinant rotaviruses entirely from cloned cDNAs, we generated NSP6-deficient viruses to directly address its significance in the viral replication cycle. Viable recombinant NSP6-deficient viruses could be engineered. Single-step growth curves and plaque formation of the NSP6-deficient viruses confirmed that NSP6 expression is of limited significance for RVA replication in cell culture, although the NSP6 protein seemed to promote efficient virus growth. IMPORTANCE Rotavirus is one of the most important pathogens of severe diarrhea in young children worldwide. The rotavirus genome, consisting of 11 segments of double-stranded RNA, encodes six structural proteins (VP1 to VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6). Although specific functions have been ascribed to each of the 12 viral proteins, the role of NSP6 in the viral replication cycle remains unknown. In this study, we demonstrated that the NSP6 protein is not essential for viral replication in cell culture by using a recently developed plasmid-only-based reverse genetics system. This reverse genetics approach will be successfully applied to answer questions of great interest regarding the roles of rotaviral proteins in replication and pathogenicity, which can hardly be addressed by conventional approaches. Copyright © 2017 American Society for Microbiology.

  4. Systemic Inflammation and the Brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Roman eSankowski

    2015-02-01

    Full Text Available The nervous and immune systems have evolved in parallel from the early bilaterians, in which innate immunity and a central nervous system coexisted for the first time, to jawed vertebrates and the appearance of adaptive immunity. The central nervous system (CNS feeds from, and integrates efferent signals in response to, somatic and autonomic sensory information. The CNS receives input also from the periphery about inflammation and infection. Cytokines, chemokines, damage-associated soluble mediators of systemic inflammation can also gain access to the CNS via blood flow. In response to systemic inflammation, those soluble mediators can access directly through the circumventricular organs, as well as open the blood-brain barrier (BBB. The resulting translocation of inflammatory mediators can interfere with neuronal and glial well-being, leading to a break of balance in brain homeostasis. This in turn results in cognitive and behavioral manifestations commonly present during acute infections -including anorexia, malaise, depression, and decreased physical activity- collectively known as the sickness behavior (SB. While SB manifestations are transient and self-limited, under states of persistent systemic inflammatory response the cognitive and behavioral changes can become permanent. For example, cognitive decline is almost universal in sepsis survivors, and a common finding in patients with systemic lupus erythematosus (SLE. Here, we review recent genetic evidence suggesting an association between neurodegenerative disorders and persistent immune activation; clinical and experimental evidence indicating previously unidentified immune-mediated pathways of neurodegeneration; and novel immunomodulatory targets and their potential relevance for neurodegenerative disorders.

  5. Optimal Energy Management, Location and Size for Stationary Energy Storage System in a Metro Line Based on Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Huan Xia

    2015-10-01

    Full Text Available The installation of stationary super-capacitor energy storage system (ESS in metro systems can recycle the vehicle braking energy and improve the pantograph voltage profile. This paper aims to optimize the energy management, location, and size of stationary super-capacitor ESSes simultaneously and obtain the best economic efficiency and voltage profile of metro systems. Firstly, the simulation platform of an urban rail power supply system, which includes trains and super-capacitor energy storage systems, is established. Then, two evaluation functions from the perspectives of economic efficiency and voltage drop compensation are put forward. Ultimately, a novel optimization method that combines genetic algorithms and a simulation platform of urban rail power supply system is proposed, which can obtain the best energy management strategy, location, and size for ESSes simultaneously. With actual parameters of a Chinese metro line applied in the simulation comparison, certain optimal scheme of ESSes’ energy management strategy, location, and size obtained by a novel optimization method can achieve much better performance of metro systems from the perspectives of two evaluation functions. The simulation result shows that with the increase of weight coefficient, the optimal energy management strategy, locations and size of ESSes appear certain regularities, and the best compromise between economic efficiency and voltage drop compensation can be obtained by a novel optimization method, which can provide a valuable reference to subway company.

  6. Genetic variants associated with the root system architecture of oilseed rape (Brassica napus L.) under contrasting phosphate supply.

    Science.gov (United States)

    Wang, Xiaohua; Chen, Yanling; Thomas, Catherine L; Ding, Guangda; Xu, Ping; Shi, Dexu; Grandke, Fabian; Jin, Kemo; Cai, Hongmei; Xu, Fangsen; Yi, Bin; Broadley, Martin R; Shi, Lei

    2017-08-01

    Breeding crops with ideal root system architecture for efficient absorption of phosphorus is an important strategy to reduce the use of phosphate fertilizers. To investigate genetic variants leading to changes in root system architecture, 405 oilseed rape cultivars were genotyped with a 60K Brassica Infinium SNP array in low and high P environments. A total of 285 single-nucleotide polymorphisms were associated with root system architecture traits at varying phosphorus levels. Nine single-nucleotide polymorphisms corroborate a previous linkage analysis of root system architecture quantitative trait loci in the BnaTNDH population. One peak single-nucleotide polymorphism region on A3 was associated with all root system architecture traits and co-localized with a quantitative trait locus for primary root length at low phosphorus. Two more single-nucleotide polymorphism peaks on A5 for root dry weight at low phosphorus were detected in both growth systems and co-localized with a quantitative trait locus for the same trait. The candidate genes identified on A3 form a haplotype 'BnA3Hap', that will be important for understanding the phosphorus/root system interaction and for the incorporation into Brassica napus breeding programs. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  7. Parameter identification of the glazed photovoltaic thermal system using Genetic Algorithm–Fuzzy System (GA–FS) approach and its comparative study

    International Nuclear Information System (INIS)

    Singh, Sonveer; Agrawal, Sanjay

    2015-01-01

    Highlights: • Optimization using Genetic Algorithm–Fuzzy System approach. • Overall exergy efficiency has been evaluated with different optimization tools. • Comparative analysis has been done. • GA–FS is very efficient and fast technique. • Overall exergy efficiency has been improved. - Abstract: In this paper, Genetic Algorithm–Fuzzy System (GA–FS) approach is used to identify the optimized parameters of the glazed photovoltaic thermal (PVT) system and to improve its overall exergy efficiency. The fuzzy knowledge base is used to improve the efficiency of Genetic Algorithm (GA). It is observed that three GA parameters, namely: (i) crossover probability (P cross ), (ii) mutation probability (P mut ) and (iii) population size are changing dynamically during the program, according to fuzzy knowledge base to maximize the efficiency of the GA. Here, overall exergy efficiency is considered as an objective function during the optimization process for GA–FS approach. The effort has been made to identify the different optimized parameters like; length and depth of the channel, velocity of flowing fluid, overall heat transfer coefficient from solar cell to ambient and flowing fluid and overall back loss heat transfer coefficient from flowing fluid to the ambient to maximize the overall exergy efficiency using GA–FS approach. Performance of glazed PVT using GA–FS approach has been compared with performance using GA approach and without GA. It has also been observed that the GA–FS approach is a better approach as compared to GA approach because it converges faster as compare to GA because the use of the fuzzy knowledge base with GA and take less time for identification of optimized system parameters.

  8. Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork

    Directory of Open Access Journals (Sweden)

    Druka Arnis

    2008-11-01

    Full Text Available Abstract Background A typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community. Description Using a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork http://www.genenetwork.org. GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits. Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them. Conclusion By

  9. Analysis of viral (zucchini yellow mosaic virus) genetic diversity during systemic movement through a Cucurbita pepo vine.

    Science.gov (United States)

    Dunham, J P; Simmons, H E; Holmes, E C; Stephenson, A G

    2014-10-13

    Determining the extent and structure of intra-host genetic diversity and the magnitude and impact of population bottlenecks is central to understanding the mechanisms of viral evolution. To determine the nature of viral evolution following systemic movement through a plant, we performed deep sequencing of 23 leaves that grew sequentially along a single Cucurbita pepo vine that was infected with zucchini yellow mosaic virus (ZYMV), and on a leaf that grew in on a side branch. Strikingly, of 112 genetic (i.e. sub-consensus) variants observed in the data set as a whole, only 22 were found in multiple leaves. Similarly, only three of the 13 variants present in the inoculating population were found in the subsequent leaves on the vine. Hence, it appears that systemic movement is characterized by sequential population bottlenecks, although not sufficient to reduce the population to a single virion as multiple variants were consistently transmitted between leaves. In addition, the number of variants within a leaf increases as a function of distance from the inoculated (source) leaf, suggesting that the circulating sap may serve as a continual source of virus. Notably, multiple mutational variants were observed in the cylindrical inclusion (CI) protein (known to be involved in both cell-to-cell and systemic movement of the virus) that were present in multiple (19/24) leaf samples. These mutations resulted in a conformational change, suggesting that they might confer a selective advantage in systemic movement within the vine. Overall, these data reveal that bottlenecks occur during systemic movement, that variants circulate in the phloem sap throughout the infection process, and that important conformational changes in CI protein may arise during individual infections. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Development of a laser-activated mesoporous silica nanocarrier delivery system for applications in molecular and genetic research

    Science.gov (United States)

    Davidson, Lien M.; Barkalina, Natalia; Yeste, Marc; Jones, Celine; Coward, Kevin

    2016-11-01

    Nanoparticles have revolutionized medical research over the last decade. One notable emerging area of nanomedicine is research developments in the reproductive sciences. Since increasing evidence indicates links between abnormal gene expression and previously unexplained states of infertility, there is a strong impetus to develop tools, such as nanoparticle platforms, to elucidate the pathophysiological mechanisms underlying such states. Mesoporous silica nanoparticles (MSNPs) represent a powerful and safe delivery tool for molecular and genetic investigations. Nevertheless, ongoing progress is restricted by low efficiency and unpredictable control of cargo delivery. Here, we describe for the first time, the development of a laser-activated MSNP system with heat-responsive cargo. Data derived from human embryonic kidney cells (HEK293T) indicate that when driven by a heat-shock promoter, MSNP cargo exhibits a significantly increased expression following infrared laser stimulus to stimulate a heat-shock response, without adverse cytotoxic effects. This delivery platform, with increased efficiency and the ability to impart spatial and temporal control, is highly useful for molecular and genetic investigations. We envision that this straightforward stimuli-responsive system could play a significant role in developing efficient nanodevices for research applications, for example in reproductive medicine.

  11. Optimization of the method of stages through genetic algorithms for unavailable protection systems analysis considering aging effects

    International Nuclear Information System (INIS)

    Nunes, Marcos Eduardo Costa

    2001-03-01

    When a safety system is under aging the failure times follow non-exponential distributions, and its interstate transition rates become time-dependent. It follows, therefore, that the stochastic process employed in the modeling becomes Nonmarkovian. In this thesis, this analysis is developed using an alternative method, called the device of stages which allows the transformation of Nonmarkovian models into equivalent Markovian ones. That transformation consists in reshaping the state transition diagram with time-dependent transition rates into a new one where fictitious states (called stages) are added and whose transition rates are constant. The number of added stages and their connections are identification parameters of the device of stages used for the equivalent Markovian model and requires a robust and efficient optimization tool. In order to perform a global search in such a topologically complex space, a genetic algorithm has been developed to automatically determine the stages combination and set of parameters which better represent the analyzed distribution. The developed genetic algorithm has demonstrated a good ability for optimizing the method of stages. Results concerning the application to a nuclear reactor protection system are shown and commented, in which the Weibull distribution is employed for modelling failure times. (author)

  12. Prediction of China's coal production-environmental pollution based on a hybrid genetic algorithm-system dynamics model

    International Nuclear Information System (INIS)

    Yu Shiwei; Wei Yiming

    2012-01-01

    This paper proposes a hybrid model based on genetic algorithm (GA) and system dynamics (SD) for coal production–environmental pollution load in China. GA has been utilized in the optimization of the parameters of the SD model to reduce implementation subjectivity. The chain of “Economic development–coal demand–coal production–environmental pollution load” of China in 2030 was predicted, and scenarios were analyzed. Results show that: (1) GA performs well in optimizing the parameters of the SD model objectively and in simulating the historical data; (2) The demand for coal energy continuously increases, although the coal intensity has actually decreased because of China's persistent economic development. Furthermore, instead of reaching a turning point by 2030, the environmental pollution load continuously increases each year even under the scenario where coal intensity decreased by 20% and investment in pollution abatement increased by 20%; (3) For abating the amount of “three types of wastes”, reducing the coal intensity is more effective than reducing the polluted production per tonne of coal and increasing investment in pollution control. - Highlights: ► We propos a GA-SD model for China's coal production-pollution prediction. ► Genetic algorithm (GA) can objectively and accurately optimize parameters of system dynamics (SD) model. ► Environmental pollution in China is projected to grow in our scenarios by 2030. ► The mechanism of reducing waste production per tonne of coal mining is more effective than others.

  13. Probabilistic expert systems for forensic inference from DNA markers in horses: applications to confirm genealogies with lack of genetic data.

    Science.gov (United States)

    Dobosz, Marina; Bocci, Chiara; Bonuglia, Margherita; Grasso, Cinzia; Merigioli, Sara; Russo, Alessandra; De Iuliis, Paolo

    2010-01-01

    Microsatellites have been used for parentage testing and individual identification in forensic science because they are highly polymorphic and show abundant sequences dispersed throughout most eukaryotic nuclear genomes. At present, genetic testing based on DNA technology is used for most domesticated animals, including horses, to confirm identity, to determine parentage, and to validate registration certificates. But if genetic data of one of the putative parents are missing, verifying a genealogy could be questionable. The aim of this paper is to illustrate a new approach to analyze complex cases of disputed relationship with microsatellites markers. These cases were solved by analyzing the genotypes of the offspring and other horses' genotypes in the pedigrees of the putative dam/sire with probabilistic expert systems (PESs). PES was especially efficient in supplying reliable, error-free Bayesian probabilities in complex cases with missing pedigree data. One of these systems was developed for forensic purposes (FINEX program) and is particularly valuable in human analyses. We applied this program to parentage analysis in horses, and we will illustrate how different cases have been successfully worked out.

  14. Natural fracture systems on planetary surfaces: Genetic classification and pattern randomness

    Science.gov (United States)

    Rossbacher, Lisa A.

    1987-01-01

    One method for classifying natural fracture systems is by fracture genesis. This approach involves the physics of the formation process, and it has been used most frequently in attempts to predict subsurface fractures and petroleum reservoir productivity. This classification system can also be applied to larger fracture systems on any planetary surface. One problem in applying this classification system to planetary surfaces is that it was developed for ralatively small-scale fractures that would influence porosity, particularly as observed in a core sample. Planetary studies also require consideration of large-scale fractures. Nevertheless, this system offers some valuable perspectives on fracture systems of any size.

  15. The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis

    National Research Council Canada - National Science Library

    Zhou, Xiaodong

    2008-01-01

    .... To develop a comprehensive statistical analysis in study of dynamic properties of fibroblasts, we employed widely used state-space equations in systems science to model biological systems, and used...

  16. Translocation-based genetic sexing system to enhance the sterile insect technique against the melon fly (Diptera: Tephritidae)

    International Nuclear Information System (INIS)

    McCombs, S.D.; Lee, S.G.; Saul, S.H.

    1993-01-01

    The autosomal recessive bubble wing (bw) mutant was used to construct a translocation-based genetic sex sorting system in the melon fly, Bactrocera cucurbitae (Coquillett). The translocation stock has females with the bubble wing phenotype that are unable to fly, but the males are wild-type and fly normally. The bubble wing translocation strain has lower egg hatch, larval viability, and eclosion rates than the wild-type strain. Expression of the bubble wing trait is temperature-dependent, with high expression of the trait in 92% of adults at 23°C but in only 15% of adults at 28°C. This translocation-based sex sorting system is the only method available for automatic separation of male and female melon flies in sterile insect release programs

  17. Multi-objective optimization of the control strategy of electric vehicle electro-hydraulic composite braking system with genetic algorithm

    Directory of Open Access Journals (Sweden)

    Zhang Fengjiao

    2015-03-01

    Full Text Available Optimization of the control strategy plays an important role in improving the performance of electric vehicles. In order to improve the braking stability and recover the braking energy, a multi-objective genetic algorithm is applied to optimize the key parameters in the control strategy of electric vehicle electro-hydraulic composite braking system. Various limitations are considered in the optimization process, and the optimization results are verified by a software simulation platform of electric vehicle regenerative braking system in typical brake conditions. The results show that optimization objectives achieved a good astringency, and the optimized control strategy can increase the brake energy recovery effectively under the condition of ensuring the braking stability.

  18. Optimization of the test intervals of a nuclear safety system by genetic algorithms, solution clustering and fuzzy preference assignment

    Energy Technology Data Exchange (ETDEWEB)

    Zio, E. [Ecole Centrale Paris- Supelec, Paris (France); Bazzo, R. [Politecnico di Milano, Milano (Italy)

    2010-08-15

    In this paper, a procedure is developed for identifying a number of representative solutions manageable for decision-making in a multiobjective optimization problem concerning the test intervals of the components of a safety system of a nuclear power plant. Pareto Front solutions are identified by a genetic algorithm and then clustered by subtractive clustering into 'families'. On the basis of the decision maker's preferences, each family is then synthetically represented by a 'head of the family' solution. This is done by introducing a scoring system that ranks the solutions with respect to the different objectives: a fuzzy preference assignment is employed to this purpose. Level Diagrams are then used to represent, analyze and interpret the Pareto Fronts reduced to the head-of-the-family solutions

  19. Fuzzy Logic Controller Based on Observed Signals and a Genetic Algorithm Application with STATCOM for Power System Stabilization

    Science.gov (United States)

    Hongesombut, Komsan; Mitani, Yasunori; Tsuji, Kiichiro

    Fuzzy logic control has been applied to various applications in power systems. Its control rules and membership functions are typically obtained by trial and error methods or experience knowledge. Proposed here is the application of a micro-genetic algorithm (micro-GA) to simultaneously design optimal membership functions and control rules for STATCOM. First, we propose a simple approach to extract membership functions and fuzzy logic control rules based on observed signals. Then a proposed GA will be applied to optimize membership functions and its control rules. To validate the effectiveness of the proposed approach, several simulation studies have been performed on a multimachine power system. Simulation results show that the proposed fuzzy logic controller with STATCOM can effectively and robustly enhance the damping of oscillations.

  20. Genetic and epigenetic control of gene expression by CRISPR–Cas systems [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Albert Lo

    2017-05-01

    Full Text Available The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR–CRISPR-associated (Cas systems has revolutionized the way researchers edit genomes. Engineering of catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas] combined with transcriptional repressors, activators, or epigenetic modifiers enable sequence-specific regulation of gene expression and chromatin state. These CRISPR–Cas-based technologies have contributed to the rapid development of disease models and functional genomics screening approaches, which can facilitate genetic target identification and drug discovery. In this short review, we will cover recent advances of CRISPR–dCas9 systems and their use for transcriptional repression and activation, epigenome editing, and engineered synthetic circuits for complex control of the mammalian genome.

  1. Optimization of the test intervals of a nuclear safety system by genetic algorithms, solution clustering and fuzzy preference assignment

    International Nuclear Information System (INIS)

    Zio, E.; Bazzo, R.

    2010-01-01

    In this paper, a procedure is developed for identifying a number of representative solutions manageable for decision-making in a multiobjective optimization problem concerning the test intervals of the components of a safety system of a nuclear power plant. Pareto Front solutions are identified by a genetic algorithm and then clustered by subtractive clustering into 'families'. On the basis of the decision maker's preferences, each family is then synthetically represented by a 'head of the family' solution. This is done by introducing a scoring system that ranks the solutions with respect to the different objectives: a fuzzy preference assignment is employed to this purpose. Level Diagrams are then used to represent, analyze and interpret the Pareto Fronts reduced to the head-of-the-family solutions

  2. Eimeria species occurrence varies between geographic regions and poultry production systems and may influence parasite genetic diversity.

    Science.gov (United States)

    Chengat Prakashbabu, B; Thenmozhi, V; Limon, G; Kundu, K; Kumar, S; Garg, R; Clark, E L; Srinivasa Rao, A S R; Raj, D G; Raman, M; Banerjee, P S; Tomley, F M; Guitian, J; Blake, D P

    2017-01-15

    Coccidiosis is one of the biggest challenges faced by the global poultry industry. Recent studies have highlighted the ubiquitous distribution of all Eimeria species which can cause this disease in chickens, but intriguingly revealed a regional divide in genetic diversity and population structure for at least one species, Eimeria tenella. The drivers associated with such distinct geographic variation are unclear, but may impact on the occurrence and extent of resistance to anticoccidial drugs and future subunit vaccines. India is one of the largest poultry producers in the world and includes a transition between E. tenella populations defined by high and low genetic diversity. The aim of this study was to identify risk factors associated with the prevalence of Eimeria species defined by high and low pathogenicity in northern and southern states of India, and seek to understand factors which vary between the regions as possible drivers for differential genetic variation. Faecal samples and data relating to farm characteristics and management were collected from 107 farms from northern India and 133 farms from southern India. Faecal samples were analysed using microscopy and PCR to identify Eimeria occurrence. Multiple correspondence analysis was applied to transform correlated putative risk factors into a smaller number of synthetic uncorrelated factors. Hierarchical cluster analysis was used to identify poultry farm typologies, revealing three distinct clusters in the studied regions. The association between clusters and presence of Eimeria species was assessed by logistic regression. The study found that large-scale broiler farms in the north were at greatest risk of harbouring any Eimeria species and a larger proportion of such farms were positive for E. necatrix, the most pathogenic species. Comparison revealed a more even distribution for E. tenella across production systems in south India, but with a lower overall occurrence. Such a polarised region- and

  3. Optimising electrical system architecture using genetic algorithms; Optimierung der Bordnetzarchitektur mit Hilfe genetischer Algorithmen

    Energy Technology Data Exchange (ETDEWEB)

    Luebke, A. [Volkswagen AG, Wolfsburg (Germany). Fahrzeug-Elektrik/ -Elektronik Vorentwicklung; Reuss, H.C. [Technische Univ. Dresden (Germany). Inst. fuer Verbrennungsmotoren und Kraftfahrzeuge

    2000-06-01

    Control units in vehicles are increasingly being networked. Framework conditions, for example the cost of network nodes, change so rapidly that an optimised network rarely survives one model generation. This article describes the possible applications of a genetic algorithm which can be used to optimise the architecture of the datanet quickly and easily. (orig.) [German] Die Vernetzung der Steuergeraete im Kraftfahrzeug nimmt staendig zu. Dabei aendern sich die Randbedingungen, zum Beispiel die Kosten von Netzknoten, laufend, so dass eine einmal optimierte Architektur der Vernetzung schon fuer das naechste Fahrzeugmodell nicht mehr das Optimum darstellt. Der vorliegende Artikel beschreibt die Anwendungsmoeglichkeit eines genetischen Algorithmus, mit dessen Hilfe sich die Architektur des Datennetzes schnell und zuverlaessig optimieren laesst. (orig.)

  4. Nuclear Electric Vehicle Optimization Toolset (NEVOT): Integrated System Design Using Genetic Algorithms

    Science.gov (United States)

    Tinker, Michael L.; Steincamp, James W.; Stewart, Eric T.; Patton, Bruce W.; Pannell, William P.; Newby, Ronald L.; Coffman, Mark E.; Qualls, A. L.; Bancroft, S.; Molvik, Greg

    2003-01-01

    The Nuclear Electric Vehicle Optimization Toolset (NEVOT) optimizes the design of all major Nuclear Electric Propulsion (NEP) vehicle subsystems for a defined mission within constraints and optimization parameters chosen by a user. The tool uses a Genetic Algorithm (GA) search technique to combine subsystem designs and evaluate the fitness of the integrated design to fulfill a mission. The fitness of an individual is used within the GA to determine its probability of survival through successive generations in which the designs with low fitness are eliminated and replaced with combinations or mutations of designs with higher fitness. The program can find optimal solutions for different sets of fitness metrics without modification and can create and evaluate vehicle designs that might never be conceived of through traditional design techniques. It is anticipated that the flexible optimization methodology will expand present knowledge of the design trade-offs inherent in designing nuclear powered space vehicles and lead to improved NEP designs.

  5. Modeling Nonlinear Systems by a Fuzzy Logic Neural Network Using Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Abdel-Fattah Attia

    2001-01-01

    Full Text Available The main aim of this work is to optimize the parameters of the constrained membership function of the Fuzzy Logic Neural Network (FLNN. The constraints may be an indirect definition of the search ranges for every membership shape forming parameter based on 2nd order fuzzy set specifications. A particular method widely applicable in solving global optimization problems is introduced. This approach uses a Linear Adapted Genetic Algorithm (LAGA to optimize the FLNN parameters. In this paper the derivation of a 2nd order fuzzy set is performed for a membership function of Gaussian shape, which is assumed for the neuro-fuzzy approach. The explanation of the optimization method is presented in detail on the basis of two examples.

  6. Genetic or mechanical sexing system for the Mediterranean fruit fly, Ceratitis capitata (Wied.)

    International Nuclear Information System (INIS)

    Walder, J.M.M.

    1990-01-01

    A black puparium, monofactorial mutant was isolated in 1983 from a laboratory colony of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann). The mutant was used to construct a genetic sexing strain based on pupal sorting. Translocations were induced in wild male adults, 48 hours old, by gamma radiation (55 Gy; 60 Co). These males were crossed to black pupae females and produced two pupal sorting strains (T-44 and T-213) in 1987. These strains were lost after six generations. In another series of translocation inductions the strain T-87B was screened. Rearing the strain for eight generations in the laboratory provided no indication of instability in the strain. T-87B is now being mass reared. (author). 16 refs, 4 tabs

  7. Estimation of genetic risk and detriment from barite examinations of the digestive system in Malaga (Spain)

    International Nuclear Information System (INIS)

    Ruiz Cruces, R.; Perez Martinez, M.; Diez de los Rios Delgado, A.

    1997-01-01

    The objective of the study is to estimate the populations involved in barite examinations of the digestive apparatus. The values of genetically significant dose (DGS), somatically significant dose (DSS) and damage (G) are presented, as derived from the calculation of dose-area, doses in organs and effective doses. At first glance, these complex examinations contribute higher values than the simple examinations. However, our data demonstrate the opposite: DGS = 0.9 mSv; DSS = 1.89 mSv and G = 0.28 radiogenetic cancers per year. These values contradict the data determined for simple examinations for the same population. Although the reasons for this are multiple, the principal underlying cause might be the average age of the patients. These changes are more emphasized in the DGS, which affects the doses in the gonads of the patients after the irradiation. These results must be further compared with other work done in other countries

  8. The effect of genetic merit and production system on dairy cow fertility, measured using progesterone profiles and on-farm recording.

    Science.gov (United States)

    Pollott, G E; Coffey, M P

    2008-09-01

    The recent decline in dairy cow fertility appears to be a feature of several countries and is often linked to increased milk production, but its causes are not always obvious. A fully recorded 200-cow dairy herd, split into 2 genetic lines maintained on 2 production systems, was used to investigate the relationship between several measures of fertility, production, and energy balance. The 2 genetic lines were composed of a selection line, derived from the highest genetic merit bulls available, and a control line, maintained at the average of UK genetic merit at the time of mating. The production systems were a high-concentrate and a high-forage system. Thrice-weekly milk progesterone samples allowed an objective measurement of luteal cycling activity, and farm observations of estrus, services, and calving provided data on various measures of fertility. Energy balance in early lactation was calculated from daily live weight and weekly BCS measurements. Control line cows commenced luteal activity (C-LA) 6 d before selection line cows, had their first heat 14 d earlier, and had longer gestation periods by 3.7 d. They also had a lower incidence of silent heats. Cows on the high-forage system commenced luteal activity 6 d before those on the high-concentrate system, had longer gestation intervals by 3.9 d, held to first service better, had longer luteal phases and shorter interluteal periods in their estrus cycles. Characteristics of energy balance were used to see if they could account for the fertility differences between both genetic lines and systems. The commencement of luteal activity and day of first heat were analyzed using a REML mixed model approach. Mean energy content and mean energy balance over the first 25 d of lactation had an effect on C-LA and accounted for the differences found between production systems but not genetic lines. Day of energy balance nadir, mean energy content in the first 25 d, and C-LA affected day of first heat, but the differences

  9. Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

    Directory of Open Access Journals (Sweden)

    Martin Johnsson

    2015-05-01

    Full Text Available Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL and expression QTL (eQTL mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

  10. Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Herpertz-Dahlmann Beate

    2008-11-01

    Full Text Available Abstract Background Several lines of evidence indicate that the central cannabinoid receptor 1 (CNR1 as well as the major endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH, N-acylethanolamine-hydrolyzing acid amidase (NAAA and monoglyceride lipase (MGLL are implicated in mediating the orexigenic effects of cannabinoids. The aim of this study was to analyse whether nucleotide sequence variations in the CNR1, FAAH, NAAA and MGLL genes are associated with anorexia nervosa (AN. Methods We analysed the association of a previously described (AATn repeat in the 3' flanking region of CNR1 as well as a total of 15 single nucleotide polymorphisms (SNPs representative of regions with restricted haplotype diversity in CNR1, FAAH, NAAA or MGLL in up to 91 German AN trios (patient with AN and both biological parents using the transmission-disequilibrium-test (TDT. One SNP was additionally analysed in an independent case-control study comprising 113 patients with AN and 178 normal weight controls. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, ARMS-PCR or using 3730xl capillary sequencers. Results The TDT revealed no evidence for association for any of the SNPs or the (AATn repeat with AN (all two-sided uncorrected p-values > 0.05. The lowest p-value of 0.11 was detected for the A-allele of the CNR1 SNP rs1049353 for which the transmission rate was 59% (95% confidence interval 47%...70%. Further genotyping of rs1049353 in 113 additional independent patients with AN and 178 normal weight controls could not substantiate the initial trend for association (p = 1.00. Conclusion As we found no evidence for an association of genetic variation in CNR1, FAAH, NAAA and MGLL with AN, we conclude that genetic variations in these genes do not play a major role in the etiology of AN in our study groups.

  11. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    OpenAIRE

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.; Novembre, Francis J.

    2009-01-01

    The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our S...

  12. Use of noninvasive ‘bug-eggs’ to enable comparative inferences on genetic mating system with and without parental information: A study in a cattle egret colony

    Science.gov (United States)

    de Souza, Elaine Dantas; Moralez-Silva, Emmanuel; Valdes, Talita Alvarenga; Cortiço Corrêa Rodrigues, Vera Lúcia

    2017-01-01

    Colonial waterbirds such as herons, egrets and spoonbills exhibit ecological characteristics that could have promoted the evolution of conspecific brood parasitism and extra-pair copulation. However, an adequate characterization of the genetic mating systems of this avian group has been hindered by the lack of samples of elusive candidate parents which precluded conducting conventional parentage allocation tests. Here, we investigate the genetic mating system of the invasive cattle egret using hematophagous insects contained in fake eggs to collect blood from incubating adults in a wild breeding colony. We tested a protocol with a previously unused Neotropical Triatominae, Panstrongylus megistus, obtained blood samples from males and females in 31 nests built on trees, drew blood from 89 nestlings at those nests, and genotyped all samples at 14 microsatellite loci, including six new species-specific loci. We comparatively addressed the performance of parentage allocation versus kinship classification of nestlings to infer the genetic mating system of cattle egrets. In line with previous behavioral observations, we found evidence in support of a non-monogamous genetic mating system, including extra-pair paternity (EPP) and conspecific brood parasitism (CBP). Parentage allocation tests detected a higher percentage of nests with alternative reproductive tactics (EPP: 61.7%; CBP: 64.5%) than the kinship classification method (EPP: 50.0%; CBP: 43.3%). Overall, these results indicate that rates of alternative reproductive tactics inferred in the absence of parental genetic information could be underestimated and should be interpreted with caution. This study highlights the importance of incorporating samples from candidate parents to adequately determine the genetic mating system of a species. We expand knowledge on the reproductive tactics of colonial waterbirds, contributing novel data on the genetic mating system of the cattle egret, valuable for the design of

  13. Use of noninvasive 'bug-eggs' to enable comparative inferences on genetic mating system with and without parental information: A study in a cattle egret colony.

    Directory of Open Access Journals (Sweden)

    Carolina Isabel Miño

    Full Text Available Colonial waterbirds such as herons, egrets and spoonbills exhibit ecological characteristics that could have promoted the evolution of conspecific brood parasitism and extra-pair copulation. However, an adequate characterization of the genetic mating systems of this avian group has been hindered by the lack of samples of elusive candidate parents which precluded conducting conventional parentage allocation tests. Here, we investigate the genetic mating system of the invasive cattle egret using hematophagous insects contained in fake eggs to collect blood from incubating adults in a wild breeding colony. We tested a protocol with a previously unused Neotropical Triatominae, Panstrongylus megistus, obtained blood samples from males and females in 31 nests built on trees, drew blood from 89 nestlings at those nests, and genotyped all samples at 14 microsatellite loci, including six new species-specific loci. We comparatively addressed the performance of parentage allocation versus kinship classification of nestlings to infer the genetic mating system of cattle egrets. In line with previous behavioral observations, we found evidence in support of a non-monogamous genetic mating system, including extra-pair paternity (EPP and conspecific brood parasitism (CBP. Parentage allocation tests detected a higher percentage of nests with alternative reproductive tactics (EPP: 61.7%; CBP: 64.5% than the kinship classification method (EPP: 50.0%; CBP: 43.3%. Overall, these results indicate that rates of alternative reproductive tactics inferred in the absence of parental genetic information could be underestimated and should be interpreted with caution. This study highlights the importance of incorporating samples from candidate parents to adequately determine the genetic mating system of a species. We expand knowledge on the reproductive tactics of colonial waterbirds, contributing novel data on the genetic mating system of the cattle egret, valuable for the

  14. Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis.

    Directory of Open Access Journals (Sweden)

    Charles R Farber

    2011-04-01

    Full Text Available Significant advances have been made in the discovery of genes affecting bone mineral density (BMD; however, our understanding of its genetic basis remains incomplete. In the current study, genome-wide association (GWA and co-expression network analysis were used in the recently described Hybrid Mouse Diversity Panel (HMDP to identify and functionally characterize novel BMD genes. In the HMDP, a GWA of total body, spinal, and femoral BMD revealed four significant associations (-log10P>5.39 affecting at least one BMD trait on chromosomes (Chrs. 7, 11, 12, and 17. The associations implicated a total of 163 genes with each association harboring between 14 and 112 genes. This list was reduced to 26 functional candidates by identifying those genes that were regulated by local eQTL in bone or harbored potentially functional non-synonymous (NS SNPs. This analysis revealed that the most significant BMD SNP on Chr. 12 was a NS SNP in the additional sex combs like-2 (Asxl2 gene that was predicted to be functional. The involvement of Asxl2 in the regulation of bone mass was confirmed by the observation that Asxl2 knockout mice had reduced BMD. To begin to unravel the mechanism through which Asxl2 influenced BMD, a gene co-expression network was created using cortical bone gene expression microarray data from the HMDP strains. Asxl2 was identified as a member of a co-expression module enriched for genes involved in the differentiation of myeloid cells. In bone, osteoclasts are bone-resorbing cells of myeloid origin, suggesting that Asxl2 may play a role in osteoclast differentiation. In agreement, the knockdown of Asxl2 in bone marrow macrophages impaired their ability to form osteoclasts. This study identifies a new regulator of BMD and osteoclastogenesis and highlights the power of GWA and systems genetics in the mouse for dissecting complex genetic traits.

  15. [Use of a synthetic peptide of HIV-2 glycoprotein 36 in antigen mixtures for the immunodiagnosis of HIV types 1 and 2].

    Science.gov (United States)

    Ramos Martínez, Grisell; Valdespino-Díaz, Marcos Antonio; Hernández Marín, Milenen; Valle Carvajal, Elizabeth; Selles León, María Elena; Pozo Peña, Lilliam

    2015-12-01

    The HIV-2 glycoprotein 36 (gp36) is often used in ELISA. An evaluation of the diagnostic indexes of antigen mixtures with a synthetic peptide of HIV2 gp36 (5) is performed in this study. Five mixtures of gp36 (5) and the recombinant proteins of HIV1/2 were prepared. A total of 1306 samples were evaluated with UMELISA HIV1+2 RECOMBINANT used as reference. The variant (V-1) showed very good agreement as regards the reference method. The V-1 variant was shown to be highly effective in the immunodiagnosis of HIV 1/2. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  16. Revalidation of CoaguChek XS Plus System for INR Monitoring in Taiwanese Patients: Effects of Clinical and Genetic Factors

    Directory of Open Access Journals (Sweden)

    Chao-Hua Fu

    2014-12-01

    Full Text Available Background:In this study, we evaluated the performance of a point-of-care device, the CoaguChek XS Plus system, in the determination of prothrombin time and international normalized ratio (INR based on ISO17593: 2007 criteria in Taiwanese patients. The underlying clinical and genetic factors were also investigated. Methods: Fifty patients receiving warfarin therapy were enrolled in this study. The accuracy of the CoaguChek XS Plus system was evaluated with linear regression analysis and bias plot by comparing with the data measured using Sysmex CA-1500. The clinical and genetic factors that may have caused a bias of ΃ 0.5 INR were evaluated with Fisher's exact test. Results: From the 50 patients, 93 INR values were collected by each method. Linear regression analysis indicated a high correlation with r = 0.96, a slope of 1.05, and an intercept of - 0.14. Eight patients showed an INR bias ΃0.5 between the two methods. Only aspartate aminotransferase (AST >34 U/L (3/8, 37.5% vs. 3/42, 7.1%; p = 0.044 and alanine aminotransferase (ALT >36 U/L (3/8, 37.5% vs. 3/42, 7.1%; p = 0.044 were significantly different from each other. No differences were observed for hypoalbuminemia, elevated creatinine, anemia, and the polymorphisms of VKORC1 and CYP2C9. Conclusions: The CoaguChek XS Plus system presented results that were comparable with those obtained using laboratory CA-1500 method. Both methods fell within INR in the range of 2-4.5 defined by ISO17593:2007 and the clinically recognized therapeutic INR range of 2-3.5. Elevated AST and ALT levels might have interfered with the INR results.

  17. Genetic background of methane emission by Dutch Holstein Friesian cows measured with infrared sensors in automatic milking systems.

    Science.gov (United States)

    van Engelen, S; Bovenhuis, H; van der Tol, P P J; Visker, M H P W

    2018-03-01

    International environmental agreements have led to the need to reduce methane emission by dairy cows. Reduction could be achieved through selective breeding. The aim of this study was to quantify the genetic variation of methane emission by Dutch Holstein Friesian cows measured using infrared sensors installed in automatic milking systems (AMS). Measurements of CH 4 and CO 2 on 1,508 Dutch Holstein Friesian cows located on 11 commercial dairy farms were available. Phenotypes per AMS visit were the mean of CH 4 , mean of CO 2 , mean of CH 4 divided by mean of CO 2 , and their log 10 -transformations. The repeatabilities of the log 10 -transformated methane phenotypes were 0.27 for CH 4 , 0.31 for CO 2 , and 0.14 for the ratio. The log 10 -transformated heritabilities of these phenotypes were 0.11 for CH 4 , 0.12 for CO 2 , and 0.03 for the ratio. These results indicate that measurements taken using infrared sensors in AMS are repeatable and heritable and, thus, could be used for selection for lower CH 4 emission. Furthermore, it is important to account for farm, AMS, day of measurement, time of day, and lactation stage when estimating genetic parameters for methane phenotypes. Selection based on log 10 -transformated CH 4 instead of the ratio would be expected to give a greater reduction of CH 4 emission by dairy cows. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  18. Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein

    International Nuclear Information System (INIS)

    Albariño, César G.; Wiggleton Guerrero, Lisa; Lo, Michael K.; Nichol, Stuart T.; Towner, Jonathan S.

    2015-01-01

    Previous studies have demonstrated the potential application of reverse genetics technology in studying a broad range of aspects of viral biology, including gene regulation, protein function, cell entry, and pathogenesis. Here, we describe a highly efficient reverse genetics system used to generate recombinant Ebola virus (EBOV) based on a recent isolate from a human patient infected during the 2014–2015 outbreak in Western Africa. We also rescued a recombinant EBOV expressing a fluorescent reporter protein from a cleaved VP40 protein fusion. Using this virus and an inexpensive method to quantitate the expression of the foreign gene, we demonstrate its potential usefulness as a tool for screening antiviral compounds and measuring neutralizing antibodies. - Highlights: • Recombinant Ebola virus (EBOV) derived from Makona variant was rescued. • New protocol for viral rescue allows 100% efficiency. • Modified EBOV expresses a green fluorescent protein from a VP40-fused protein. • Modified EBOV was tested as tool to screen antiviral compounds and measure neutralizing antibodies

  19. Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein

    Energy Technology Data Exchange (ETDEWEB)

    Albariño, César G., E-mail: calbarino@cdc.gov; Wiggleton Guerrero, Lisa; Lo, Michael K.; Nichol, Stuart T.; Towner, Jonathan S.

    2015-10-15

    Previous studies have demonstrated the potential application of reverse genetics technology in studying a broad range of aspects of viral biology, including gene regulation, protein function, cell entry, and pathogenesis. Here, we describe a highly efficient reverse genetics system used to generate recombinant Ebola virus (EBOV) based on a recent isolate from a human patient infected during the 2014–2015 outbreak in Western Africa. We also rescued a recombinant EBOV expressing a fluorescent reporter protein from a cleaved VP40 protein fusion. Using this virus and an inexpensive method to quantitate the expression of the foreign gene, we demonstrate its potential usefulness as a tool for screening antiviral compounds and measuring neutralizing antibodies. - Highlights: • Recombinant Ebola virus (EBOV) derived from Makona variant was rescued. • New protocol for viral rescue allows 100% efficiency. • Modified EBOV expresses a green fluorescent protein from a VP40-fused protein. • Modified EBOV was tested as tool to screen antiviral compounds and measure neutralizing antibodies.

  20. An Expert Diagnosis System for Parkinson Disease Based on Genetic Algorithm-Wavelet Kernel-Extreme Learning Machine.

    Science.gov (United States)

    Avci, Derya; Dogantekin, Akif

    2016-01-01

    Parkinson disease is a major public health problem all around the world. This paper proposes an expert disease diagnosis system for Parkinson disease based on genetic algorithm- (GA-) wavelet kernel- (WK-) Extreme Learning Machines (ELM). The classifier used in this paper is single layer neural network (SLNN) and it is trained by the ELM learning method. The Parkinson disease datasets are obtained from the UCI machine learning database. In wavelet kernel-Extreme Learning Machine (WK-ELM) structure, there are three adjustable parameters of wavelet kernel. These parameters and the numbers of hidden neurons play a major role in the performance of ELM. In this study, the optimum values of these parameters and the numbers of hidden neurons of ELM were obtained by using a genetic algorithm (GA). The performance of the proposed GA-WK-ELM method is evaluated using statical methods such as classification accuracy, sensitivity and specificity analysis, and ROC curves. The calculated highest classification accuracy of the proposed GA-WK-ELM method is found as 96.81%.

  1. PREDICTIVE CONTROL OF A BATCH POLYMERIZATION SYSTEM USING A FEEDFORWARD NEURAL NETWORK WITH ONLINE ADAPTATION BY GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    A. Cancelier

    Full Text Available Abstract This study used a predictive controller based on an empirical nonlinear model comprising a three-layer feedforward neural network for temperature control of the suspension polymerization process. In addition to the offline training technique, an algorithm was also analyzed for online adaptation of its parameters. For the offline training, the network was statically trained and the genetic algorithm technique was used in combination with the least squares method. For online training, the network was trained on a recurring basis and only the technique of genetic algorithms was used. In this case, only the weights and bias of the output layer neuron were modified, starting from the parameters obtained from the offline training. From the experimental results obtained in a pilot plant, a good performance was observed for the proposed control system, with superior performance for the control algorithm with online adaptation of the model, particularly with respect to the presence of off-set for the case of the fixed parameters model.

  2. Mathematical modeling of continuous ethanol fermentation in a membrane bioreactor by pervaporation compared to conventional system: Genetic algorithm.

    Science.gov (United States)

    Esfahanian, Mehri; Shokuhi Rad, Ali; Khoshhal, Saeed; Najafpour, Ghasem; Asghari, Behnam

    2016-07-01

    In this paper, genetic algorithm was used to investigate mathematical modeling of ethanol fermentation in a continuous conventional bioreactor (CCBR) and a continuous membrane bioreactor (CMBR) by ethanol permselective polydimethylsiloxane (PDMS) membrane. A lab scale CMBR with medium glucose concentration of 100gL(-1) and Saccharomyces cerevisiae microorganism was designed and fabricated. At dilution rate of 0.14h(-1), maximum specific cell growth rate and productivity of 0.27h(-1) and 6.49gL(-1)h(-1) were respectively found in CMBR. However, at very high dilution rate, the performance of CMBR was quite similar to conventional fermentation on account of insufficient incubation time. In both systems, genetic algorithm modeling of cell growth, ethanol production and glucose concentration were conducted based on Monod and Moser kinetic models during each retention time at unsteady condition. The results showed that Moser kinetic model was more satisfactory and desirable than Monod model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    Science.gov (United States)

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  4. The African Lupus Genetics Network (ALUGEN) registry: standardized, prospective follow-up studies in African patients with systemic lupus erythematosus.

    Science.gov (United States)

    Hodkinson, B; Mapiye, D; Jayne, D; Kalla, A; Tiffin, N; Okpechi, I

    2016-03-01

    The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. Data of patients recently (≤ 5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies. © The Author(s) 2015.

  5. Rapid genetic diagnosis with transcription-reverse transcription concerted reaction system for peritoneal recurrence and survival in colorectal cancer patients.

    Science.gov (United States)

    Hayama, Tamuro; Iinuma, Hisae; Watanabe, Toshiaki

    2007-10-01

    The prediction of peritoneal recurrence in colorectal cancer patients is required for improvement of prognosis. In this study, we focused on establishing a novel rapid RNA direct amplification system with transcription-reverse transcription concerted reaction (TRC) to detect carcinoembryonic antigen (CEA) mRNA in peritoneal washings, and its usefulness as a prophylactic tool for peritoneal recurrence and survival in patients with colorectal cancer. Peritoneal washes were obtained from 161 patients with colorectal cancer during laparotomy. CEA mRNA and porphobilinogen deaminase (PBGD) mRNA levels of peritoneal washes were detected using the TRC method. Genetic detection in the CEA mRNA of peritoneal washes by TRC showed a significant correlation to the depth of invasion, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination and stage. The overall survival and peritoneal recurrence-free survival rates of CEA mRNA-positive patients were significantly poorer than those of marker gene-negative patients. CEA mRNA levels in peritoneal washes were a significant independent prognostic factor for overall survival and peritoneal recurrence-free survival. In conclusion, our study demonstrated that the detection of CEA mRNA in peritoneal washings by TRC is a useful, rapid genetic diagnosis for the prediction of peritoneal recurrence and survival in patients with colorectal cancer.

  6. Minimally Sufficient Conditions for the Evolution of Social Learning and the Emergence of Non-Genetic Evolutionary Systems.

    Science.gov (United States)

    Gonzalez, Miguel; Watson, Richard; Bullock, Seth

    2017-01-01

    Social learning, defined as the imitation of behaviors performed by others, is recognized as a distinctive characteristic in humans and several other animal species. Previous work has claimed that the evolutionary fixation of social learning requires decision-making cognitive abilities that result in transmission bias (e.g., discriminatory imitation) and/or guided variation (e.g., adaptive modification of behaviors through individual learning). Here, we present and analyze a simple agent-based model that demonstrates that the transition from instinctive actuators (i.e., non-learning agents whose behavior is hardcoded in their genes) to social learners (i.e., agents that imitate behaviors) can occur without invoking such decision-making abilities. The model shows that the social learning of a trait may evolve and fix in a population if there are many possible behavioral variants of the trait, if it is subject to strong selection pressure for survival (as distinct from reproduction), and if imitation errors occur at a higher rate than genetic mutation. These results demonstrate that the (sometimes implicit) assumption in prior work that decision-making abilities are required is incorrect, thus allowing a more parsimonious explanation for the evolution of social learning that applies to a wider range of organisms. Furthermore, we identify genotype-phenotype disengagement as a signal for the imminent fixation of social learners, and explain the way in which this disengagement leads to the emergence of a basic form of cultural evolution (i.e., a non-genetic evolutionary system).

  7. Genetic Algorithm Based Multi-Agent System Applied to Test Generation

    Science.gov (United States)

    Meng, Anbo; Ye, Luqing; Roy, Daniel; Padilla, Pierre

    2007-01-01

    Automatic test generating system in distributed computing context is one of the most important links in on-line evaluation system. Although the issue has been argued long since, there is not a perfect solution to it so far. This paper proposed an innovative approach to successfully addressing such issue by the seamless integration of genetic…

  8. A versatile selection system for folding competent proteins using genetic complementation in a eukaryotic host

    DEFF Research Database (Denmark)

    Lyngsø, C.; Kjaerulff, S.; Muller, S.

    2010-01-01

    -control systems to retain misfolded proteins in the ER and redirect them for cytosolic degradation, thereby only allowing folded proteins to reach the cell surface. Accordingly, the folding potential of the tested protein determines the ability of autotrophic colony growth. This system was successfully...

  9. Molecular genetics of rhodopsin and phototrans duction in the visual system of Drosophila

    International Nuclear Information System (INIS)

    Zuker, C.; Cowman, A.; Montell, C.; Rubin, G.

    1987-01-01

    The authors have isolated the genes encoding four Drosophila visual pigments. Each of these opsins is expressed in a set of functionally and anatomically distinct photoreceptor cells of the eye. One is expressed in the six outer photoreceptor cells (R1-R6), the second in the central R8 photoreceptor cell, and the other two in the UV sensitive R7 photoreceptor cells. They have determined the structure and nucleotide sequence of each of these genes. They have used P element-mediated gene transfer to introduce the cloned structural gene for the R1-R6 opsin in the Drosophila germline and restored the ninaE mutant phenotype to wild-type. In an attempt to study the contribution of the various opsins to the specific functional properties of the different photoreceptor cell types, they have genetically engineered Drosophila lines that express R8 opsin in the R1-R6 photoreceptor cells. In collaboration with Drs. Ozaki and Pak at Purdue University, they have used oligonucleotide site-directed mutagenesis to mutate selected amino acids and regions of the rhodopsin molecule and reintroduced the mutated genes into Drosophila to analyze structure-function relationships in the rhodopsin molecule

  10. Genetic programming system for building block analysis to enhance data analysis and data mining techniques

    Science.gov (United States)

    Eick, Christoph F.; Sanz, Walter D.; Zhang, Ruijian

    1999-02-01

    Recently, many computerized data mining tools and environments have been proposed for finding interesting patterns in large data collections. These tools employ techniques that originate from research in various areas, such as machine learning, statistical data analysis, and visualization. Each of these techniques makes assumptions concerning the composition of the data collection to be analyzed. If the particular data collection does not meet these assumptions well, the technique usually performs poorly. For example, decision tree tools, such as C4.5, rely on rectangular approximations, which do not perform well if the boundaries between different classes have other shapes, such as a 45 degree line or elliptical shapes. However, if we could find a transformation f that transforms the original attribute space, in which class boundaries are more, better rectangular approximations could be obtained. In this paper, we address the problem of finding such transformations f. We describe the features of the tool, WOLS, whose goal is the discovery of ingredients for such transformation functions f, which we call building blocks. The tool employs genetic programming and symbolic regression for this purpose. We also present and discuss the results of case studies, using the building block analysis tool, in the areas of decision tree learning and regression analysis.

  11. Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview

    Directory of Open Access Journals (Sweden)

    Hwa Chia Chai

    2012-01-01

    Full Text Available SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian populatio